Sample records for chronic clozapine treatment

  1. F3. A CASE OF LEUKOCYTOSIS ASSOCIATED WITH CLOZAPINE TREATMENT FOR THE MANAGEMENT OF CHRONIC SCHIZOPHRENIA

    PubMed Central

    Song, Min-Kyu; Bahk, Won-Myong; Kwon, Young Joon; Yoon, Bo-Hyun; Lee, Sang-Yeol; Jon, Duk-In; Park, Sung-Yong; Lim, Eunsung

    2018-01-01

    Abstract Background Clozapine is an atypical antipsychotic drug with therapeutic efficacy through serotonin-dopamine antagonism. It has been used for the management of treatment-resistant schizophrenia and reducing the risk of suicidal behavior. In addition to agranulocytosis and leukopenia, clozapine has also been reported to be associated with other types of blood dyscrasias, including leukocytosis. We wish to report a case of leukocytosis associated with clozapine treatment in a patient of chronic schizophrenia. Methods Our patient is a 48-year-old woman with a diagnosis of schizophrenia since the age of 22. She has a history of numerous hospitalizations and substantial treatment with conservative antipsychotics. We evaluated her medical and psychiatric history as well as mental status. Then We assumed that she might have treatment-resistant schizophrenia and accordingly commenced treatment with clozapine. At the time of admission, her WBC count was 8.01 × 109/L and ANC was 5110. Clozapine was started at 3rd hospital day. We stopped aripiprazole and gradually increased clozapine. Only 2mg of lorazepam was used in combination with clozapine. Remission was achieved with 450 mg/day of clozapine. WBC on the 1st day of treatment was 12.41 × 109/L (ANC; 9481) and clozapine was 300mg/day. WBC on the 18th day of treatment was 15.32 × 109/L (ANC; 12501), and at that time, her clozapine dosage was 450mg/day. At this point, her vital sign was within normal range and physical examination did not showed any infectious signs. On the 25th day of treatment, WBC count was 22.1 × 109/L and ANC was 17680. However, no general medical condition to explain the leukocytosis was found. We concluded that her leukocytosis was linked to clozapine, and decided to taper out clozapine despite there being no medical contraindication. After two weeks from starting blonanserin and olanzapine, WBC count normalized. Fortunately, despite replacing the medication, the remission was maintained

  2. Persistent effects of chronic clozapine on the cellular and behavioral responses to LSD in mice

    PubMed Central

    Moreno, José L.; Holloway, Terrell; Umali, Adrienne; Rayannavar, Vinayak; Sealfon, Stuart C.

    2013-01-01

    Rationale In schizophrenia patients, optimal treatment with antipsychotics requires weeks to months of sustained drug therapy. However, single administration of antipsychotic drugs can reverse schizophrenia-like behavioral alterations in rodent models of psychosis. This raises questions about the physiological relevance of such antipsychotic-like activity. Objective This study evaluates the effects of chronic treatment with clozapine on the cellular and behavioral responses induced by the hallucinogenic serotonin 5-HT2A receptor agonist lysergic acid diethylamide (LSD) as a mouse model of psychosis. Method Mice were treated chronically (21 days) with 25 mg/kg/day clozapine. Experiments were conducted 1, 7, 14, and 21 days after the last clozapine administration. [3H]Ketanserin binding and 5-HT2A mRNA expression were determined in mouse somatosensory cortex. Head-twitch behavior, expression of c-fos, which is induced by all 5-HT2A agonists, and expression of egr-1 and egr-2, which are LSD-like specific, were assayed. Results Head-twitch response was decreased and [3H]ketanserin binding was downregulated in 1, 7, and 14 days after chronic clozapine. 5-HT2A mRNA was reduced 1 day after chronic clozapine. Induction of c-fos, but not egr-1 and egr-2, was rescued 7 days after chronic clozapine. These effects were not observed after short treatment (2 days) with clozapine or chronic haloperidol (1 mg/kg/day). Conclusion Our findings provide a murine model of chronic atypical antipsychotic drug action and suggest downregulation of the 5-HT2A receptor as a potential mechanism involved in these persistent therapeutic-like effects. PMID:22842765

  3. Chronic clozapine treatment improves prenatal infection-induced working memory deficits without influencing adult hippocampal neurogenesis.

    PubMed

    Meyer, Urs; Knuesel, Irene; Nyffeler, Myriel; Feldon, Joram

    2010-03-01

    Converging evidence indicates that prenatal exposure to immune challenge can induce long-term cognitive deficits relevant to schizophrenia. Such cognitive impairments may be related to deficient hippocampal neurogenesis at adult age. In the present study, we sought evidence for the possibility that chronic treatment with the reference atypical antipsychotic drug clozapine may improve prenatal infection-induced cognitive dysfunctions by stimulating adult hippocampal neurogenesis. This hypothesis was tested in a well-established mouse model of prenatal immune challenge which is based on prenatal administration of the viral mimic, polyriboinosinic-polyribocytidilic acid (PolyI:C). We found that maternal PolyI:C (5 mg/kg, i.v.) exposure on gestation day 17 led to significant spatial working memory impairment and reduced hippocampal neurogenesis in the resulting offspring at adult age. The latter effect was apparent in postmortem immunohistochemical analyses of the cell proliferation marker bromodeoxyuridine and the microtubule-associated protein doublecortin, a marker of newborn neuronal cells. Chronic (3 weeks) administration of clozapine (5 mg/kg/day, i.p.) significantly improved the prenatal PolyI:C-induced working memory deficits, while at the same time, it negatively affected working memory performance in adult offspring born to control mothers. These bidirectional cognitive effects of clozapine were not paralleled by concomitant effects on adult hippocampal neurogenesis. Our findings do not support the hypothesis that the atypical antipsychotic drug clozapine may influence cognitive functions by acting on adult neurogenesis in the hippocampus, regardless of whether the drug is administered to subjects with or without a neurodevelopmental predisposition to adult neuropathology.

  4. Comparative study of clozapine, electroshock and the combination of ECT with clozapine in treatment-resistant schizophrenic patients.

    PubMed

    Masoudzadeh, A; Khalilian, A R

    2007-12-01

    The aim of this study was to compare the results of treatment with clozapine alone, Electroshock (ECT) alone and the combination of clozapine with ECT in treatment-resistant schizophrenic patients. Eighteen treatment-resistant schizophrenic patients were assigned to three equal groups: one group was given clozapine; one group was treated with ECT and one group was treated with the combination of clozapine and ECT. The treatment response was evaluated using the PANSS criteria and the data were analyzed with ANOVA. Combination therapy was superior to single modality therapy. The reduction of PANSS scores was 46% in the clozapine group, 40% in the ECT groups and 71% in the combination group, the difference between the combination group and the other groups was statistically significant (p < 0.05). Patients had a quick response to combination treatment, which resulted in a higher cure rate of positive and negative symptoms and improved the patients general performance. There were no significant adverse effects with combination treatment. Combination treatment with clozapine and ECT was safe and effective in treatment-resistant schizophrenic patients. It should be considered for the treatment of treatment-resistant schizophrenic patients.

  5. Treatment of Hypochondriasis in Two Schizophrenia Patients Using Clozapine

    PubMed Central

    2017-01-01

    Hypochondriasis (HYPO), an obsessive-compulsive spectrum disorder, is frequent in patients with schizophrenia (SCH) (20%), especially among those treated with clozapine (36.7%). Treatment options for OCS/OCD in patients under clozapine (CLZ) include combining clozapine with amisulpride/aripiprazole or a mood stabilizer, augmenting clozapine with a serotoninergic reuptake inhibitor, adding cognitive behavioural therapy, and gradually reducing dosage. No treatments have been proposed for HYPO in patients using clozapine so we examine these options in 2 cases and report the results. Among treatments delivered, only dosage reduction adequately worked. We recommend caution when thinking about escalating treatment and suggest trying it only when alternative interventions were not successful and weighing risk and benefits of this therapeutic strategy. Further research is needed to confirm the hypothesis that CLZ treatment induces hypochondriac symptoms, to investigate the prevalence of the phenomenon, and, mostly, to identify possible treatment strategies. PMID:28642831

  6. Rapid clozapine titration in treatment-refractory bipolar disorder.

    PubMed

    Ifteni, Petru; Correll, Christoph U; Nielsen, Jimmi; Burtea, Victoria; Kane, John M; Manu, Peter

    2014-09-01

    Clozapine is effective in treatment-refractory bipolar disorder (BD). Guidelines recommend slow titration to prevent seizures, hypotension and myocarditis, but this stance is not supported by comparative data. To evaluate the safety and effectiveness of rapid clozapine titration in BD. Analysis of a consecutive cohort of treatment-refractory BD patients with mixed/manic episode admitted on alternate days to one of two units of a psychiatric hospital. On one unit, clozapine was started at 25mg followed by 25-50mg as needed every 6h (maximum=100mg/day) on day 1, followed by increases of 25-100mg/day. On the other unit, clozapine was initiated with 25mg in day 1, followed by increases of 25-50mg/day. The primary outcome was the number of days from starting clozapine until readiness for discharge, adjusted in logistic regression for the number of antipsychotics tried during the hospitalization, psychotropic co-treatments and presence of psychotic features. Patients subject to rapid (N=44) and standard (N=23) titration were similar in age, gender, smoking status, body mass index, illness severity at baseline and discharge, and highest clozapine dose. Clozapine was discontinued due to hypotension (N=1) and pneumonia (N=1) during rapid titration, and for excessive sedation (N=1) in each titration group. The number of hospital days from starting clozapine until readiness for discharge was 3.8 days shorter in the rapid titration group (12.7±6.3 vs. 16.5±5.8, p=0.0077). Rapid clozapine titration appeared safe and effective for treatment-refractory BD. The potential for shorter hospital stays justifies prospective trials of this method. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Treatment pathway and patterns of clozapine prescribing for schizophrenia in New Zealand.

    PubMed

    Wheeler, Amanda J

    2008-06-01

    To describe the treatment pathway and patterns of clozapine use in patients with schizophrenia, including coprescribed psychotropic medications, and compare the extent of coprescribing of clozapine with that of non-clozapine schizophrenia treatment in community mental health services in the Auckland and Northland regions of New Zealand. A retrospective chart review was conducted for adult outpatients receiving care from community mental health services on October 31, 2004. Data collected for all patients prescribed an antipsychotic included demographics (sex, age, ethnicity); principal diagnosis (Diagnostic and Statistical Manual of Mental Disorders, 4th edition); comorbid conditions; duration of mental illness; psychiatric admissions; and treatment information (psychotropic medications, with dose and route of administration). If clozapine had been started after the introduction of full government prescription subsidy (February 1999), additional data, including year of initiation and prior antipsychotic history, were collected. Analysis included all outpatients with a diagnosis of schizophrenia (including schizoaffective disorder). Antipsychotics were prescribed for 2796 schizophrenia patients; 32.8% were prescribed clozapine, with a mean dose of 372 mg/day and an average duration of illness of 9.7 years before starting clozapine. Patients who had started treatment after clozapine was funded by the government (59.3%) had received a median of 3 antipsychotic drugs prior to starting clozapine; most of the treatment regimens included 1 second-generation antipsychotic (91.2%). Clozapine patients were less likely to be coprescribed another antipsychotic compared with non-clozapine patients (11.7% vs 17.6%; p < 0.001). Both the clozapine and non-clozapine groups had a low total number of psychotropic medications prescribed (median 2); for clozapine patients, the second drug was most likely to be for treatment of hypersalivation. Outpatients with treatment

  8. Hemoperfusion in the treatment of acute clozapine intoxication in China.

    PubMed

    He, Jia-Li; Xiang, Yu-Tao; Li, Wen-Biao; Cai, Zhuo-Ji; Ungvari, Gabor Sandor

    2007-12-01

    No systematic study has focused on the characteristics and outcome of acute clozapine intoxication, although clozapine is the most widely used antipsychotic agent in China. The study reported herein examined the features of clozapine intoxication and the therapeutic effect of hemoperfusion (HP). In a retrospective chart review, the notes of 47 patients who attempted suicide by ingesting large amounts of clozapine and were treated at the only psychiatric emergency service in Beijing were analyzed. Of the 20 unconscious patients with plasma clozapine concentrations of more than 2000 ng/mL, 14 received a combination of HP and symptomatic treatment, whereas the other 6 and the remaining 27 patients received only symptomatic treatment. Patients' psychiatric conditions and both plasma clozapine and norclozapine concentrations were closely monitored and registered. One patient died of pulmonary edema and subsequent heart failure, but the rest of the patients recovered without any sequelae. Patients who received HP regained consciousness significantly faster than their counterparts with the same level of clozapine plasma concentration (>2000 ng/mL) who did not receive HP. A combination of HP and symptomatic treatment is the best therapeutic option when plasma clozapine concentration is high.

  9. Eosinophilia and parotitis occurring early in clozapine treatment.

    PubMed

    Saguem, Bochra Nourhène; Bouhlel, Saoussen; Ben Salem, Chaker; Ben Hadj Ali, Bechir

    2015-12-01

    Mr. S is a 32-year-old male with schizophrenia. Due to poor responses to various antipsychotic medications, he was started on clozapine with the dose titrated to 300 mg/day during a 4-week period. The weekly checks of the complete blood cell count showed gradual increases in the eosinophil count from normal values to 4320 per mm(3). Mr. S did not have any symptoms except some increased salivation. Clozapine was suspended, and eosinophils gradually began to decline to the normal range. Clozapine was subsequently re-started and there were no changes in eosinophil counts. Mr. S exhibited improvement of symptoms but complained of acute auricular pain and increased salivation, 8 weeks after clozapine rechallenge. He also developed a swelling of his both parotid glands. The diagnosis of clozapine-induced parotitis was suggested. Symptomatic medication was prescribed with a favorable outcome. We report a case of a patient who developed eosinophilia shortly after clozapine use, and then developed parotitis. There is debate in the literature over how to manage these complications of clozapine treatment. Generally they do not warrant clozapine discontinuation.

  10. Clozapine potentiation of GABA mediated cortical inhibition in treatment resistant schizophrenia.

    PubMed

    Kaster, Tyler S; de Jesus, Danilo; Radhu, Natasha; Farzan, Faranak; Blumberger, Daniel M; Rajji, Tarek K; Fitzgerald, Paul B; Daskalakis, Zafiris J

    2015-07-01

    Cortical inhibition (CI) deficits have been demonstrated in schizophrenia using transcranial magnetic stimulation (TMS). These CI deficits may be related to decreased GABA activity which may be involved in schizophrenia pathophysiology. Previous cross-sectional studies have also demonstrated greater CI in patients treated with clozapine than other typical/atypical antipsychotics. However, it is not clear if these differences in CI are a result of treatment-resistant illness which necessitates clozapine or are related to clozapine treatment. TMS measures of CI (i.e., cortical silent period (CSP) and short-interval cortical inhibition (SICI)) were measured over the motor cortex in 16 patients with schizophrenia before starting clozapine, then 6 weeks and 6 months after starting clozapine. CSP was significantly longer after 6 weeks of treatment with clozapine (p=0.014). From 6 weeks to 6 months, there was no significant difference in CSP (p>0.05). Short-interval cortical inhibition (SICI) was not significantly different at any time after treatment with clozapine (p>0.05). This prospective-longitudinal study demonstrates that treatment with clozapine is associated with an increase in GABAB mediated inhibitory neurotransmission. Potentiation of GABAB may be a novel neurotransmitter mechanism that is involved in the pathophysiology and treatment of schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Reduced cardiovascular fitness associated with exposure to clozapine in individuals with chronic schizophrenia.

    PubMed

    Kim, David D; Lang, Donna J; Procyshyn, Ric M; Woodward, Melissa L; Kaufman, Kai; White, Randall F; Honer, William G; Warburton, Darren E R

    2018-04-01

    Studies show that individuals with schizophrenia have impaired cardiovascular fitness (i.e., low peak aerobic power (VO 2 peak)). It is speculated that antipsychotics with adverse cardiovascular and metabolic profiles, in particular clozapine, have a significant impact on VO 2 peak. In this cross-sectional study, we examined whether exposure to clozapine was associated with further reduced VO 2 peak compared with non-clozapine antipsychotics. Thirty participants with chronic schizophrenia or schizoaffective disorder were divided into clozapine and non-clozapine groups. Mean daily doses of antipsychotics were standardized to chlorpromazine equivalents and haloperidol equivalents for antagonism of alpha 1 - and alpha 2 -adrenergic receptors. Participants completed an incremental-to-maximal symptom-limited exercise test on a cycle ergometer for the assessment of VO 2 peak. The clozapine group demonstrated significantly lower VO 2 peak than the non-clozapine group. Haloperidol equivalents for alpha-adrenergic receptor antagonism, but not chlorpromazine equivalents, demonstrated significant inverse associations with VO 2 peak. The clozapine group had a significantly higher amount of antagonistic activity at alpha-adrenergic receptors than the non-clozapine group. In conclusion, exposure to clozapine was associated with further reduced cardiovascular fitness, which may be explained by the drug's greater antagonistic activity at alpha-adrenergic receptors. Cardiovascular fitness needs to be promoted in individuals treated with antipsychotics, particularly clozapine, to prevent the risk of cardiovascular disease and mortality. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Rapid Clozapine Titration in Patients with Treatment Refractory Schizophrenia.

    PubMed

    Poyraz, Cana Aksoy; Özdemir, Armağan; Sağlam, Nazife Gamze Usta; Turan, Şenol; Poyraz, Burç Çağrı; Tomruk, Nesrin; Duran, Alaattin

    2016-06-01

    The aim of this study is to evaluate the safety and effectiveness of rapid clozapine titration in patients with schizophrenia in hospital settings. We conducted a retrospective two-center cohort study to compare the safety and effectiveness of clozapine with different titration rates in treatment-refractory patients with schizophrenia. In the first center, clozapine was started at 25-50 mg followed by 50-100 mg as needed every 6 h on day 1, followed by increases of 50-100 mg/day. In the second center, titration was slower; clozapine initiated with 12.5-50 mg on day 1 followed by increases of 25-50 mg/day. The number of days between starting of clozapine until discharge was shorter in the rapid titration group (22.4 ± 8.72 vs 27.0 ± 10.5, p = 0.1). Number of days of total hospital stay were significantly shorter in the rapid titration group (29.6 ± 10.6 vs 41.2 ± 14.8, p = 0.002). Hypotension was more common in the rapid titration group and one patient had suspected myocarditis. Rapid clozapine titration appeared safe and effective. The length of stay following initiation of clozapine was shorter in the rapid-titration group, although this was not statistically significant. However starting clozapine earlier together with rapid titration has significantly shortened the length of hospital stay in patients with treatment refractory schizophrenia.

  13. Prevalence of extrapyramidal syndromes in psychiatric inpatients and the relationship of clozapine treatment to tardive dyskinesia.

    PubMed

    Modestin, J; Stephan, P L; Erni, T; Umari, T

    2000-05-05

    In 200 inpatients on regular neuroleptics, point prevalence of extrapyramidal syndromes, including Parkinson syndrome, akathisia and tardive dyskinesia (TD), was studied and found to be 20, 11 and 22%, respectively. A total of 46 patients have currently, and for a longer time, (average about 3years, median over 1year) been treated with clozapine, and 127 with typical neuroleptics (NLs). Comparing both groups, higher TD scores were found in the clozapine sample. Investigating the influence of a set of seven clinical variables on the TD score with the help of multiple regression analysis, the influence of the treatment modality disappeared, whereas the age proved to be the only significant variable. Studying the role of past clozapine therapy in patients currently on typical NLs and comparing 10 matched pairs of chronic patients with and without TD in whom a complete life-time cumulative dose of NLs was identified, a relationship between TD and length of current typical NL therapy and life-time typical NL dosage could be demonstrated. On the whole, long-term relatively extensive use of clozapine has not markedly reduced the prevalence of extrapyramidal syndromes in our psychiatric inpatient population. In particular, we failed to demonstrate a beneficial effect of clozapine on prevalence of TD. There are certainly patients who suffer from TD in spite of a long-term intensive clozapine treatment.

  14. Treatment with clozapine and its effect on plasma homovanillic acid and norepinephrine concentrations in schizophrenia.

    PubMed

    Davidson, M; Kahn, R S; Stern, R G; Hirschowitz, J; Apter, S; Knott, P; Davis, K L

    1993-02-01

    Measurement of plasma concentrations of the dopamine metabolite, homovanillic acid (pHVA), is an indirect tool to assess changes in dopamine turnover. Levels of pHVA have been reported to decrease during treatment with conventional antidopaminergic, neuroleptics, with the decrement correlating with symptomatic improvement in schizophrenic symptoms. Clozapine, an atypical neuroleptic, is the only drug proved to be effective in treatment-refractory patients. However, the mechanism mediating this unique efficacy has not been fully elucidated. This study examined the effect of clozapine on pHVA concentrations in schizophrenic patients. Since clozapine potently binds to alpha 2-adrenergic receptors, plasma norepinephrine (pNE) concentrations were also measured. Twenty-eight treatment-refractory schizophrenic patients (24 men, 4 women) were treated with clozapine (up to 600 mg/day) for 5 weeks, after a minimum 1-week drug-free period. Symptomatology and pHVA and pNE concentrations were measured at the last drug-free day and weekly for 5 weeks. Fourteen patients responded to clozapine treatment, while an equal number did not. Mean pHVA concentrations did not significantly change during treatment with clozapine. Although clozapine tended to lower pHVA concentrations in treatment responders, the effect was small and not significant. Clozapine treatment significantly raised pNE concentrations, but this did not differentiate responders from nonresponders to clozapine. These findings suggest that clozapine's effect on DA turnover is small and that clozapine may be effective in treatment-refractory schizophrenia by mechanisms other than, or in addition to, dopamine receptor blockade. However, since about one-third of NE is metabolized into HVA, the clozapine-induced increase in pNE may have overshadowed a possible lowering effect of clozapine on pHVA.

  15. Clozapine-induced EEG abnormalities and clinical response to clozapine.

    PubMed

    Risby, E D; Epstein, C M; Jewart, R D; Nguyen, B V; Morgan, W N; Risch, S C; Thrivikraman, K V; Lewine, R L

    1995-01-01

    The authors hypothesized that patients who develop gross EEG abnormalities during clozapine treatment would have a less favorable outcome than patients who did not develop abnormal EEGs. The clinical EEGs and the Brief Psychiatric Rating Scale (BPRS) scores of 12 patients with schizophrenia and 4 patients with schizoaffective disorder were compared before and during treatment with clozapine. Eight patients developed significant EEG abnormalities on clozapine; 1 showed worsening of an abnormal pre-clozapine EEG; none of these subjects had clinical seizures. BPRS scores improved significantly in the group of patients who developed abnormal EEGs but not in the group who did not. Findings are consistent with previous reports of a high incidence of clozapine-induced EEG abnormalities and a positive association between these abnormalities and clinical improvement.

  16. Clozapine Titration for People in Early Psychosis: A Chart Review and Treatment Guideline.

    PubMed

    Ballon, Jacob S; Ashfaq, Hera; Noordsy, Douglas L

    2018-06-01

    The use of clozapine, particularly in young people, is often limited by early treatment-emergent adverse effects including drowsiness and lethargy. Concerns about adverse effects, medication adherence, and the need for blood monitoring often impede the use of clozapine in this population, leading to repeated trials of less effective medications. Current clozapine dosing recommendations are based on people further in the course of their illness and thus reflect different responsiveness and sensitivities to antipsychotic medication. As such, there is a need for evidence-based guidelines for titration and dosing of clozapine among people in early psychosis. We performed a chart review of 14 people treated with clozapine within our early psychosis team. Data regarding dose titration, response, time to discontinuation, symptom severity, weight gain, and other adverse effects were gathered at clozapine initiation, 3 months, and last available visit on clozapine. People treated with slow titration within their first year of psychosis onset achieved sustained response at very low maintenance doses (mean dose = 81 mg/d, mean duration of treatment = 200 weeks) compared with slow titration with longer duration of illness (mean dose = 350 mg/d, mean duration of treatment = 68 weeks) or standard dose titration in early psychosis (mean dose = 112 mg/d, mean duration of treatment = 38 weeks). The most common adverse effects in all groups were weight gain and sedation, with the groups requiring higher mean doses reporting a broader range of adverse effects. There was no apparent difference in the clinical global impression for severity or improvement between the slow titration and standard titration groups in people with early psychosis. These observations are synthesized into a proposed treatment guideline for use of clozapine among people in early psychosis. We describe development of a slow titration approach to initiating clozapine among people in early psychosis. This

  17. Chronic administration of fluoxetine or clozapine induces oxidative stress in rat liver: a histopathological study.

    PubMed

    Zlatković, Jelena; Todorović, Nevena; Tomanović, Nada; Bošković, Maja; Djordjević, Snežana; Lazarević-Pašti, Tamara; Bernardi, Rick E; Djurdjević, Aleksandra; Filipović, Dragana

    2014-08-01

    Chronic exposure to stress contributes to the etiology of mood disorders, and the liver as a target organ of antidepressant and antipsychotic drug metabolism is vulnerable to drug-induced toxicity. We investigated the effects of chronic administration of fluoxetine (15mg/kg/day) or clozapine (20mg/kg/day) on liver injury via the measurement of liver enzymes, oxidative stress and histopathology in rats exposed to chronic social isolation (21days), an animal model of depression, and controls. The activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the liver content of carbonyl groups, malonyldialdehyde (MDA), reduced glutathione (GSH), cytosolic glutathione S-transferase (GST) and nitric oxide (NO) metabolites were determined. We also characterized nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and CuZn-superoxide dismutase (CuZnSOD) protein expression as well as histopathological changes. Increased serum ALT activity in chronically-isolated and control animals treated with both drugs was found while increased AST activity was observed only in fluoxetine-treated rats (chronically-isolated and controls). Increased carbonyl content, MDA, GST activity and decreased GSH levels in drug-treated controls/chronically-isolated animals suggest a link between drugs and hepatic oxidative stress. Increased NO levels associated with NF-κB activation and the concomitant increased COX-2 expression together with compromised CuZnSOD expression in clozapine-treated chronically-isolated rats likely reinforce oxidative stress, observed by increased lipid peroxidation and GSH depletion. In contrast, fluoxetine reduced NO levels in chronically-isolated rats. Isolation induced oxidative stress but histological changes were similar to those observed in vehicle-treated controls. Chronic administration of fluoxetine in both chronically-isolated and control animals resulted in more or less normal hepatic architecture, while clozapine in both groups

  18. [Proposal of informed consent by representation for treatment with clozapine].

    PubMed

    Mercurio, Ezequiel; Rodante, Demián

    2017-09-01

    Clozapine-induced agranulocytosis, a potentially serious adverse effect, is a limiting factor for its therapeutic use, leading to the suspension of the drug. Its annual incidence in Argentina is 0.05%. In 2000, under provision number 935, the ANMAT approved the Monitoring Program for Ambulatory and Inpatient Patients Treated with Clozapine. In this provision arises the obligation to sign the informed consent where the patient is informed of the risks and benefts of the treatment. In psychiatric care practice patients may not possess, because of their altered psychic state, the level of competence necessary to sign informed consent for their treatment with clozapine. The objective of the present work is to analyze the doctrine of Informed Consent by Representation for the users of clozapine, as well as to propose a decision algorithm for its application in clinical practice.

  19. Dramatic weight loss associated with commencing clozapine.

    PubMed

    Lally, John; McDonald, Colm

    2011-11-08

    The authors report the case of a 44-year-old man with a long history of chronic enduring schizophrenia who experienced dramatic weight loss after commencing treatment with clozapine, an antipsychotic medication characteristically associated with the greatest degree of weight gain among medical treatments for schizophrenia. He was obese with a body mass index (BMI) of 41.5 kg/m(2), but after commencing clozapine therapy he experienced an improvement in psychotic symptoms and 40% loss of his body weight attained through an altered diet and exercise regime, which resulted in him attaining a normal BMI of 24.8 kg/m(2).

  20. Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland.

    PubMed

    Ingimarsson, Oddur; MacCabe, James H; Haraldsson, Magnús; Jónsdóttir, Halldóra; Sigurdsson, Engilbert

    2016-12-12

    Data on the haematological outcomes of patients who continue clozapine treatment following neutropenia are very rare as even mild neutropenia results in mandatory discontinuation of clozapine in most countries. However, in Iceland where clozapine monitoring is less stringent allows an observational study to be done on the risk of agranulocytosis and neutropenia during treatment with clozapine compared with other antipsychotics among patients with schizophrenia. The present study is a part of a wider ongoing longitudinal study of schizophrenia in Iceland. We identified 201 patients with schizophrenia treated with clozapine and 410 patients with schizophrenia who had never been on clozapine by searching the electronic health records of Landspitali, the National University Hospital. Neutrophil counts were searched in electronic databases to identify patients who developed neutropenia/agranulocytosis and the frequency of neutrophil measurements was examined as well. The median number of days between neutrophil measurements during the first 18 weeks of clozapine treatment was 25 days but after the first 18 weeks on the drug the median became 124 days. Thirty four cases of neutropenia were identified during clozapine treatment with an average follow up time of 9.2 years. The majority, 24 individuals developed mild neutropenia (1500-1900 neutrophils/mm 3 ). None of these progressed to agranulocytosis. The remaining 10 patients developed neutropenia in the range 500-1400 /mm 3 of whom one developed agranulocytosis, three stopped clozapine use and 6 patients continued on clozapine for at least a year without developing agranulocytosis. Unexpectedly, schizophrenia patients on other antipsychotics had an equal risk of developing neutropenia as those on clozapine. Neutropenia is common both in patients with schizophrenia on clozapine treatment and in those never on clozapine. Therefore a large part of neutropenia during clozapine treatment is probably not caused by

  1. Is There a Role for Clozapine in the Treatment of Children and Adolescents?

    ERIC Educational Resources Information Center

    Findling, Robert L.; Frazier, Jean A.; Gerbino-Rosen, Ginny; Kranzler, Harvey N.; Kumra, Sanjiv; Kratochvil, Christopher J.

    2007-01-01

    This article presents responses to the question of whether clozapine is ever appropriate to use in the pediatric population. Among others, Jean A. Frazier also agreed that clozapine is appropriate for use in the pediatric population. Clozapine has truly revolutionized the treatment of refractory patients with schizophrenia at any age. This agent…

  2. [Clozapine-induced parotitis: a case study].

    PubMed

    Gouzien, C; Valiamé, A; Misdrahi, D

    2014-02-01

    Clozapine is the drug of choice for patients with an unsatisfactory response to routine antipsychotic treatment. Side effects such as sedation, weight gain, hypotension and hypersialorrhea are frequently reported whereas clozapine-induced parotitis is a less known complication. We report the case of a 32-year-old woman with a refractory schizoaffective disorder, bipolar type. The failure to respond to at least two well-conducted antipsychotic trials with flupentixol and risperidone, led clinicians to prescribe clozapine, which was started three years earlier. Since its introduction, clozapine induced sialorrhea, which has been managed until now with anticholinergic medication. Recently, Mrs B. was hospitalized for a new relapse. Once treatment compliance checked (good level of plasmatic dosage), we decided to increase the dose of clozapine from 350 mg/d to 500 mg/d. Twenty days later, Mrs B. exhibited improvement of symptoms but complained of acute bilateral auricular pain and odynophagia. The bilateral and comparative clinical exam displayed a bilateral filling of the retromandibular depression, the painful swelling of the parotid gland, along with ptyalism and a slight inflammatory oedema of the Stenon duct orifice. Mrs B. was apyretic, with physiological constants within the limits of normal values. The biological analyses displayed a discrete inflammatory syndrome (mild hyperleucocytosis and anemia), a negative mumps IgM test and positive mumps IgG test, and a 1050 ng/mL clozapine blood level. Once viral parotitis was ruled out, the involvement of clozapine was evoked. Symptomatic medication was prescribed with per os analgesic (paracetamol) and antiseptic mouthwash (Éludril). Clozapine dosage was lowered to 400 mg/d. A week later, clinical examination confirmed improvement of the medical and psychiatric conditions. We report the case of a patient who developed a parotitis following clozapine dose adjustment. Clozapine induced parotitis was retained once the

  3. Clozapine Treatment of Childhood-Onset Schizophrenia: Evaluation of Effectiveness, Adverse Effects, and Long-Term Outcome

    ERIC Educational Resources Information Center

    Sporn, Alexandra L.; Vermani, Anoop; Greenstein, Deanna K.; Bobb, Aaron J.; Spencer, Edgar P.; Clasen, Liv S.; Tossell, Julia W.; Stayer, Catherine C.; Gochman, Peter A.; Lenane, Marge C.; Rapoport, Judith L.; Gogtay, Nitin

    2007-01-01

    Objective: Clozapine is a unique atypical antipsychotic with superior efficacy in treatment-resistant schizophrenia. Plasma concentration of clozapine and its major metabolite N-desmethylclozapine (NDMC) as well as the ratio of NDMC to clozapine have been reported to be predictors of clozapine response. Here we evaluate these as well as other…

  4. Progressive Brain Atrophy and Cortical Thinning in Schizophrenia after Commencing Clozapine Treatment.

    PubMed

    Ahmed, Mohamed; Cannon, Dara M; Scanlon, Cathy; Holleran, Laurena; Schmidt, Heike; McFarland, John; Langan, Camilla; McCarthy, Peter; Barker, Gareth J; Hallahan, Brian; McDonald, Colm

    2015-09-01

    Despite evidence that clozapine may be neuroprotective, there are few longitudinal magnetic resonance imaging (MRI) studies that have specifically explored an association between commencement of clozapine treatment for schizophrenia and changes in regional brain volume or cortical thickness. A total of 33 patients with treatment-resistant schizophrenia and 31 healthy controls matched for age and gender underwent structural MRI brain scans at baseline and 6-9 months after commencing clozapine. MRI images were analyzed using SIENA (Structural Image Evaluation, using Normalization, of Atrophy) and FreeSurfer to investigate changes over time in brain volume and cortical thickness respectively. Significantly greater reductions in volume were detected in the right and left medial prefrontal cortex and in the periventricular area in the patient group regardless of treatment response. Widespread further cortical thinning was observed in patients compared with healthy controls. The majority of patients improved symptomatically and functionally over the study period, and patients who improved were more likely to have less cortical thinning of the left medial frontal cortex and the right middle temporal cortex. These findings demonstrate on-going reductions in brain volume and progressive cortical thinning in patients with schizophrenia who are switched to clozapine treatment. It is possible that this gray matter loss reflects a progressive disease process irrespective of medication use or that it is contributed to by switching to clozapine treatment. The clinical improvement of most patients indicates that antipsychotic-related gray matter volume loss may not necessarily be harmful or reflect neurotoxicity.

  5. Differential gene expression profiles in neurons generated from lymphoblastoid B-cell line-derived iPS cells from monozygotic twin cases with treatment-resistant schizophrenia and discordant responses to clozapine.

    PubMed

    Nakazawa, Takanobu; Kikuchi, Masataka; Ishikawa, Mitsuru; Yamamori, Hidenaga; Nagayasu, Kazuki; Matsumoto, Takuya; Fujimoto, Michiko; Yasuda, Yuka; Fujiwara, Mikiya; Okada, Shota; Matsumura, Kensuke; Kasai, Atsushi; Hayata-Takano, Atsuko; Shintani, Norihito; Numata, Shusuke; Takuma, Kazuhiro; Akamatsu, Wado; Okano, Hideyuki; Nakaya, Akihiro; Hashimoto, Hitoshi; Hashimoto, Ryota

    2017-03-01

    Schizophrenia is a chronic psychiatric disorder with complex genetic and environmental origins. While many antipsychotics have been demonstrated as effective in the treatment of schizophrenia, a substantial number of schizophrenia patients are partially or fully unresponsive to the treatment. Clozapine is the most effective antipsychotic drug for treatment-resistant schizophrenia; however, clozapine has rare but serious side-effects. Furthermore, there is inter-individual variability in the drug response to clozapine treatment. Therefore, the identification of the molecular mechanisms underlying the action of clozapine and drug response predictors is imperative. In the present study, we focused on a pair of monozygotic twin cases with treatment-resistant schizophrenia, in which one twin responded well to clozapine treatment and the other twin did not. Using induced pluripotent stem (iPS) cell-based technology, we generated neurons from iPS cells derived from these patients and subsequently performed RNA-sequencing to compare the transcriptome profiles of the mock or clozapine-treated neurons. Although, these iPS cells similarly differentiated into neurons, several genes encoding homophilic cell adhesion molecules, such as protocadherin genes, showed differential expression patterns between these two patients. These results, which contribute to the current understanding of the molecular mechanisms of clozapine action, establish a new strategy for the use of monozygotic twin studies in schizophrenia research. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Treatment of clozapine- and molindone-induced agranulocytosis with granulocyte colony-stimulating factor.

    PubMed

    Geibig, C B; Marks, L W

    1993-10-01

    To report a case of clozapine- and molindone-induced agranulocytosis and to discuss treatment using filgrastim, a granulocyte colony-stimulating factor. A 64-year-old woman who had been on long-term clozapine therapy for schizophrenia was hospitalized with presumed drug-induced agranulocytosis. She had also been on short-term molindone therapy. A bone marrow biopsy and the initial white blood cell (WBC) count were consistent with drug-induced agranulocytosis. Following seven days of treatment with subcutaneous filgrastim 300 micrograms/d, her absolute neutrophil count was above 500 x 10(6)/L. Reports in the literature discussing antipsychotic drug-induced agranulocytosis are reviewed. A relationship between treatment with filgrastim and WBC response is postulated. Filgrastim may be useful in ameliorating the effects of clozapine- and molindone-induced agranulocytosis.

  7. Comparative efficacy between clozapine and other atypical antipsychotics on depressive symptoms in patients with schizophrenia: analysis of the CATIE phase 2E data.

    PubMed

    Nakajima, Shinichiro; Takeuchi, Hiroyoshi; Fervaha, Gagan; Plitman, Eric; Chung, Jun Ku; Caravaggio, Fernando; Iwata, Yusuke; Mihashi, Yukiko; Gerretsen, Philip; Remington, Gary; Mulsant, Benoit; Graff-Guerrero, Ariel

    2015-02-01

    The comparative antidepressant effects of clozapine and other atypical antipsychotics for schizophrenia remain elusive, leading us to examine this question using the data from the Clinical Antipsychotic Trials of Intervention Effectiveness phase 2E. Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone because of inadequate efficacy were randomly assigned to open-label treatment with clozapine (n=49) or double-blind treatment with another atypical antipsychotic not previously received in the trial (olanzapine [n=19], quetiapine [n=15], or risperidone [n=16]). The primary outcome was the Calgary Depression Scale for Schizophrenia (CDSS) total score. Antidepressant effects of clozapine and the other atypical antipsychotics were compared in patients with chronic schizophrenia and those with a major depressive episode (MDE) at baseline (i.e. ≥6 on the CDSS), using mixed models. No differences in the baseline CDSS total scores were found between the treatment groups regardless of presence of an MDE. Clozapine was more effective than quetiapine in antidepressant effects for chronic schizophrenia (p<.01 for the whole sample and p=.01 for those with an MDE), and comparable to olanzapine and risperidone. The present findings suggest that clozapine demonstrates superior antidepressant effects to quetiapine and comparable effects to olanzapine and risperidone in chronic schizophrenia regardless of presence of MDE. Given the indication of clozapine for treatment-resistant schizophrenia (TRS) and the negative impacts of depressive symptoms on clinical outcomes in schizophrenia, further research is warranted to investigate antidepressant effects of clozapine in TRS with an MDE. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Continuing clozapine treatment with lithium in schizophrenic patients with neutropenia or leukopenia: brief review of literature with case reports

    PubMed Central

    Aydin, Memduha; Ilhan, Bilge Cetin; Calisir, Saliha; Yildirim, Seda; Eren, Ibrahim

    2016-01-01

    Objective: Clozapine is a second-generation antipsychotic used for treatment-resistant schizophrenia. Despite its effectiveness, clozapine is largely underused due to serious side effects such as leukopenia or neutropenia. We aimed to review whether to continue, discontinue or rechallenge clozapine treatment after such haematological side effects. Methods: We reviewed and summarized the literature on the use of clozapine, how to deal with its side effects, and suitable options in case of any haematological problems. Then, we described several cases successfully treated with clozapine and lithium after development of neutropenia or leukopenia Results: We present three patients with treatment-resistant schizophrenia. While they had demonstrated poor response to multiple antipsychotic trials, clozapine was started. Clozapine induced neutropenia; or leukopenia developed in some cases that was successfully reversed after lithium onset. Increased serious side effects related with coprescription of lithium and clozapine were not observed. Conclusion: Lithium increases neutrophil and total white blood cell count as a side effect that may be useful in patients who develop neutropenia or leukopenia while being treated with clozapine. PMID:26913176

  9. Continuing clozapine treatment with lithium in schizophrenic patients with neutropenia or leukopenia: brief review of literature with case reports.

    PubMed

    Aydin, Memduha; Ilhan, Bilge Cetin; Calisir, Saliha; Yildirim, Seda; Eren, Ibrahim

    2016-02-01

    Clozapine is a second-generation antipsychotic used for treatment-resistant schizophrenia. Despite its effectiveness, clozapine is largely underused due to serious side effects such as leukopenia or neutropenia. We aimed to review whether to continue, discontinue or rechallenge clozapine treatment after such haematological side effects. We reviewed and summarized the literature on the use of clozapine, how to deal with its side effects, and suitable options in case of any haematological problems. Then, we described several cases successfully treated with clozapine and lithium after development of neutropenia or leukopenia. We present three patients with treatment-resistant schizophrenia. While they had demonstrated poor response to multiple antipsychotic trials, clozapine was started. Clozapine induced neutropenia; or leukopenia developed in some cases that was successfully reversed after lithium onset. Increased serious side effects related with coprescription of lithium and clozapine were not observed. Lithium increases neutrophil and total white blood cell count as a side effect that may be useful in patients who develop neutropenia or leukopenia while being treated with clozapine.

  10. Risks and Benefits of Rapid Clozapine Titration.

    PubMed

    Lochhead, Jeannie D; Nelson, Michele A; Schneider, Alan L

    2016-05-18

    Clozapine is often considered the gold standard for the treatment of schizophrenia. Clinical guidelines suggest a gradual titration over 2 weeks to reduce the risks of adverse events such as seizures, hypotension, agranulocytosis, and myocarditis. The slow titration often delays time to therapeutic response. This raises the question of whether, in some patients, it may be safe to use a more rapid clozapine titration. The following case illustrates the potential risks associated with the use of multiple antipsychotics and rapid clozapine titration. We present the case of a young man with schizophrenia who developed life threatening neuroleptic malignant syndrome (NMS) during rapid clozapine titration and treatment with multiple antipsychotics. We were unable to find another case in the literature of NMS associated with rapid clozapine titration. This case is meant to urge clinicians to carefully evaluate the risks and benefits of rapid clozapine titration, and to encourage researchers to further evaluate the safety of rapid clozapine titration. Rapid clozapine titration has implications for decreasing health care costs associated with prolonged hospitalizations, and decreasing the emotional suffering associated with uncontrolled symptoms of psychosis. Clozapine is considered the most effective antipsychotic available thus efforts should focus on developing strategies that would allow for safest and most efficient use of clozapine to encourage its utilization for treatment resistance schizophrenia.

  11. An association between autumn birth and clozapine treatment in patients with schizophrenia: a population-based analysis.

    PubMed

    Sørensen, Holger J; Foldager, Leslie; Røge, Rasmus; Pristed, Sofie Gry; Andreasen, Jesper T; Nielsen, Jimmi

    2014-08-01

    Numerous studies on seasonality of birth and schizophrenia risk have been published but it is uncertain whether, among those with schizophrenia, refractory illness exhibits any predilection for birth month. We hypothesized and examined whether a season of birth effect was present in patients with schizophrenia with a history of clozapine treatment. Using record linkage with Danish registers, we examined patients with schizophrenia born between 1950 and 1970, and between 1995 and 2009 and Cox regression analysis was used to examine season of birth in relation to history of clozapine treatment. In a study population corresponding to 60,062 person-years from 5328 individuals with schizophrenia of which 1223 (23%) received at least one clozapine prescription, birth in the autumn (September-November) was associated with clozapine treatment (HR = 1.24; 95% CI 1.07-1.46) when compared with birth in the spring (March-May). Although replication studies are needed, this is the first evidence from a nationwide study suggesting a possible season-associated risk of clozapine treatment in schizophrenia. The reasons for this relationship remain to be further investigated but might be partially explained by early exposures such as winter flu season and low vitamin D levels.

  12. A review of the use of clozapine levels to guide treatment and determine cause of death.

    PubMed

    Stark, Anne; Scott, James

    2012-09-01

    To review the literature to examine the use of clozapine levels to (i) guide therapy and prevent toxicity in clinical care and (ii) determine cause of death in post-mortem examination of patients who were treated with clozapine. MEDLINE was searched in December 2010 using the following keywords: 'clozapine levels', 'clozapine and toxicity', 'clozapine and death', 'clozapine and mortality' and 'post-mortem redistribution'. Data was also collected from the 2010 MIMS Annual. The literature reported significant variation in clozapine levels attained with any given dose, and considerable variability in the clinical response achieved at any given clozapine level. The lowest effective clozapine levels ranged from 250 to 550 µg/L, while the recommended upper limit to prevent toxicity varied from 600 to 2000 µg/L. There was minimal correlation between clozapine levels and side effects, with the exception of sedation, hypotension and seizure activity. The risk of seizures increased with plasma clozapine levels greater than 600 µg/L or rapid upward titration. In addition to prescribed dose, there are many factors that influence plasma clozapine levels. After death, the process of post-mortem drug redistribution resulted in 3.00 to 4.89 times increases in clozapine levels in central blood vessels and 1.5 fold increases in peripheral vessels compared to ante-mortem levels. The exact range of clozapine levels that corresponds to toxicity remains unclear. However, levels between 350 µg/L and 1000 µg/L achieved with gradual upward titration are more likely to be effective and less likely to cause toxicity. Ongoing clozapine level monitoring is indicated, especially when (i) prescribing higher doses (> 600 mg/day) of clozapine, (ii) there has been a change in a patient's concomitant pharmacotherapy or cigarette use and (iii) there has been a suboptimal response to treatment. The use of post-mortem clozapine levels to determine clozapine toxicity as a cause of death is

  13. Phenylpropanolamine appears not to promote weight loss in patients with schizophrenia who have gained weight during clozapine treatment.

    PubMed

    Borovicka, Mary C; Fuller, Matthew A; Konicki, P Eric; White, John C; Steele, Vickie M; Jaskiw, George E

    2002-04-01

    Weight gain is a common side effect of clozapine treatment and may expose patients to obesity-associated health risks. We proposed that concomitant treatment with an appetite suppressant such as phenylpropanolamine (PPA) would lead to a decrease in appetite and therefore loss of weight. This was a 12-week, double-blind, randomized, placebo-controlled trial of PPA, 75 mg/day, in outpatients with treatment-refractory schizophrenia (DSM-IV) who were stable on clozapine treatment for at least 4 months and had gained > 10% of their baseline body weight since starting clozapine. Patients were evaluated for adverse effects and weighed weekly. A Positive and Negative Syndrome Scale (PANSS) assessment, a short dietary quiz, and blood indices were completed monthly. Sixteen patients were equally randomly assigned to receive PPA or placebo. The groups did not differ in mean age, baseline weight, dose of clozapine, baseline PANSS scores, or the percent of weight gained since the start of clozapine. There was no significant effect of treatment on weight (t = 0.219, df = 10, p = .831). There was no significant change in either the total PANSS scores (t = -0.755, df = 10, p = .468), the positive or negative symptom cluster scores, or any of the remaining variables. Phenylpropanolamine 75 mg/day was well tolerated but was not effective in reversing established weight gain associated with clozapine treatment in stable outpatients with schizophrenia.

  14. Combining Clozapine and Talk Therapies.

    ERIC Educational Resources Information Center

    Mulroy, Kevin

    Clozapine is an antipsychotic medication used in the treatment of schizophrenia. This paper reviews articles concerning clozapine therapy. It considers its benefits and dangers in various situations, and how it can be successfully combined with talk therapies. Studies are reviewed concerning patients in outpatient clinics, partial hospitalization…

  15. Clozapine-Induced Febrile Neutropenia and Cellulitis.

    PubMed

    Yaylaci, Selcuk; Yilmaz, Emine Ulku; Guclu, Ertugrul; Kumsar, Neslihan Akkisi; Tamer, Ali; Karabay, Oguz

    2014-03-01

    Clozapine is one of the atypical antipsychotics and is frequently prescribed to patients with treatment-resistant schizophrenia. Agranulocytosis is a major side effect that may lead to death, which limits its use. This is a case report of a patient that developed febrile neutropenia and cellulitis after treatment with clozapine for 20 weeks.

  16. Hearts and Minds: Real-Life Cardiotoxicity With Clozapine in Psychosis.

    PubMed

    Joy, George; Whiskey, Eromona; Bolstridge, Mark; Porras-Segovia, Alejandro; McDonagh, Theresa A; Plymen, Carla M; Shergill, Sukhi S

    2017-12-01

    Schizophrenia has a 1% prevalence in the population; 30% of these patients are treatment refractory. Clozapine is the only drug licensed to treat treatment refractory psychosis, but concerns about potential adverse effects result in only a proportion of eligible patients being treated. Although a well-documented neutropenia risk is mitigated by routine blood testing, cardiac toxicity is a commonly cited reason to discontinue clozapine treatment. However, there is little data on the real-life cardiac outcomes in those receiving clozapine treatment. Retrospective review of electrocardiogram, echocardiogram, and clinical outcomes in 39 inpatients with treatment-refractory schizophrenia, treated with clozapine and other antipsychotic medication, referred for cardiology opinion. Commonest reasons for referral were development of left ventricular (LV) impairment or sinus tachycardia with normal LV function. Patients were reviewed by a range of cardiologists, receiving varied interventions.Median LV ejection fraction in the clozapine group was normal (52%). Serial echocardiograms demonstrated that clozapine-treated patients with LV impairment had no change in LV ejection fraction over a 4-month follow-up. Left ventricular ejection fraction did not differ between patients treated with clozapine and other antipsychotics. However, over an 11-year follow-up period, 48% of patients had discontinued clozapine treatment. This naturalistic study demonstrates that clozapine is not associated with significant cardiac mortality or morbidity. There is a real need for multidisciplinary working between specialist cardiologists and psychiatrists caring for these complex patients to facilitate optimal long-term physical and mental health outcomes.

  17. Differential patterns of induction of NGFI-B, Nor1 and c-fos mRNAs in striatal subregions by haloperidol and clozapine.

    PubMed

    Werme, M; Ringholm, A; Olson, L; Brené, S

    2000-04-28

    Disturbances of retinoid activated transcription mechanisms have recently been implicated as risk factors for schizophrenia. In this study we have compared the regulation of mRNAs for the nuclear orphan receptor NGFI-B, which forms a functional heterodimer with the retinoid x receptor and the related orphan nuclear receptor Nor1 with c-fos mRNA after acute and chronic treatments with haloperidol and clozapine. The antipsychotic drugs haloperidol and clozapine have different clinical profiles. Haloperidol is a typical neuroleptic giving extrapyramidal side effects (EPS), whereas the atypical compound clozapine does not. Acute haloperidol treatment increased NGFI-B, Nor1 and c-fos mRNAs in nucleus accumbens shell and core as well as medial and lateral caudate putamen. In contrast, clozapine lead to an increase of NGFI-B, Nor1 and c-fos only in the accumbens shell. No haloperidol or clozapine effect on these mRNAs was detected in cingulate, sensory or motor cortex. Chronic haloperidol lead to an increase of NGFI-B mRNA in the accumbens core. Acutely, it is possible that the increased levels of NGFI-B, Nor1 and c-fos mRNA levels in striatum and accumbens might indicate a neural activation which possibly can be used when screening for drugs that do not produce EPS. Also, the increased levels of NGFI-B, which is an important component in retinoid signaling, both after acute and chronic treatments of haloperidol suggests altered sensitivity to retinoids which could be an important component for the beneficial antipsychotic effect.

  18. Ziprasidone versus clozapine in the treatment of dually diagnosed (DD) patients with schizophrenia and cannabis use disorders: a randomized study.

    PubMed

    Schnell, Thomas; Koethe, Dagmar; Krasnianski, Anna; Gairing, Stefanie; Schnell, Knut; Daumann, Jörg; Gouzoulis-Mayfrank, Euphrosyne

    2014-01-01

    Clozapine is considered to be particularly effective in the treatment of dually diagnosed (DD) patients with psychosis and substance use disorders. However, its use is restricted by potentially severe side effects. The aim of the present pilot study was to compare the effects of clozapine with the newer second generation antipsychotic (SGA) ziprasidone in DD-patients. Thirty (n = 30) patients with schizophrenia and cannabis abuse/dependence were randomized to ziprasidone or clozapine and were followed up for up to 12 months. Cannabis use was reduced in both groups during follow-up. Clozapine treatment was associated with less positive symptoms of schizophrenia, more side effects and poorer compliance with treatment. Results from this small pilot RCT suggest beneficial effects of both clozapine and ziprasidone in the treatment of cannabis use disorders in psychotic patients. Larger-scale RCTs are needed in order to assess advantages and disadvantages of the different SGAs in dually diagnosed populations. © American Academy of Addiction Psychiatry.

  19. Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine.

    PubMed

    De Berardis, Domenico; Rapini, Gabriella; Olivieri, Luigi; Di Nicola, Domenico; Tomasetti, Carmine; Valchera, Alessandro; Fornaro, Michele; Di Fabio, Fabio; Perna, Giampaolo; Di Nicola, Marco; Serafini, Gianluca; Carano, Alessandro; Pompili, Maurizio; Vellante, Federica; Orsolini, Laura; Martinotti, Giovanni; Di Giannantonio, Massimo

    2018-05-01

    Clozapine, a dibenzodiazepine developed in 1961, is a multireceptorial atypical antipsychotic approved for the treatment of resistant schizophrenia. Since its introduction, it has remained the drug of choice in treatment-resistant schizophrenia, despite a wide range of adverse effects, as it is a very effective drug in everyday clinical practice. However, clozapine is not considered as a top-of-the-line treatment because it may often be difficult for some patients to tolerate as some adverse effects can be particularly bothersome (i.e. sedation, weight gain, sialorrhea etc.) and it has some other potentially dangerous and life-threatening side effects (i.e. myocarditis, seizures, agranulocytosis or granulocytopenia, gastrointestinal hypomotility etc.). As poor treatment adherence in patients with resistant schizophrenia may increase the risk of a psychotic relapse, which may further lead to impaired social and cognitive functioning, psychiatric hospitalizations and increased treatment costs, clozapine adverse effects are a common reason for discontinuing this medication. Therefore, every effort should be made to monitor and minimize these adverse effects in order to improve their early detection and management. The aim of this paper is to briefly summarize and provide an update on major clozapine adverse effects, especially focusing on those that are severe and potentially life threatening, even if most of the latter are relatively uncommon.

  20. Clozapine-Related EEG Changes and Seizures: Dose and Plasma-Level Relationships

    PubMed Central

    Varma, Seema; Bishara, Delia; Besag, Frank M. C.; Taylor, David

    2011-01-01

    Clozapine is a widely used atypical antipsychotic with a unique effectiveness in treatment-resistant schizophrenia. An important adverse effect is seizures, which have been observed at all stages of clozapine treatment. Valproate has traditionally been considered the drug of choice for the prophylaxis of clozapine seizures, however it may not be the most suitable choice for all patients. There is disagreement as to the best point to prescribe valproate or a suitable antiepileptic: as seizure prophylaxis at a certain clozapine dose or level, or only as remedial treatment. In this review, we examine the relevant literature with an aim to evaluate the following relationships: clozapine dose and electroencephalogram (EEG) abnormalities, plasma levels and EEG abnormalities, dose and occurrence of seizures and plasma levels and occurrence of seizures. Weighted linear regression models were fitted to investigate these relationships. There was a strong relationship between clozapine dose and plasma level and occurrence of clozapine-induced EEG abnormalities. However, a statistically significant relationship between dose and occurrence of seizures was not found. A relationship between clozapine plasma level and occurrence of seizures was not established because of the scarcity of useful data although our review found three case reports which suggested that there is a very substantial risk of seizures with clozapine plasma levels exceeding 1300 μg/l. Seizures are more common during the initiation phase of clozapine treatment, suggesting a slow titration to target plasma levels is desirable. An antiepileptic drug should be considered when the clozapine plasma level exceeds 500 μg/l, if the EEG shows clear epileptiform discharges, if seizures, myoclonic jerks or speech difficulties occur and when there is concurrent use of epileptogenic medication. The antiepileptics of choice for the treatment and prophylaxis of clozapine-induced seizures are valproate (particularly where

  1. Clozapine for Drug-Refractory Irritability in Individuals with Developmental Disability.

    PubMed

    Wink, Logan K; Badran, Ismail; Pedapati, Ernest V; Sorensen, Rena; Benton, Stacy C; Johnson, Mark C; Wissel, Gregory; Erickson, Craig A

    2016-11-01

    In this case series, we describe the acute clinical impact and tolerability of rapid titration of clozapine for treatment of refractory irritability in five hospitalized youth with developmental disability. We offer this descriptive report in an effort to expand the evidence base guiding treatment of refractory aggression in this population. Five youth with developmental disability and severe irritability were admitted to a 10-bed psychiatric crisis stabilization unit where they received thorough psychiatric and medical evaluation. Informed consent was obtained in each case, and each patient underwent rapid titration onto clozapine. Clozapine monitoring guidelines were followed for all patients throughout treatment, and clinical severity at baseline and improvement with treatment was measured by use of the Clinical Global Impressions-Severity scale (CGI-S) and the Clinical Global Impressions-Improvement scale (CGI-I). One female and four males diagnosed with developmental disability and at least one other psychiatric diagnosis, mean age of 13.1 ± 2.1 years, and mean CGI-S at baseline of 5.8, each received clozapine treatment by rapid titration. The mean therapeutic total daily dose of clozapine was 380 ± 200 mg. All patients demonstrated acute clinical improvement with the mean final CGI-I of 2.0, or "much improved." These initial results support the potential utility of clozapine rapid titration for treatment of severe refractory irritability in youth with developmental disability. These patients tolerated clozapine treatment in the short term. Future studies are needed to thoroughly evaluate the long-term safety of clozapine treatment in this population.

  2. Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine

    PubMed Central

    De Berardis, Domenico; Rapini, Gabriella; Olivieri, Luigi; Di Nicola, Domenico; Tomasetti, Carmine; Valchera, Alessandro; Fornaro, Michele; Di Fabio, Fabio; Perna, Giampaolo; Di Nicola, Marco; Serafini, Gianluca; Carano, Alessandro; Pompili, Maurizio; Vellante, Federica; Orsolini, Laura; Martinotti, Giovanni; Di Giannantonio, Massimo

    2018-01-01

    Clozapine, a dibenzodiazepine developed in 1961, is a multireceptorial atypical antipsychotic approved for the treatment of resistant schizophrenia. Since its introduction, it has remained the drug of choice in treatment-resistant schizophrenia, despite a wide range of adverse effects, as it is a very effective drug in everyday clinical practice. However, clozapine is not considered as a top-of-the-line treatment because it may often be difficult for some patients to tolerate as some adverse effects can be particularly bothersome (i.e. sedation, weight gain, sialorrhea etc.) and it has some other potentially dangerous and life-threatening side effects (i.e. myocarditis, seizures, agranulocytosis or granulocytopenia, gastrointestinal hypomotility etc.). As poor treatment adherence in patients with resistant schizophrenia may increase the risk of a psychotic relapse, which may further lead to impaired social and cognitive functioning, psychiatric hospitalizations and increased treatment costs, clozapine adverse effects are a common reason for discontinuing this medication. Therefore, every effort should be made to monitor and minimize these adverse effects in order to improve their early detection and management. The aim of this paper is to briefly summarize and provide an update on major clozapine adverse effects, especially focusing on those that are severe and potentially life threatening, even if most of the latter are relatively uncommon. PMID:29796248

  3. Clozapine-associated weight loss.

    PubMed

    Hanwella, R; de Silva, V; Wijeratne, C; Ketharanathan, T; de Silva, J

    2010-07-01

    Clozapine is associated with weight gain. We report three patients with substantial weight loss following treatment with clozapine. The weight loss observed in the three patients was 33, 18 and 14.4 kg with percentage loss of body weight of 49, 18 and 21 respectively. Two patients had diabetes mellitus. History, physical examination and extensive investigations in the three patients did not reveal any cause that could account for the weight loss.

  4. Clozapine

    MedlinePlus

    Clozapine is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual ... dispose of any leftover rinse water. Clozapine controls schizophrenia but does not cure it. It may take ...

  5. Tachycardia in patients treated with clozapine versus antipsychotic long-acting injections.

    PubMed

    Nilsson, Björn M; Edström, Oscar; Lindström, Leif; Wernegren, Petter; Bodén, Robert

    2017-07-01

    Tachycardia is a known adverse effect during clozapine treatment. However, prevalence reported differs widely between studies and hitherto there are no studies comparing clozapine-treated patients with a similar control group. The present study was carried out to assess the prevalence of tachycardia in patients treated with clozapine and antipsychotic long-acting injections (LAI). Data on heart rate (HR), concomitant medication, and relevant anthropometric and laboratory measurements were collected for all clozapine-treated patients (n=174) in a defined catchment area and compared with data on patients treated with LAI (n=87). In total, 33% of patients on long-term clozapine treatment had tachycardia (HR>100) compared with 16% in the LAI group (P<0.001). The mean HR was 91 in the clozapine group and 82 in the LAI group (P<0.001). Clozapine dose correlated with HR. The majority of patients with HR more than 100 received no specific treatment for tachycardia. In conclusion, the prevalence of tachycardia was twice as high in patients treated with clozapine as in a similar patient group with severe schizophrenia spectrum disorder. The tachycardia was in many cases clinically unnoticed. Tachycardia during antipsychotic treatment is a common phenomenon that must be monitored for actively and, when noticed, further investigated and treated.

  6. Clozapine-induced dysphagia with secondary substantial weight loss.

    PubMed

    Osman, Mugtaba; Devadas, Vekneswaran

    2016-08-19

    Dysphagia is listed as a 'rare' side effect following clozapine treatment. In this case report, we describe how significant clozapine-induced dysphagia has led to significant reduction of nutritional intake with subsequent substantial weight loss. An 18-year-old single man with an established diagnosis of treatment-resistant paranoid schizophrenia recovered well on a therapeutic dose of clozapine. However, he was noted to lose weight significantly (up to 20% of his original weight) as the dose was uptitrated. This was brought about by development of dysphagia, likely to be due to clozapine. Addition of nutritional supplementary liquids and initiation of a modified behavioural dietary/swallowing programme, while repeatedly mastering the Mendelsohn manoeuvre technique, alleviated the swallowing difficulties and restored his weight. 2016 BMJ Publishing Group Ltd.

  7. Granulocyte colony stimulating factor (G-CSF) can allow treatment with clozapine in a patient with severe benign ethnic neutropaenia (BEN): a case report.

    PubMed

    Spencer, Benjamin W J; Williams, Hugh R J; Gee, Siobhan H; Whiskey, Eromona; Rodrigues, Joseph P; Mijovic, Aleksandar; MacCabe, James H

    2012-09-01

    Clozapine is the treatment of choice for treatment-resistant schizophrenia, but it is associated with a risk of neutropaenia and agranulocytosis. Clozapine use is regulated by mandatory blood monitoring in the UK, requiring cessation of treatment should the absolute neutrophil count (ANC) drop below specified values. Benign reductions in the ANC in non-white populations are common, and this can preclude a patient from receiving treatment with clozapine. A diagnosis of benign ethnic neutropaenia can reduce these treatment restrictions (UK specific), but the degree of neutropaenia can be significant enough to still prevent treatment. In this report, we show that response to granulocyte colony stimulating factor (G-CSF) may be quite variable and difficult to predict, but with careful monitoring it can be used to increase the ANC count and allow continued treatment with clozapine.

  8. Clozapine: an effective treatment for seriously violent and psychopathic men with antisocial personality disorder in a UK high-security hospital.

    PubMed

    Brown, Darcy; Larkin, Fintan; Sengupta, Samrat; Romero-Ureclay, Jose L; Ross, Callum C; Gupta, Nitin; Vinestock, Morris; Das, Mrigendra

    2014-10-01

    A number of studies have demonstrated the anti-aggressive properties of clozapine in schizophrenia and its positive effect in borderline personality disorder. There is no published literature on the treatment of antisocial personality disorder (ASPD) with clozapine. We present a case series of 7 patients with primary ASPD and high psychopathic traits treated with clozapine, having a significant history of serious violence and currently detained in a UK based high-security hospital. A retrospective review of case notes was carried out to formulate Clinical Global Impression (CGI) scores and record incidents of violence and aggression. Effect on specific symptom domains (cognitive-perceptual, impulsive-behavioural dyscontrol, affective dysregulation) was also noted. Metabolic parameters and serum clozapine levels were also sampled. All 7 patients showed significant improvement on clozapine. It was shown to benefit all symptom domains, especially impulsive behavioral dyscontrol and anger. The number of violent incidents committed by 6 of the 7 patients reduced significantly, and all patients' risk of violence reduced. Clozapine serum levels for 6 of the 7 patients were in the range 150-350 ng/mL. Clozapine is of benefit in reducing the clinical severity of ASPD. It improved all symptom domains, especially impulsive-behavioral dyscontrol and anger, and reduced levels of aggression and violence, especially at lower doses (serum levels <350 ng/m). To our knowledge, this is the first account of clozapine treatment in patients with ASPD and high psychopathy.

  9. Organizational Characteristics of Veterans Affairs Clinics With High and Low Utilization of Clozapine.

    PubMed

    Gören, Jessica L; Rose, Adam J; Engle, Ryann L; Smith, Eric G; Christopher, Melissa L D; Rickles, Nathaniel M; Semla, Todd P; McCullough, Megan B

    2016-11-01

    Twenty to thirty percent of patients with schizophrenia experience treatment resistance. Clozapine is the only medication proven effective for treatment-resistant schizophrenia. However, in most settings less than 25% of patients with treatment-resistant schizophrenia receive clozapine. This study was conducted to identify facilitators of and barriers to clozapine use to inform development of interventions to maximize appropriate clozapine utilization. Seventy semistructured phone interviews were conducted with key informants of clozapine processes at U.S. Department of Veterans Affairs medical centers in various U.S. regions, including urban and rural areas, with high (N=5) and low (N=5) rates of clozapine utilization. Interviewees included members of mental health leadership, psychiatrists, clinical pharmacists, and advanced practice nurses. Interviews were analyzed by using an emergent thematic strategy to identify barriers and facilitators related to clozapine prescribing. High utilization was associated with integration of nonphysician psychiatric providers and clear organizational processes and infrastructure for treatment of severe mental illness, for example, use of clozapine clinics and mental health intensive case management. Low utilization was associated with a lack of champions to support clozapine processes and with limited-capacity care systems. Obstacles identified at both high- and low-utilization sites included complex, time-consuming paperwork; reliance on a few individuals to facilitate processes; and issues related to transportation for patients living far from care facilities. Implementation efforts to organize, streamline, and simplify clozapine processes; development of a multidisciplinary clozapine clinic; increased capacity of existing clinics; and provision of transportation are reasonable targets to increase clozapine utilization.

  10. Prescriber and institutional barriers and facilitators of clozapine use: A systematic review.

    PubMed

    Verdoux, Hélène; Quiles, Clélia; Bachmann, Christian J; Siskind, Dan

    2018-06-04

    As clozapine is under-prescribed in persons with treatment-resistant schizophrenia (TRS), it is necessary to better identify the determinants of health inequalities in access to clozapine use. To identify mental health professionals' characteristics or attitudes and institutional characteristics facilitating or limiting clozapine prescribing. We systematically searched multiple electronic databases for articles reporting: (i) mental health professionals' attitudes and characteristics favoring or limiting clozapine prescribing; (ii) institutional characteristics associated with variations in clozapine prescribing; (iii) interventions aimed at enhancing clozapine prescribing. Data were synthesized narratively. A total of 31 articles reporting findings of 29 studies published from 1993 to 2017 in 11 countries fulfilled our inclusion criteria. The main prescriber-related barriers to clozapine prescribing are lack of personal prescribing experience and concern with pharmacological characteristics of clozapine (blood monitoring and adverse effects). Lack of knowledge about the effectiveness of clozapine does not appear as a major determinant of under-prescription. Institutional-related characteristics favoring clozapine prescribing are prescribers' adherence to evidence-based medicine principles and learning by modelling from experienced clozapine prescribers. Effective strategies to increase access to clozapine in persons with TRS include implementation of integrated clozapine clinics, simplification of blood monitoring, education for prescribers and contact with experienced prescribers. Programs addressing barriers in clozapine prescription need to be disseminated more broadly to ensure persons with TRS have access to evidenced based treatments such as clozapine. Inequality in access to clozapine care should be more systematically handled by mental health facilities and health regulatory agencies. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Clozapine response and plasma catecholamines and their metabolites.

    PubMed

    Green, A I; Alam, M Y; Sobieraj, J T; Pappalardo, K M; Waternaux, C; Salzman, C; Schatzberg, A F; Schildkraut, J J

    1993-02-01

    The atypical neuroleptic clozapine has an unusual profile of clinical effects and a distinctive spectrum of pharmacological actions. Plasma measures of catecholamines and their metabolites have been used in the past to study the action of typical neuroleptics. We obtained longitudinal assessments of plasma measures of dopamine (pDA), norepinephrine (pNE), and their metabolites, homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG), in eight treatment-resistant or treatment-intolerant schizophrenic patients who were treated with clozapine for 12 weeks following a prolonged drug-washout period. Our findings from the study of these eight patients suggest the following: Plasma levels of HVA and possibly NE derived from the neuroleptic-free baseline period may predict response to clozapine; plasma levels of HVA and MHPG decrease during the initial weeks of treatment in responders but not in nonresponders; and plasma levels of DA and NE increase in both responders and nonresponders to clozapine.

  12. Clozapine in borderline personality disorder: a review of the evidence.

    PubMed

    Beri, Anand; Boydell, Jane

    2014-05-01

    Borderline personality disorder (BPD) is a serious mental disorder that is difficult to treat. Possible targets for pharmacotherapy include affective symptoms, cognitive disturbances, and impulsive, self-injurious behaviors. Although many of the medications tested for treatment of BPD have been demonstrated to be useful, no clear pharmacologic treatment has emerged. Clozapine is one of the medications that has been evaluated for the treatment of severe BPD. The aim of this review is to summarize the evidence examining the effectiveness of clozapine in the treatment of BPD. A comprehensive search of the health science databases PubMed, EMBASE, CINAHL, PsycINFO, Web of Science, Cochrane Library, and Google Scholar was performed for studies describing the use of clozapine in the treatment of BPD. After the initial search, no randomized controlled trials evaluating the effectiveness of clozapine in BPD were identified. Therefore, case reports and case series were reviewed, with 12 articles selected for final review. This review suggests that clozapine may be a beneficial treatment option for BPD especially in controlling symptom severity, psychotic symptoms, impulsivity, self-mutilation, number of days on enhanced observation, use of restraint, and overall functioning.

  13. [Retrospective study of clozapine use in Ile-de-France].

    PubMed

    Hiltgen, S; Mantelet, S; Pinabel, F; Enjaume, F

    2006-10-01

    Clozapine, synthesized in the sixties, is an atypical antipsychotic drug whose history has been marked by its haematological toxicity. The purpose of this study was, ten years after it had been replaced at French psychiatrists' disposal, to gather data on the prescription modalities of clozapine, assess whether some factors could affect its efficacy, and describe the population of schizophrenic patients concerned. Psychiatrists in the Paris region were asked to answer a questionnaire about their patients treated with clozapine. The information collected was about socio-demographic data, history of psychiatric disorder and the way clozapine was used. It was a retrospective study concerning 98 patients. Subjects were 57 men and 41 women, with a mean age of 38 years. The majority of patients came from metropolitan France. Patients suffered from various clinical subtypes of schizophrenia, as assessed according to DSM IV criteria. Predominant symptomatology during lifetime was most often auditory hallucinations (41%). Mean duration of lifetime neuroleptic treatment was 10.3 years and breaks in follow-up were rare. Mean number of hospitalisations was 6.9 and a little less than half of the patients had been committed involuntarily. Lastly, 38% of patients had attempted suicide at least once and 35% had expressed hetero-agressive behavior. Main indication of clozapine was resistant schizophrenia (88.5% of patients) and mean duration of treatment was 2 years and 4 months. Treatment efficacy was assessed as good or medium in 77.9% of patients, at mean doses (322 mg per day) in keeping with data from the literature. Tolerance was considered on the whole as satisfactory by half of the clinicians. Among the 98 patients of the study, 21.6% had stopped taking clozapine. The reasons for withdrawal were: inefficacy (6.2%), granulopenia (5.2%), epilepsy (1%) and 8.2% for various reasons (half of these cases being non-compliance with treatment). The study of the 5 cases of

  14. Obsessive-compulsive symptoms in clozapine-treated schizophrenic patients.

    PubMed

    Ertugrul, Aygun; Anil Yagcioglu, A Elif; Eni, Nurhayat; Yazici, Kâzim M

    2005-04-01

    The aim of the present study was to assess the occurrence of obsessive-compulsive symptoms (OCS) in schizophrenic patients treated with clozapine, and to examine the relationship between OCS and other clinical variables. The results support earlier findings which suggest that clozapine produces or unmasks OCS. In addition, the severity of OCS was not related to other dimensions of psychopathology, severity of illness, clinical improvement or dose and duration of clozapine treatment.

  15. Clozapine Treatment of Psychosis Associated with Velo-Cardio-Facial Syndrome: Benefits and Risks

    ERIC Educational Resources Information Center

    Gladston, S.; Clarke, D. J.

    2005-01-01

    Clozapine is licensed for the treatment of psychotic illnesses resistant to other antipsychotic medications. Velo-cardio-facial syndrome (VCFS) is associated with a vulnerability to psychotic illness that may be resistant to treatment with conventional typical and atypical antipsychotics. A 32-year-old man with intellectual disability (ID) and a…

  16. Clozapine use in childhood and adolescent schizophrenia: A nationwide population-based study.

    PubMed

    Schneider, Carolina; Papachristou, Efstathios; Wimberley, Theresa; Gasse, Christiane; Dima, Danai; MacCabe, James H; Mortensen, Preben Bo; Frangou, Sophia

    2015-06-01

    Early onset schizophrenia (EOS) begins in childhood or adolescence. EOS is associated with poor treatment response and may benefit from timely use of clozapine. This study aimed to identify the predictors of clozapine use in EOS and characterize the clinical profile and outcome of clozapine-treated youths with schizophrenia. We conducted a nationwide population-based study using linked data from Danish medical registries. We examined all incident cases of EOS (i.e., cases diagnosed prior to their 18th birthday) between December 31st 1994 and December 31st 2006 and characterized their demographic, clinical and treatment profiles. We then used multivariable cox proportional hazard models to identify predictors of clozapine treatment in this patient population. We identified 662 EOS cases (1.9% of all schizophrenia cases), of whom 108 (17.6%) had commenced clozapine by December 31st 2008. Patients had on average 3 antipsychotic trials prior to clozapine initiation. The mean interval between first antipsychotic treatment and clozapine initiation was 3.2 (2.9) years. Older age at diagnosis of schizophrenia [HR=1.2, 95% CI (1.05-1.4), p=0.01], family history of schizophrenia [HR=2.1, 95% CI (1.1-3.04), p=0.02] and attempted suicide [HR=1.8, 95% CI (1.1-3.04), p=0.02] emerged as significant predictors of clozapine use. The majority of patients (n=96, 88.8%) prescribed clozapine appeared to have a favorable clinical response as indicated by continued prescription redemption and improved occupational outcomes. Our findings support current recommendations for the timely use of clozapine in EOS. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  17. Treating methamphetamine-induced resistant psychosis with clozapine.

    PubMed

    Seddigh, Ruohollah; Keshavarz-Akhlaghi, Amir-Abbas; Shariati, Behnam

    2014-01-01

    Background. Methamphetamine-induced psychosis (MIP) in Iran has turned into a serious issue in terms of health and treatment, lacking any obvious treatment methods for its resistant cases. Aims of Case Report. In the present study, a number of two cases of treatment of MIP with clozapine, which were resistant to the treatment with other antipsychotics, have been reported. Both cases completely responded to the treatment in only 2 weeks and no signs of psychosis relapse were seen in an 8-9 follow-up. Conclusion. Because of its particular pharmacologic features, clozapine may be effective in treating MIP.

  18. Clozapine Rechallenge After Neutropenia or Leucopenia.

    PubMed

    Prokopez, Cintia R; Armesto, Arnaldo R; Gil Aguer, María F; Balda, María V; Papale, Rosa M; Bignone, Inés M; Daray, Federico M

    2016-08-01

    To rechallenge with clozapine for a patient who previously has experienced neutropenia or leucopenia or during clozapine treatment is a difficult clinical decision. Herein, we analyzed the results of such a rechallenge in 19 patients. We analyzed all the reports, from the database of the pharmacovigilance department of the Argentine National Administration of Drugs, Foods, and Medical Devices, of patients who were rechallenged with clozapine after a leucopenia or a neutropenia. Nineteen cases of rechallenge after leucopenia or neutropenia were reported between 1996 and 2014. One third of the patients re-exposed to clozapine developed a new hematologic adverse reaction. The second blood dyscrasia was less severe in 83% of the cases and had a shorter median latency as compared with the first (8 weeks vs 182 weeks, P = 0.0045). There were no significant differences for demographic and clinical characteristics of patients who developed a second dyscrasia as compared with those who did not. The present study shows that almost 70% of the patients rechallenged with clozapine after a leucopenia or a neutropenia did not develop a new hematological adverse effect, whereas the remaining 30% had a faster but less serious neutropenia.

  19. Evaluation of the Safety of Clozapine Use in Patients with Benign Neutropenia

    PubMed Central

    Richardson, Charles M.; Davis, Erica A.; Vyas, Gopal R.; DiPaula, Bethany A.; McMahon, Robert P.; Kelly, Deanna L.

    2017-01-01

    Objective Determine if clozapine can be safely utilized in a population of psychiatric patients with current or a history of benign neutropenia. Method A single-center, retrospective chart review was conducted in an inpatient psychiatric hospital. Patients included had benign neutropenia prior to receiving clozapine and received clozapine using modified monitoring guidelines. All available laboratory values for absolute neutrophil count (ANC) before clozapine initiation and during treatment were evaluated. The primary endpoint was the difference in ANC after initiation of clozapine compared to before clozapine treatment. Results A total of 26 patients were reviewed. Mean age was 34 years at clozapine initiation. The majority were African-American (73%), with more males than females (73% vs. 27%). The mean lowest ANC value was not significantly different after clozapine initiation compared to before (1.5 and 1.4×103 cells/mm3, respectively; p=0.22). There were no cases of agranulocytosis (ANC <0.5 ×103 cells/mm3) and no patients were discontinued for falling below limits set by modified guidelines. There were fewer occurrences of mild neutropenia (ANC <2.0×103 cells/mm3) after clozapine initiation than before (16% and 31.4%, respectively; p<0.001). There were also fewer occurrences of moderate neutropenia (ANC <1.5×103 cells/mm3) with 2.1% after clozapine and 13.3% before (p<0.001). Occurrence of ANC <1.0×103 cells/mm3 did not differ (0.4% before, 0.3% after, p=0.79). Conclusion Twenty-six patients with benign neutropenia were safely treated with clozapine. Their pre-clozapine neutropenia did not predict increased risk for agranulocytosis with clozapine. Patients had significantly fewer episodes of mild and moderate neutropenia after receiving clozapine compared to before. PMID:27736047

  20. Health literacy and the clozapine patient.

    PubMed

    Brosnan, Susan; Barron, Elizabeth; Sahm, L J

    2012-01-01

    To estimate the prevalence of limited health literacy in patients receiving clozapine for schizophrenia. To develop and produce a pharmacist-designed clozapine patient information leaflet (PIL) which has a higher readability score than the company-produced PIL. This was a cross sectional prevalence study. Ethical approval for the study was granted by the local ethics committee. Patients, over 18 years, attending the Clozapine Clinic of a Cork urban teaching hospital, were asked to participate in the study. Demographics such as gender, age, employment and smoking status, were gathered from all participants. The total daily clozapine dose, duration of clozapine treatment, and information regarding the clozapine DVD was also noted. The Rapid Estimate of Adult Literacy in Medicine (REALM) health literacy (HL) screening tool was then administered to each patient. A user-friendly PIL on clozapine was designed by the pharmacist, which was assessed for readability and compared to the company-produced PIL using the FRES and FKGL. Data were analysed using SPSS Version 15. Forty patients (65% male, 95% unemployed and 70% smokers) of average age 38.0 years (+/- 11.2) completed the REALM. The average score was 60.6 (+/- 8.7). Twenty-nine patients (72.5%) were found to have "adequate" health literacy. The remaining eleven patients were found to have either "marginal" or "low" health literacy. The pharmacist-designed PIL would have been readable by 95% of the study population, in contrast to 72.5% with the company-designed PIL. More than a quarter of the population were found to have marginal or low health literacy. Patient information should be matched to the health literacy level of the target population.

  1. Combined use of clozapine and ECT: a review.

    PubMed

    Grover, Sandeep; Hazari, Nandita; Kate, Natasha

    2015-06-01

    This paper aims to review the available evidence for the use of clozapine and electroconvulsive therapy (ECT) in combination. Electronic searches were carried out to identify reports describing the combined use of clozapine and ECT. Forty reports including 208 patients were identified. The majority of reports were in the form of case reports and case series, with few retrospective and open-label studies. The majority of patients were aged between 18 and 65 years and diagnosed with schizophrenia or schizoaffective disorder. Most of the patients refractory to clozapine were started on ECT as an augmentation therapy; however, in some reports, both ECT and clozapine were started concurrently, and in few cases clozapine was started after ECT. In terms of effectiveness, 37.5-100% patients improved in short-term, and sustained long-term improvement (3 weeks to 24 months) was described in few studies. In terms of the side-effect profile, five patients each had delirium and tachycardia and only four patients were described to have prolonged seizures. Overall, the combination was considered effective and safe. There is evidence for the effectiveness and safety of the clozapine-ECT combination and it should be used in patients with treatment-resistant schizophrenia who do not respond to clozapine.

  2. Is electroconvulsive therapy effective as augmentation in clozapine-resistant schizophrenia?

    PubMed

    Kittsteiner Manubens, Lucas; Lobos Urbina, Diego; Aceituno, David

    2016-10-14

    Clozapine is considered to be the most effective antipsychotic drug for patients with treatment resistant schizophrenia, but up to a third of the patients do not respond to this treatment. Various strategies have been tried to augment the effect of clozapine in non-responders, one of these strategies being electroconvulsive therapy. However, its efficacy and safety are not yet clear. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including 55 studies, among them six randomized controlled trials addressing clozapine-resistant schizophrenia. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded electroconvulsive therapy probably augments response to clozapine in patients with treatment resistant schizophrenia, but it is not possible to determine if it leads to cognitive adverse effects because the certainty of the evidence is very low.

  3. Community pharmacists' attitudes and opinions towards supplying clozapine.

    PubMed

    Gan, Yuh-Lin; O'Reilly, Claire L

    2018-06-23

    Background Clozapine is very effective for treatment-resistant schizophrenia, but its use has been limited due to the risk of agranulocytosis. From July 2015, clozapine has been accessible from Australian community pharmacies following regulatory changes, but pharmacists' attitudes towards these changes remain unknown. Objective To explore pharmacists' perspectives and experiences in supplying clozapine. Setting Australian community pharmacists. Methods A cross-sectional study with a mixed methods approach involving two phases. An online survey containing Likert-type and open-response questions was distributed to community pharmacists (n = 134) via ClopineCentral™ (clozapine monitoring system). Participants were then invited to participate in semi-structured telephone interviews (n = 12) regarding clozapine supply. Quantitative data were statistically analysed, while qualitative responses were thematically content-analysed. Main outcome measures Pharmacists' responses to surveys and interviews. Results Community pharmacists were supportive towards supplying clozapine as it increased access for consumers. Better patient-pharmacist relationships and holistic care approach were identified to benefit both consumers and pharmacists. Pharmacists reported to be confident (89.6%), have adequate support (73.1%), knowledge (86.6%) and skills (93.3%) in dispensing clozapine. Training and support received facilitated pharmacists' roles, whereas administrative issues, especially in obtaining valid haematology results, posed challenges. Educational and technical improvements were suggested to improve service provision. Conclusion Community pharmacists welcomed the regulatory changes positively and were confident in supporting consumers taking clozapine. Despite challenges present, benefits and facilitators identified supported the feasibility of this service in community pharmacies. Future research should explore other aspects of clozapine supply, such as attitudes of

  4. Health status and health care costs for publicly funded patients with schizophrenia started on clozapine.

    PubMed

    Blieden, N; Flinders, S; Hawkins, K; Reid, M; Alphs, L D; Arfken, C L

    1998-12-01

    The study examined the effect of clozapine treatment on the health care costs and health status of people with schizophrenia who are supported by public funds. Thirty-three patients with schizophrenia hospitalized in a state facility were interviewed within one week of starting clozapine and six months later. Health status was assessed with four clinical rating scales measuring severity of psychopathology, negative symptoms, depression, and quality of life. Cost and health care utilization data were collected for the six months before and after initiation of clozapine. Only 52 percent of the subjects stayed on clozapine for six months. Subjects who continued on clozapine were more likely to be discharged within six months than those who did not continue. Six months after clozapine was started, health care costs showed a sayings of $11,464 per person, even after adjustment for pretreatment costs, and health status was improved. For subjects who continued on clozapine for six months, clozapine treatment was associated with reduced days of psychiatric hospital care, reduced overall costs despite increased outpatient treatment and residential costs, and improved health status.

  5. Clozapine-induced systemic lupus erythematosus.

    PubMed

    Rami, Abu Fanne; Barkan, Daniel; Mevorach, Dror; Leitersdorf, Eran; Caraco, Yoseph

    2006-05-01

    To report a case of classic clozapine-induced systemic lupus erythematosus that also developed on rechallenge. A 32-year-old white woman diagnosed with schizophrenia presented in 1996 with clinical characteristics and laboratory markers consistent with drug-induced lupus (DIL). Clozapine, started 1 year prior, was withdrawn, with complete biological and clinical remission within 3 months. In 2004, 1 week after rechallenge with clozapine for uncontrolled schizophrenia, the patient developed clinical and biological signs and symptoms consistent with the diagnosis of DIL. Again, discontinuation of clozapine was followed by full remission within 2-3 months. DIL was first described more than 50 years ago, with multiple drugs implicated in the causation. Clozapine-induced lupus was reported recently, but does not meet the usual criteria for a diagnosis of DIL. We report a classic case of clozapine-induced lupus that, according to the Naranjo probability scale, demonstrates a highly probable relationship between DIL and clozapine. DIL demands a high index of suspicion for diagnosis. Although clozapine has an extensive safety profile, DIL must be considered as one of its serious adverse effects.

  6. Hematological Adverse Events in Clozapine-Treated Children and Adolescents

    ERIC Educational Resources Information Center

    Gerbino-Rosen, Ginny; Roofeh, David; Tompkins, D. Andrew; Feryo, Doug; Nusser, Laurie; Kranzler, Harvey; Napolitano, Barbara; Frederickson, Anne; Henderson, Inika; Rhinewine, Joe; Kumra, Sanjiv

    2005-01-01

    Objective: To retrospectively examine rates of hematological adverse events (HAEs) in psychiatrically ill, hospitalized children treated with clozapine. Method: Clozapine treatment was administered in an open-label fashion using a flexible titration schedule, and data from weekly complete blood counts was obtained. The rate of neutropenia and…

  7. Metformin for Clozapine Associated Obesity: A Systematic Review and Meta-Analysis.

    PubMed

    Siskind, Dan J; Leung, Janni; Russell, Anthony W; Wysoczanski, Daniel; Kisely, Steve

    2016-01-01

    Although clozapine is the gold-standard for treatment refractory schizophrenia, it has the worst metabolic profile of all antipsychotics. This is partly mediated by clozapine's impact on glucagon-like peptide (GLP-1). There is an absence of robust evidence for effective treatments for clozapine associated weight gain and metabolic syndrome. Metformin, with its role in increasing GLP-1 may aid weight loss among people on clozapine. We conducted a systematic-review and meta-analysis of metformin versus placebo for change in weight and metabolic syndrome for people on clozapine without diabetes mellitus. We searched the Cochrane Schizophrenia Group's trial register, Pubmed and Embase, as well as the following Chinese databases: the Chinese Biomedical Literature Service System and China Knowledge Resource Integrated Database. This was supplemented by hand searches of key papers. Eight studies, of which three were from Chinese databases, with 478 participants were included. We found that metformin was superior to placebo in terms of weight loss (-3.12kg, 95%CI -4.88kg to -1.37kg) and BMI (-1.18kg/m2, 95%CI -1.76kg/m2 to -0.61kg/m2). Metformin significantly improved three of the five components of metabolic syndrome; waist circumference, fasting glucose and triglycerides. Sensitivity analysis on study quality and duration did not greatly impact results. Metformin led to clinically meaningful weight loss among people on clozapine, and may reduce the rates of metabolic syndrome. Inclusion of metformin into the treatment protocols of people on clozapine, as tolerated, should be considered. PROSPERO registration number: CRD42015029723.

  8. Case Report: Successful Use of the Combination of Electroconvulsive Therapy and Clozapine in Treating Treatment-Resistant Schizophrenia and Catatonia in an Adult with Intellectual Disability.

    PubMed

    Desarkar, Pushpal; Blumberger, Daniel; Daskalakis, Zafiris Jeff

    2018-04-25

    There is paucity of empirical data regarding the use of either clozapine or electroconvulsive therapy (ECT) in the acute phase and maintenance treatment of schizophrenia in adults with intellectual disability. Herein we report the successful acute and long-term remission of psychotic symptoms and catatonia with the combination of clozapine and ECT in a 26-year-old female with moderate ID and treatment-resistant schizophrenia. To our knowledge, this is the first case example of the successful use of the combination of bilateral, standard-pulse ECT and clozapine in both acute and long-term treatment of treatment-resistant schizophrenia and catatonia in an adult with ID. Our report adds further support to the emerging evidence regarding the efficacy and safety of this combination in treatment-resistant schizophrenia.

  9. The Use of Clozapine in Adults with Intellectual Disability

    ERIC Educational Resources Information Center

    Thalayasingam, S.; Alexander, R. T.; Singh, I.

    2004-01-01

    There are not many studies on the use of clozapine in patients with intellectual disability (ID). The authors describe a case series of patients treated with clozapine, drawn from a medium secure unit, a low secure assessment and treatment service and a community team in the London region. A retrospective file-review of patients treated in these…

  10. Ziprasidone as an adjuvant for clozapine- or olanzapine-associated medical morbidity in chronic schizophrenia

    PubMed Central

    Henderson, David C.; Fan, Xiaoduo; Copeland, Paul M.; Sharma, Bikash; Borba, Christina P.; Forstbauer, Sharon I.; Miley, Kate; Boxill, Ryan; Freudenreich, Oliver; Cather, Corey; Evins, A. Eden; Goff, Donald C.

    2015-01-01

    Objective This study sought to examine the effect of ziprasidone on olanzapine or clozapine associated medical morbidity such as insulin resistance, diabetes mellitus and impaired fasting glucose, obesity and hyperlipidemia in patients with schizophrenia or schizoaffective disorder. Method This was a six-week, open label trial of ziprasidone 160 mg/day added to a stable dose of olanzapine or clozapine in twenty-one schizophrenia or schizoaffective patients with diabetes mellitus, impaired fasting glucose, or insulin resistance. Results Ten olanzapine-treated subjects and eleven clozapine-treated subjects were enrolled in the study. There were no significant differences between the two groups at baseline for age, gender, education, ethnicity, BMI, cholesterol levels, or fasting glucose. At week six, there were no significant changes in weight, BMI, cholesterol levels, or fasting glucose. There was no significant difference in psychotic, negative or depressive symptoms. QTc significantly increased at week 2 but not at week 6. Conclusions The addition of 160 mg/day of ziprasidone was well tolerate but did not produce significant improvement in fasting glucose, insulin resistance, hyperlipidemia or lead to weight loss in olanzapine- or clozapine-treated subjects with schizophrenia or schizoaffective disorder. PMID:19283774

  11. Pattern of use of clozapine in Spain. Variability and under-prescription.

    PubMed

    Sanz-Fuentenebro, Francisco Javier; Uriarte, Jose Juan Uriarte; Bonet Dalmau, Pere; Molina Rodriguez, Vicente; Bernardo Arroyo, Miquel

    2018-04-06

    International studies on clozapine use usually show lower than expected prescription proportions, under-dosing and delayed initiation of treatment, which has led to a number of initiatives aimed at improving its use and reducing the striking variability observed among practitioners. There are no similar studies on the Spanish population. Therefore we planned initial data collection from 4 territorial samples. We hypothesized that clozapine prescription would also be low and variable in our country. If this hypothesis were confirmed, a reflection on possible strategies would be necessary. We accessed data on clozapine prescription in Catalonia, Castile and Leon, the Basque Country and the Clinical Management Area of the Hospital 12 de Octubre (Madrid). Patients diagnosed with schizophrenia under treatment in these territories comprise around .3% of their total population; treatment with clozapine ranges between 33.0 and 57.0 per 10000 inhabitants; patients diagnosed with schizophrenia on current treatment with clozapine range between 13.7% and 18.6% of the total number of patients with this diagnosis. The coefficient of variation between centres and prescribers is often higher than 50%. Although below the figures suggested as desirable in the literature, global prescribing data for clozapine in the areas we studied are not as low as the data collected in other international studies, and are in the range of countries in our environment. However, the variability in prescription is large and apparently not justified; this heterogeneity increases as we focus on smaller areas, and there is great heterogeneity at the level of individual prescription. Copyright © 2018 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Prediction of changes in memory performance by plasma homovanillic acid levels in clozapine-treated patients with schizophrenia.

    PubMed

    Sumiyoshi, Tomiki; Roy, A; Kim, C-H; Jayathilake, K; Lee, M A; Sumiyoshi, C; Meltzer, H Y

    2004-12-01

    Cognitive dysfunction in schizophrenia has been demonstrated to be dependent, in part, on dopaminergic activity. Clozapine has been found to improve some domains of cognition, including verbal memory, in patients with schizophrenia. This study tested the hypothesis that plasma homovanillic acid (pHVA) levels, a peripheral measure of central dopaminergic activity, would predict the change in memory performance in patients with schizophrenia treated with clozapine. Twenty-seven male patients with schizophrenia received clozapine treatment for 6 weeks. Verbal list learning (VLL)-Delayed Recall (VLL-DR), a test of secondary verbal memory, was administered before and after clozapine treatment. Blood samples to measure pHVA levels were collected at baseline. Baseline pHVA levels were negatively correlated with change in performance on VLL-DR; the lower baseline pHVA level was associated with greater improvement in performance on VLL-DR during treatment with clozapine. Baseline pHVA levels in subjects who showed improvement in verbal memory during clozapine treatment ( n=13) were significantly lower than those in subjects whose memory performance did not improve ( n=14). The results of this study indicate that baseline pHVA levels predict the ability of clozapine to improve memory performance in patients with schizophrenia.

  13. Recombinant human granulocyte colony-stimulating factor (rhG-CSF; filgrastim) treatment of clozapine-induced agranulocytosis.

    PubMed

    Nielsen, H

    1993-11-01

    After 10 weeks of treatment with clozapine, severe agranulocytosis was diagnosed in a 33-year-old female. The patient was treated with filgrastim (granulocyte colony-stimulating factor [G-CSF]) 5 micrograms kg-1 day-1. The neutrophil count was 0.234 x 10(9) l-1 on admission, with a further decrease the next day to < 0.050 x 10(9) l-1, and this complete agranulocytosis continued for 10 days. As no response was obtained after 1 week the dosage of filgrastim was increased to 10 micrograms kg-1 day-1 with immediate improvement. A rapid and pronounced leucocytosis developed with maximal value of neutrophil granulocytes (including immature forms) of 33.108 x 10(9) l-1 on day 12 after admission. The patient only had minor infectious complications during the neutropenic period. In conclusion, early treatment with filgrastim seems warranted in severe cases of clozapine-induced agranulocytosis. A dosage of 10 micrograms kg-1 day-1 can be recommended.

  14. Treatment of clozapine-associated obesity and diabetes with exenatide (CODEX) in adults with schizophrenia: study protocol for a pilot randomised controlled trial.

    PubMed

    Mayfield, Karla; Siskind, Dan; Winckel, Karl; Hollingworth, Samantha; Kisely, Steve; Russell, Anthony W

    2015-06-01

    Clozapine causes significant metabolic disturbances including obesity and type 2 diabetes. Recent evidence that reduced glucagon-like-peptide-1 (GLP-1) may contribute to aetiology of clozapine-associated metabolic dysregulation suggests a potential therapeutic role for GLP-1 agonists. This open-label, pilot randomised controlled trial evaluates the effect of exenatide in clozapine-treated obese adults who have schizophrenia, with or without poorly controlled diabetes. Sixty out-patients will be randomised to once weekly extended release exenatide or treatment as usual for 24 weeks. To evaluate the feasibility of larger studies regarding methodology, acceptability, tolerability and estimate efficacy for glycaemic control or weight loss. Secondary outcomes are psychosis severity and metabolic parameters. This is the first trial investigating GLP-1 agonists for glycaemic control and weight loss in clozapine-treated patients with either diabetes or obesity. Clozapine-associated obesity and diabetes with exenatide (CODEX) will provide proof-of-concept empirical evidence addressing whether this novel treatment is practical and worthy of further investigation. A.W.R. has received speaker honoraria and travel grants from AstraZeneca, BoehringerIngelheim, Eli Lilly, MSD, Novo Nordisk and Sanofi and has participated on advisory panels for MSD and Novo Nordisk. © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

  15. The Use of Clozapine among Individuals with Intellectual Disability: A Review

    ERIC Educational Resources Information Center

    Singh, Ashvind N.; Matson, Johnny L.; Hill, B. D.; Pella, Russell D.; Cooper, Christopher L.; Adkins, Angela D.

    2010-01-01

    Clozapine has been approved in the United States since 1990 for refractory or treatment resistant schizophrenia in the general population. However, as with many other antipsychotic medications, it is being prescribed for reasons other than those indicated. Among individuals with intellectual disabilities, clozapine is increasingly being prescribed…

  16. Experiences of women in secure care who have been prescribed clozapine for borderline personality disorder.

    PubMed

    Dickens, Geoffrey L; Frogley, Catherine; Mason, Fiona; Anagnostakis, Katina; Picchioni, Marco M

    2016-01-01

    Clozapine is an atypical antipsychotic medicine which can cause significant side-effects. It is often prescribed off-license in severe cases of borderline personality disorder contrary to national treatment guidelines. Little is known about the experiences of those who take clozapine for borderline personality disorder. We explored the lived-experience of women in secure inpatient care who were prescribed clozapine for borderline personality disorder. Adult females ( N  = 20) participated in audio-taped semi-structured interviews. Transcripts were subject to thematic analysis. The central themes related to evaluation, wellbeing, understanding and self-management; for many, their subjective wellbeing on clozapine was preferred to prior levels of functioning and symptomatology, sometimes profoundly so. The negative and potentially adverse effects of clozapine were explained as regrettable but relatively unimportant. When psychological interventions are, at least initially, ineffective then clozapine treatment is likely to be evaluated positively by a group of women with borderline personality disorder in secure care despite the potential disadvantages.

  17. Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, Added to Clozapine for the Treatment of Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Trial.

    PubMed

    Lin, Chieh-Hsin; Lin, Ching-Hua; Chang, Yue-Cune; Huang, Yu-Jhen; Chen, Po-Wei; Yang, Hui-Ting; Lane, Hsien-Yuan

    2017-12-26

    Clozapine is the last-line antipsychotic agent for refractory schizophrenia. To date, there is no convincing evidence for augmentation on clozapine. Activation of N-methyl-D-aspartate receptors, including inhibition of D-amino acid oxidase that may metabolize D-amino acids, has been reported to be beneficial for patients receiving antipsychotics other than clozapine. This study aimed to examine the efficacy and safety of a D-amino acid oxidase inhibitor, sodium benzoate, for schizophrenia patients who had poor response to clozapine. We conducted a randomized, double-blind, placebo-controlled trial. Sixty schizophrenia inpatients that had been stabilized with clozapine were allocated into three groups for 6 weeks' add-on treatment of 1 g/day sodium benzoate, 2 g/day sodium benzoate, or placebo. The primary outcome measures were Positive and Negative Syndrome Scale (PANSS) total score, Scale for the Assessment of Negative Symptoms, Quality of Life Scale, and Global Assessment of Functioning. Side effects and cognitive functions were also measured. Both doses of sodium benzoate produced better improvement than placebo in the Scale for the Assessment of Negative Symptoms. The 2 g/day sodium benzoate also produced better improvement than placebo in PANSS-total score, PANSS-positive score, and Quality of Life Scale. Sodium benzoate was well tolerated without evident side effects. The changes of catalase, an antioxidant, were different among the three groups and correlated with the improvement of PANSS-total score and PANSS-positive score in the sodium benzoate group. Sodium benzoate adjuvant therapy improved symptomatology of patients with clozapine-resistant schizophrenia. Further studies are warranted to elucidate the optimal dose and treatment duration as well as the mechanisms of sodium benzoate for clozapine-resistant schizophrenia. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  18. Effects of olanzapine, sertindole and clozapine on MK-801 induced visual memory deficits in mice.

    PubMed

    Mutlu, Oguz; Ulak, Güner; Celikyurt, Ipek Komsuoglu; Akar, Füruzan Yildiz; Erden, Faruk; Tanyeri, Pelin

    2011-10-01

    We investigated the effects of the second generation antipsychotics olanzapine, sertindole and clozapine on visual recognition memory using the novel object recognition (NOR) test in naive and MK-801-treated animals. The effects of drug treatment on locomotion and anxiety were also determined using the open field test. Male Balb-c mice were treated with olanzapine (0.2, 0.4 and 0.6 mg/kg; i.p.), sertindole (0.63, 1.3 and 2.5mg/kg; s.c.) or clozapine (0.5 and 1mg/kg; i.p.), and cognitive deficits were induced by MK-801 (0.2mg/kg; i.p.) administration. Olanzapine treatment decreased the ratio index in the NOR test, whereas sertindole and clozapine had no effect in naive mice. MK-801-induced cognitive impairment was reversed by treatment with olanzapine, sertindole or clozapine. While olanzapine, sertindole and clozapine had no effect on the anxiety of naive mice as determined by the open field test, MK-801 significantly increased the total distance traveled, time spent in the center zone and the velocity of the animals. MK-801-induced effects on locomotion and anxiety in the open field test were reversed by olanzapine, sertindole or clozapine treatment. The results of the present study demonstrated that olanzapine, sertindole and clozapine improved cognition in MK-801 treated mice, and indicate that these drugs have a potential to improve cognition in schizophrenia. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. CLOZAPINE-INDUCED AGRANULOCYTOSIS AND USE OF G-CSF

    PubMed Central

    Srinivasan, T.N.; Thomas, Kuruvilla

    1998-01-01

    Use of clozapine is attended with the serious though rare risk of agranulocytosis. Clozapineinduced agranulocytosis is reversible with the use of cytokines like granulocyte-colony stimulating factor (G-CSF). Reports of the haematological complication of clozapine have not been forthcoming from India though it has been in use for nearly three years. This report is on an young patient who developed total absence of granulocytes during the 4th month of treatment who was successfully treated with G-CSF. PMID:21494447

  20. From Clozapine to Cognitive Remediation

    PubMed Central

    Quinn, Jason

    2016-01-01

    Objective: Although a minority of persons with schizophrenia (SCZ) commits violent acts, SCZ remains a risk factor for violence. Here, we present a broad overview of evidence-based treatments for violence in SCZ, including biological and psychosocial interventions. Method: We conducted MEDLINE and PsychINFO literature searches to retrieve articles relating to treatments for violent, hostile, or aggressive behaviours in SCZ. Results: Clozapine shows the strongest evidence for treating the acute violence of SCZ. Other atypical antipsychotics also possess antiaggressive effects, although the evidence is not as robust as that for clozapine. Psychosocial treatments can be useful adjuncts to pharmacotherapy once patients’ positive symptoms have stabilized. Cognitive behavioural therapy for psychosis and cognitive remediation are 2 psychosocial interventions that have demonstrated positive outcomes for violence in SCZ. Most psychosocial studies that examined violence as an outcome were conducted in forensic psychiatric settings. Conclusions: Effective treatments exist for persons with SCZ who pose a risk for violent and aggressive behaviour, although the overall evidence base remains relatively weak. More randomized controlled trials of programs showing evidence for reduction of violence in SCZ are required. Further research should delineate which patients could benefit from multimodal treatment and where and when such treatments are optimally delivered. PMID:27335156

  1. Persistent tachycardia in clozapine treated patients: A 24-hour ambulatory electrocardiogram study.

    PubMed

    Nilsson, Björn M; Lindström, Leif; Mohsen, Issam; Holmlöv, Karolina; Bodén, Robert

    2018-03-27

    Tachycardia is associated with cardiovascular mortality. Tachycardia is also a known clozapine adverse effect. However, whether clozapine-associated tachycardia is persistent is not known. Thirty clozapine-treated patients with clinical tachycardia were investigated with 24-hour ambulatory electrocardiography (ECG). Baseline peripheral heart rate (HR) was 106.7±7.8. The ambulatory ECG 24-hour-HR was 98.7±9.7. Baseline HR and 24-hour-HR correlated strongly (r=0.74, p=0.000003). Daytime HR was 106.4±9.9 and nighttime HR 89.2±12.0. Low dose bisoprolol reduced HR significantly. The high 24-hour-HR indicates a persistent tachycardia. Tachycardia should not discourage from clozapine use but the findings indicate a need of guidelines for detection and treatment of clozapine-associated tachycardia. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Increased FasL expression correlates with apoptotic changes in granulocytes cultured with oxidized clozapine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Husain, Zaheed; Department of Pathology, Harvard Medical School, Boston, MA; Almeciga, Ingrid

    Clozapine has been associated with a 1% incidence of agranulocytosis. The formation of an oxidized intermediate clozapine metabolite has been implicated in direct polymorphonuclear (PMN) toxicity. We utilized two separate systems to analyze the role of oxidized clozapine in inducing apoptosis in treated cells. Human PMN cells incubated with clozapine (0-10 {mu}M) in the presence of 0.1 mM H{sub 2}O{sub 2} demonstrated a progressive decrease of surface CD16 expression along with increased apoptosis. RT-PCR analysis showed decreased CD16 but increased FasL gene expression in clozapine-treated PMN cells. No change in constitutive Fas expression was observed in treated cells. In HL-60more » cells induced to differentiate with retinoic acid (RA), a similar increase in FasL expression, but no associated changes in CD16 gene expression, was observed following clozapine treatments. Our results demonstrate increased FasL gene expression in oxidized clozapine-induced apoptotic neutrophils suggesting that apoptosis in granulocytes treated with clozapine involves Fas/FasL interaction that initiates a cascade of events leading to clozapine-induced agranulocytosis.« less

  3. An eight-year clinic experience with clozapine use in a Parkinson's disease clinic setting.

    PubMed

    Hack, Nawaz; Fayad, Sarah M; Monari, Erin H; Akbar, Umer; Hardwick, Angela; Rodriguez, Ramon L; Malaty, Irene A; Romrell, Janet; Shukla, Aparna A Wagle; McFarland, Nikolaus; Ward, Herbert E; Okun, Michael S

    2014-01-01

    To examine our eight year clinic-based experience in a Parkinson's disease expert clinical care center using clozapine as a treatment for refractory psychosis in Parkinson's disease (PD). The study was a retrospective chart review which covered eight years of clozapine registry use. Statistical T-tests, chi-square, correlations and regression analysis were used to analyze treatment response for potential associations of age, disease duration, and Hoehn & Yahr (H&Y) score, and degree of response to clozapine therapy. There were 36 participants included in the analysis (32 PD, 4 parkinsonism-plus). The characteristics included 30.6% female, age 45-87 years (mean 68.3±10.15), disease duration of 17-240 months (mean 108.14±51.13) and H&Y score of 2 to 4 (mean 2.51±0.51). The overall retention rate on clozapine was 41% and the most common reasons for discontinuation were frequent blood testing (28%), nursing home (NH) placement (11%) and leucopenia (8%). Responses to clozapine across the cohort were: complete (33%), partial (33%), absent (16%), and unknown (16%). Age (r = -0.36, p<0.01) and H&Y score (r = -0.41, p<0.01) were shown to be related to response to clozapine therapy, but disease duration was not an associated factor (r = 0.21, p>0.05). This single-center experience highlights the challenges associated with clozapine therapy in PD psychosis. Frequent blood testing remains a significant barrier for clozapine, even in patients with therapeutic benefit. Surprisingly, all patients admitted to a NH discontinued clozapine due to logistical issues of administration and monitoring within that setting. Consideration of the barriers to clozapine therapy will be important to its use and to its continued success in an outpatient setting.

  4. The Presynaptic Component of the Serotonergic System is Required for Clozapine's Efficacy

    PubMed Central

    Yadav, Prem N; Abbas, Atheir I; Farrell, Martilias S; Setola, Vincent; Sciaky, Noah; Huang, Xi-Ping; Kroeze, Wesley K; Crawford, LaTasha K; Piel, David A; Keiser, Michael J; Irwin, John J; Shoichet, Brian K; Deneris, Evan S; Gingrich, Jay; Beck, Sheryl G; Roth, Bryan L

    2011-01-01

    Clozapine, by virtue of its absence of extrapyramidal side effects and greater efficacy, revolutionized the treatment of schizophrenia, although the mechanisms underlying this exceptional activity remain controversial. Combining an unbiased cheminformatics and physical screening approach, we evaluated clozapine's activity at >2350 distinct molecular targets. Clozapine, and the closely related atypical antipsychotic drug olanzapine, interacted potently with a unique spectrum of molecular targets. This distinct pattern, which was not shared with the typical antipsychotic drug haloperidol, suggested that the serotonergic neuronal system was a key determinant of clozapine's actions. To test this hypothesis, we used pet1−/− mice, which are deficient in serotonergic presynaptic markers. We discovered that the antipsychotic-like properties of the atypical antipsychotic drugs clozapine and olanzapine were abolished in a pharmacological model that mimics NMDA-receptor hypofunction in pet1−/− mice, whereas haloperidol's efficacy was unaffected. These results show that clozapine's ability to normalize NMDA-receptor hypofunction, which is characteristic of schizophrenia, depends on an intact presynaptic serotonergic neuronal system. PMID:21048700

  5. Effects of adjunctive treatment with aripiprazole on body weight and clinical efficacy in schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Fleischhacker, W Wolfgang; Heikkinen, Martti E; Olié, Jean-Pierre; Landsberg, Wally; Dewaele, Patricia; McQuade, Robert D; Loze, Jean-Yves; Hennicken, Delphine; Kerselaers, Wendy

    2010-09-01

    Clozapine is associated with significant weight gain and metabolic disturbances. This multicentre, randomized study comprised a double-blind, placebo-controlled treatment phase of 16 wk, and an open-label extension phase of 12 wk. Outpatients who met DSM-IV-TR criteria for schizophrenia, who were not optimally controlled while on stable dosage of clozapine for > or =3 months and had experienced weight gain of > or =2.5 kg while taking clozapine, were randomized (n=207) to aripiprazole at 5-15 mg/d or placebo, in addition to a stable dose of clozapine. The primary endpoint was mean change from baseline in body weight at week 16 (last observation carried forward). Secondary endpoints included clinical efficacy, body mass index (BMI) and waist circumference. A statistically significant difference in weight loss was reported for aripiprazole vs. placebo (-2.53 kg vs. -0.38 kg, respectively, difference=-2.15 kg, p<0.001). Aripiprazole-treated patients also showed BMI (median reduction 0.8 kg/m(2)) and waist circumference reduction (median reduction 2.0 cm) vs. placebo (no change in either parameter, p<0.001 and p=0.001, respectively). Aripiprazole-treated patients had significantly greater reductions in total and low-density lipoprotein (LDL) cholesterol. There were no significant differences in Positive and Negative Syndrome Scale total score changes between groups but Clinical Global Impression Improvement and Investigator's Assessment Questionnaire scores favoured aripiprazole over placebo. Safety and tolerability were generally comparable between groups. Combining aripiprazole and clozapine resulted in significant weight, BMI and fasting cholesterol benefits to patients suboptimally treated with clozapine. Improvements may reduce metabolic risk factors associated with clozapine treatment.

  6. Clozapine and risperidone in moderately refractory schizophrenia: a 6-month randomized double-blind comparison.

    PubMed

    Schooler, Nina R; Marder, Stephen R; Chengappa, K N R; Petrides, Georgios; Ames, Donna; Wirshing, William C; McMeniman, Marjorie; Baker, Robert W; Parepally, Haranath; Umbricht, Daniel; Kane, John M

    2016-05-01

    Clozapine remains the only medication indicated for refractory schizophrenia. As new antipsychotic drugs become available, their efficacy compared to clozapine, particularly in moderately ill patients, is of great clinical interest. We compared risperidone, the first of these, to clozapine in partially responsive patients. Further, since participation of patients usually excluded from clinical trials is increasingly important, we broadened inclusion to a wider patient population. We compared clozapine (n = 53) to risperidone (n = 54) in a randomized, double-blind, 29-week trial in schizophrenia patients (diagnosed using DSM-IV) at 3 research outpatient clinics. Randomization was stratified by "narrow" or "broad" inclusion criteria. The study was conducted between December 1995 and October 1999. Time to treatment discontinuation for lack of efficacy and time to 20% improvement in the Brief Psychiatric Rating Scale psychotic symptom cluster were the primary outcome measures. There were no differences in all-cause discontinuation; clozapine-treated participants were significantly less likely to discontinue for lack of efficacy (15%) than risperidone-treated participants (38%) (Wilcoxon χ(2)1 = 6.10, P = .01). Clozapine resulted in significantly more global improvement (F2,839 = 6.07, P < .01) and asociality improvement (F2,315 = 6.64, P < .01) than risperidone. There was no difference in proportions meeting an a priori criterion of psychosis improvement (risperidone: 57%; clozapine: 71%). Significant adverse effect differences in salivation (F1 = 4.05, P < .05) (F1 = 12.13, P < .001), sweating (F1 = 5.07, P < .05), and tachycardia (F1 = 6.51, P < .05) favored risperidone. Clozapine-treated partially responsive patients were less likely to discontinue treatment for lack of efficacy and improved more globally than those treated with risperidone, although psychotic symptoms did not differ. These findings suggest that clozapine should not be restricted to the most

  7. Consumer access to clozapine in Australia: how does this compare to New Zealand and the United Kingdom?

    PubMed

    Knowles, Sally-Anne; Mcmillan, Sara S; Wheeler, Amanda J

    2016-01-01

    Clozapine is an antipsychotic medication used in treatment resistant schizophrenia. However, clozapine is associated with a significant adverse effect profile and extensive monitoring is required to optimise consumer safety. Traditionally, clozapine can only be prescribed by a psychiatrist and dispensed at a hospital or hospital affiliated pharmacy in Australia. These restrictions could result in significant treatment burden for consumers taking clozapine. To identify (1) the different models of supply that exist for people living in the community taking clozapine in Australia and compare to those in New Zealand and the United Kingdom, and (2) explore how these supply models may impact on consumer burden from the perspective of professionals involved in the supply of clozapine. Key informants were interviewed (n=8) from Australia, New Zealand and the United Kingdom regarding how consumers, who lived in the community, accessed clozapine. Data were analysed and led to the development of four clozapine supply models. These four models were further validated by an online survey of a wider sample (n=30). Data were analysed thematically and via simple descriptive statistics. Clozapine supply varied depending on location. A secondary care model was utilised in the United Kingdom compared to a community based (primary care) model in New Zealand; Australia utilised a mixture of both secondary and primary care. A key theme from all study participants was that community pharmacy should be utilised to dispense clozapine to consumers living in the community, provided adequate training and safeguards are in place. It was noted that the utilisation of community pharmacies could improve access and flexibility, thereby reducing treatment burden for these consumers. There are predominately two models for supply of clozapine to consumers living in the community in Australia, New Zealand and the United Kingdom. One model utilises secondary care facilities and the other community

  8. Moclobemide treatment of clozapine-induced hypersalivation: pilot open study.

    PubMed

    Kreinin, Anatoly; Miodownik, Chanoch; Libov, Igor; Shestakova, Diana; Lerner, Vladimir

    2009-01-01

    Clozapine-induced hypersalivation (CIHS) affects a mean of approximately 30% patients and is a troublesome adverse effect that leads to massive compliance problems in patients with schizophrenia. For the management of this distressing adverse effect, different pharmacological agents have been recommended, yet none of them have been proven to be effective. The aim of our study was to investigate moclobemide, a reversible monoamine oxidase inhibitor-A, as an additional possibility for controlling or at least minimizing CIHS. We enrolled 14 patients with schizophrenia who experienced CIHS. Moclobemide (150-300 mg/d) was added to their conventional regular treatment during 14 days. Hypersalivation was assessed at the start of the treatment and at its end point by the 5-point Nocturnal Hypersalivation Rating Scale. Two thirds of the subjects who experienced CIHS have demonstrated a beneficial effect after the addition of moclobemide, whereas one third of them have been nonresponders. None of the patients had any adverse effects. We assume that moclobemide can be another additional and safe medication for the treatment of CIHS; however, more data, based on controlled studies, are needed.

  9. Prevalence and Predictors of Clozapine-Associated Constipation: A Systematic Review and Meta-Analysis

    PubMed Central

    Shirazi, Ayala; Stubbs, Brendon; Gomez, Lucia; Moore, Susan; Gaughran, Fiona; Flanagan, Robert J.; MacCabe, James H.; Lally, John

    2016-01-01

    Constipation is a frequently overlooked side effect of clozapine treatment that can prove fatal. We conducted a systematic review and meta-analysis to estimate the prevalence and risk factors for clozapine-associated constipation. Two authors performed a systematic search of major electronic databases from January 1990 to March 2016 for articles reporting the prevalence of constipation in adults treated with clozapine. A random effects meta-analysis was conducted. A total of 32 studies were meta-analyzed, establishing a pooled prevalence of clozapine-associated constipation of 31.2% (95% CI: 25.6–37.4) (n = 2013). People taking clozapine were significantly more likely to be constipated versus other antipsychotics (OR 3.02 (CI: 1.91–4.77), p < 0.001, n = 11 studies). Meta-regression identified two significant study-level factors associated with constipation prevalence: significantly higher (p = 0.02) rates of constipation were observed for those treated in inpatient versus outpatient or mixed settings and for those studies in which constipation was a primary or secondary outcome measure (36.9%) compared to studies in which constipation was not a specified outcome measure (24.8%, p = 0.048). Clozapine-associated constipation is common and approximately three times more likely than with other antipsychotics. Screening and preventative strategies should be established and appropriate symptomatic treatment applied when required. PMID:27271593

  10. An Eight-Year Clinic Experience with Clozapine Use in a Parkinson’s Disease Clinic Setting

    PubMed Central

    Hack, Nawaz; Fayad, Sarah M.; Monari, Erin H.; Akbar, Umer; Hardwick, Angela; Rodriguez, Ramon L.; Malaty, Irene A.; Romrell, Janet; Shukla, Aparna A. Wagle.; McFarland, Nikolaus; Ward, Herbert E.; Okun, Michael S.

    2014-01-01

    Background To examine our eight year clinic-based experience in a Parkinson’s disease expert clinical care center using clozapine as a treatment for refractory psychosis in Parkinson's disease (PD). Methods The study was a retrospective chart review which covered eight years of clozapine registry use. Statistical T-tests, chi-square, correlations and regression analysis were used to analyze treatment response for potential associations of age, disease duration, and Hoehn & Yahr (H&Y) score, and degree of response to clozapine therapy. Results There were 36 participants included in the analysis (32 PD, 4 parkinsonism-plus). The characteristics included 30.6% female, age 45–87 years (mean 68.3±10.15), disease duration of 17–240 months (mean 108.14±51.13) and H&Y score of 2 to 4 (mean 2.51±0.51). The overall retention rate on clozapine was 41% and the most common reasons for discontinuation were frequent blood testing (28%), nursing home (NH) placement (11%) and leucopenia (8%). Responses to clozapine across the cohort were: complete (33%), partial (33%), absent (16%), and unknown (16%). Age (r = −0.36, p<0.01) and H&Y score (r = −0.41, p<0.01) were shown to be related to response to clozapine therapy, but disease duration was not an associated factor (r = 0.21, p>0.05). Conclusions This single-center experience highlights the challenges associated with clozapine therapy in PD psychosis. Frequent blood testing remains a significant barrier for clozapine, even in patients with therapeutic benefit. Surprisingly, all patients admitted to a NH discontinued clozapine due to logistical issues of administration and monitoring within that setting. Consideration of the barriers to clozapine therapy will be important to its use and to its continued success in an outpatient setting. PMID:24646688

  11. NeuN+ Neuronal Nuclei in Non-Human Primate Prefrontal Cortex and Subcortical White Matter After Clozapine Exposure

    PubMed Central

    Halene, Tobias B.; Kozlenkov, Alexey; Jiang, Yan; Mitchell, Amanda; Javidfar, Behnam; Dincer, Aslihan; Park, Royce; Wiseman, Jennifer; Croxson, Paula; Giannaris, Eustathia Lela; Hof, Patrick R.; Roussos, Panos; Dracheva, Stella; Hemby, Scott E.; Akbarian, Schahram

    2016-01-01

    Increased neuronal densities in subcortical white matter have been reported for some cases with schizophrenia. The underlying cellular and molecular mechanisms remain unresolved. We exposed 26 young adult macaque monkeys for 6 months to either clozapine, haloperidol or placebo and measured by structural MRI frontal gray and white matter volumes before and after treatment, followed by observer-independent, flow-cytometry-based quantification of neuronal and non-neuronal nuclei and molecular fingerprinting of cell-type specific transcripts. After clozapine exposure, the proportion of nuclei expressing the neuronal marker NeuN increased by approximately 50% in subcortical white matter, in conjunction with a more subtle and non-significant increase in overlying gray matter. Numbers and proportions of nuclei expressing the oligodendrocyte lineage marker, OLIG2, and cell-type specific RNA expression patterns, were maintained after antipsychotic drug exposure. Frontal lobe gray and white matter volumes remained indistinguishable between antipsychotic-drug-exposed and control groups. Chronic clozapine exposure increases the proportion of NeuN+ nuclei in frontal subcortical white matter, without alterations in frontal lobe volumes or cell type-specific gene expression. Further exploration of neurochemical plasticity in non-human primate brain exposed to antipsychotic drugs is warranted. PMID:26776227

  12. Can valproic acid be an inducer of clozapine metabolism?

    PubMed Central

    Diaz, Francisco J.; Eap, Chin B.; Ansermot, Nicolas; Crettol, Severine; Spina, Edoardo; de Leon, Jose

    2014-01-01

    Introduction Prior clozapine studies indicated no effects, mild inhibition or induction of valproic acid (VPA) on clozapine metabolism. The hypotheses that 1) VPA is a net inducer of clozapine metabolism, and 2) smoking modifies this inductive effect were tested in a therapeutic drug monitoring study. Methods After excluding strong inhibitors and inducers, 353 steady-state total clozapine (clozapine plus norclozapine) concentrations provided by 151 patients were analyzed using a random intercept linear model. Results VPA appeared to be an inducer of clozapine metabolism since total plasma clozapine concentrations in subjects taking VPA were significantly lower (27% lower; 95% confidence interval, 14% to 39%) after controlling for confounding variables including smoking (35% lower, 28% to 56%). Discussion Prospective studies are needed to definitively establish that VPA may 1) be an inducer of clozapine metabolism when induction prevails over competitive inhibition, and 2) be an inducer even in smokers who are under the influence of smoking inductive effects on clozapine metabolism. PMID:24764199

  13. Role of cytokine changes in clozapine-induced fever: A cohort prospective study.

    PubMed

    Hung, Yuan-Pin; Wang, Carol S-M; Yen, Chia-Nan; Chang, Hsun-Cheng; Chen, Po See; Lee, I Hui; Chen, Kao Chin; Yang, Yen Kuang; Lu, Ru-Band; Wang, Tzu-Yun

    2017-06-01

    Clozapine-associated fever is common but the specific cytokine changes and treatment durations that may cause fever remain unknown. We investigated the association between inflammatory cytokine changes and clozapine-induced fever in patients who were treated with clozapine. Forty-three patients with schizophrenia or schizoaffective disorder, diagnosed by using the Chinese Version of the Mini International Neuropsychiatric Interview, were treated with clozapine for the first time (first-time use group, n = 22) or for more than 6 months (long-term use group, n = 21). The Positive and Negative Syndrome Scale, tympanic temperature, and levels of tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), interleukin-2 (IL-2), and interleukin-6 (IL-6) were determined at baseline and weeks 1, 2, 3, 4, and 6. A multiple linear regression with generalized estimating equation methods was used to analyze the association between the changes in the cytokine levels and clozapine-induced fever in the different groups. The IL-6 level changes were significantly different between the two groups (P = 0.04). In the first-time use group, the fever rate was increased (47.1%) compared with the long-term use group (5.6%, P = 0.005). Moreover, in these patients, the TNF-α, INF-γ, IL-2, and IL-6 levels were significantly (P < 0.001) different from patients who did not develop a fever. An interaction effect with the different treatment duration groups and fever development was only significant for IL-6 (P < 0.001). Patients who were treated with clozapine for the first time have an increased rate of developing a fever, and IL-6 might have a specific role in the interaction effect between treatment duration and fever development. © 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

  14. Vitamin D Supplementation in Chronic Schizophrenia Patients Treated with Clozapine: A Randomized, Double-Blind, Placebo-controlled Clinical Trial.

    PubMed

    Krivoy, Amir; Onn, Roy; Vilner, Yael; Hochman, Eldar; Weizman, Shira; Paz, Amir; Hess, Shmuel; Sagy, Roi; Kimhi-Nesher, Shiri; Kalter, Ehud; Friedman, Tal; Friedman, Zvi; Bormant, Gil; Trommer, Sharon; Valevski, Avi; Weizman, Abraham

    2017-12-01

    While accumulating evidence suggests that vitamin D deficiency may be involved in the risk to develop schizophrenia and its outcome, there are no studies on vitamin D supplementation in this context. We sought to assess the effect of vitamin D supplementation on psychiatric, cognitive and metabolic parameters in chronic clozapine-treated schizophrenia patients. This eight-week, randomized, double-blind, placebo-controlled clinical trial, recruited schizophrenia patients who had been maintained on clozapine treatment for at least 18weeks and had low levels of vitamin D (<75nmol/l) and total PANSS scores >70 (to ascertain the presence of residual symptoms). Patients were randomly allocated to either weekly oral drops of vitamin D (14,000IU) or placebo and subsequently assessed at two-week intervals for psychosis severity, mood, cognition and metabolic profile. Twenty four patients were randomly assigned to vitamin D (aged 39.4±9.6years, 75% males) and the other 23 patients to the placebo arm (aged 42.5±11.2years, 60.9% males). After eight weeks, the vitamin D group exhibited a significant increase in vitamin D levels (31.4 vs -0.4nmol/l, p<0.0001). There was no significant effect of vitamin D on psychotic, depressive or metabolic parameters. However, in the vitamin D group, there was a trend towards improved cognition (effect size=0.17, significance lost following Bonferroni correction). Vitamin D supplementation was associated with a trend towards improved cognition, but did not affect psychosis, mood or metabolic status. It is possible that the robust decrease in the PANSS scores in both groups may have obscured an effect of vitamin D supplementation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Clozapine counteracts a ketamine-induced depression of hippocampal-prefrontal neuroplasticity and alters signaling pathway phosphorylation

    PubMed Central

    Rame, Marion; Caudal, Dorian; Schenker, Esther; Svenningsson, Per; Spedding, Michael; Jay, Thérèse M.

    2017-01-01

    Single sub-anesthetic doses of ketamine can exacerbate the symptoms of patients diagnosed with schizophrenia, yet similar ketamine treatments rapidly reduce depressive symptoms in major depression. Acute doses of the atypical antipsychotic drug clozapine have also been shown to counteract ketamine-induced psychotic effects. In the interest of understanding whether these drug effects could be modeled with alterations in neuroplasticity, we examined the impact of acutely-administered ketamine and clozapine on in vivo long-term potentiation (LTP) in the rat’s hippocampus-to-prefrontal cortex (H-PFC) pathway. We found that a low dose of ketamine depressed H-PFC LTP, whereas animals that were co-administrated the two drugs displayed LTP that was similar to a saline-treated control. To address which signaling molecules might mediate such effects, we also examined phosphorylation and total protein levels of GSK3β, GluA1, TrkB, ERK, and mTOR in prefrontal and hippocampal sub-regions. Among the statistically significant effects that were detected (a) both ketamine and clozapine increased the phosphorylation of Ser9-GSK3β throughout the prefrontal cortex and of Ser2481-mTOR in the dorsal hippocampus (DH), (b) clozapine increased the phosphorylation of Ser831-GluA1 throughout the prefrontal cortex and of Ser845-GluA1 in the ventral hippocampus, (c) ketamine treatment increased the phosphorylation of Thr202/Tyr204-ERK in the medial PFC (mPFC), and (d) clozapine treatment was associated with decreases in the phosphorylation of Tyr705-TrkB in the DH and of Try816-TrkB in the mPFC. Further analyses involving phosphorylation effect sizes also suggested Ser831-GluA1 in the PFC displayed the highest degree of clozapine-responsivity relative to ketamine. These results provide evidence for how ketamine and clozapine treatments affect neuroplasticity and signaling pathways in the stress-sensitive H-PFC network. They also demonstrate the potential relevance of H-PFC pathway

  16. Prediction of short-term changes in symptom severity by baseline plasma homovanillic acid levels in schizophrenic patients receiving clozapine.

    PubMed

    Sumiyoshi, T; Hasegawa, M; Jayathilake, K; Meltzer, H Y

    1997-03-24

    The relationship between pretreatment levels of plasma homovanillic acid (pHVA) and the outcome of clozapine treatment was studied in 18 male patients with schizophrenia who were resistant to treatment with conventional neuroleptics. After 6 months of clozapine treatment, 7 patients demonstrated > or = 20% decrease in the Brief Psychiatric Rating Scale (BPRS) (responders), while 11 patients did not (non-responders). Responders and non-responders did not differ with respect to the baseline pHVA level. The BPRS Positive Symptom scores at 6 weeks and 3 months, but not those at baseline and 6 months, following initiation of clozapine treatment negatively correlated with pHVA levels for all patients. The correlations became stronger when only responders were included. No significant correlation between Positive Symptom scores and pHVA levels was observed for non-responders. The BPRS Total and Negative Symptom scores did not correlate with pHVA for all patients, responders or non-responders at any time. The percent decrease in the BPRS Positive Symptom scores from baseline at 6 weeks following clozapine treatment correlated significantly with pHVA levels in responders. These results suggest that pretreatment levels of pHVA can be used to predict relatively short-term changes in the positive symptoms of patients with schizophrenia receiving clozapine treatment, particularly for clozapine responders.

  17. Prefrontal cortical glutathione-dependent defense and proinflammatory mediators in chronically isolated rats: Modulation by fluoxetine or clozapine.

    PubMed

    Todorović, Nevena; Filipović, Dragana

    2017-07-04

    Chronic psychosocial stress modulates brain antioxidant systems and causes neuroinflammation that plays a role in the pathophysiology of depression. Although the antidepressant fluoxetine (FLX) represents the first-line treatment for depression and the atypical antipsychotic clozapine (CLZ) is considered as a second-line treatment for psychotic disorders, the downstream mechanisms of action of these treatments, beyond serotonergic or dopaminergic signaling, remain elusive. We examined behavioral changes, glutathione (GSH)-dependent defense and levels of proinflammatory mediators in the prefrontal cortex (PFC) of adult male Wistar rats exposed to 21days of chronic social isolation (CSIS). We also tested the ability of FLX (15mg/kg/day) or CLZ (20mg/kg/day), applied during CSIS, to prevent stress-induced changes. CSIS caused depressive- and anxiety-like behaviors, compromised GSH-dependent defense, and induced nuclear factor-kappa B (NF-κB) activation with a concomitant increase in cytosolic levels of proinflammatory mediators cyclooxigenase-2, interleukin-1beta and tumor necrosis factor-alpha in the PFC. NF-κB activation and proinflammatory response in the PFC were not found in CSIS rats treated with FLX or CLZ. In contrast, only FLX preserved GSH content in CSIS rats. CLZ not only failed to protect against CSIS-induced GSH depletion, but it diminished its levels when applied to non-stressed rats. In conclusion, prefrontal cortical GSH depletion and the proinflammatory response underlying depressive- and anxiety-like states induced by CSIS were prevented by FLX. The protective effect of CLZ, which was equally effective as FLX on the behavioral level, was limited to proinflammatory components. Hence, different mechanisms underlie the protective effects of these two drugs in CSIS rats. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Prescription and Underprescription of Clozapine in Dutch Ambulatory Care.

    PubMed

    van der Zalm, Yvonne C; Termorshuizen, Fabian; Schulte, Peter F; Bogers, Jan P; Marcelis, Machteld; Sommer, Iris E; Selten, Jean Paul

    2018-01-01

    Purpose: To our knowledge, no study has examined in a structured way the extent of underprescription of clozapine in ambulatory patients with Non-Affective Psychotic Disorder (NAPD). In the Netherlands, psychiatric care for such patients is provided by Flexible Assertive Community Treatment (FACT) teams and by early intervention teams. In 20 FACT teams and 3 early intervention teams we assessed the proportion of patients who: use clozapine (type 1 patients), previously used this drug (type 2), have an unfulfilled indication for this drug, by type of indication (type 3), or were at least markedly psychotic, but had not yet received two adequate treatments with other antipsychotic drugs (type 4). We expected to find major differences between teams. To rule out that these differences are caused by differences in severity of psychopathology, we also calculated the proportions of patients who use clozapine given an indication at any time (number of type 1 patients divided by the sum of type 1, 2, and 3 patients). Materials and methods: The nurse practitioner of each team identified the patients already on clozapine. Next, using a highly-structured decision tree, the nurse practitioner and psychiatrist assessed whether the remaining patients had an indication for this drug. Indications were treatment-resistant positive symptoms, tardive dyskinesia, aggression and suicidality. The severity of positive symptoms was determined using the Clinical Global Impression-Schizophrenia Scale (CGI-SCH). Results: In the participating FACT-teams 2,286 NAPD patients were assessed. The range among teams in proportions was: type 1: 8.8-34.7% (mean: 23.0%), type 2: 0-8.2% (mean: 3.5%), type 3: 1.7-15.6% (mean: 6.9%), type 4: 1.8-16.3% (mean: 8.6%). The range in proportions of patients using this drug given an indication was 49.0-90.9% (mean: 68.8%). These figures were lower in early intervention teams. Conclusions: The proportion of patients in FACT-teams who have an unfulfilled indication

  19. Modafinil for Clozapine-Treated Schizophrenia Patients: A Double-Blind, Placebo-Controlled Pilot Trial

    PubMed Central

    Freudenreich, Oliver; Henderson, David C.; Macklin, Eric A.; Evins, A. Eden; Fan, Xiaoduo; Cather, Cori; Walsh, Jared P.; Goff, Donald C.

    2016-01-01

    Background Patients with schizophrenia often suffer from cognitive deficits and negative symptoms that are poorly responsive to antipsychotics including clozapine. Clozapine-induced sedation can worsen cognition and impair social and occupational functioning. Objectives To evaluate the efficacy, tolerability, and safety of modafinil for negative symptoms, cognition, and wakefulness/fatigue in DSM-IV–diagnosed schizophrenia patients treated with clozapine. Method A double-blind, placebo-controlled, flexible-dosed 8-week pilot trial was conducted between September 2003 and September 2007, adding modafinil up to 300 mg/d to stabilized schizophrenia outpatients receiving clozapine. Psychopathology, cognition, and wakefulness/fatigue were assessed with standard rating scales. Results Thirty-five patients were randomly assigned to treatment with study drug and included in the analysis. Modafinil did not reduce negative symptoms or wakefulness/fatigue or improve cognition compared to placebo. Modafinil was well tolerated and did not worsen psychosis. Conclusions Results of this pilot trial do not support routine use of modafinil to treat negative symptoms, cognitive deficits, or wakefulness/fatigue in patients on clozapine. However, given our limited power to detect a treatment effect and the clear possibility of a type II error, larger trials are needed to resolve or refute a potential therapeutic effect of uncertain magnitude. Trial Registration clinicaltrials.gov Identifier: NCT00573417 PMID:19689921

  20. Augmentation of clozapine with amisulpride: an effective therapeutic strategy for violent treatment-resistant schizophrenia patients in a UK high-security hospital.

    PubMed

    Hotham, James E; Simpson, Patrick J D; Brooman-White, Rosalie S; Basu, Amlan; Ross, Callum C; Humphreys, Sharon A; Larkin, Fintan; Gupta, Nitin; Das, Mrigendra

    2014-10-01

    Clozapine is used in the management of treatment-resistant schizophrenia and is effective in reducing aggression; however a subgroup of patients is poorly responsive. For violent patients in this group, there is limited literature on the use of strategies to augment clozapine with other agents. Here we present a case series of 6 schizophrenia patients, within a high-security hospital, who have a history of serious violence and who were treated with clozapine augmented with amisulpride. We reviewed case notes and health records for evidence of violence/aggression and positive factors such as engagement in activities, and Clinical Global Impression (CGI) scores were formulated. We also examined metabolic parameters before and after augmentation. All 6 of the patients showed clinical improvement in symptoms and a reduction in their risk of violence to others. Five patients had a reduction in number of violent/aggressive incidents, and all patients showed improvement in engagement in occupational, vocational, and/or psychological work. Metabolic parameters were largely unchanged except for 1 patient whose Body Mass Index (BMI) increased. Five patients reported side effects as unchanged or improved. These schizophrenia patients with a history of violence showed clinical improvement and reduced aggression and violence with amisulpride augmentation of clozapine. To our knowledge, this is the first report of an antiaggressive benefit of this combination in forensic psychiatric patients. Further studies are warranted to establish the efficacy and anti-aggressive effects of amisulpride augmentation of clozapine.

  1. Memantine augmentation in clozapine-refractory schizophrenia: a randomized, double-blind, placebo-controlled crossover study.

    PubMed

    Veerman, S R T; Schulte, P F J; Smith, J D; de Haan, L

    2016-07-01

    Dysfunction of neuroplasticity due to N-methyl-d-aspartate (NMDA) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia. Deregulation of NMDA transmission in the prefrontal cortex may also explain negative and positive symptoms. Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study. We evaluate effects of memantine add-on treatment to clozapine for memory and executive function, and negative and positive symptoms in schizophrenia. Clozapine-treated patients with refractory schizophrenia were randomly assigned to 12 weeks of double-blind adjunctive treatment with memantine (n = 26) or placebo (n = 26). Crossover occurred after a 2-week placebo wash-out period. Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale. When compared with placebo, memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB (effect size = 0.30) and PANSS negative subscale score (effect size = 0.29). Side effects were mild and transient. In patients with clozapine-treated refractory schizophrenia, memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects. These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia.

  2. Effect of Clozapine vs Other Second-Generation Antipsychotics on Hospitalization and Seclusion: A Retrospective Mirror-Image Study in a Japanese Public Psychiatric Hospital.

    PubMed

    Misawa, Fuminari; Suzuki, Takefumi; Fujii, Yasuo

    2017-12-01

    Clozapine has been regarded as the gold standard for patients with treatment-resistant schizophrenia, but a recent network meta-analysis has questioned its relative superiority over other second-generation antipsychotics (SGAs) such as olanzapine and risperidone. We conducted a retrospective mirror-image study of clozapine vs other SGAs to evaluate real-world effectiveness of clozapine in terms of the duration of hospitalization and seclusion, both of which represent a critical outcome. We included all patients who initiated clozapine at the Yamanashi Prefectural KITA Hospital and had continued to take any SGA(s) other than clozapine for at least 1 year before the initiation of clozapine. We obtained data on hospitalization and seclusion during 1 year of SGA treatment (SGA phase) and 1 year after the treatment was switched to clozapine (clozapine phase). The study included 35 patients (21 men, 31 with schizophrenia, 4 with schizoaffective disorder) with the average ± SD age of 37.3 ± 11.1 years. The results indicated that total hospitalization days did not differ significantly between SGA and clozapine treatment. However, total duration of seclusion was significantly shorter in the clozapine phase than in the SGA phase. Furthermore, the number of patients who were secluded at least once was significantly smaller in the clozapine phase than in the SGA phase. The results were essentially unchanged when outlier patients were excluded and only when patients taking olanzapine and/or risperidone during the SGA phase were considered. Although the findings from this retrospective analysis need to be further tested in prospective trials, they endorse the relative effectiveness of clozapine over other SGAs in the real world.

  3. Training in a Clozapine Clinic for Psychiatry Residents: A Plea and Suggestions for Implementation

    ERIC Educational Resources Information Center

    Freudenreich, Oliver; Henderson, David C.; Sanders, Kathy M.; Goff, Donald C.

    2013-01-01

    Objective: The authors sought to develop a model educational clinic and curriculum for psychiatric residents, to increase knowledge and comfort about clozapine prescribing. This matters because clozapine is an important evidence-based treatment for refractory schizophrenia that remains underutilized in clinical practice. Method: This is a…

  4. Amisulpride versus moclobemide in treatment of clozapine-induced hypersalivation.

    PubMed

    Kreinin, Anatoly; Miodownik, Chanoch; Sokolik, Shmuel; Shestakova, Diana; Libov, Igor; Bergman, Joseph; Lerner, Vladimir

    2011-12-01

    Previous publications demonstrated substitute benzamides as effective agents in treatment of clozapine-induced sialorrhea (CIS). The aim of this study was to compare efficacy of amisulpride and moclobemide (both from the substitute benzamide group) in controlling, or at least minimizing, CIS. The study was designed as a 6-week, two-center, fixed-dose, comparison study of 400 mg/day of amisulpride versus 300 mg/day of moclobemide as an adjunctive treatment in 53 schizophrenia and schizoaffective disorder patients (diagnosed according to DSM-IV) suffering from CIS. The patients were treated with each medication during 2 weeks, followed by a washout period of 2 weeks. Primary outcome measures included the reduction in the five-point Nocturnal Hypersalivation Rating Scale (NHRS). Secondary outcomes included the Positive and Negative Syndrome Scale (PANSS), Manic State Assessment Scale, and Extrapyramidal Symptom Rating Scale (ESRS). Both amisulpride and moclobemide were very effective in reducing CIS. Almost 74% of patients treated with amisulpride and 83% of patients treated with moclobemide showed some level of improvement on NHRS. Only in one patient treated with amisulpride, CIS worsened. Both medications were safe and effective as treatment of CIS. Although moclobemide exceeded amisulpride in antisalivation activity, treatment of CIS with amisulpride leads to improvement in psychotic symptoms.

  5. International trends in clozapine use: a study in 17 countries.

    PubMed

    Bachmann, C J; Aagaard, L; Bernardo, M; Brandt, L; Cartabia, M; Clavenna, A; Coma Fusté, A; Furu, K; Garuoliené, K; Hoffmann, F; Hollingworth, S; Huybrechts, K F; Kalverdijk, L J; Kawakami, K; Kieler, H; Kinoshita, T; López, S C; Machado-Alba, J E; Machado-Duque, M E; Mahesri, M; Nishtala, P S; Piovani, D; Reutfors, J; Saastamoinen, L K; Sato, I; Schuiling-Veninga, C C M; Shyu, Y-C; Siskind, D; Skurtveit, S; Verdoux, H; Wang, L-J; Zara Yahni, C; Zoëga, H; Taylor, D

    2017-07-01

    There is some evidence that clozapine is significantly underutilised. Also, clozapine use is thought to vary by country, but so far no international study has assessed trends in clozapine prescribing. Therefore, this study aimed to assess clozapine use trends on an international scale, using standardised criteria for data analysis. A repeated cross-sectional design was applied to data extracts (2005-2014) from 17 countries worldwide. In 2014, overall clozapine use prevalence was greatest in Finland (189.2/100 000 persons) and in New Zealand (116.3/100 000), and lowest in the Japanese cohort (0.6/100 000), and in the privately insured US cohort (14.0/100 000). From 2005 to 2014, clozapine use increased in almost all studied countries (relative increase: 7.8-197.2%). In most countries, clozapine use was highest in 40-59-year-olds (range: 0.6/100 000 (Japan) to 344.8/100 000 (Finland)). In youths (10-19 years), clozapine use was highest in Finland (24.7/100 000) and in the publicly insured US cohort (15.5/100 000). While clozapine use has increased in most studied countries over recent years, clozapine is still underutilised in many countries, with clozapine utilisation patterns differing significantly between countries. Future research should address the implementation of interventions designed to facilitate increased clozapine utilisation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Clozapine-induced acute gastrointestinal necrosis: a case report.

    PubMed

    Osterman, Mark T; Foley, Caitlin; Matthias, Isaac

    2017-09-23

    Clozapine is known to cause fecal impaction and ileus with resultant colonic necrosis due to compression of colonic mucosa. There are rare reports of clozapine causing necrosis of other portions of the gastrointestinal tract unrelated to constipation. We describe a case of acute necrosis of the upper gastrointestinal tract and small bowel to due to clozapine and quetiapine. A 66-year-old white man with a past medical history of schizophrenia, maintained on clozapine and quetiapine, presented with hypoxic respiratory failure caused by aspiration of feculent emesis due to impacted stool throughout his colon. His constipation resolved with discontinuation of clozapine and quetiapine, and his clinical condition improved. These medicines were restarted after 2 weeks, resulting in acute gastrointestinal necrosis from the mid esophagus through his entire small bowel. He died due to septic shock with Gram-negative rod bacteremia. Clozapine may cause acute gastrointestinal necrosis.

  7. Neurochemical variables in schizophrenic patients during switching from neuroleptics to clozapine.

    PubMed

    Hatzimanolis, J; Lykouras, L; Markianos, M; Oulis, P

    1998-10-01

    1. The study aimed to search for the effect of clozapine on the levels of the main metabolites of dopamine homovanillic acid (HVA), serotonin 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine 3-methoxy-4-hydroxyphenylglycol (MHPG) in urine as well as on plasma levels of HVA, 5-HIAA, prolactin (PRL) and cortisol. 2. Seventeen male patients diagnosed as suffering from DSM-IIIR schizophrenia completed the study. 3. The patients were switched from classical antipsychotics to clozapine. After six weeks treatment with clozapine the severity of psychopathology (total BPRS score) decreased significantly (p = 0.00004). pHVA and -5-HIAA did not change significantly. uMHPG increased significantly (p = 0.017). Both PRL and cortisol levels decreased significantly (p = 0.0002, p = 0.032 respectively). Patients with high HVA levels in both plasma and urine at baseline had a lower BPRS score at the end of treatment period (p = 0.0001, p = 0.049 respectively).

  8. Topiramate augmentation in clozapine-treated patients with schizophrenia: clinical and metabolic effects.

    PubMed

    Hahn, Margaret K; Remington, Gary; Bois, Daniel; Cohn, Tony

    2010-12-01

    Clozapine represents the treatment of choice for refractory psychosis, although a significant number of individuals demonstrate suboptimal response to it as well, leading to clozapine augmentation strategies. A variety of agents have been investigated in this regard, including mood stabilizers, such as anticonvulsants. Within this group of medications, topiramate is unique in that it is associated with weight loss, making it an attractive option because of clozapine's notable risk for associated metabolic disturbance. A 12-week naturalistic, open study was carried out to examine the potential benefits of topiramate in clozapine-treated individuals with schizophrenia demonstrating a suboptimal clinical response. We were specifically interested in clinical symptoms, changes in metabolic parameters, and tolerability. A total of 20 subjects were enrolled, and 16 completed the study, including 5 individuals with type 2 diabetes. Topiramate augmentation led to a 14% improvement in total Brief Psychiatric Rating Scale scores (P = 0.0003), a 2.5% decrease in body weight (P = 0.015), and was generally well tolerated, paraesthesia being the most common side effect. These findings support topiramate as a viable augmentation strategy in clozapine partial responders, with evidence of both clinical and metabolic benefits.

  9. Clozapine Associated with Autoimmune Reaction, Fever and Low Level Cardiotoxicity - A Case Report.

    PubMed

    Gerasimou, Charilaos; Vitali, Georgia Phaedra; Vavougios, George D; Papageorgiou, Charalabos; Douzenis, Athanasios; Kokoris, Styliani I; Liappas, Ioannis; Rizos, Emmanouil

    2017-01-02

    Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia. Fever induced by clozapine is a rather frequent side-effect which usually occurs in the first 4 weeks of treatment. Despite its effectiveness, there are potentially life-threatening adverse effects, such as cardiotoxicity. We present the case of a 31-year-old caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein and high troponin levels, without presenting any other signs to myocarditis, on the 13th day under clozapine treatment, which declined progressively upon discontinuation of the drug. This case hints at the presence of initially subclinical cardiotoxicity as an underlying factor in patients developing fever. Taking advantage of more sensitive methods for measuring troponin, clinicians would be promptly aware of this possible side-effect. This would allow for significant reduction of the risk of cardiac dysfunction, further attained by carefully monitoring the patient. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. 41.4 DEPLOYMENT OF DEDICATED NURSING STAFF TO STIMULATE THE INITIATION OF CLOZAPINE. A CLUSTER-RANDOMIZED TRIAL

    PubMed Central

    Van der Zalm, Yvonne; Schulte, Raphael; Bogers, Jan; Marcelis, Machteld; Sommer, Iris; Selten, Jean-Paul

    2018-01-01

    Abstract Background For patients with refractory schizophrenia, clozapine is the drug of first choice. However, many refractory patients never receive this drug. The underutilization of clozapine may be caused by the labour-intensive white blood cell monitoring during the first months and the concerns about the safety of outpatient clozapine initiation. A recent survey concluded that professionals “perceived the presence of dedicated staff to arrange and monitor the initiation of clozapine in outpatients as the factor that would enable the use of clozapine most”. We examined whether the presence of such staff in Dutch teams for ambulatory care makes a difference. The primary objective is to examine whether clozapine monitoring by a Nurse Practitioner (NP) is at least as safe as monitoring by a physician. The secondary objective is to examine whether physicians are more likely to prescribe clozapine if they can delegate the monitoring tasks to a NP. Methods In this cluster-randomized trial, 23 Dutch ambulatory care teams were randomized into 2 conditions: (A) coordination of clozapine monitoring by a Nurse Practitioner, versus (B) Treatment As Usual: coordination of clozapine monitoring by the responsible physician (usually a psychiatrist). We followed the teams for 15 months, during which period we counted the numbers of patients who started with clozapine. We assessed the safety of the clozapine monitoring by measuring the number of weekly lab exams performed during the first 18 weeks of treatment and counting serious adverse events (SAE). It is important to note that the staff of teams remained blind to the secondary research question. Results Of the 2643 patients with a diagnosis of non-affective psychotic disorder, 66 patients started using clozapine during the follow-up, 48 in condition A and 18 in condition B (RR: 2.14, 95% CI: 1.24–3.70; p=.005). The provisional results showed no significant differences between conditions A and B in the mean number of

  11. The Glasgow antipsychotic side-effects scale for clozapine in inpatients and outpatients with schizophrenia or schizoaffective disorder.

    PubMed

    Ignjatović Ristić, Dragana; Cohen, Dan; Obradović, Andrea; Nikić-Đuričić, Katarina; Drašković, Marija; Hinić, Darko

    2018-02-01

    The inconsistency in clinician and patient ratings of clozapine-induced side effects underscore the need to supplement clinician-based estimates of side effects with patient-reported ones. The main aims of the study are validation of the Glasgow antipsychotic side-effects scale for clozapine (GASS-C) in Serbian inpatients/outpatients with schizophrenia or schizo-affective disorder and recommendations for its future use, based on common and rare clozapine-associated side-effects. The GASS-C was administered to 95 outpatients/inpatients diagnosed with schizophrenia, schizoaffective, or chronic psychotic disorder. The scale showed good overall reliability, with an internal consistency coefficient of α = 0.84, an average retest coefficient of rho = 0.76, and a Spearman-Brown coefficient of validity of 0.81. Side effects were absent or mild in 64.2% of the patients, moderate in 31.6%, severe in 4.2%; 14% of the subjects considered their symptoms distressing. The most commonly reported side-effects were drowsiness, thirst, frequent urination, and dry mouth. Women reported more side effects than men, and patients not in a relationship reported significantly fewer side effects than patients in a relationship. Results indicate a weak positive correlation (rho = 0.231; p = .025) between severity of side effects and clozapine dose. The GASS-C showed good psychometric characteristics in clinical population of patients on clozapine. In future studies, clozapine serum concentrations should be measured when using the GASS-C to monitor side effects.

  12. Population pharmacokinetic/pharmacodynamic model of clozapine for characterizing the relationship between accumulated exposure and PANSS scores in patients with schizophrenia.

    PubMed

    Shang, De-Wei; Li, Li-Jun; Wang, Xi-Pei; Wen, Yu-Guan; Ren, Yu-Peng; Guo, Wei; Li, Wen-Biao; Li, Liang; Zhou, Tian-Yan; Lu, Wei; Wang, Chuan-Yue

    2014-06-01

    The aim of this study was to characterize the relationship between accumulated exposure of clozapine and changes in Positive and Negative Syndrome Scale (PANSS) score in Chinese patients with schizophrenia by pharmacokinetic/pharmacodynamic (PK/PD) modeling. Sparse clozapine PK data and PANSS scores were collected from 2 clinical studies of Chinese inpatients with schizophrenia. Two other rich PK data sets were included for more accurate assessment of clozapine PK characteristics. The relationship between clozapine-accumulated exposure and PANSS score was investigated using linear, log-linear, E(max), and sigmoid models, and each model was evaluated using visual predictive condition and normalized prediction distribution error methods. Simulations based on the final PK/PD model were preformed to investigate the effect of clozapine on PANSS scores under different dose regimens. A total of 1391 blood clozapine concentrations from 198 subjects (180 patients and 18 healthy volunteers) and 576 PANSS scores from 137 patients were included for PK and PK/PD analysis. A first-order 2-compartment PK model with covariates gender and smoking status influencing systemic clearance adequately described the PK profile of clozapine. The decrease in total PANSS score during treatment was best characterized using cumulated clozapine area under the curve (AUC) data in the E(max) model. The maximum decrease in PANSS during clozapine treatment (Emax) was 55.4%, and the cumulated AUC(50) (cAUC(50)) required to attain half of E(max) was 296 mg·L(-1)·h(-1)·d(-1). The simulations demonstrated that the accelerated dose titration and constant dose regimens achieved a similar maximum drug response but with a slower relief of symptoms in dose titration regimen. The PK/PD model can describe the clinical response as measured by decreasing PANSS score during treatment and may be useful for optimizing the dose regimen for individual patients.

  13. Clozapine Associated with Autoimmune Reaction, Fever and Low Level Cardiotoxicity – A Case Report

    PubMed Central

    GERASIMOU, CHARILAOS; PHAEDRA VITALI, GEORGIA; D. VAVOUGIOS, GEORGE; PAPAGEORGIOU, CHARALABOS; DOUZENIS, ATHANASIOS; I. KOKORIS, STYLIANI; LIAPPAS, IOANNIS; RIZOS, EMMANOUIL

    2017-01-01

    Background: Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia. Fever induced by clozapine is a rather frequent side-effect which usually occurs in the first 4 weeks of treatment. Despite its effectiveness, there are potentially life-threatening adverse effects, such as cardiotoxicity. Case Report: We present the case of a 31- year-old caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein and high troponin levels, without presenting any other signs to myocarditis, on the 13th day under clozapine treatment, which declined progressively upon discontinuation of the drug. Discussion: This case hints at the presence of initially subclinical cardiotoxicity as an underlying factor in patients developing fever. Conclusion: Taking advantage of more sensitive methods for measuring troponin, clinicians would be promptly aware of this possible side-effect. This would allow for significant reduction of the risk of cardiac dysfunction, further attained by carefully monitoring the patient. PMID:28064233

  14. Catatonia Secondary to Sudden Clozapine Withdrawal: A Case with Three Repeated Episodes and a Literature Review

    PubMed Central

    Bilbily, John; McCollum, Betsy

    2017-01-01

    A literature search identified 9 previously published cases that were considered as possible cases of catatonia secondary to sudden clozapine withdrawal. Two of these 9 cases did not provide enough information to make a diagnosis of catatonia according to the Diagnostic and Statistical Manual, 5th Edition (DSM-5). The Liverpool Adverse Drug Reaction (ADR) Causality Scale was modified to assess ADRs secondary to drug withdrawal. From the 7 published cases which met DSM-5 catatonia criteria, using the modified scale, we established that 3 were definitive and 4 were probable cases of catatonia secondary to clozapine withdrawal. A new definitive case is described with three catatonic episodes which (1) occurred after sudden discontinuation of clozapine in the context of decades of follow-up, (2) had ≥3 of 12 DSM-5 catatonic symptoms and serum creatinine kinase elevation, and (3) required medical hospitalization and intravenous fluids. Clozapine may be a gamma-aminobutyric acid (GABA) receptor agonist; sudden clozapine withdrawal may explain a sudden decrease in GABA activity that may contribute to the development of catatonic symptoms in vulnerable patients. Based on the limited information from these cases, the pharmacological treatment for catatonia secondary to sudden clozapine withdrawal can include benzodiazepines and/or restarting clozapine. PMID:28396815

  15. Dopamine dynamics during emotional cognitive processing: Implications of the specific actions of clozapine compared with haloperidol.

    PubMed

    Kawano, Masahiko; Oshibuchi, Hidehiro; Kawano, Takaaki; Muraoka, Hiroyuki; Tsutsumi, Takahiro; Yamada, Makiko; Inada, Ken; Ishigooka, Jun

    2016-06-15

    Clozapine has improved efficacy relative to typical antipsychotics in schizophrenia treatment, particularly regarding emotional symptoms. However, the mechanisms underlying its therapeutic benefits remain unclear. Using a methamphetamine-sensitised rat model, we measured changes in dopamine levels in the amygdalae in response to a fear-conditioned cue, serving as a biochemical marker of emotional cognitive processing disruption in psychosis, for analysing the biochemical mechanisms associated with the clinical benefits of clozapine. We also compared how clozapine and haloperidol affected basal dopamine levels and phasic dopamine release in response to the fear-conditioned cue. Extracellular dopamine was collected from the amygdalae of freely moving rats via microdialysis and was analysed by high-performance liquid chromatography. Clozapine or haloperidol was injected during microdialysis, followed by exposure to the fear-conditioned cue. We analysed the ratio of change in dopamine levels from baseline. Haloperidol treatment increased the baseline dopamine levels in both non-sensitised and sensitised rats. Conversely, clozapine only increased the basal dopamine levels in the non-sensitised rats, but not in the sensitised rats. Although both antipsychotics attenuated phasic dopamine release in both the non-sensitised and sensitised rats, the attenuation extent was greater for clozapine than for haloperidol under both dopaminergic conditions. Our findings indicate that stabilized dopamine release in the amygdalae is a common therapeutic mechanism of antipsychotic action during emotional processing. However, the specific dopaminergic state-dependent action of clozapine on both basal dopamine levels and stress-induced dopamine release may be the underlying mechanism for its superior clinical effect on emotional cognitive processing in patients with schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Assessing prescribing practices of clozapine before and after the implementation of an updated risk evaluation and mitigation strategy

    PubMed Central

    2018-01-01

    Introduction: Clozapine is an atypical antipsychotic medication approved for treatment-resistant schizophrenia and suicidal behavior in schizophrenia or schizoaffective disorders. Despite its therapeutic efficacy, clozapine is associated with several adverse effects, including agranulocytosis. In late 2015, the Food and Drug Administration updated the risk evaluation and mitigation strategy (REMS) for clozapine with new requirements for monitoring, prescribing, and dispensing. The purpose of this study was to evaluate clozapine prescribing practices at a Kentucky state psychiatric hospital before and after the implementation of the updated REMS program. Methods: The primary outcome of this study was to evaluate clozapine prescribing practices by identifying the number of patients on clozapine therapy in the 6 months pre and post updated REMS implementation. Included in the study were patients at a Kentucky state psychiatric hospital on clozapine therapy for the 24 months before the updated REMS implementation and in the 6-month study period after the implementation. The secondary objective of this study examined psychiatrist comfort level of prescribing clozapine. Results: Since the implementation of the updated REMS program, there has been an increased percentage of patients that were prescribed clozapine at a Kentucky state psychiatric hospital. This increase was not statistically significant (P = .2610). Discussion: The prescribing practices of clozapine within this facility did not differ significantly comparing pre- and post-REMS change in terms of number of patients prescribed clozapine, patient's dose, and therapy duration. Data from this study contributes to the body of knowledge evaluating this new standard of practice under the updated REMS.

  17. Treatment of clozapine-associated obesity and diabetes with exenatide in adults with schizophrenia: A randomized controlled trial (CODEX).

    PubMed

    Siskind, Dan J; Russell, Anthony W; Gamble, Clare; Winckel, Karl; Mayfield, Karla; Hollingworth, Sam; Hickman, Ingrid; Siskind, Victor; Kisely, Steve

    2018-04-01

    Clozapine causes obesity and type 2 diabetes (T2DM). Glucagon-like peptide-1 (GLP-1) receptor agonists (e.g. exenatide) can counter clozapine-associated GLP-1 dysregulation in animals, and may be beneficial in people on clozapine. This randomized, controlled, open-label, pilot trial evaluated weekly exenatide for weight loss among clozapine-treated obese adults with schizophrenia, with or without T2DM. A total of 28 outpatients were randomized to once-weekly extended-release subcutaneous exenatide or usual care for 24 weeks. The primary outcome was proportion of participants with >5% weight loss. All 28 participants completed the study; 3/14 in the exenatide group and 2/14 in the usual care group had T2DM. Six people on exenatide achieved >5% weight loss vs one receiving usual care (P = .029). Compared with usual care, participants on exenatide had greater mean weight loss (-5.29 vs -1.12 kg; P = .015) and body mass index reduction (-1.78 vs -0.39 kg/m 2 ; P = .019), and reduced fasting glucose (-0.34 vs 0.39 mmol/L; P = .036) and glycated haemoglobin levels (-0.21% vs 0.03%; P = .004). There were no significant differences in other metabolic syndrome components. Exenatide may be a promising therapeutic agent for glycaemic control and weight loss in clozapine-treated people with obesity, and could assist in reducing clozapine-associated cardio-metabolic morbidity and mortality. © 2017 John Wiley & Sons Ltd.

  18. Hormonal and metabolic effects of olanzapine and clozapine related to body weight in rodents.

    PubMed

    Albaugh, Vance L; Henry, Cathy R; Bello, Nicholas T; Hajnal, Andras; Lynch, Susan L; Halle, Beth; Lynch, Christopher J

    2006-01-01

    To characterize a model of atypical antipsychotic drug-induced obesity and evaluate its mechanism. Chronically, olanzapine or clozapine was self-administered via cookie dough to rodents (Sprague-Dawley or Wistar rats; C57Bl/6J or A/J mice). Chronic studies measured food intake, body weight, adiponectin, active ghrelin, leptin, insulin, tissue wet weights, glucose, clinical chemistry endpoints, and brain dopaminergic D2 receptor density. Acute studies examined food intake, ghrelin, leptin, and glucose tolerance. Olanzapine (1 to 8 mg/kg), but not clozapine, increased body weight in female rats only. Weight changes were detectable within 2 to 3 days and were associated with hyperphagia starting approximately 24 hours after the first dose. Chronic administration (12 to 29 days) led to adiposity, hyperleptinemia, and mild insulin resistance; no lipid abnormalities or changes in D2 receptor density were observed. Topiramate, which has reversed weight gain from atypical antipsychotics in humans, attenuated weight gain in rats. Acutely, olanzapine, but not clozapine, lowered plasma glucose and leptin. Increases in glucose, insulin, and leptin following a glucose challenge were also blunted. A model of olanzapine-induced obesity was characterized which shares characteristics of patients with atypical antipsychotic drug-induced obesity; these characteristics include hyperphagia, hyperleptinemia, insulin resistance, and weight gain attenuation by topiramate. This model may be a useful and inexpensive model of uncomplicated obesity amenable to rapid screening of weight loss drugs. Olanzapine-induced weight gain may be secondary to hyperphagia associated with acute lowering of plasma glucose and leptin, as well as the inability to increase plasma glucose and leptin following a glucose challenge.

  19. Hormonal and Metabolic Effects of Olanzapine and Clozapine Related to Body Weight in Rodents

    PubMed Central

    Albaugh, Vance L.; Henry, Cathy R.; Bello, Nicholas T.; Hajnal, Andras; Lynch, Susan L.; Halle, Beth; Lynch, Christopher J.

    2009-01-01

    Objective To characterize a model of atypical antipsychotic drug-induced obesity and evaluate its mechanism. Research Methods and Procedures Chronically, olanzapine or clozapine was self-administered via cookie dough to rodents (Sprague-Dawley or Wistar rats; C57Bl/6J or A/J mice). Chronic studies measured food intake, body weight, adiponectin, active ghrelin, leptin, insulin, tissue wet weights, glucose, clinical chemistry endpoints, and brain dopaminergic D2 receptor density. Acute studies examined food intake, ghrelin, leptin, and glucose tolerance. Results Olanzapine (1 to 8 mg/kg), but not clozapine, increased body weight in female rats only. Weight changes were detectable within 2 to 3 days and were associated with hyperphagia starting ~24 hours after the first dose. Chronic administration (12 to 29 days) led to adiposity, hyperleptinemia, and mild insulin resistance; no lipid abnormalities or changes in D2 receptor density were observed. Topiramate, which has reversed weight gain from atypical anti-psychotics in humans, attenuated weight gain in rats. Acutely, olanzapine, but not clozapine, lowered plasma glucose and leptin. Increases in glucose, insulin, and leptin following a glucose challenge were also blunted. Discussion A model of olanzapine-induced obesity was characterized which shares characteristics of patients with atypical antipsychotic drug-induced obesity; these characteristics include hyperphagia, hyperleptinemia, insulin resistance, and weight gain attenuation by topiramate. This model may be a useful and inexpensive model of uncomplicated obesity amenable to rapid screening of weight loss drugs. Olanzapine-induced weight gain may be secondary to hyperphagia associated with acute lowering of plasma glucose and leptin, as well as the inability to increase plasma glucose and leptin following a glucose challenge. PMID:16493121

  20. Clozapine and GABA transmission in schizophrenia disease models: establishing principles to guide treatments.

    PubMed

    O'Connor, William T; O'Shea, Sean D

    2015-06-01

    Schizophrenia disease models are necessary to elucidate underlying changes and to establish new therapeutic strategies towards a stage where drug efficacy in schizophrenia (against all classes of symptoms) can be predicted. Here we summarise the evidence for a GABA dysfunction in schizophrenia and review the functional neuroanatomy of five pathways implicated in schizophrenia, namely the mesocortical, mesolimbic, ventral striopallidal, dorsal striopallidal and perforant pathways including the role of local GABA transmission and we describe the effect of clozapine on local neurotransmitter release. This review also evaluates psychotropic drug-induced, neurodevelopmental and environmental disease models including their compatibility with brain microdialysis. The validity of disease models including face, construct, etiological and predictive validity and how these models constitute theories about this illness is also addressed. A disease model based on the effect of the abrupt withdrawal of clozapine on GABA release is also described. The review concludes that while no single animal model is entirely successful in reproducing schizophreniform symptomatology, a disease model based on an ability to prevent and/or reverse the abrupt clozapine discontinuation-induced changes in GABA release in brain regions implicated in schizophrenia may be useful for hypothesis testing and for in vivo screening of novel ligands not limited to a single pharmacological class. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Clozapine Use During Pregnancy and Lactation: A Case-Series Report.

    PubMed

    Imaz, M Luisa; Oriolo, Giovanni; Torra, Mercè; Soy, Dolors; García-Esteve, Lluïsa; Martin-Santos, Rocio

    2018-01-01

    The current prescription of clozapine in psychotic women of reproductive age makes it crucial to understand its pharmacokinetics during pregnancy and lactation as well as its risk profile for neonatal outcome. The aim of this case series was to provide new evidence on the pharmacokinetic features of clozapine that determine its passage through the placenta and amniotic fluid, as well as the neonatal clozapine elimination half-life (t1/2). This case series demonstrates for the first time that clozapine might show partial placental passage similar to other atypical antipsychotics. Clozapine levels decreased during the first few days in nursing infants. The half-life of clozapine in neonates was slightly higher than previously estimated. Clozapine use in pregnancy may be associated with diabetes mellitus, especially if there is a family history of this disease. Although no acute toxicological effects were observed in the intrauterine exposed newborn, close follow-up of pregnancy is recommended. However, these results must be taken with caution being a case series with small sample size.

  2. Clozapine modifies the differentiation program of human adipocytes inducing browning.

    PubMed

    Kristóf, E; Doan-Xuan, Q-M; Sárvári, A K; Klusóczki, Á; Fischer-Posovszky, P; Wabitsch, M; Bacso, Z; Bai, P; Balajthy, Z; Fésüs, L

    2016-11-29

    Administration of second-generation antipsychotic drugs (SGAs) often leads to weight gain and consequent cardio-metabolic side effects. We observed that clozapine but not six other antipsychotic drugs reprogrammed the gene expression pattern of differentiating human adipocytes ex vivo, leading to an elevated expression of the browning marker gene UCP1, more and smaller lipid droplets and more mitochondrial DNA than in the untreated white adipocytes. Laser scanning cytometry showed that up to 40% of the differentiating single primary and Simpson-Golabi-Behmel syndrome (SGBS) adipocytes had the characteristic morphological features of browning cells. Furthermore, clozapine significantly upregulated ELOVL3, CIDEA, CYC1, PGC1A and TBX1 genes but not ZIC1 suggesting induction of the beige-like and not the classical brown phenotype. When we tested whether browning induced by clozapine can be explained by its known pharmacological effect of antagonizing serotonin (5HT) receptors, it was found that browning cells expressed 5HT receptors 2A, 1D, 7 and the upregulation of browning markers was diminished in the presence of exogenous 5HT. Undifferentiated progenitors or completely differentiated beige or white adipocytes did not respond to clozapine administration. The clozapine-induced beige cells displayed increased basal and oligomycin-inhibited (proton leak) oxygen consumption, but these cells showed a lower response to cAMP stimulus as compared with control beige adipocytes indicating that they are less capable to respond to natural thermogenic anti-obesity cues. Our data altogether suggest that novel pharmacological stimulation of these masked beige adipocytes can be a future therapeutic target for the treatment of SGA-induced weight gain.

  3. Clozapine modifies the differentiation program of human adipocytes inducing browning

    PubMed Central

    Kristóf, E; Doan-Xuan, Q-M; Sárvári, A K; Klusóczki, Á; Fischer-Posovszky, P; Wabitsch, M; Bacso, Z; Bai, P; Balajthy, Z; Fésüs, L

    2016-01-01

    Administration of second-generation antipsychotic drugs (SGAs) often leads to weight gain and consequent cardio-metabolic side effects. We observed that clozapine but not six other antipsychotic drugs reprogrammed the gene expression pattern of differentiating human adipocytes ex vivo, leading to an elevated expression of the browning marker gene UCP1, more and smaller lipid droplets and more mitochondrial DNA than in the untreated white adipocytes. Laser scanning cytometry showed that up to 40% of the differentiating single primary and Simpson–Golabi–Behmel syndrome (SGBS) adipocytes had the characteristic morphological features of browning cells. Furthermore, clozapine significantly upregulated ELOVL3, CIDEA, CYC1, PGC1A and TBX1 genes but not ZIC1 suggesting induction of the beige-like and not the classical brown phenotype. When we tested whether browning induced by clozapine can be explained by its known pharmacological effect of antagonizing serotonin (5HT) receptors, it was found that browning cells expressed 5HT receptors 2A, 1D, 7 and the upregulation of browning markers was diminished in the presence of exogenous 5HT. Undifferentiated progenitors or completely differentiated beige or white adipocytes did not respond to clozapine administration. The clozapine-induced beige cells displayed increased basal and oligomycin-inhibited (proton leak) oxygen consumption, but these cells showed a lower response to cAMP stimulus as compared with control beige adipocytes indicating that they are less capable to respond to natural thermogenic anti-obesity cues. Our data altogether suggest that novel pharmacological stimulation of these masked beige adipocytes can be a future therapeutic target for the treatment of SGA-induced weight gain. PMID:27898069

  4. [Clozapine rechallenge after neutropenia in resistant schizophrenia: A review].

    PubMed

    Simon, L; Cazard, F

    2016-08-01

    clozapine despite lower blood counts. Then, rechallenge choice has to be done on a case-by-case basis and only after considering the benefits and risks of such a treatment. Most of the time, clinical advice of rechallenge arises from the inefficiency of other antipsychotics and even sismotherapy failure. Patients and sometimes families have to be informed and give their consent. Preventive measures have been found such as taking a hematologic recommendation and doing twice-a-week blood sample monitoring. With regards lithium and G-CSF, some efficient doses are assumed (lithium: 0,4-1,1 mEq/L and G-CSF>0,3 mg/week). Lithium as G-CSF may have other adverse effects which need to be considered. There is no successful rechallenge reported after agranulocytosis. Some publications highlight that if neutropenia occurs on rechallenge, it will do so more quickly and more severe than at the time of initial trial of clozapine. There is emerging evidence of successful clozapine rechallenging. However, further investigations are required as randomized controlled trials to reassess guidelines and establish the safety and effectiveness of the different procedures. Because of the practical and ethical difficulties of designing such studies, referral hospitals could be elected, and common background writing proposed in order to ease data comparison. Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  5. Blockade of HERG human K+ channels and IKr of guinea-pig cardiomyocytes by the antipsychotic drug clozapine.

    PubMed

    Lee, So-Young; Kim, Young-Jin; Kim, Kyong-Tai; Choe, Han; Jo, Su-Hyun

    2006-06-01

    Clozapine, a commonly used antipsychotic drug, can induce QT prolongation, which may lead to torsades de pointes and sudden death. To investigate the arrhythmogenic side effects of clozapine, we studied the impact of clozapine on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes and HEK293 cells, and on the delayed rectifier K(+) currents of guinea-pig cardiomyocytes. Clozapine dose-dependently decreased the amplitudes of the currents at the end of voltage steps, and the tail currents of HERG. The IC(50) for the clozapine blockade of HERG currents in Xenopus oocytes progressively decreased relative to depolarization (39.9 microM at -40 mV, 28.3 microM at 0 mV and 22.9 microM at +40 mV), whereas the IC(50) for the clozapine-induced blockade of HERG currents in HEK293 cells at 36 degrees C was 2.5 microM at +20 mV. The clozapine-induced blockade of HERG currents was time dependent: the fractional current was 0.903 of the control at the beginning of the pulse, but declined to 0.412 after 4 s at a test potential of 0 mV. The clozapine-induced blockade of HERG currents was use-dependent, exhibiting more rapid onset and greater steady state blockade at higher frequencies of activation, with a partial relief of blockade observed when the frequency of activation was decreased. In guinea-pig ventricular myocytes held at 36 degrees C, treatment with 1 and 5 microM clozapine blocked the rapidly activating delayed rectifier K(+) current (I(Kr)) by 24.7 and 79.6%, respectively, but did not significantly block the slowly activating delayed rectifier K(+) current (I(Ks)). Our findings collectively suggest that blockade of HERG currents and I(Kr), but not I(Ks), may contribute to the arrhythmogenic side effects of clozapine.

  6. [Reversible catatonia after the abrupt discontinuation of clozapine: Case report].

    PubMed

    Jaafari, M; Bout, A; Rammouz, I; Aalouane, R

    2016-12-01

    In this paper, we report the case of a patient, aged 26, with schizophrenia who was admitted to psychiatric emergencies for catatonia, one week after abrupt discontinuation of clozapine. An improvement was seen after only two days of the reintroduction of clozapine alone. This catatonia is reversible and it responds magnificently to the reintroduction of clozapine. And we conclude that patients and their caregivers need to be educated about the effects of abrupt cessation of clozapine administration. Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  7. Concentrations in plasma clozapine levels in schizophrenic and schizoaffective patients.

    PubMed

    Iglesias García, Celso; Iglesias Alonso, Ana; Bobes, Julio

    There is great variability in plasma levels of clozapine. The objective of this study is to know the characteristics of patients treated with clozapine and the relationship between them and the variability of plasma levels. Descriptive, cross-sectional study of all patients currently treated with clozapine in a Psychiatric Service with a diagnosis of schizophrenic psychosis or schizoaffective disorder. The present study assessed physical situation, psychopathology and functionality of the patients and explored the associations and correlations between clinical variables and plasma levels. We studied 39 patients, predominantly men, with negative and depressive symptoms and cardiovascular risk factors (metabolic syndrome and smoking). Significant variability in dose and even greater in clozapine levels were observed. The levels of clozapine at equal doses/kg of body weight were higher in non-smokers, they had positive correlation with BMI and negative correlation with systolic BP, disruptive behaviors and number of cigarettes consumed. Plasma level monitoring clozapine is an important tool to avoid clozapine plasma levels monitoring and minimize undesirable clinical situations (metabolic syndrome, sedation, negative symptoms and functional impairment). It is also important to control the effects of a smoking habit for optimum drug bioavailability. Copyright © 2017 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. A double-blind, placebo-controlled trial of sibutramine for clozapine-associated weight gain.

    PubMed

    Henderson, D C; Fan, X; Copeland, P M; Borba, C P; Daley, T B; Nguyen, D D; Zhang, H; Hayden, D; Freudenreich, O; Cather, C; Evins, A E; Goff, D C

    2007-02-01

    This study sought to examine the effectiveness of sibutramine, a weight loss agent, on clozapine-associated weight gain. This was a 12-week double-blind, placebo controlled, randomized trial of sibutramine for weight loss in obese clozapine-treated schizophrenia or schizoaffective disorder subjects. Ten patients were enrolled into the placebo group and 11 patients into the sibutramine group. There were no significant baseline differences between the two groups on age, gender, education, ethnicity, diagnosis, weight, body mass index (BMI), and blood pressure. At week 12, there were no significant differences in changes in weight, BMI, abdominal and waist circumferences, Hba1c, fasting glucose, or cholesterol levels. Sibutramine treatment did not show significant weight loss compared with placebo in clozapine-treated patients with schizophrenia or schizoaffective disorder. Further research with a larger sample size and longer follow-up duration is warranted.

  9. Use of anticonvulsants as prophylaxis for seizures in patients on clozapine.

    PubMed

    Caetano, Dorgival

    2014-02-01

    The aim of this study is to conduct a critical review of the literature regarding the use of anticonvulsants in the prophylaxis of clozapine-induced seizures, to examine the relationship of the latter with clozapine daily dose, serum concentration and other factors than dosage that effect clozapine blood concentration, and to make recommendations for the management of clozapine-induced seizures. A systematic review of English-language MEDLINE articles was undertaken. Clozapine-induced seizures may occur at any dose; the risk increases with dose and goes up to 4% at ≥ 600 mg/day. Some authors have advocated that patients on that dose regimen have anticonvulsant added as a primary prophylactic measure. The author discusses the pitfalls of this recommendation and highlights that seizures are better predicted from serum concentration (1300 ng/ml) rather than dose alone, and that serum concentration is strongly influenced by sex, age, smoking habit, drug-drug interactions and variations in the 1A2, 2D6 and 3A4 genotypes. Anticonvulsants are not recommended as a primary prophylaxis for clozapine-induced seizures. When deemed necessary as secondary prophylaxis, the clinician's choice should consider drug-drug interactions that may increase/decrease clozapine serum concentration and lead to more side effects, including neutropenia/agranulocytosis and seizures, or compromise therapeutic response. Recommendations for primary and secondary prophylaxis of clozapine related-seizures are provided.

  10. Effect of Environmental Cues on Behavioral Efficacy of Haloperidol, Olanzapine and Clozapine in Rats

    PubMed Central

    Sun, Tao; Liu, Xinfeng; Li, Ming

    2014-01-01

    Previous studies have reported that context can powerfully modulate the inhibitory effect of an antipsychotic drug on phencyclidine (PCP)-induced hyperlocomotion (a behavioral test used to evaluate putative antipsychotic drugs). The present study investigated the experimental conditions under which environmental stimuli exert their influence through associative conditioning processes. Experiment 1 examined the extent to which prior antipsychotic treatment in the home cages affected a drug’s ability to inhibit PCP-induced hyperlocomotion in a novel motor activity test apparatus. Five days of repeated haloperidol (0.05 mg/kg, sc) and olanzapine (2.0 mg/kg, sc) treatment in the home cages still potentiated their inhibition of PCP-induced hyperlocomotion (i.e. sensitization) assessed in a new environment, whereas the clozapine (10.0 mg/kg, sc) treatment enhanced the development of clozapine tolerance, indicating a lack of environmental modulation of antipsychotic efficacy. Experiment 2 assessed the impact of different numbers of antipsychotic administrations in either the home environment or test environment (e.g. 4, 2 or 0) on a drug’s ability to inhibit PCP-induced hyperlocomotion. Repeated administration of clozapine (5.0 mg/kg, sc) or olanzapine (1.0 mg/kg, sc) for 4 consecutive days, regardless of where these treatments occurred, caused a similar level of inhibition on PCP-induced hyperlocomotion. However, 4-day haloperidol (0.03 mg/kg, sc) treatment in the test apparatus caused a significant higher inhibition than 4-day home cage treatment. Thus, more exposures to the test environment under the influence of haloperidol (but not clozapine or olanzapine) cause a stronger inhibition than fewer exposures, indicating a strong environmental modulation. Collectively, these findings suggest that prior antipsychotic treatment in one environment could alter later antipsychotic-like response assessed in a different environment under certain test conditions. Therefore

  11. Blockade of HERG human K+ channels and IKr of guinea-pig cardiomyocytes by the antipsychotic drug clozapine

    PubMed Central

    Lee, So-Young; Kim, Young-Jin; Kim, Kyong-Tai; Choe, Han; Jo, Su-Hyun

    2006-01-01

    Clozapine, a commonly used antipsychotic drug, can induce QT prolongation, which may lead to torsades de pointes and sudden death. To investigate the arrhythmogenic side effects of clozapine, we studied the impact of clozapine on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes and HEK293 cells, and on the delayed rectifier K+ currents of guinea-pig cardiomyocytes. Clozapine dose-dependently decreased the amplitudes of the currents at the end of voltage steps, and the tail currents of HERG. The IC50 for the clozapine blockade of HERG currents in Xenopus oocytes progressively decreased relative to depolarization (39.9 μM at −40 mV, 28.3 μM at 0 mV and 22.9 μM at +40 mV), whereas the IC50 for the clozapine-induced blockade of HERG currents in HEK293 cells at 36°C was 2.5 μM at +20 mV. The clozapine-induced blockade of HERG currents was time dependent: the fractional current was 0.903 of the control at the beginning of the pulse, but declined to 0.412 after 4 s at a test potential of 0 mV. The clozapine-induced blockade of HERG currents was use-dependent, exhibiting more rapid onset and greater steady state blockade at higher frequencies of activation, with a partial relief of blockade observed when the frequency of activation was decreased. In guinea-pig ventricular myocytes held at 36°C, treatment with 1 and 5 μM clozapine blocked the rapidly activating delayed rectifier K+ current (IKr) by 24.7 and 79.6%, respectively, but did not significantly block the slowly activating delayed rectifier K+ current (IKs). Our findings collectively suggest that blockade of HERG currents and IKr, but not IKs, may contribute to the arrhythmogenic side effects of clozapine. PMID:16633353

  12. Case Report. Prevention of Clozapine-Induced Granulocytopenia/Agranulocytosis with Granulocyte-Colony Stimulating Factor (G-CSF) in an Intellectually Disabled Patient with Schizophrenia

    ERIC Educational Resources Information Center

    Rajagopal, G.; Graham, J. G.; Haut, F. F. A.

    2007-01-01

    Background: While clozapine is an effective treatment for refractory schizophrenia, its use is limited by haematological side effects. Treatment options that allow continued prescription of clozapine by tackling these side effects will greatly aid patients for whom this medication is all too often their only hope of recovery. Method: In this case…

  13. Individual changes in clozapine levels after smoking cessation: results and a predictive model.

    PubMed

    Meyer, J M

    2001-12-01

    Published reports document 20-40% lower mean serum clozapine concentrations in smokers compared with nonsmokers due to enzyme induction. Despite the increase in nonsmoking psychiatric facilities in the United States, previous studies have not tracked individual changes in serum clozapine levels after smoking cessation. Clozapine level changes were analyzed in 11 patients at Oregon State Hospital who were on stable clozapine doses, before and after implementation of a hospital-wide nonsmoking policy. A mean increase in clozapine levels of 71.9% (442.4 ng/ml +/- 598.8 ng/ml) occurred upon smoking cessation (p < .034) from a baseline level of 550.2 ng/ml (+/- 160.18 ng/ml). One serious adverse event, aspiration pneumonia, was associated with a nonsmoking serum clozapine level of 3066 ng/ml. Elimination of statistically extreme results generated a mean increase of 57.4 % or 284.1 ng/ml (+/- 105.2 ng/ml) for the remaining cases (p < .001) and permitted construction of a linear model which explains 80.9% of changes in clozapine levels upon smoking cessation (F = 34.9;p = .001): clozapine level as nonsmoker = 45.3 + 1.474 (clozapine level as smoker). These findings suggest that significant increases in clozapine levels upon smoking cessation may be predicted by use of a model. Those with high baseline levels should be monitored for serious adverse events.

  14. Response to clozapine in a clinically identifiable subtype of schizophrenia

    PubMed Central

    Butcher, Nancy J.; Fung, Wai Lun Alan; Fitzpatrick, Laura; Guna, Alina; Andrade, Danielle M.; Lang, Anthony E.; Chow, Eva W. C.; Bassett, Anne S.

    2015-01-01

    Background Genetic testing in psychiatry promises to improve patient care through advances in personalised medicine. However, there are few clinically relevant examples. Aims To determine whether patients with a well-established genetic subtype of schizophrenia show a different response profile to the antipsychotic clozapine than those with idiopathic schizophrenia. Method We retrospectively studied the long-term safety and efficacy of clozapine in 40 adults with schizophrenia, half with a 22q11.2 deletion (22q11.2DS group) and half matched for age and clinical severity but molecularly confirmed to have no pathogenic copy number variant (idiopathic group). Results Both groups showed similar clinical improvement and significant reductions in hospitalisations, achieved at a lower median dose for those in the 22q11.2DS group. Most common side-effects were similarly prevalent between the two groups, however, half of the 22q11.2DS group experienced at least one rare serious adverse event compared with none of the idiopathic group. Many were successfully retried on clozapine. Conclusions Individuals with 22q11.2DS-schizophrenia respond as well to clozapine treatment as those with other forms of schizophrenia, but may represent a disproportionate number of those with serious adverse events, primarily seizures. Lower doses and prophylactic (for example anticonvulsant) management strategies can help ameliorate side-effect risks. This first systematic evaluation of antipsychotic response in a genetic subtype of schizophrenia provides a proof-of-principle for personalised medicine and supports the utility of clinical genetic testing in schizophrenia. PMID:25745132

  15. Pharmacogenetics of clozapine treatment response and side-effects in schizophrenia: an update.

    PubMed

    Sriretnakumar, Venuja; Huang, Eric; Müller, Daniel J

    2015-01-01

    Clozapine (CLZ) is the most effective treatment for treatment-resistant schizophrenia (SCZ) patients, with potential added benefits of reduction in suicide risk and aggression. However, CLZ is also mainly underused due to its high risk for the potentially lethal side-effect of agranulocytosis as well as weight gain and related metabolic dysregulation. Pharmacogenetics promises to enable the prediction of patient treatment response and risk of adverse effects based on patients' genetics, paving the way toward individualized treatment. This article reviews pharmacogenetics studies of CLZ response and side-effects with a focus on articles from January 2012 to February 2015, as an update to the previous reviews. Pharmacokinetic genes explored primarily include CYP1A2, while pharmacodynamic genes consisted of traditional pharmacogenetic targets such as brain-derived neurotrophic factor as well novel mitochondrial genes, NDUFS-1 and translocator protein. Pharmacogenetics is a promising avenue for individualized medication of CLZ in SCZ, with several consistently replicated gene variants predicting CLZ response and side-effects. However, a large proportion of studies have yielded mixed results. Large-scale Genome-wide association studies (e.g., CRESTAR) and targeted gene studies with standardized designs (response measurements, treatment durations, plasma level monitoring) are required for further progress toward clinical translation. Additionally, in order to improve study quality, we recommend accounting for important confounders, including polypharmacy, baseline measurements, treatment duration, gender, and age at onset.

  16. Uric acid levels in patients with schizophrenia on clozapine monotherapy.

    PubMed

    Wysokiński, Adam; Kłoszewska, Iwona

    2015-08-01

    We tested the hypothesis that uric acid levels are higher in subjects with schizophrenia treated with clozapine than in healthy control and they correlate with anthropometric measurements, laboratory tests and results of bioimpedance analysis of body composition. Data for 24 subjects with schizophrenia treated with clozapine and 24 age- and sex-matched healthy volunteers was analyzed. There was no difference of fasting uric acid concentrations between clozapine and control groups (4.5 ± 1.4 vs. 4.3 ± 1.3 mg/dl, P = 0.87). Regarding the whole group, uric acid levels were significantly higher in men (5.2 ± 1.2 vs. 3.6 ± 0.9, P < 0.001). Uric acid levels correlated with weight (R = 0.58, P = 0.003), body mass index (BMI; R = 0.49, P = 0.01), abdominal circumference (R = 0.45, P = 0.03), waist circumference (R = 0.47, P = 0.02), waist-to-hip ratio (R = 0.42, P = 0.04), insulin (R = 0.50, P = 0.01), homoeostasis model assessment of insulin resistance 2 (HOMA2-IR; R = 0.49, P = 0.01), basal metabolic rate (R = 0.56, P = 0.004), lean body mass (R = 0.55, P = 0.005) and body water (R = 0.55, P = 0.005). There were no significant differences of uric acid levels for smoking status, impaired fasting glucose, abdominal obesity, obesity/overweight and dyslipidemia. Uric acid levels did not correlate with age, duration of clozapine treatment, clozapine dose, leg circumference, systolic blood pressure, diastolic blood pressure, total body fat, triglycerides, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), homocysteine, corrected calcium, glucose and homoeostasis model assessment of insulin resistance 1 (HOMA1-IR). We did not find significant differences in blood uric acid levels between subjects with schizophrenia and controls. Association with weight, BMI, abdominal and waist circumferences, insulin levels and insulin resistance may support uric acid role as an important cardiovascular risk factor. Association with lean weight may explain

  17. Significant weight loss following clozapine use, how is it possible? A case report and review of published cases and literature relevant to the subject.

    PubMed

    Tungaraza, Tongeji E

    2016-10-01

    It has been repeatedly shown that clozapine is more efficacious than other antipsychotics in the management of treatment-resistant schizophrenia. However, clozapine is associated with a number of side effects including weight gain. Antipsychotic-induced weight gain has been linked with a number of untoward events including psychological factors such as stigma and low self-esteem, and physical factors such as metabolic syndromes and untimely death. The mechanism underlying antipsychotic (including clozapine)-induced weight gain is not clearly understood, although it is said to involve several brain areas, several neurotransmitters, neuropeptides and genetic factors. To some individuals however, clozapine use is associated with significant weight loss (13.5-50% of body weight). The observed weight loss in these groups of patients has not been attributed to any underlying diagnosable physical disorders. There have been a handful cases published with this phenomenon, which seems to be contrary to what is expected when clozapine is prescribed. From the currently published cases three groups emerge - those who lost weight simply by taking clozapine, those who lost weight due to improved mental state, engaging in diet and increased exercise, and those for whom weight loss was a sign of a poor response to clozapine. A case of JX who has a diagnosis of schizoaffective disorder is presented. JX lost over 26% of her body weight when she was prescribed clozapine. A detailed review of other published cases is undertaken. The underlying mechanisms involving weight loss are discussed and the implications to clinicians are highlighted. Coordinated studies to examine these groups of patients may provide some insight, not only in the mechanism of clozapine-induced weight loss, but also in the better management of patients with treatment-resistant schizophrenia involving clozapine use.

  18. Clozapine and gastro-oesophageal reflux disease (GORD) - an investigation of temporal association.

    PubMed

    van Veggel, M; Olofinjana, O; Davies, G; Taylor, D

    2013-01-01

    To establish the temporal relationship between prescription of acid-suppressant therapy, GORD and clozapine prescribing. In this retrospective cohort study, we identified out-patients prescribed clozapine and other atypical antipsychotics (AAP) and compared times and rates of prescribing of acid-suppressant therapy. Odds ratios were calculated. Of 352 patients on clozapine and 358 patients on other AAP, there were 74 (21.0%) and 23 (6.7%) patients prescribed acid-suppressant therapy respectively [OR = 3.9 (95% CI: 2.4-6.4) P ≤ 0.0001]. In 67 of 74 cases (90.5%) vs. 18 of 23 cases (81.8%), acid-suppressant therapy began after the start of the antipsychotic. Clozapine patients were more likely to be prescribed acid-suppressant therapy within the first 5 years of initiation than those on other AAP (P = 0.039). Where indication for acid-suppressant therapy was known, it was prescribed for GORD in 44 of 62 (71.0%) of the clozapine patients and 6 of 13 (46.2%) of those on other AAP (P = 0.109). Rate of known GORD was 44 of 352 (12.5%) for clozapine and 6 of 358 (1.7%) for other atypicals [OR = 8.4 (95% CI: 3.5-19.9) P ≤ 0.0001]. Clozapine was associated with higher rates of GORD and acid-suppressant therapy prescribing than other AAP. There was a clear temporal relationship between the prescribing of clozapine and the later use of acid-suppressant therapy. These observations strongly suggest that prescription of clozapine was associated with the onset of GORD. © 2012 John Wiley & Sons A/S.

  19. Clozapine in Three Individuals with Mild Mental Retardation and Treatment-Refractory Psychiatric Disorders.

    ERIC Educational Resources Information Center

    Pary, Robert J.

    1994-01-01

    Although clozapine is a drug specifically approved for people with schizophrenia, it has not been systematically evaluated with dually diagnosed individuals having mental retardation. This article reviews the drug's use in the general population, discusses potential difficulties in prescribing it for individuals with mental retardation, and…

  20. Development of a method of clozapine dosage by selective electrode to the iodides.

    PubMed

    Teyeb, Hassen; Douki, Wahiba; Najjar, Mohamed Fadhel

    2012-07-01

    Clozapine (Leponex(®)), the main neuroleptic indicated in the treatment of resistant schizophrenia, requires therapeutic monitoring because of its side effects and the individual variability in metabolism. In addition, several cases of intoxication by this drug were described in the literature. In this work, we studied the indirect dosage of clozapine by selective electrode to the iodides for the optimization of an analytical protocol allowing therapeutic monitoring and the diagnosis of intoxication and/or overdose. Our results showed that the developed method is linear between 0.05 and 12.5 µg/mL (r = 0.980), with a limit of detection of 0.645.10(-3) µg/mL. It presents good precision (coefficient of variation less than 4%) and accuracy (coefficient less than 10%) for all the studied concentrations. With a domain of linearity covering a wide margin of concentrations, this method can be applicable to the dosage of clozapine in tablets and in different biological matrices, such as plasma, urines, and postmortem samples.

  1. Effects of a smoking ban on clozapine plasma concentrations in a nonsecure psychiatric unit.

    PubMed

    Gee, Siobhan H; Taylor, David M; Shergill, Sukhwinder S; Flanagan, Robert; MacCabe, James H

    2017-02-01

    Tobacco smoke is known to affect plasma levels of some drugs, including the antipsychotic clozapine. The effects of suddenly stopping smoking on patients who take clozapine can be severe, as plasma concentrations are expected to rapidly rise, potentially leading to toxicity. A ban on smoking at South London and the Maudsley NHS Foundation Trust (SLaM) was implemented in 2014, and this was expected to affect the plasma concentrations of clozapine for inpatients at the time. This study aimed to determine whether plasma concentrations of clozapine were affected, and additionally, in line with observations from other authors, whether levels of reported violence would also be affected. The smoking habits of all patients at SLaM who smoked and were prescribed clozapine were recorded both before and after the ban. The Glasgow Antipsychotic Side Effect Scale for Clozapine (GASS-C) scale was used to evaluate side-effect burden. Clozapine doses and plasma concentrations were also collected. In total, 31 patients were included in this study. The mean clozapine dose before the ban was 502 mg/day, and this did not change significantly after the ban. Similarly, there were no significant changes in clozapine or norclozapine plasma concentrations, or in GASS-C scores. There was no change in the amount of tobacco patients reported smoking before or after the ban. A modest but statistically significant reduction in violent incidences was observed. Our data suggest that a ban on smoking for patients taking clozapine on open wards at inpatient hospital sites had little impact on clozapine plasma concentrations, because patients continued to smoke tobacco if allowed to leave. Smoking bans may result in a reduction in violent incidences.

  2. Clozapine in Reducing Aggression and Violence in Forensic Populations.

    PubMed

    Patchan, Kathleen; Vyas, Gopal; Hackman, Ann L; Mackowick, Marie; Richardson, Charles M; Love, Raymond C; Wonodi, Ikwunga; Sayer, MacKenzie A; Glassman, Matthew; Feldman, Stephanie; Kelly, Deanna L

    2018-03-01

    Popular media often portray people with a mental illness as being aggressive, violent, and incarcerated as a result of their behavior. Despite exaggeration in the media, risks for some aggressive behaviors are in fact higher in individuals with schizophrenia. This is often the case with influence of comorbid substance use disorders. It is essential that mental health professionals are aware of treatments that may help with attenuating and treating behaviors that contribute to violence, aggression and incarceration. This paper reviews violence and incarceration in individuals with schizophrenia as well as recommendations, guidelines and benefits for the use of clozapine in this population. Clozapine remains one of the most underutilized evidence-based medications available in the psychiatric arena in the United States. It is a viable and recommended option in the forensic population and it may be helpful on the path to recovery as well as bring substantial savings to the criminal justice system.

  3. Bioconcentration of two basic pharmaceuticals, verapamil and clozapine, in fish.

    PubMed

    Nallani, Gopinath C; Edziyie, Regina E; Paulos, Peter M; Venables, Barney J; Constantine, Lisa A; Huggett, Duane B

    2016-03-01

    The present study examined the bioconcentration of 2 basic pharmaceuticals: verapamil (a calcium channel blocker) and clozapine (an antipsychotic compound) in 2 fresh water fishes, fathead minnow and channel catfish. In 4 separate bioconcentration factor (BCF) experiments (2 chemicals × 1 exposure concentration × 2 fishes), fathead minnow and channel catfish were exposed to 190 μg/L and 419 μg/L of verapamil (500 μg/L nominal) or 28.5 μg/L and 40 μg/L of clozapine (50 μg/L nominal), respectively. Bioconcentration factor experiments with fathead consisted of 28 d uptake and 14 d depuration, whereas tests conducted on catfish involved a minimized test design, with 7 d each of uptake and depuration. Fish (n = 4-5) were sampled during exposure and depuration to collect different tissues: muscle, liver, gills, kidneys, heart (verapamil tests only), brain (clozapine tests only), and blood plasma (catfish tests only). Verapamil and clozapine concentrations in various tissues of fathead and catfish were analyzed using liquid chromatography-mass spectrometry. In general, higher accumulation rates of the test compounds were observed in tissues with higher perfusion rates. Accumulation was also high in tissues relevant to pharmacological targets in mammals (i.e. heart in verapamil test and brain in the clozapine test). Tissue-specific BCFs (wet wt basis) for verapamil and clozapine ranged from 0.7 to 75 and from 31 to 1226, respectively. Tissue-specific concentration data were used to examine tissue-blood partition coefficients. © 2016 SETAC.

  4. Suicidality in clozapine-treated patients with schizophrenia: role of obsessive-compulsive symptoms.

    PubMed

    Szmulewicz, Alejandro G; Smith, José M; Valerio, Marina P

    2015-11-30

    Patients with schizophrenia have an increased lifetime risk of comorbid obsessive-compulsive symptoms. Up to 30% of these patients experience such symptoms and 12% may be diagnosed with obsessive-compulsive disorder. The presence of these symptoms in schizophrenia seems to be associated with poor outcomes including a greater suicidal risk. A subgroup of patients develops this symptomatology after the initiation with Second Generation Antipsychotics (SGA). Also, there is evidence of a causal relationship for this association, particularly for clozapine. The primary aim of this study was to investigate the association of this comorbidity with suicidality in a population of clozapine-medicated schizophrenic and schizoaffective patients (N=65). The prevalence of obsessive-compulsive symptoms in our sample was 29.2% (N=19) and the prevalence of obsessive-compulsive disorder was 13.8% (N=9). Significant positive correlations between suicidality and total Y-BOCS score and between Y- BOCS score and depressive symptoms were found. Further analysis indicated that a Y-BOCS score greater or equal than 8 was an independent predictor of suicide attempt during clozapine treatment. Routine screening for this adverse event should be warranted for this population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Double-blind, randomized, clinical trial of metformin as add-on treatment with clozapine in treatment of schizophrenia disorder.

    PubMed

    Hebrani, Paria; Manteghi, Ali Akhoundpour; Behdani, Fatemeh; Hessami, Elham; Rezayat, Kambiz Akhavan; Marvast, Majid Nabizadeh; Rezayat, Amir Akhavan

    2015-04-01

    One of the major causes of death in schizophrenia is a metabolic syndrome. The clozapine has the highest rate of weight gain among antipsychotics. It has been shown that metformin can promote weight loss. We aimed to investigate the effect of metformin as an adjunctive therapy with clozapine to prevent metabolic syndrome in patients with schizophrenia. A total of 37 patients consisting metformin group (19 cases) and a group of placebo consisting of 18 cases were evaluated. A brief psychiatric rating scale score (BPRS) and metabolic profiles was determined for all patients. All of the variables were also determined at 2, 8, 16, and 20 weeks after the onset of the study. The mean age of the group of metformin was 47.2 ± 10.4 compared with 45.8 ± 10.2 for the group of placebo. The difference in mean waist circumference and serum level of triglyceride at baseline compared with the end of study showed a statistically significant difference between two groups (P = 0. 000). A statistically significant difference was also observed in a comparison of mean difference of weight and body mass index at baseline compared with end of study (P = 0. 000). There was a statistically significant difference of fasting blood sugar (P = 0.011) and serum high-density lipoprotein (P = 0.000) between two groups but this difference was not significant for mean BPRS scores, mean systolic and diastolic blood pressure, serum level of triiodothyronine, thyroxin and thyroid stimulating hormone, serum low-density lipoprotein and serum cholesterol. Metformin could be considered an adjunctive therapy with clozapine to prevent metabolic syndrome in schizophrenic patients.

  6. Placebo-controlled trial of atomoxetine for weight reduction in people with schizophrenia treated with clozapine or olanzapine.

    PubMed

    Ball, M Patricia; Warren, Kimberly R; Feldman, Stephanie; McMahon, Robert P; Kelly, Deanna L; Buchanan, Robert W

    2011-04-01

    In recent years, several pharmacological and psychosocial interventions have examined ways to prevent or treat weight gain in people receiving second-generation antipsychotics. While there has been some success, in general, results have not been compelling. Atomoxetine is a selective norepinepherine reuptake inhibitor found to be associated with appetite suppression. Therefore, we examined whether atomoxetine may be of benefit for those who have gained weight on either clozapine or olanzapine. The study was a double-blind, placebo-controlled trial. All participants received the same psychosocial platform: a structured support and exercise group. People with schizophrenia or schizoaffective disorder, on olanzapine or clozapine, who had gained at least 7% of their pre-clozapine or pre-olanzapine weight were eligible for a 24-week, randomized, parallel group, double-blind comparison of adjunctive atomoxetine or placebo. Thirty-seven participants (20 atomoxetine, 17 placebo) were randomized and 26 participants (14 atomoxetine, 12 placebo; 70.2%) completed the study. There were no significant group differences in baseline BMI (atomoxetine: 34.5±4.9; placebo: 35.7±7.0) or weight (atomoxetine: 102.2±15.7 kg; placebo: 104.3±17.5 kg). Both treatment groups showed modest, not significant, trends in weight loss, averaging about 2 kg. Gender or baseline antipsychotic treatment did not modify treatment effects on weight. Secondary outcomes included neuropsychological assessments, symptom assessments (BPRS, SANS) and safety assessments. Of these, only the group difference in Gordon distractibility test scores was statistically significant and favored treatment with atomoxetine. Atomoxetine is not effective for weight loss in this population, but both olanzapine and clozapine participants can lose weight with structured group support and exercise.

  7. Effect of MK-801 and Clozapine on the Proteome of Cultured Human Oligodendrocytes

    PubMed Central

    Cassoli, Juliana S.; Iwata, Keiko; Steiner, Johann; Guest, Paul C.; Turck, Christoph W.; Nascimento, Juliana M.; Martins-de-Souza, Daniel

    2016-01-01

    Separate lines of evidence have demonstrated the involvement of N-methyl-D-aspartate (NMDA) receptor and oligodendrocyte dysfunctions in schizophrenia. Here, we have carried out shotgun mass spectrometry proteome analysis of oligodendrocytes treated with the NMDA receptor antagonist MK-801 to gain potential insights into these effects at the molecular level. The MK-801 treatment led to alterations in the levels of 68 proteins, which are associated with seven distinct biological processes. Most of these proteins are involved in energy metabolism and many have been found to be dysregulated in previous proteomic studies of post-mortem brain tissues from schizophrenia patients. Finally, addition of the antipsychotic clozapine to MK-801-treated oligodendrocyte cultures resulted in changes in the levels of 45 proteins and treatment with clozapine alone altered 122 proteins and many of these showed opposite changes to the MK-801 effects. Therefore, these proteins and the associated energy metabolism pathways should be explored as potential biomarkers of antipsychotic efficacy. In conclusion, MK-801 treatment of oligodendrocytes may provide a useful model for testing the efficacy of novel treatment approaches. PMID:26973466

  8. Prediction of working memory performance in schizophrenia by plasma ratio of clozapine to N-desmethylclozapine.

    PubMed

    Rajji, Tarek K; Mulsant, Benoit H; Davies, Simon; Kalache, Sawsan M; Tsoutsoulas, Christopher; Pollock, Bruce G; Remington, Gary

    2015-06-01

    Clozapine's potent antagonism of muscarinic M1 receptors is thought to worsen working memory deficits associated with schizophrenia. In contrast, its major metabolite, N-desmethylclozapine (NDMC), is thought to enhance working memory via its M1 receptor agonist activity. The authors hypothesized that the ratio of serum clozapine and NDMC concentrations would be inversely associated with working memory performance in schizophrenia. Thirty patients with schizophrenia or schizoaffective disorder who were receiving clozapine monotherapy at bedtime completed the MATRICS Consensus Cognitive Battery (MCCB) on the day their blood was collected to assess concentrations of clozapine and NDMC as well as serum anticholinergic activity. The clozapine/NDMC ratio was significantly and negatively associated with working memory performance after controlling for age, gender, education, and symptom severity. No significant associations were found between individual clozapine and NDMC concentrations and working memory performance. Serum anticholinergic activity was significantly associated with clozapine concentration, but not with working memory performance or NDMC concentration. No significant associations were found between any pharmacological measure and performance on other MCCB cognitive domains. This hypothesis-driven study confirms that clozapine/NDMC ratio is a strong predictor of working memory performance in patients with schizophrenia. This finding suggests that manipulating the clozapine/NDMC ratio could enhance cognition in patients with schizophrenia treated with clozapine. It also supports the study of procholinergic agents, such as M1 receptor-positive allosteric modulators, to enhance cognition in schizophrenia.

  9. Supraventricular tachycardia in a patient receiving ECT, clozapine, and caffeine.

    PubMed

    Beale, M D; Pritchett, J T; Kellner, C H

    1994-09-01

    A patient receiving electroconvulsive therapy (ECT), clozapine, and intravenous caffeine sodium benzoate developed supraventricular tachycardia. This was rapidly treated with intravenous verapamil. Subsequent maintenance ECT given without caffeine was well tolerated. We believe the combination of clozapine and caffeine at the time of ECT was responsible for the arrhythmia.

  10. Involvement of the histamine H{sub 4} receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Goto, Aya; Mouri, Akihiro; Nagai, Tomoko

    Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100 μM)more » and doxorubicin (0.2 µM) decreased the cell survival rate, but olanzapine (1–100 µM) did not. Under granulocytic differentiation for 5 days, clozapine, even at a concentration of 25 μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H{sub 4} receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H{sub 4} receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H{sub 4} receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H{sub 4} receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic

  11. Actively Negotiating the Mind-Body Divide: How Clozapine-Treated Schizophrenia Patients Make Health for Themselves.

    PubMed

    Brown, Julia E H; Dennis, Simone

    2017-09-01

    It is well recognised that antipsychotic treatments impact the whole body, not just the target area of the brain. For people with refractory schizophrenia on clozapine, the gold standard antipsychotic treatment in England and Australia, the separation of mental and physical regimes of health is particularly pronounced, resulting in multiple, compartmentalised treatment registers. Clinicians often focus on the mental health aspects of clozapine use, using physical indicators to determine whether treatment can continue. Our observations of 59 participants in England and Australia over 18 months revealed that patients did not observe this hierarchisation of mental treatments and physical outcomes. Patients often actively engaged in the management of their bodily symptoms, leading us to advance the figure of the active, rather than passive, patient. In our paper, we do not take the position that the facility for active management is a special one utilised only by these patients. We seek instead to draw attention to what is currently overlooked as an ordinary capacity to enact some sort of control over life, even under ostensibly confined and confining circumstances. We argue that clozapine-treated schizophrenia patients utilise the clinical dichotomy between mental and physical domains of health to rework what health means to them. This permits patients to actively manage their own phenomenological 'life projects' (Rapport, I am Dynamite: an Alternative Anthropology of Power, Routledge, London 2003), and forces us to reconsider the notion of clinical giveness of what health means. This making of one's own meanings of health may be critical to the maintenance of a sense of self.

  12. The effect of clozapine on mRNA expression for genes encoding G protein-coupled receptors and the protein components of clathrin-mediated endocytosis

    PubMed Central

    Hu, Ying; Weymer, Jon F.; Rizig, Mie; McQuillin, Andrew; Hunt, Stephen P.; Gurling, Hugh M.D.

    2013-01-01

    Objectives Clathrin-mediated endocytosis (CME) is an intracellular trafficking mechanism for packaging cargo, including G protein-coupled receptors (GPCRs), into clathrin-coated vesicles (CCVs). The antipsychotic chlorpromazine inhibits CCV assembly of adaptor protein AP2 whereas clozapine increases serotonin2A receptor internalization. We hypothesized that clozapine alters the expression of CME genes modulating vesicle turnover and GPCR internalization. Materials and methods SH-SY5Y human neuroblastoma cells were incubated with clozapine (1–20 µmol/l) for 24–72 h. GPCR and CME-related gene mRNA expression was measured using RT-PCR. We quantified changes in the same genes using expression data from a microarray study of mice brains after 12 weeks of treatment with 12 mg/kg/day clozapine. Results The expression of genes encoding adaptor and clathrin assembly proteins, AP2A2, AP2B1, AP180, CLINT1, HIP1, ITSN2, and PICALM, increased relative to the control in SH-SY5Y cells incubated with 5–10 µmol/l clozapine for 24–72 h. The microarray study showed significantly altered expression of the above CME-related genes, with a marked 641-fold and 17-fold increase in AP180 and the serotonin1A GPCR, respectively. The expression of three serotonergic receptor and lysophosphatidic acid receptor 2 (EDG4) GPCR genes was upregulated in SH-SY5Y cells incubated with 5 µmol/l clozapine for 24 h. EDG4 expression was also increased with 10–20 µmol/l clozapine treatment at 48–72 h. Clozapine significantly decreased the expression of β-arrestin, involved in GPCR desensitization, both in vitro and vivo. Conclusion The changes we report in CME and GPCR mRNAs implicate CCV-mediated internalization of GPCRs and the serotonergic system in clozapine’s mechanism of action, which may be useful in the design of more effective and less toxic antipsychotic therapies. PMID:23811784

  13. Electroconvulsive Therapy Added to Non-Clozapine Antipsychotic Medication for Treatment Resistant Schizophrenia: Meta-Analysis of Randomized Controlled Trials.

    PubMed

    Zheng, Wei; Cao, Xiao-Lan; Ungvari, Gabor S; Xiang, Ying-Qiang; Guo, Tong; Liu, Zheng-Rong; Wang, Yuan-Yuan; Forester, Brent P; Seiner, Stephen J; Xiang, Yu-Tao

    2016-01-01

    This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of the combination of electroconvulsive therapy (ECT) and antipsychotic medication (except for clozapine) versus the same antipsychotic monotherapy for treatment-resistant schizophrenia (TRS). Two independent investigators extracted data for a random effects meta-analysis and pre-specified subgroup and meta-regression analyses. Weighted and standard mean difference (WMD/SMD), risk ratio (RR) ±95% confidence intervals (CIs), number needed to treat (NNT), and number needed to harm (NNH) were calculated. Eleven studies (n = 818, duration = 10.2±5.5 weeks) were identified for meta-analysis. Adjunctive ECT was superior to antipsychotic monotherapy regarding (1) symptomatic improvement at last-observation endpoint with an SMD of -0.67 (p<0.00001; I2 = 62%), separating the two groups as early as weeks 1–2 with an SMD of -0.58 (p<0.00001; I2 = 0%); (2) study-defined response (RR = 1.48, p<0.0001) with an NNT of 6 (CI = 4–9) and remission rate (RR = 2.18, p = 0.0002) with an NNT of 8 (CI = 6–16); (3) PANSS positive and general symptom sub-scores at endpoint with a WMD between -3.48 to -1.32 (P = 0.01 to 0.009). Subgroup analyses were conducted comparing double blind/rater-masked vs. open RCTs, those with and without randomization details, and high quality (Jadad≥adadup analyses were Jadad<3) studies. The ECT-antipsychotic combination caused more headache (p = 0.02) with an NNH of 6 (CI = 4–11) and memory impairment (p = 0.001) with an NNH of 3 (CI = 2–5). The use of ECT to augment antipsychotic treatment (clozapine excepted) can be an effective treatment option for TRS, with increased frequency of self-reported memory impairment and headache. CRD42014006689 (PROSPERO).

  14. Quo Vadis Clozapine? A Bibliometric Study of 45 Years of Research in International Context

    PubMed Central

    López-Muñoz, Francisco; Sanz-Fuentenebro, Javier; Rubio, Gabriel; García-García, Pilar; Álamo, Cecilio

    2015-01-01

    We have carried out a bibliometric study about the international scientific publications on clozapine. We have used the EMBASE and MEDLINE databases, and we applied bibliometric indicators of production, as Price’s Law on the increase of scientific literature. We also calculated the participation index (PI) of the different countries. The bibliometric data have also been correlated with some social and health data from the 12 most productive countries in biomedicine and health sciences. In addition, 5607 original documents dealing with clozapine, published between 1970 and 2013, were downloaded. Our results state non-fulfilment of Price’s Law, with scientific production on clozapine showing linear growth (r = 0.8691, vs. r = 0.8478 after exponential adjustment). Seven of the 12 journals with the highest numbers of publications on clozapine have an Impact Factor > 2. Among the countries generating clozapine research, the most prominent is the USA (PI = 24.32), followed by the UK (PI = 6.27) and Germany (PI = 5.40). The differences among countries on clozapine research are significantly related to economic variables linked to research. The scientific interest in clozapine remains remarkable, although after the application of bibliometric indicators of production, a saturation point is evident in the growth of scientific literature on this topic. PMID:26404263

  15. Clozapine-induced agranulocytosis: Evidence for an immune-mediated mechanism from a patient-specific in-vitro approach

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Regen, Francesca; Herzog, Irmelin; Hahn, Eric

    2017-02-01

    Use of the atypical antipsychotic clozapine (CZP) is compromised by the risk of potentially fatal agranulocytosis/granulocytopenia (CIAG). To address this, we have established a simple, personalized cell culture-based strategy to identify CIAG-susceptible patients, hypothesizing that an immunogenic and possibly haptene-based mechanism underlies CIAG pathophysiology. To detect a putative haptene-induced response to CZP in vitro exposure, a traditional lymphocyte stimulation assay was adapted and applied to patient-specific peripheral blood-derived mononuclear cells (PBMC). 6 patients with a history of CIAG, 6 patients under CZP treatment (without CIAG) and 12 matched healthy controls were studied. In vitro CZP exposure, even at strikingly lowmore » levels, resulted in significantly increased proliferation rates only in CIAG patients' PBMC. Other parameters including cell viability and mitogen-induced proliferation were also affected by in vitro CZP exposure, yet there was no significant difference between the groups. This personalized approach is a starting point for further investigations into a putative haptene-based mechanism underlying CIAG development, and may facilitate the future development of predictive testing. - Highlights: • Clozapine induces proliferation in PBMCs from patients with a history of CIAG. • Simple, PBMC-based assay results in robust effects of physiological clozapine levels. • Haptene-based mechanisms discussed to underlie clozapine-induced proliferation.« less

  16. Clozapine in schizophrenia patients with recurrent catatonia: report of two cases.

    PubMed

    Hung, Yi-Yung; Yang, Ping-Suen; Huang, Tiao-Lai

    2006-04-01

    Prolonged catatonia can be a source of extremely serious morbidity and mortality. Lorazepam is effective in rapidly relieving most cases of catatonia. Reports have also shown that second-generation antipsychotic drugs are also efficacious in relieving catatonia. This report describes two schizophrenia patients who demonstrated recurrent catatonic features mutism and stupor. Both patients were treated with lorazepam, diazepam or electroconvulsive therapy (ECT). Patient 1 responded well and rapidly to lorazepam each time catatonia happened; but catatonia recurred once a year under treatment with many antipsychotic drugs. Patient 2 had catatonia features associated with discontinuing or decreasing clozapine. With each recurrent episode, the duration of catatonia increased, requiring an increased dosage of benzodiazepine. The patient's response to lorazepam and ECT gradually decreased, until the patient had almost no response to lorazepam, diazepam or ECT. Both patients had no recurrence during a period of 2-year follow up with continuous clozapine therapy.

  17. Clozapine promotes glycolysis and myelin lipid synthesis in cultured oligodendrocytes

    PubMed Central

    Steiner, Johann; Martins-de-Souza, Daniel; Schiltz, Kolja; Sarnyai, Zoltan; Westphal, Sabine; Isermann, Berend; Dobrowolny, Henrik; Turck, Christoph W.; Bogerts, Bernhard; Bernstein, Hans-Gert; Horvath, Tamas L.; Schild, Lorenz; Keilhoff, Gerburg

    2014-01-01

    Clozapine displays stronger systemic metabolic side effects than haloperidol and it has been hypothesized that therapeutic antipsychotic and adverse metabolic effects of these drugs are related. Considering that cerebral disconnectivity through oligodendrocyte dysfunction has been implicated in schizophrenia, it is important to determine the effect of these drugs on oligodendrocyte energy metabolism and myelin lipid production. Effects of clozapine and haloperidol on glucose and myelin lipid metabolism were evaluated and compared in cultured OLN-93 oligodendrocytes. First, glycolytic activity was assessed by measurement of extra- and intracellular glucose and lactate levels. Next, the expression of glucose (GLUT) and monocarboxylate (MCT) transporters was determined after 6 and 24 h. And finally mitochondrial respiration, acetyl-CoA carboxylase, free fatty acids, and expression of the myelin lipid galactocerebroside were analyzed. Both drugs altered oligodendrocyte glucose metabolism, but in opposite directions. Clozapine improved the glucose uptake, production and release of lactate, without altering GLUT and MCT. In contrast, haloperidol led to higher extracellular levels of glucose and lower levels of lactate, suggesting reduced glycolysis. Antipsychotics did not alter significantly the number of functionally intact mitochondria, but clozapine enhanced the efficacy of oxidative phosphorylation and expression of galactocerebroside. Our findings support the superior impact of clozapine on white matter integrity in schizophrenia as previously observed, suggesting that this drug improves the energy supply and myelin lipid synthesis in oligodendrocytes. Characterizing the underlying signal transduction pathways may pave the way for novel oligodendrocyte-directed schizophrenia therapies. PMID:25477781

  18. CoMET: a protocol for a randomised controlled trial of co-commencement of METformin as an adjunctive treatment to attenuate weight gain and metabolic syndrome in patients with schizophrenia newly commenced on clozapine.

    PubMed

    Siskind, Dan; Friend, Nadia; Russell, Anthony; McGrath, John J; Lim, Carmen; Patterson, Sue; Flaws, Dylan; Stedman, Terry; Moudgil, Vikas; Sardinha, Savio; Suetani, Shuichi; Kisely, Steve; Winckel, Karl; Baker, Andrea

    2018-03-02

    Clozapine, while effective in treatment refractory schizophrenia, is associated with significant weight gain, heart disease and increased risk of type 2 diabetes mellitus (T2DM). Although there is evidence for weight loss with metformin for people with obesity who are already taking clozapine, there have been no published trials that have investigated the effect of metformin in attenuating weight gain at the time of clozapine initiation. A 24-week double-blind placebo-controlled trial of concomitant prescription of metformin at clozapine commencement. Eighty-six people being commenced on clozapine will be randomised to placebo or metformin (variable dose, up to 2 g/day). The primary outcome is comparative end point body weight, between the placebo and metformin groups. Secondary outcomes are comparative rates of conversion to T2DM, alteration of metabolic syndrome parameters, proportion gaining >5% body weight and changes in diet and appetite. We will additionally examine biomarkers associated with change in weight among trial participants. Ethics approval was granted by the Metro South Human Research Ethics Committee HREC/17/QPAH/538-SSA/17/QPAH/565. We plan to submit a manuscript of the results to a peer-reviewed journal, and present results at conferences, consumer forums and hospital grand rounds. ACTRN12617001547336; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Guidelines for the Use of Clozapine in Individuals with Developmental Disabilities

    ERIC Educational Resources Information Center

    Sabaawi, Mohamed; Singh, Nirbhay N.; de Leon, Jose

    2006-01-01

    Clozapine is the most effective antipsychotic medication currently in use, but there has been a paucity of well-controlled research on its efficacy with people with developmental disabilities. We present a set of guidelines to ensure proper utilization of clozapine in individuals with developmental disabilities, because it can offer them…

  20. Hormonal Correlates of Clozapine-Induced Weight Gain in Psychotic Children: An Exploratory Study

    ERIC Educational Resources Information Center

    Sporn, Alexandra L.; Bobb, Aaron J.; Gogtay, Nitin; Stevens, Hanna; Greenstein, Deanna K.; Clasen, Liv S.; Tossell, Julia W.; Nugent, Thomas; Gochman, Peter A.; Sharp, Wendy S.; Mattai, Anand; Lenane, Marge C.; Yanovski, Jack A.; Rapoport, Judith L.

    2005-01-01

    Objective: Weight gain is a serious side effect of atypical antipsychotics, especially in childhood. In this study, the authors examined six weight gain-related hormones in patients with childhood-onset schizophrenia (COS) after 6 weeks of clozapine treatment. Method: Fasting serum samples for 24 patients with COS and 21 matched healthy controls…

  1. Functional antagonistic properties of clozapine at the 5-HT3 receptor.

    PubMed

    Hermann, B; Wetzel, C H; Pestel, E; Zieglgänsberger, W; Holsboer, F; Rupprecht, R

    1996-08-23

    The atypical neuroleptic clozapine is thought to exert its psychopharmacological actions through a variety of neurotransmitter receptors. It binds preferentially to D4 and 5-HT2 receptors; however, little is known on it's interaction with the 5-HT3 receptor. Using a cell line stably expressing the 5-HT3 receptor, whole-cell voltage-clamp analysis revealed functional antagonistic properties of clozapine at low nanomolar concentrations in view of a binding affinity in the upper nanomolar range. Because the concentration of clozapine required for an interaction with the 5-HT3 receptor can be achieved with therapeutical doses, functional antagonistic properties at this ligand-gated ion channel may contribute to its unique psychopharmacological profile.

  2. Reliable clinical serum analysis with reusable electrochemical sensor: Toward point-of-care measurement of the antipsychotic medication clozapine.

    PubMed

    Kang, Mijeong; Kim, Eunkyoung; Winkler, Thomas E; Banis, George; Liu, Yi; Kitchen, Christopher A; Kelly, Deanna L; Ghodssi, Reza; Payne, Gregory F

    2017-09-15

    Clozapine is one of the most promising medications for managing schizophrenia but it is under-utilized because of the challenges of maintaining serum levels in a safe therapeutic range (1-3μM). Timely measurement of serum clozapine levels has been identified as a barrier to the broader use of clozapine, which is however challenging due to the complexity of serum samples. We demonstrate a robust and reusable electrochemical sensor with graphene-chitosan composite for rapidly measuring serum levels of clozapine. Our electrochemical measurements in clinical serum from clozapine-treated and clozapine-untreated schizophrenia groups are well correlated to centralized laboratory analysis for the readily detected uric acid and for the clozapine which is present at 100-fold lower concentration. The benefits of our electrochemical measurement approach for serum clozapine monitoring are: (i) rapid measurement (≈20min) without serum pretreatment; (ii) appropriate selectivity and sensitivity (limit of detection 0.7μM); (iii) reusability of an electrode over several weeks; and (iv) rapid reliability testing to detect common error-causing problems. This simple and rapid electrochemical approach for serum clozapine measurements should provide clinicians with the timely point-of-care information required to adjust dosages and personalize the management of schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Use of granulocyte-colony stimulating factor to prevent recurrent clozapine-induced neutropenia on drug rechallenge: A systematic review of the literature and clinical recommendations.

    PubMed

    Myles, Nicholas; Myles, Hannah; Clark, Scott R; Bird, Robert; Siskind, Dan

    2017-10-01

    Clozapine is the most effective medication for treatment-refractory schizophrenia; however, its use is contraindicated in people who have had previous clozapine-induced neutropenia. Co-prescription of granulocyte-colony stimulating factor may prevent recurrent neutropenia and allow continuation or rechallenge of clozapine. Systematic review of literature reporting the use of granulocyte-colony stimulating factor to allow rechallenge or continuation of clozapine in people with previous episodes of clozapine-induced neutropenia. The efficacy of granulocyte-colony stimulating factor and predictors of successful rechallenge will be determined to elucidate whether evidence-based recommendations can be made regarding the use of granulocyte-colony stimulating factor in this context. A total of 17 articles were identified that reported on clozapine rechallenge with granulocyte-colony stimulating factor support. In all, 76% of cases were able to continue clozapine at median follow-up of 12 months. There were no clear clinical or laboratory predictors of successful rechallenge; however, initial neutropenia was more severe in successful cases compared to unsuccessful cases. Cases co-prescribed lithium had lower success rates of rechallenge (60%) compared to those who were not prescribed lithium (81%). The most commonly reported rechallenge strategy was use of filgrastim 150-480 µg between daily to three times a week. There were no medication-specific side effects of granulocyte-colony stimulating factor reported apart from euphoria in one case. Three cases who failed granulocyte-colony stimulating factor had bacterial infection at time of recurrent neutropenia. No deaths were reported. Preliminary data suggest granulocyte-colony stimulating factor is safe and effective in facilitating rechallenge with clozapine. Clinical recommendations for use are discussed.

  4. Outcome definitions and clinical predictors influence pharmacogenetic associations between HTR3A gene polymorphisms and response to clozapine in patients with schizophrenia.

    PubMed

    Rajkumar, A P; Poonkuzhali, B; Kuruvilla, A; Srivastava, A; Jacob, M; Jacob, K S

    2012-12-01

    Pharmacogenetics of schizophrenia has not yet delivered anticipated clinical dividends. Clinical heterogeneity of schizophrenia contributes to the poor replication of the findings of pharmacogenetic association studies. Functionally important HTR3A gene single-nucleotide polymorphisms (SNPs) were reported to be associated with response to clozapine. The aim of this study was to investigate how the association between HTR3A gene SNP and response to clozapine is influenced by various clinical predictors and by differing outcome definitions in patients with treatment-resistant schizophrenia (TRS). We recruited 101 consecutive patients with TRS, on stable doses of clozapine, and evaluated their HTR3A gene SNP (rs1062613 and rs2276302), psychopathology, and serum clozapine levels. We assessed their socio-demographic and clinical profiles, premorbid adjustment, traumatic events, cognition, and disability using standard assessment schedules. We evaluated their response to clozapine, by employing six differing outcome definitions. We employed appropriate multivariate statistics to calculate allelic and genotypic association, accounting for the effects of various clinical variables. T allele of rs1062613 and G allele of rs2276302 were significantly associated with good clinical response to clozapine (p = 0.02). However, varying outcome definitions make these associations inconsistent. rs1062613 and rs2276302 could explain only 13.8 % variability in the responses to clozapine, while combined clinical predictors and HTR3A pharmacogenetic association model could explain 38 % variability. We demonstrated that the results of pharmacogenetic studies in schizophrenia depend heavily on their outcome definitions and that combined clinical and pharmacogenetic models have better predictive values. Future pharmacogenetic studies should employ multiple outcome definitions and should evaluate associated clinical variables.

  5. Cannabidiol Attenuates Sensorimotor Gating Disruption and Molecular Changes Induced by Chronic Antagonism of NMDA receptors in Mice

    PubMed Central

    Issy, Ana Carolina; Ferreira, Frederico R.; Viveros, Maria-Paz; Del Bel, Elaine A.; Guimarães, Francisco S.

    2015-01-01

    Background: Preclinical and clinical data suggest that cannabidiol (CBD), a major non-psychotomimetic compound from Cannabis sativa, induces antipsychotic-like effects. However, the antipsychotic properties of repeated CBD treatment have been poorly investigated. Behavioral changes induced by repeated treatment with glutamate N-methyl-D-aspartate receptor (NMDAR) antagonists have been proposed as an animal model of schizophrenia-like signs. In the present study, we evaluated if repeated treatment with CBD would attenuate the behavioral and molecular modifications induced by chronic administration of one of these antagonists, MK-801. Methods: Male C57BL/6J mice received daily i.p. injections of MK-801 (0.1, 0.5, or 1mg/kg) for 14, 21, or 28 days. Twenty-four hours after the last injection, animals were submitted to the prepulse inhibition (PPI) test. After that, we investigated if repeated treatment with CBD (15, 30, and 60mg/kg) would attenuate the PPI impairment induced by chronic treatment with MK-801 (1mg/kg; 28 days). CBD treatment began on the 6th day after the start of MK-801 administration and continued until the end of the treatment. Immediately after the PPI, the mice brains were removed and processed to evaluate the molecular changes. We measured changes in FosB/ΔFosB and parvalbumin (PV) expression, a marker of neuronal activity and a calcium-binding protein expressed in a subclass of GABAergic interneurons, respectively. Changes in mRNA expression of the NMDAR GluN1 subunit gene (GRN1) were also evaluated. CBD effects were compared to those induced by the atypical antipsychotic clozapine. Results: MK-801 administration at the dose of 1mg/kg for 28 days impaired PPI responses. Chronic treatment with CBD (30 and 60mg/kg) attenuated PPI impairment. MK-801 treatment increased FosB/ΔFosB expression and decreased PV expression in the medial prefrontal cortex. A decreased mRNA level of GRN1 in the hippocampus was also observed. All the molecular changes were

  6. Cannabidiol attenuates sensorimotor gating disruption and molecular changes induced by chronic antagonism of NMDA receptors in mice.

    PubMed

    Gomes, Felipe V; Issy, Ana Carolina; Ferreira, Frederico R; Viveros, Maria-Paz; Del Bel, Elaine A; Guimarães, Francisco S

    2014-10-31

    Preclinical and clinical data suggest that cannabidiol (CBD), a major non-psychotomimetic compound from Cannabis sativa, induces antipsychotic-like effects. However, the antipsychotic properties of repeated CBD treatment have been poorly investigated. Behavioral changes induced by repeated treatment with glutamate N-methyl-D-aspartate receptor (NMDAR) antagonists have been proposed as an animal model of schizophrenia-like signs. In the present study, we evaluated if repeated treatment with CBD would attenuate the behavioral and molecular modifications induced by chronic administration of one of these antagonists, MK-801. Male C57BL/6J mice received daily i.p. injections of MK-801 (0.1, 0.5, or 1mg/kg) for 14, 21, or 28 days. Twenty-four hours after the last injection, animals were submitted to the prepulse inhibition (PPI) test. After that, we investigated if repeated treatment with CBD (15, 30, and 60mg/kg) would attenuate the PPI impairment induced by chronic treatment with MK-801 (1mg/kg; 28 days). CBD treatment began on the 6th day after the start of MK-801 administration and continued until the end of the treatment. Immediately after the PPI, the mice brains were removed and processed to evaluate the molecular changes. We measured changes in FosB/ΔFosB and parvalbumin (PV) expression, a marker of neuronal activity and a calcium-binding protein expressed in a subclass of GABAergic interneurons, respectively. Changes in mRNA expression of the NMDAR GluN1 subunit gene (GRN1) were also evaluated. CBD effects were compared to those induced by the atypical antipsychotic clozapine. MK-801 administration at the dose of 1mg/kg for 28 days impaired PPI responses. Chronic treatment with CBD (30 and 60mg/kg) attenuated PPI impairment. MK-801 treatment increased FosB/ΔFosB expression and decreased PV expression in the medial prefrontal cortex. A decreased mRNA level of GRN1 in the hippocampus was also observed. All the molecular changes were attenuated by CBD. CBD by

  7. Adjunctive memantine in clozapine-treated refractory schizophrenia: an open-label 1-year extension study.

    PubMed

    Veerman, S R T; Schulte, P F J; Deijen, J B; de Haan, L

    2017-01-01

    In a recent placebo-controlled, double-blind crossover trial (n = 52), significant beneficial effects on memory (d = 0.30) and negative symptoms (d = 0.29) were found after 12 weeks of memantine augmentation in patients with clozapine-refractory schizophrenia. In this open-label 1-year extension study we report the long-term effects and tolerability of memantine add-on therapy to clozapine. Completers of the first trial who experienced beneficial effects during 12 weeks of memantine treatment received memantine for 1 year. Primary endpoints were memory and executive function using the Cambridge Neuropsychological Test Automated Battery, the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression Severity Scale (CGI-S). Of 31 randomized controlled trial completers who experienced beneficial effects from memantine, 24 received memantine for 1 year. The small improvement in memory found in the memantine condition in the placebo-controlled trial remained stable in the extension study. Executive function did not improve. After 26 weeks of memantine add-on therapy to clozapine, PANSS negative symptoms (r = 0.53), PANSS positive symptoms (r = 0.50) and PANSS total symptoms (r = 0.54) significantly improved. Even further significant improvement in all these measures was observed between 26 weeks and 52 weeks of memantine, with effect sizes varying from 0.39 to 0.51. CGI-S showed a non-significant moderate improvement at 26 weeks (r = 0.36) and 52 weeks (r = 0.34). Memantine was well tolerated without serious adverse effects. In the 1-year extension phase the favourable effect of adjunctive memantine on memory was sustained and we observed further improvement of negative, positive and overall symptoms in patients with clozapine-treated refractory schizophrenia.

  8. COMT Val158Met and 5-HT1A-R -1019 C/G polymorphisms: effects on the negative symptom response to clozapine.

    PubMed

    Bosia, Marta; Lorenzi, Cristina; Pirovano, Adele; Guglielmino, Carmelo; Cocchi, Federica; Spangaro, Marco; Bramanti, Placido; Smeraldi, Enrico; Cavallaro, Roberto

    2015-01-01

    Clozapine is still considered the gold standard for treatment-resistant schizophrenia patients; however, up to 40% of patients do not respond adequately. Identifying potential predictors of clinical response to this last-line antipsychotic could represent an important goal for treatment. Among these, functional polymorphisms involved in dopamine system modulation, known to be disrupted in schizophrenia, may play a role. We examined the COMT Val158Met polymorphism, which plays a key role in dopamine regulation at the prefrontal level, and the 5-HT1A-R -1019 C/G polymorphism, a target of clozapine activity involved in the interaction between the serotonin and dopamine systems. 107 neuroleptic-refractory, biologically unrelated Italian patients (70 males and 37 females) with a DSM-IV diagnosis of schizophrenia who were being treated with clozapine were recruited. Psychopathology was assessed by the Positive and Negative Symptoms Scale (PANSS) at the beginning of treatment, and at weeks 8 and 12. Genomic DNA was extracted from venous blood samples. COMT rs4680 (Val158Met) and 5-HT1A-R rs6295 (-1019 C/G) polymorphisms were analyzed by PCR-based restriction fragment length and direct sequencing, respectively. We found a significant effect of COMT and 5-HT1A-R on the PANSS Negative Subscale variation, with greater improvement among COMT Val/Val and 5-HT1A-R G/G subjects. The findings support the hypothesis that COMT rs4680 and 5-HT1A-R rs6295 polymorphisms could influence the negative symptom response to clozapine, probably through modulation of the dopaminergic system.

  9. ABCB1 polymorphisms are associated with clozapine plasma levels in psychotic patients.

    PubMed

    Consoli, Giorgio; Lastella, Marianna; Ciapparelli, Antonio; Catena Dell'Osso, Mario; Ciofi, Laura; Guidotti, Emanuele; Danesi, Romano; Dell'Osso, Liliana; Del Tacca, Mario; Di Paolo, Antonello

    2009-08-01

    ABCB1 is a transmembrane transporter that is expressed in excretory organs (kidneys and liver), in intestine mucosa and on the blood-brain barrier. Because of the particular distribution of the protein, the activity of ABCB1 may significantly affect drug pharmacokinetics during absorption and distribution. Of note, several SNPs of ABCB1 are known and many of them affect transporter activity and/or expression. In this view, changes in the pharmacokinetics of drugs that are ABCB1 substrates could be clinically relevant and the evaluation of ABCB1 SNPs should deserve particular attention. Therefore, the aim of the present study was to investigate the possible association between ABCB1 polymorphisms and clozapine plasma levels in psychotic patients. c.1236C>T (exon 12), c.2677G>T (exon 21) and c.3435C>T (exon 26) SNPs of ABCB1 were evaluated by PCR techniques, while plasma levels of clozapine and norclozapine were measured by HPLC in 40 men (aged, 47.6 +/- 16.6 years, median: 42 years) and 20 women (aged 40.7 +/- 11.4 years, median: 38 years) 1 month after the start of clozapine administration. A total of three SNPs were in Hardy-Weinberg equilibrium, with a calculated frequency of the wild-type alleles of 0.54, 0.55 and 0.45 for SNPs on exons 12, 21 and 26, respectively. Patients with c.3435CC or c.2677GG genotypes had significantly lower dose-normalized clozapine levels than those who were heterozygous or TT carriers. More interestingly, c.3435CC patients (15 subjects) needed significantly higher daily doses of clozapine (246 +/- 142 mg/day) compared with the remaining 24 CT and 21 TT patients (140 +/- 90 mg/day) in order to achieve the same clinical benefit. c.3435CC patients require higher clozapine doses to achieve the same plasma concentrations as CT or TT patients, and ABCB1 genotyping should be considered as a novel strategy that should improve drug use.

  10. An observational study of clozapine induced sedation and its pharmacological management.

    PubMed

    Ramos Perdigués, Sònia; Sauras Quecuti, Rosa; Mané, Anna; Mann, Louisa; Mundell, Clare; Fernandez-Egea, Emilio

    2016-01-01

    Clozapine induced sedation is common but its management is unclear. We analyzed the factors associated with clozapine-induced sedation and the efficacy of common pharmacological strategies. We conducted a naturalistic observational study using two years electronic records of a cohort patients and three analyses: a cross sectional analysis of factors associated with total number of hours slept (as an objective proxy of sedation), and two prospective analyses of which factors were associated with changes in hours slept and the efficacy of two pharmacological strategies. 133 patients were included, of which 64.7% slept at least 9h daily. Among monotherapy patients (n=30), only norclozapine levels (r=.367, p=.03) correlated with hours slept. Using the prospective cohort (n=107), 42 patients decreased the number of hours slept, due to decreasing clozapine (40%) or augmenting with aripiprazole (36%). These two strategies were recommended to 22 (20.6%) and 23 (21.5%) subjects respectively but the majority (81.8% and 73.9%) did not reduce number of hours slept. Thus, pharmacological and non-pharmacological factors are involved in sedation. Norclozapine plasma levels correlated with total sleeping hours. Reducing clozapine and aripiprazole augmentation were associated to amelioration of sedation, although both strategies were effective only in a limited numbers of subjects. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  11. Left Ventricular Thrombus as a Complication of Clozapine-Induced Cardiomyopathy: A Case Report and Brief Literature Review.

    PubMed

    Malik, Shahbaz A; Malik, Sarah; Dowsley, Taylor F; Singh, Balwinder

    2015-01-01

    A 48-year-old male with history of schizoaffective disorder on clozapine presented with chest pain, dyspnea, and new left bundle branch block. He underwent coronary angiography, which revealed no atherosclerosis. The patient's workup was unrevealing for a cause for the cardiomyopathy and thus it was thought that clozapine was the offending agent. The patient was taken off clozapine and started on guideline directed heart failure therapy. During the course of hospitalization, he was also discovered to have a left ventricular (LV) thrombus for which he received anticoagulation. To our knowledge, this is the first case report of clozapine-induced cardiomyopathy complicated by a LV thrombus.

  12. Effects of haloperidol, clozapine and olanzapine on the survival of human neuronal and immune cells in vitro.

    PubMed

    Heiser, Philip; Enning, Frank; Krieg, Jürgen-Christian; Vedder, Helmut

    2007-11-01

    Cytotoxic effects on neuronal as well as on immune cells have been reported for both typical and atypical antipsychotic drugs. We evaluated the effects of different concentrations of a typical (haloperidol) and two atypical (clozapine, olanzapine) antipsychotics on the survival of human neuronal (SH-SY5Y cells) and immune cells (U937 cells) by determining the metabolic activity after 24 h of incubation by the modified tetrazolium method. The dopaminergic neuroblastoma SH-SY5Y and the lymphoma U-937 cell line are well established models for in vitro investigations. To further elucidate possible mechanisms of action we also determined the ATP content in the cultured cells. After experimental treatment, significant effects were detected by Kruskal Wallis test for all treatment conditions. Post-hoc tests (Dunn's method) showed that haloperidol and clozapine at the two highest concentrations (25 and 50 microg/ml) caused a significant decrease of metabolic activity in both cell systems, which was also detectable after treatment with clozapine at a concentration of 12.5 microg/ml in U937 cells. In contrast, olanzapine induced a significant increase in metabolic activity of SH-SY5Y cells at all concentrations except for the concentration of 3.1 microg/ml, whereas the metabolic activity in U937 cells was increased at concentrations of 1.6 and 6.25 microg/ml. For the determination of ATP content, the LD(50) values of the metabolic activity were used, except for olanzapine for which no distinct LD(50) value was available. Significant changes were detected for all treatments and post-hoc tests revealed that haloperidol caused a significant decrease compared to the control condition in both cell systems. These findings suggest that antipsychotic substances of different classes exert differential metabolic effects in both neuronal and immune cell systems.

  13. Genome-wide common and rare variant analysis provides novel insights into clozapine-associated neutropenia.

    PubMed

    Legge, S E; Hamshere, M L; Ripke, S; Pardinas, A F; Goldstein, J I; Rees, E; Richards, A L; Leonenko, G; Jorskog, L F; Chambert, K D; Collier, D A; Genovese, G; Giegling, I; Holmans, P; Jonasdottir, A; Kirov, G; McCarroll, S A; MacCabe, J H; Mantripragada, K; Moran, J L; Neale, B M; Stefansson, H; Rujescu, D; Daly, M J; Sullivan, P F; Owen, M J; O'Donovan, M C; Walters, J T R

    2017-10-01

    The antipsychotic clozapine is uniquely effective in the management of schizophrenia; however, its use is limited by its potential to induce agranulocytosis. The causes of this, and of its precursor neutropenia, are largely unknown, although genetic factors have an important role. We sought risk alleles for clozapine-associated neutropenia in a sample of 66 cases and 5583 clozapine-treated controls, through a genome-wide association study (GWAS), imputed human leukocyte antigen (HLA) alleles, exome array and copy-number variation (CNV) analyses. We then combined associated variants in a meta-analysis with data from the Clozapine-Induced Agranulocytosis Consortium (up to 163 cases and 7970 controls). In the largest combined sample to date, we identified a novel association with rs149104283 (odds ratio (OR)=4.32, P=1.79 × 10 -8 ), intronic to transcripts of SLCO1B3 and SLCO1B7, members of a family of hepatic transporter genes previously implicated in adverse drug reactions including simvastatin-induced myopathy and docetaxel-induced neutropenia. Exome array analysis identified gene-wide associations of uncommon non-synonymous variants within UBAP2 and STARD9. We additionally provide independent replication of a previously identified variant in HLA-DQB1 (OR=15.6, P=0.015, positive predictive value=35.1%). These results implicate biological pathways through which clozapine may act to cause this serious adverse effect.

  14. Genome-wide common and rare variant analysis provides novel insights into clozapine-associated neutropenia

    PubMed Central

    Legge, S E; Hamshere, M L; Ripke, S; Pardinas, A F; Goldstein, J I; Rees, E; Richards, A L; Leonenko, G; Jorskog, L F; Goldstein, Jacqueline I; Jarskog, L Fredrik; Hilliard, Chris; Alfirevic, Ana; Duncan, Laramie; Fourches, Denis; Huang, Hailiang; Lek, Monkol; Neale, Benjamin M; Ripke, Stephan; Shianna, Kevin; Szatkiewicz, Jin P; Tropsha, Alexander; van den Oord, Edwin JCG; Cascorbi, Ingolf; Dettling, Michael; Gazit, Ephraim; Goff, Donald C; Holden, Arthur L; Kelly, Deanna L; Malhotra, Anil K; Nielsen, Jimmi; Pirmohamed, Munir; Rujescu, Dan; Werge, Thomas; Levy, Deborah L; Josiassen, Richard C; Kennedy, James L; Lieberman, Jeffrey A; Daly, Mark J; Sullivan, Patrick F; Chambert, K D; Collier, D A; Genovese, G; Giegling, I; Holmans, P; Jonasdottir, A; Kirov, G; McCarroll, S A; MacCabe, J H; Mantripragada, K; Moran, J L; Neale, B M; Stefansson, H; Rujescu, D; Daly, M J; Sullivan, P F; Owen, M J; O'Donovan, M C; Walters, J T R

    2017-01-01

    The antipsychotic clozapine is uniquely effective in the management of schizophrenia; however, its use is limited by its potential to induce agranulocytosis. The causes of this, and of its precursor neutropenia, are largely unknown, although genetic factors have an important role. We sought risk alleles for clozapine-associated neutropenia in a sample of 66 cases and 5583 clozapine-treated controls, through a genome-wide association study (GWAS), imputed human leukocyte antigen (HLA) alleles, exome array and copy-number variation (CNV) analyses. We then combined associated variants in a meta-analysis with data from the Clozapine-Induced Agranulocytosis Consortium (up to 163 cases and 7970 controls). In the largest combined sample to date, we identified a novel association with rs149104283 (odds ratio (OR)=4.32, P=1.79 × 10−8), intronic to transcripts of SLCO1B3 and SLCO1B7, members of a family of hepatic transporter genes previously implicated in adverse drug reactions including simvastatin-induced myopathy and docetaxel-induced neutropenia. Exome array analysis identified gene-wide associations of uncommon non-synonymous variants within UBAP2 and STARD9. We additionally provide independent replication of a previously identified variant in HLA-DQB1 (OR=15.6, P=0.015, positive predictive value=35.1%). These results implicate biological pathways through which clozapine may act to cause this serious adverse effect. PMID:27400856

  15. Effects of clozapine on adipokine secretions/productions and lipid droplets in 3T3-L1 adipocytes.

    PubMed

    Tsubai, Tomomi; Yoshimi, Akira; Hamada, Yoji; Nakao, Makoto; Arima, Hiroshi; Oiso, Yutaka; Noda, Yukihiro

    2017-02-01

    Clozapine, a second-generation antipsychotic (SGA), is a cause of side effects related to metabolic syndrome. The participation of serotonin 5-HT 2C and histamine H 1 receptors in the central nervous system has been reported as a mechanism of the weight gain caused by clozapine. In the present study, we investigated the direct pharmacological action of clozapine on the 3T3-L1 adipocytes and compared it to that of blonanserin, an SGA with low affinity for both receptors. Short-term exposure to clozapine decreased secretion and mRNA expression of leptin. Long-term exposure decreased leptin as well as adiponectin secretion, and further increased lipid droplets accumulation. However, short- and long-term exposures to blonanserin did not affect these parameters. A selective serotonin 5-HT 2C , but not a histamine H 1 , receptor antagonist enhanced the decreased secretion of leptin induced by short-term exposure to clozapine, but did not affect the increased accumulation of lipid droplets. Our findings indicate that clozapine, but not blonanserin, strongly and directly affected the secretion of adipokines, such as leptin, in adipocytes and caused adipocyte enlargement. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  16. Association study of the HTR2C, leptin and adiponectin genes and serum marker analyses in clozapine treated long-term patients with schizophrenia.

    PubMed

    Klemettilä, J-P; Kampman, O; Seppälä, N; Viikki, M; Hämäläinen, M; Moilanen, E; Mononen, N; Lehtimäki, T; Leinonen, E

    2015-02-01

    Clozapine treatment is associated with weight gain and cardio-metabolic consequences among patients with schizophrenia. Polymorphisms of leptin, serotonin receptor HTR2C and adiponectin genes have been associated with antipsychotic-induced weight gain and metabolic comorbidity. However, the results of the studies so far are inconclusive. The aim of the present study was first to test for a possible role of serum leptin and adiponectin levels as a marker of weight gain in association with inflammatory cytokines/adipokines (IL-6, IL-1Ra, hs-CRP and adipsin), and second to study associations between SNPs LEP rs7799039 (-2548 A/G), ADIPOQ rs1501299 and HTR2C rs1414334 and weight gain and levels of leptin and adiponectin, in 190 patients with schizophrenia on clozapine treatment, with retrospectively assessed weight change and cross-sectionally measured cytokine levels. A strong association was found between serum levels of leptin and weight gain and cytokines/adipokines related to metabolic comorbidity, especially among female patients (in women leptin vs. weight gain, IL-6 and IL-1Ra, P<0.001; in men leptin vs. weight gain, P=0.026, leptin vs. IL-1Ra, P<0.001). In male patients low adiponectin level was a more specific marker of clozapine-induced weight gain (P=0.037). The results of the present study do not support a major role of SNPs LEP rs7799039, ADIPOQ rs1501299 and HTR2C rs1414334 in the regulation of weight gain or association of serum levels of leptin and adiponectin and corresponding studied SNPs in patients with schizophrenia on clozapine treatment. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  17. Genetic risk factors for clozapine-induced neutropenia and agranulocytosis in a Dutch psychiatric population.

    PubMed

    van der Weide, K; Loovers, H; Pondman, K; Bogers, J; van der Straaten, T; Langemeijer, E; Cohen, D; Commandeur, J; van der Weide, J

    2017-10-01

    Prescription of clozapine is complicated by the occurrence of clozapine-induced reduction of neutrophils. The aim of this study was to identify genetic risk factors in a population of 310 Dutch patients treated with clozapine, including 38 patients developing neutropenia and 31 patients developing agranulocytosis. NQO2 1541AA (NRH quinone oxidoreductase 2; protects cells against oxidative metabolites) was present at a higher frequency in agranulocytosis patients compared with control (23% versus 7%, P=0.03), as was ABCB1 (ABC-transporter-B1; drug efflux transporter) 3435TT (32% versus 20%, P=0.05). In patients developing neutropenia, ABCB1 3435TT and homozygosity for GSTT1 null (glutathione-S-transferase; conjugates reactive clozapine metabolites into glutathione) were more frequent compared with control (34% versus 20%, P=0.05 and 31% versus 14%, P=0.03), whereas GSTM1 null was less frequent in these patients (31% versus 52%, P=0.03). To investigate whether combinations of the identified genetic risk factors have a higher predictive value, should be confirmed in a larger case-control study.

  18. Effect of clozapine and molindone on plasma and brain levels of mescaline in mice.

    PubMed

    Shah, N S; Gulati, O D

    1984-01-01

    Levels of unchanged mescaline were examined in the plasma and brain of albino Swiss-Webster mice pretreated with various doses of either clozapine or molindone. In clozapine treated mice, the mescaline levels were statistically significantly higher at 2 and 3 h with 7.5 and 15.0 mg/kg and at 1, 2 and 3 h with 30 mg/kg. Molindone at 4.0 and 8.0 mg/kg produced no significant effect; at 16.0 and 48.0 mg/kg, the levels were significantly higher at 1 and 2 h. Elevated brain levels of mescaline by clozapine and molindone indicate an adverse metabolic interaction between a hallucinogen and drugs that are commonly used to treat mescaline-induced psychosis.

  19. Inhibition of recombinant Ca(v)3.1 (alpha(1G)) T-type calcium channels by the antipsychotic drug clozapine.

    PubMed

    Choi, Kee-Hyun; Rhim, Hyewhon

    2010-01-25

    Low voltage-activated T-type calcium channels are involved in the regulation of the neuronal excitability, and could be subject to many antipsychotic drugs. The effects of clozapine, an atypical antipsychotic drug, on recombinant Ca(v)3.1 T-type calcium channels heterologously expressed in human embryonic kidney 293 cells were examined using whole-cell patch-clamp recordings. At a standard holding potential of -100 mV, clozapine inhibited Ca(v)3.1 currents with an IC(50) value of 23.7+/-1.3 microM in a use-dependent manner. However, 10 microM clozapine inhibited more than 50% of the Ca(v)3.1 currents in recordings at a more physiologically relevant holding potential of -75 mV. Clozapine caused a significant hyperpolarizing shift in the steady-state inactivation curve of the Ca(v)3.1 channels, which is presumably the main mechanism accounting for the inhibition of the Ca(v)3.1 currents. In addition, clozapine slowed Ca(v)3.1 deactivation and inactivation kinetics but not activation kinetics. Clozapine-induced changes in deactivation and inactivation rates of the Ca(v)3.1 channel gating would likely facilitate calcium influx via Ca(v)3.1 T-type calcium channels. Thus, clozapine may exert its therapeutic and/or side effects by altering cell's excitability and firing properties through actions on T-type calcium channels.

  20. Addition of aripiprazole to the clozapine may be useful in reducing anxiety in treatment-resistant schizophrenia.

    PubMed

    Chanachev, Aleksandar; Ansermot, Nicolas; Crettol Wavre, Séverine; Nowotka, Ute; Stamatopoulou, Maria-Eleni; Conus, Philippe; Eap, Chin B

    2011-01-01

    There exist many case reports and studies on the antipsychotic augmentation by aripirazole in partial responders to clozapine, the most seem to be finding a slight difference in the PANSS and CGI scores after the aripirazole addition. The results of our report are compatible with those of other studies but, we have found a considerable antianxiety action in both of the cases. The 5HT1A agonism of aripirazole could be hypothesized as mechanism contributing to this effect.

  1. LORETA functional imaging in antipsychotic-naive and olanzapine-, clozapine- and risperidone-treated patients with schizophrenia.

    PubMed

    Tislerova, Barbora; Brunovsky, Martin; Horacek, Jiri; Novak, Tomas; Kopecek, Miloslav; Mohr, Pavel; Krajca, Vladimír

    2008-01-01

    The aim of our study was to detect changes in the distribution of electrical brain activity in schizophrenic patients who were antipsychotic naive and those who received treatment with clozapine, olanzapine or risperidone. We included 41 subjects with schizophrenia (antipsychotic naive = 11; clozapine = 8; olanzapine = 10; risperidone = 12) and 20 healthy controls. Low-resolution brain electromagnetic tomography was computed from 19-channel electroencephalography for the frequency bands delta, theta, alpha-1, alpha-2, beta-1, beta-2 and beta-3. We compared antipsychotic-naive subjects with healthy controls and medicated patients. (1) Comparing antipsychotic-naive subjects and controls we found a general increase in the slow delta and theta frequencies over the fronto-temporo-occipital cortex, particularly in the temporolimbic structures, an increase in alpha-1 and alpha-2 in the temporal cortex and an increase in beta-1 and beta-2 in the temporo-occipital and posterior limbic structures. (2) Comparing patients who received clozapine and those who were antipsychotic naive, we found an increase in delta and theta frequencies in the anterior cingulate and medial frontal cortex, and a decrease in alpha-1 and beta-2 in the occipital structures. (3) Comparing patients taking olanzapine with those who were antipsychotic naive, there was an increase in theta frequencies in the anterior cingulum, a decrease in alpha-1, beta-2 and beta-3 in the occipital cortex and posterior limbic structures, and a decrease in beta-3 in the frontotemporal cortex and anterior cingulum. (4) In patients taking risperidone, we found no significant changes from those who were antipsychotic naive. Our results in antipsychotic-naive patients are in agreement with existing functional findings. Changes in those taking clozapine and olanzapine versus those who were antipsychotic naive suggest a compensatory mechanism in the neurobiological substrate for schizophrenia. The lack of difference in

  2. Clozapine-associated neutropenia and agranulocytosis in Argentina (2007-2012).

    PubMed

    Balda, María V; Garay, Osvaldo U; Papale, Rosa M; Bignone, Inés; Bologna, Viviana G; Brandolini, Andrés; Prokopez, Cintia R; Balasini, Juan I; Baldessarini, Ross J; Daray, Federico M

    2015-03-01

    The risks of severe leukopenia and agranulocytosis have varied over time and among geographical regions and cultures, with little information available on South American populations. Accordingly, we reviewed and analyzed data from a 6-year experience monitored by an Argentine national registry to which reporting of adverse events reports is required. We analyzed data for 2007-2012 from the pharmacovigilance program of the Argentine drug-regulatory agency (ANMAT) using standard bivariate and multivariate statistical methods and survival analysis. We identified 378 cases of adverse hematological events over 6 years among an average of 12 305 individuals/year treated with clozapine (308±133 mg/day) to estimate the mean annualized rates of leukopenia [0.19 (95% confidence interval [CI] 0.11-0.27)], neutropenia [0.38 (95% CI 0.34-0.43)], and agranulocytosis [0.05 (95% CI 0.02-0.08)] % per year [median latency 2 (95% CI 1.3-2.1) months]; fatalities related to agranulocytosis averaged 4.2 (95% CI 0.0-9.2) per 100 000 treated individuals/year. Factors associated significantly and independently with agranulocytosis were female sex, older age, and use of other drugs in addition to clozapine. With monitoring by international standards, recent risks of clozapine-associated agranulocytosis in Argentina were lower, but fatality rates were higher than that in other regions of the world. Risk factors include the use of multiple psychotropic drugs, female sex, and older age.

  3. Clozapine protects PC-12 cells from death due to oxidative stress induced by hydrogen peroxide via a cell-type specific mechanism involving inhibition of extracellular signal-regulated kinase phosphorylation.

    PubMed

    Magliaro, Brian C; Saldanha, Colin J

    2009-08-04

    Recent evidence suggests that some atypical antipsychotic drugs may protect against oxidative stress and consequent neurodegeneration by mechanisms that remain unclear. Using the neuron-like rat pheochromocytoma (PC-12) cell line, Clozapine and N-desmethylclozapine were tested for their ability to protect against cell death due to oxidative stress induced by hydrogen peroxide (H(2)O(2)). These drugs demonstrated significant protection of PC-12 cells, as measured by both the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide (MTT) and Alamar Blue cell viability assays. However, neither viability assay detected a protective effect of Clozapine on human embryonic kidney (HEK293), rat primary cortical neurons, or human neuroblastoma (SH-SY5Y) exposed to H(2)O(2) treatment. The mechanism of protection involves a PC-12 cell-specific differential response to H(2)O(2) treatment vs. the other cell lines. Pre-treatment with 250 microM or 125 microM diethyldithiocarbamate (DETC), a superoxide dismutase (SOD) inhibitor, unexpectedly showed protection of the PC-12 cells from H(2)O(2) treatment. Western blots revealed that Clozapine, N-desmethylclozapine, and DETC reduce the phosphorylation of extracellular signal-regulated kinase (ERK) that is caused by H(2)O(2) exposure in PC-12 cells. In both HEK293 and SH-SY5Y cells, H(2)O(2) exposure did not increase ERK phosphorylation over control, demonstrating a different response to H(2)O(2) vs. PC-12 cells, and explaining why Clozapine could not protect these cells. Also, U0126, a specific MEK inhibitor, was able to protect PC-12 cells from H(2)O(2) exposure, showing that inhibiting ERK phosphorylation is sufficient to provide protection. Cumulatively, these results indicate that Clozapine, N-desmethylclozapine, DETC, and U0126 protect PC-12 cells by blocking the cell-type specific H(2)O(2) induced increase in ERK phosphorylation.

  4. Addition of Aripiprazole to the Clozapine May Be Useful in Reducing Anxiety in Treatment-Resistant Schizophrenia

    PubMed Central

    Chanachev, Aleksandar; Ansermot, Nicolas; Crettol Wavre, Séverine; Nowotka, Ute; Stamatopoulou, Maria-Eleni; Conus, Philippe; Eap, Chin B.

    2011-01-01

    There exist many case reports and studies on the antipsychotic augmentation by aripirazole in partial responders to clozapine, the most seem to be finding a slight difference in the PANSS and CGI scores after the aripirazole addition. The results of our report are compatible with those of other studies but, we have found a considerable antianxiety action in both of the cases. The 5HT1A agonism of aripirazole could be hypothesized as mechanism contributing to this effect. PMID:22937411

  5. Attenuation of acute d-amphetamine-induced disruption of conflict resolution by clozapine, but not α-flupenthixol in rats.

    PubMed

    Reichelt, Amy C; Good, Mark A; Killcross, Simon

    2013-11-01

    Previous research demonstrates that disruption of forebrain dopamine systems impairs the use of high-order information to guide goal-directed performance, and that this deficit may be related to impaired use of task-setting cues in patients with schizophrenia. Such deficits can be interrogated through conflict resolution, which has been demonstrated to be sensitive to prefrontal integrity in rodents. We sought to examine the effects of acute systemic d-amphetamine administration on the contextual control of response conflict in rats, and whether deficits were reversed through pre-treatment with clozapine or the D₁/D₂ antagonist α-flupenthixol. Acute d-amphetamine (1.5 mg/kg) disrupted the utilisation of contextual cues; therefore rats were impaired during presentation of stimulus compounds that require conflict resolution. Evidence suggested that this effect was attenuated through pre-treatment with the atypical antipsychotic clozapine (5.0 mg/kg), but not the typical antipsychotic α-flupenthixol (0.25 mg/kg), at doses previously shown to attenuate d-amphetamine-induced cognitive deficits. These studies therefore demonstrate a potentially viable model of disrupted executive function such as that seen in schizophrenia.

  6. Clozapine and Olanzapine Exhibit an Intrinsic Anxiolytic Property in Two Conditioned Fear Paradigms: Contrast with Haloperidol and Chlordiazepoxide

    PubMed Central

    Mead, Alexa; Li, Ming; Kapur, Shitij

    2008-01-01

    Psychotic fear and anxiety disturbances are seen at a relatively high frequency in patients with schizophrenia. Atypical antipsychotics are believed to show superior efficacy in reducing these symptoms. However, clinical and preclinical evidence regarding their anxiolytic efficacy has been mixed. In this study, we evaluated the possible anxiolytic property of two atypicals clozapine and olanzapine and compared them with typical haloperidol and chlordiazepoxide (a prototype of sedative-anxiolytic drug) in two preclinical models of fear. In Experiment 1, we used a fear-induced passive avoidance and conditioned place aversion paradigm and examined the effects of clozapine (20 mg/kg, sc), haloperidol (0.05 mg/kg, sc) and chlordiazepoxide (10 mg/kg, ip). In Experiments 2 and 3, we used a two-way active avoidance conditioning paradigm and further compared the effects of clozapine (20 mg/kg, sc), haloperidol (0.05 mg/kg, sc), chlordiazepoxide (10 mg/kg, ip) and three doses of olanzapine (0.5, 1.0, and 2.0 mg/kg, sc). Results show that clozapine and chlordiazepoxide, but not haloperidol, significantly attenuated the shock conditioning-induced place aversion, decreased the amount of defecations and the number of the 22 kHz vocalizations. Clozapine also reduced the shock conditioning-induced hyperthermia. Similar to clozapine, olanzapine also significantly decreased the amount of defecations and reduced the shock conditioning-induced hyperthermia, but it did not inhibit the 22 kHz vocalizations. This study demonstrates that clozapine and olanzapine possess an intrinsic anxiolytic property, which is not attributable to its superior anti-“psychotic” effect or its favorable effects on motor functions or learning and memory processes. These findings also suggest that the combined use of passive avoidance and active avoidance conditioning models can be useful in better differentiating typical and atypical antipsychotics as well as anxiolytics. PMID:18547622

  7. Testing the hypothesis that vitamin C deficiency is a risk factor for clozapine-induced agranulocytosis using guinea pigs and ODS rats.

    PubMed

    Ip, Julia; Wilson, John X; Uetrecht, Jack P

    2008-04-01

    The use of clozapine is limited by a relatively high incidence of drug-induced agranulocytosis. Clozapine is oxidized by bone marrow cells to a reactive nitrenium ion. Although many idiosyncratic drug reactions are immune-mediated, the fact that patients with a history of clozapine-induced agranulocytosis do not immediately develop agranulocytosis on rechallenge suggests that some other factor may be responsible for the idiosyncratic nature of this reaction. The reactive nitrenium ion is very rapidly reduced back to clozapine by vitamin C, and many schizophrenic patients are vitamin C deficient. We set out to test the hypothesis that vitamin C deficiency is a major risk factor for clozapine-induced agranulocytosis using a vitamin C deficient guinea pig model. Although the vitamin C deficient guinea pigs did not develop agranulocytosis, the amount of clozapine covalent binding in these animals was less than we had previously observed in samples from rats and humans. Therefore, we studied ODS rats that also cannot synthesize vitamin C. Vitamin C deficient ODS rats also did not develop agranulocytosis, and furthermore, although covalent binding in the bone marrow was greater than that in the guinea pig, it was not increased in the vitamin C deficient ODS rats relative to ODS rats that had adequate vitamin C in their diet. Therefore, it is very unlikely that vitamin C deficiency is a major risk factor for clozapine-induced agranulocytosis.

  8. Hypochondriasis and obsessive-compulsive disorder in schizophrenic patients treated with clozapine vs other atypical antipsychotics.

    PubMed

    Grassi, Giacomo; Poli, Lorenzo; Cantisani, Andrea; Righi, Lorenzo; Ferrari, Gabriella; Pallanti, Stefano

    2014-08-01

    The aim of the study was to investigate the prevalence rates of obsessive-compulsive disorder (OCD) and hypochondriasis in schizophrenic patients treated with atypical antipsychotics (AAPs) and to investigate the different comorbidity rates of OCD and hypochondriasis between clozapine-treated patients and patients treated with other AAPs. We therefore recruited 60 schizophrenic patients treated with clozapine or other AAPs. We assessed the prevalence rates of OCD or OC symptoms and hypochondriasis or hypochondriac symptoms in the whole group of patients and in clozapine-treated patients versus patients treated with other AAPs. Schizophrenic patients had a higher comorbidity rate of OCD (26.6% vs 1-3%) and hypochondriasis (20% vs 1%) than the general population. These comorbidities were more frequent in schizophrenic patients treated with clozapine versus patients treated with other AAPs (36.7% vs 16.7% and 33.3% vs 6.7%). Clozapine-treated patients showed a higher mean Y-BOCS and HY-BOCS score when compared to patients treated with other AAPs (10.90 vs 5.90, p = .099; 15.40 vs 8.93, p = .166). A statistical significant correlation was found between the Y-BOCS and HY-BOCS scores of the whole group (r = .378, p = 0.03). Furthermore, we found an inverse correlation between the global level of functioning and the diagnosis of hypochondriasis (p = .048) and the severity of hypochondriac symptoms (p = .047). Hypochondriasis could represent an important clinical feature of schizophrenic patients treated with atypical antipsychotics, and further research is needed in this field.

  9. Clozapine, Diabetes Mellitus, Cardiovascular Risk and Mortality: Results of a 21-year Naturalistic Study in Patients with Schizophrenia and Schizoaffective Disorder.

    PubMed

    Nemani, Katlyn L; Greene, M Claire; Ulloa, Melissa; Vincenzi, Brenda; Copeland, Paul M; Al-Khadari, Sulaiman; Henderson, David C

    2017-11-22

    The goal of this 21-year naturalistic study of clozapine treated patients was to examine the cardiovascular risk factors following clozapine initiation and resultant mortality estimates from cardiovascular disease. Data was collected from medical records of clozapine treated patients with schizophrenia or schizoaffective disorder from January 1992 to February 2012. Demographics, clozapine dosage and laboratory results were extracted at 12-month intervals. At clozapine initiation, the mean age of 96 patients was 36.4 years ±7.6 years; N=27(28%) were women. The mean duration of clozapine use was 13 years. The Kaplan-Meier estimate for 21-year cardiovascular events was 29%, while the Kaplan-Meier estimate for 21-year mortality from cardiovascular disease was 10%. The mean cardiovascular risk increased during the first ten years (p<.01), while a slight decrease occurred beyond ten years (p<.01). Patients involved in cardiometabolic research showed a greater decrease in cardiovascular risk factors over 21 years (p = .05). The Kaplan-Meier estimate for 21-year all-cause mortality was 22%. Forty-one patients were diagnosed with diabetes (42.7%), compared to a nationwide prevalence of 13.7% in a similar age group. These results support the hypothesis that clozapine-treated patients are at risk for cardiovascular events and death secondary to an increased risk of medical disorders. Interventions that target weight loss, smoking cessation, and lipid profile improvement may alleviate the increased risk of cardiovascular mortality.

  10. Leukocyte telomere length in Hispanic schizophrenia patients under treatment with olanzapine.

    PubMed

    Monroy-Jaramillo, Nancy; Rodríguez-Agudelo, Yaneth; Aviña-Cervantes, Luis Carlos; Roberts, David L; Velligan, Dawn I; Walss-Bass, Consuelo

    2017-07-01

    Different lines of evidence indicate that patients with schizophrenia (SZ) exhibit accelerated aging. Leukocyte telomere length (TL), an aging marker, is associated with age-related and chronic pathologies, including schizophrenia. We analyzed leukocyte TL in 170 SZ patients of Hispanic ancestry grouped based on antipsychotic treatment, compared to 126 matched controls. The group under treatment with atypical antipsychotics was further subdivided according to the risk of medication to cause metabolic syndrome (MetS). Our results show significant erosion in the TL of SZ patients under treatment with the atypical antipsychotics clozapine and olanzapine, which cause high-risk for MetS, compared to healthy controls and patients under treatment with medium and low-risk antipsychotics. However, when the analysis was done separately for clozapine and olanzapine, a significant difference remained only for olanzapine. These findings suggest that atypical antipsychotics that cause high-risk for MetS, particularly olanzapine, may modulate leukocyte TL in SZ patients. Future research is required to elucidate if in fact atypical antipsychotics are involved in TL maintenance in SZ subjects and the mechanism by which this occurs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Measurement of Clozapine, Norclozapine, and Amisulpride in Plasma and in Oral Fluid Obtained Using 2 Different Sampling Systems.

    PubMed

    Fisher, Danielle S; Beyer, Chad; van Schalkwyk, Gerrit; Seedat, Soraya; Flanagan, Robert J

    2017-04-01

    There is a poor correlation between total concentrations of proton-accepting compounds (most basic drugs) in unstimulated oral fluid and in plasma. The aim of this study was to compare clozapine, norclozapine, and amisulpride concentrations in plasma and in oral fluid collected using commercially available collection devices [Thermo Fisher Scientific Oral-Eze and Greiner Bio-One (GBO)]. Oral-Eze and GBO samples and plasma were collected in that order from patients prescribed clozapine. Analyte concentrations were measured by liquid chromatography-tandem mass spectrometry. There were 112 participants [96 men, aged (median, range) 47 (21-65) years and 16 women, aged 44 (21-65) years]: 74 participants provided 2 sets of samples and 7 provided 3 sets (overall 2 GBO samples not collected). Twenty-three patients were co-prescribed amisulpride, of whom 17 provided 2 sets of samples and 1 provided 3 sets. The median (range) oral fluid within the GBO samples was 52 (13%-86%). Nonadherence to clozapine was identified in all 3 samples in one instance. After correction for oral fluid content, analyte concentrations in the GBO and Oral-Eze samples were poorly correlated with plasma clozapine and norclozapine (R = 0.57-0.63) and plasma amisulpride (R = 0.65-0.72). Analyte concentrations in the 2 sets of oral fluid samples were likewise poorly correlated (R = 0.68-0.84). Mean (SD) plasma clozapine and norclozapine were 0.60 (0.46) and 0.25 (0.21) mg/L, respectively. Mean clozapine and norclozapine concentrations in the 2 sets of oral fluid samples were similar to those in plasma (0.9-1.8 times higher), that is, approximately 2- to 3-fold higher than those in unstimulated oral fluid. The mean (±SD) amisulpride concentrations (microgram per liter) in plasma (446 ± 297) and in the Oral-Eze samples (501 ± 461) were comparable and much higher than those in the GBO samples (233 ± 318). Oral fluid collected using either the GBO system or the Oral-Eze system cannot be used for

  12. The association between season of birth, age at onset, and clozapine use in schizophrenia.

    PubMed

    Kim, J S; Park, C M; Choi, J A; Park, E; Tchoe, H J; Choi, M; Suh, J K; Kim, Y H; Won, S H; Chung, Y C; Bae, K Y; Lee, S K; Park, S C; Lee, S H

    2017-11-01

    This study aimed to determine whether the rate of clozapine use, an indicator of refractoriness in schizophrenia, is associated with the season of birth and age at onset in patients with schizophrenia based on nationwide data. Patients with schizophrenia (n = 114 749) who received prescriptions for antipsychotic medication between 2008 and 2014 were retrospectively identified from the Korean National Health Insurance Service database. The study population was divided into three groups based on their age at the onset of schizophrenia (early, middle, and late onset). We assessed differences in the month of birth between patients and the general population. In addition, the cumulative clozapine use was calculated. Compared to the late-onset schizophrenia group, the early- and middle-onset groups showed a higher probability of birth during the winter season. In addition, the early-onset group showed the highest cumulative clozapine use rate. In the middle-onset group, the initiation of clozapine use was significantly earlier for patients born in winter compared to those born in summer. Our results indicate that the age at onset is an important factor in predicting the prognosis of schizophrenia patients. The season of birth also affects the prognosis, but with less robustness. Specifically, it appears that early disease onset and winter birth might be associated with poor outcomes in Korean patients with schizophrenia. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. The Atypical Antipsychotic Agent, Clozapine, Protects Against Corticosterone-Induced Death of PC12 Cells by Regulating the Akt/FoxO3a Signaling Pathway.

    PubMed

    Zeng, Zhiwen; Wang, Xue; Bhardwaj, Sanjeev K; Zhou, Xuanhe; Little, Peter J; Quirion, Remi; Srivastava, Lalit K; Zheng, Wenhua

    2017-07-01

    Schizophrenia is one of the most severe psychiatric disorders. Increasing evidence implicates that neurodegeneration is a component of schizophrenia pathology and some atypical antipsychotics are neuroprotective and successful in slowing the progressive morphological brain changes. As an antipsychotic agent, clozapine has superior and unique effects, but the intracellular signaling pathways that mediate clozapine action remain to be elucidated. The phosphatidylinositol-3-kinase/protein kinase B/Forkhead box O3 (PI3K/Akt/FoxO3a) pathway is crucial for neuronal survival. However, little information is available regarding this pathway with clozapine. In the present study, we investigated the protective effect of clozapine on the PC12 cells against corticosterone toxicity. Our results showed that corticosterone decreases the phosphorylation of Akt and FoxO3a, leading to the nuclear localization of FoxO3a and the apoptosis of PC12 cells, while clozapine concentration dependently protected PC12 cells against corticosterone insult. Pathway inhibitors studies displayed that the protective effect of clozapine was reversed by LY294002 and wortmannin, two PI3K inhibitors, or Akt inhibitor VIII although several other inhibitors had no effect. The shRNA knockdown results displayed that downregulated Akt1 or FoxO3a attenuated the protective effect of clozapine. Western blot analyses revealed that clozapine induced the phosphorylation of Akt and FoxO3a by the PI3K/Akt pathway and reversed the reduction of the phosphorylated Akt and FoxO3a and the nuclear translocation of FoxO3a evoked by corticosterone. Together, our data indicates that clozapine protects PC12 cells against corticosterone-induced cell death by modulating activity of the PI3K/Akt/FoxO3a pathway.

  14. Neuroimaging findings in treatment-resistant schizophrenia: a systematic review

    PubMed Central

    Nakajima, Shinichiro; Takeuchi, Hiroyoshi; Plitman, Eric; Fervaha, Gagan; Gerretsen, Philip; Caravaggio, Fernando; Chung, Jun Ku; Iwata, Yusuke; Remington, Gary; Graff-Guerrero, Ariel

    2015-01-01

    Background Recent developments in neuroimaging have advanced understanding biological mechanisms underlying schizophrenia. However, neuroimaging correlates of treatment-resistant schizophrenia (TRS) and superior effects of clozapine on TRS remain unclear. Methods Systematic search was performed to identify neuroimaging characteristics unique to TRS and ultra-resistant schizophrenia (i.e. clozapine-resistant [URS]), and clozapine's efficacy in TRS using Embase, Medline, and PsychInfo. Search terms included (schizophreni*) and (resistan* OR refractory OR clozapine) and (ASL OR CT OR DTI OR FMRI OR MRI OR MRS OR NIRS OR PET OR SPECT). Results 25 neuroimaging studies have investigated TRS and effects of clozapine. Only 5 studies have compared TRS and non-TRS, collectively providing no replicated neuroimaging finding specific to TRS. Studies comparing TRS and healthy controls suggest hypometabolism in the prefrontal cortex, hypermetabolism in the basal ganglia, and structural anomalies in the corpus callosum contribute to TRS. Clozapine may increase prefrontal hypoactivation in TRS although this was not related to clinical improvement; in contrast, evidence has suggested a link between clozapine efficacy and decreased metabolism in the basal ganglia and thalamus. Conclusion Existing literature does not elucidate neuroimaging correlates specific to TRS or URS, which, if present, might also shed light on clozapine's efficacy in TRS. This said, leads from other lines of investigation, including the glutamatergic system can prove useful in guiding future neuroimaging studies focused on, in particular, the frontocortical-basal ganglia-thalamic circuits. Critical to the success of this work will be precise subtyping of study subjects based on treatment response/nonresponse and the use of multimodal neuroimaging. PMID:25684554

  15. Waist Circumference Is the Best Anthropometric Predictor for Insulin Resistance in Nondiabetic Patients with Schizophrenia Treated with Clozapine But Not Olanzapine

    PubMed Central

    Henderson, David C.; Fan, Xiaoduo; Sharma, Bikash; Copeland, Paul M.; Borba, Christina P.C.; Freudenreich, Oliver; Cather, Corey; Evins, A. Eden; Goff, Donald C.

    2010-01-01

    The goal of this study was to evaluate which anthropometric measure (human body measurement) best predicts insulin resistance measured by the insulin sensitivity index (SI) and the homeostasis model of assessment of insulin resistance (HOMA-IR) in nondiabetic patients with schizophrenia patients treated with clozapine or olanzapine. Methods We conducted a cross-sectional study of nondiabetic subjects with schizophrenia being treated with olanzapine or clozapine using a frequently sampled intravenous glucose tolerance test, nutritional assessment, and anthropometric measures to assess the relationship between anthropometric measures and insulin resistance. Results No difference was found between the groups treated with clozapine and olanzapine in age, gender, race, body mass index (BMI), waist circumference (WC), lipid levels, HOMA-IR, or SI. The disposition index (SI × the acute insulin response to glucose), which measures how the body compensates for insulin resistance to maintain a normal glucose level, was significantly lower in the group treated with clozapine than in the group treated with olanzapine (1067 ± 1390 vs. 2521 ± 2805; p = 0.013), suggesting that the subjects treated with clozapine had a reduced compensatory response to IR compared with the subjects treated with olanzapine. In the clozapine group, both higher WC and BMI were significantly associated with elevated HOMA-IR and lower SI; however, WC was a stronger correlate of IR than BMI, as measured by SI (−0.50 vs. −0.40). In the olanzapine group, neither WC nor BMI was significantly associated with any measure of glucose metabolism. Conclusions In this study, WC was the single best anthropometric surrogate for predicting IR in patients treated with clozapine but not olanzapine. The results suggest that WC may be a valuable screening tool for predicting IR in patients with schizophrenia being treated with clozapine who are at relatively higher risk of developing the metabolic syndrome, type 2

  16. Clozapine Reverses Phencyclidine-Induced Desynchronization of Prefrontal Cortex through a 5-HT1A Receptor-Dependent Mechanism

    PubMed Central

    Kargieman, Lucila; Riga, Maurizio S; Artigas, Francesc; Celada, Pau

    2012-01-01

    The non-competitive NMDA receptor (NMDA-R) antagonist phencyclidine (PCP)—used as a pharmacological model of schizophrenia—disrupts prefrontal cortex (PFC) activity. PCP markedly increased the discharge rate of pyramidal neurons and reduced slow cortical oscillations (SCO; 0.15–4 Hz) in rat PFC. Both effects were reversed by classical (haloperidol) and atypical (clozapine) antipsychotic drugs. Here we extended these observations to mice brain and examined the potential involvement of 5-HT2A and 5-HT1A receptors (5-HT2AR and 5-HT1AR, respectively) in the reversal by clozapine of PCP actions. Clozapine shows high in vitro affinity for 5-HT2AR and behaves as partial agonist in vivo at 5-HT1AR. We used wild-type (WT) mice and 5-HT1AR and 5-HT2AR knockout mice of the same background (C57BL/6) (KO-1A and KO-2A, respectively). Local field potentials (LFPs) were recorded in the PFC of WT, KO-1A, and KO-2A mice. PCP (10 mg/kg, intraperitoneally) reduced SCO equally in WT, KO-2A, and KO-1A mice (58±4%, 42±7%, and 63±7% of pre-drug values, n=23, 13, 11, respectively; p<0.0003). Clozapine (0.5 mg/kg, intraperitoneally) significantly reversed PCP effect in WT and KO-2A mice, but not in KO-1A mice nor in WT mice pretreated with the selective 5-HT1AR antagonist WAY-100635.The PCP-induced disorganization of PFC activity does not appear to depend on serotonergic function. However, the lack of effect of clozapine in KO-1A mice and the prevention by WAY-100635 indicates that its therapeutic action involves 5-HT1AR activation without the need to block 5-HT2AR, as observed with clozapine-induced cortical dopamine release. PMID:22012474

  17. Effectiveness of electroconvulsive therapy in patients with treatment resistant schizophrenia: A retrospective study.

    PubMed

    Grover, Sandeep; Chakrabarti, Subho; Hazari, Nandita; Avasthi, Ajit

    2017-03-01

    This study aimed to evaluate the effectiveness of electroconvulsive therapy (ECT) among patients with treatment resistant schizophrenia (TRS). Records of patients who had received ECT were reviewed to identify patients with TRS who were administered ECT in combination with clozapine. Socio-demographic, clinical data and ECT details were extracted. The most common diagnosis was of paranoid schizophrenia (49%) followed by undifferentiated schizophrenia (36%). A-fifth (22%) of the patients were judged to have poor response to clozapine. The mean number of ECTs given were 13.97 (SD-7.67) and mean clozapine dose was 287.5mgs/day (SD-100.1). About two-thirds (63%) of the patients showed >30% reduction in scores on different symptom-rating scales with combined use of clozapine and ECT. Among clozapine non-responders, approximately 69% responded to the combination. Post-ECT rise in blood pressure was the most common side effect (16.9%) followed by prolonged seizures (7%). Long-term follow-up data was available for 47 out of the 59 patients. More than two-third (N=34; 72%) followed-up for an average of 30 months (SD 32.3; range: 1-120), maintained well with continued clozapine treatment. To conclude, results of this study further endorse the effectiveness, safety and long-term benefits of the clozapine-ECT combination in TRS and clozapine-refractory schizophrenia. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  18. Effect of clozapine on locomotor activity and anxiety-related behavior in the neonatal mice administered MK-801.

    PubMed

    Pınar, Neslihan; Akillioglu, Kubra; Sefil, Fatih; Alp, Harun; Sagir, Mustafa; Acet, Ahmet

    2015-08-11

    Atypical antipsychotics have been used to treat fear and anxiety disturbance that are highly common in schizophrenic patients. It is suggested that disruptions of N-methyl-d-aspartate (NMDA)-mediated transmission of glutamate may underlie the pathophysiology of schizophrenia. The present study was conducted to analyze the effectiveness of clozapine on the anxiety-related behavior and locomotor function of the adult brain, which had previously undergone NMDA receptor blockade during a developmental period. In order to block the NMDA receptor, male mice were administered 0.25 mg/kg of MK-801 on days 7 to 10 postnatal. In adulthood, they were administered intraperitoneally 0.5 mg/kg of clozapine and tested with open-field and elevated plus maze test, to assess their emotional behavior and locomotor activity. In the group receiving MK-801 in the early developmental period the elevated plus maze test revealed a reduction in the anxiety-related behavior (p<0.05), while the open-field test indicated a decrease in locomotor activity (p<0.01). Despite these reductions, clozapine could not reverse the NMDA receptor blockade. Also, as an atypical antipsychotic agent, clozapine could not reverse impairment in the locomotor activity and anxiety-related behavior, induced by administration of the MK-801 in neonatal period.

  19. Effect of clozapine on locomotor activity and anxiety-related behavior in the neonatal mice administered MK-801

    PubMed Central

    Pinar, Neslihan; Akillioglu, Kubra; Sefil, Fatih; Alp, Harun; Sagir, Mustafa; Acet, Ahmet

    2015-01-01

    Atypical antipsychotics have been used to treat fear and anxiety disturbance that are highly common in schizophrenic patients. It is suggested that disruptions of N-methyl-d-aspartate (NMDA)-mediated transmission of glutamate may underlie the pathophysiology of schizophrenia. The present study was conducted to analyze the effectiveness of clozapine on the anxiety-related behavior and locomotor function of the adult brain, which had previously undergone NMDA receptor blockade during a developmental period. In order to block the NMDA receptor, male mice were administered 0.25 mg/kg of MK-801 on days 7 to 10 postnatal. In adulthood, they were administered intraperitoneally 0.5 mg/kg of clozapine and tested with open-field and elevated plus maze test, to assess their emotional behavior and locomotor activity. In the group receiving MK-801 in the early developmental period the elevated plus maze test revealed a reduction in the anxiety-related behavior (p<0.05), while the open-field test indicated a decrease in locomotor activity (p<0.01). Despite these reductions, clozapine could not reverse the NMDA receptor blockade. Also, as an atypical antipsychotic agent, clozapine could not reverse impairment in the locomotor activity and anxiety-related behavior, induced by administration of the MK-801 in neonatal period. PMID:26295298

  20. Risk Factors for Neutropenia in Clozapine-Treated Children and Adolescents with Childhood-Onset Schizophrenia

    PubMed Central

    Maher, Kristin N.; Tan, Marcus; Tossell, Julia W.; Weisinger, Brian; Gochman, Peter; Miller, Rachel; Greenstein, Deanna; Overman, Gerald P.; Rapoport, Judith L.

    2013-01-01

    Abstract Objective The purpose of this study was to retrospectively analyze rates of neutropenia and risk factors for neutropenia in hospitalized children and adolescents treated with clozapine. Methods A retrospective chart review was conducted for all patients who received clozapine at any time during a hospitalization at the National Institute of Mental Health (NIMH) between 1990 and 2011. All patients satisfied screening criteria for the NIMH childhood-onset schizophrenia study, including onset of psychosis before the age of 13 years. Absolute neutrophil count (ANC) values recorded during inpatient hospitalization were extracted for 87 eligible patients with a mean age of 13.35±2.46 years at hospitalization and a mean length of stay of 117±43 days. Results Mild neutropenia only (lowest ANC<2000/mm3 but>1500/mm3) was observed in 27 (31%) patients and moderate neutropenia (any ANC<1500/mm3) was observed in 17 (20%) patients. There were no cases of agranulocytosis or severe infection. Significant risk factors for mild neutropenia compared with no hematologic adverse effects (HAEs) were male gender (p=0.012) and younger age (p<0.001). Male gender was also a significant risk factor for moderate neutropenia compared with no HAEs (p=0.003). If a child of African American ethnicity developed neutropenia during hospitalization at all that child was significantly more likely to develop moderate neutropenia than mild neutropenia only (p=0.017). African American boys had the highest rate of moderate neutropenia at 47%. Sixteen of the 17 patients exhibiting moderate neutropenia were successfully treated with clozapine by the time of discharge; 8 of these 16 required adjunctive lithium carbonate administration to maintain ANC>2000/mm3. Conclusions Our study shows that the rates of neutropenia in clozapine-treated children and adolescents are considerably higher than in the adult population. Younger age, African American ethnicity, and male gender were significant risk

  1. Relation of the Allelic Variants of Multidrug Resistance Gene to Agranulocytosis Associated With Clozapine.

    PubMed

    Anıl Yağcioğlu, A Elif; Yoca, Gökhan; Ayhan, Yavuz; Karaca, R Özgür; Çevik, Lokman; Müderrisoğlu, Ahmet; Göktaş, Mustafa T; Eni, Nurhayat; Yazıcı, M Kâzım; Bozkurt, Atilla; Babaoğlu, Melih O

    2016-06-01

    Clozapine use is associated with leukopenia and more rarely agranulocytosis, which may be lethal. The drug and its metabolites are proposed to interact with the multidrug resistance transporter (ABCB1/MDR1) gene product, P-glycoprotein (P-gp). Among various P-glycoprotein genetic polymorphisms, nucleotide changes in exons 26 (C3435T), 21 (G2677T), and 12 (C1236T) have been implicated for changes in pharmacokinetics and pharmacodynamics of many substrate drugs. In this study, we aimed to investigate the association between these specific ABCB1 polymorphisms and clozapine-associated agranulocytosis (CAA). Ten patients with a history of CAA and 91 control patients without a history of CAA, despite 10 years of continuous clozapine use, were included. Patient recruitment and blood sample collection were conducted at the Hacettepe University Faculty of Medicine, Department of Psychiatry, in collaboration with the members of the Schizophrenia and Other Psychotic Disorders Section of the Psychiatric Association of Turkey, working in various psychiatry clinics. After DNA extraction from peripheral blood lymphocytes, genotyping was performed using polymerase chain reaction and endonuclease digestion. Patients with CAA had shorter duration of clozapine use but did not show any significant difference in other clinical, sociodemographic characteristics and in genotypic or allelic distributions of ABCB1 variants and haplotypes compared with control patients. Among the 10 patients with CAA, none carried the ABCB1 all-variant haplotype (TT-TT-TT), whereas the frequency of this haplotype was approximately 12% among the controls. Larger sample size studies and thorough genetic analyses may reveal both genetic risk and protective factors for this serious adverse event.

  2. Neural basis of the potentiated inhibition of repeated haloperidol and clozapine treatment on the phencyclidine-induced hyperlocomotion

    PubMed Central

    Zhao, Changjiu; Sun, Tao; Li, Ming

    2012-01-01

    Clinical observations suggest that antipsychotic effect starts early and increases progressively over time. This time course of antipsychotic effect can be captured in a rat phencyclidine (PCP)-induced hyperlocomotion model, as repeated antipsychotic treatment progressively increases its inhibition of the repeated PCP-induced hyperlocomotion. Although the neural basis of acute antipsychotic action has been studied extensively, the system that mediates the potentiated effect of repeated antipsychotic treatment has not been elucidated. In the present study, we investigated the neuroanatomical basis of the potentiated action of haloperidol (HAL) and clozapine (CLZ) treatment in the repeated PCP-induced hyperlocomotion. Once daily for five consecutive days, adult Sprague-Dawley male rats were first injected with HAL (0.05 mg/kg, sc), CLZ (10.0 mg/kg, sc) or saline, followed by an injection of PCP (3.2 mg/kg, sc) or saline 30 min later, and motor activity was measured for 90 min after the PCP injection. C-Fos immunoreactivity was assessed either after the acute (day 1) or repeated (day 5) drug tests. Behaviorally, repeated HAL or CLZ treatment progressively increased the inhibition of PCP-induced hyperlocomotion throughout the five days of drug testing. Neuroanatomically, both acute and repeated treatment of HAL significantly increased PCP-induced c-Fos expression in the nucleus accumbens shell (NAs) and the ventral tegmental area (VTA), but reduced it in the central amygdaloid nucleus (CeA). Acute and repeated CLZ treatment significantly increased PCP-induced c-Fos expression in the ventral part of lateral septal nucleus (LSv) and VTA, but reduced it in the medial prefrontal cortex (mPFC). More importantly, the effects of HAL and CLZ in these brain areas underwent a time-dependent reduction from day 1 to day 5. These findings suggest that repeated HAL achieves its potentiated inhibition of the PCP-induced hyperlocomotion by acting on the NAs, CeA and VTA, while CLZ

  3. Rare and very rare adverse effects of clozapine

    PubMed Central

    De Fazio, Pasquale; Gaetano, Raffaele; Caroleo, Mariarita; Cerminara, Gregorio; Maida, Francesca; Bruno, Antonio; Muscatello, Maria Rosaria; Moreno, Maria Jose Jaén; Russo, Emilio; Segura-García, Cristina

    2015-01-01

    Clozapine (CLZ) is the drug of choice for the treatment of resistant schizophrenia; however, its suitable use is limited by the complex adverse effects’ profile. The best-described adverse effects in the literature are represented by agranulocytosis, myocarditis, sedation, weight gain, hypotension, and drooling; nevertheless, there are other known adverse effects that psychiatrists should readily recognize and manage. This review covers the “rare” and “very rare” known adverse effects of CLZ, which have been accurately described in literature. An extensive search on the basis of predefined criteria was made using CLZ and its combination with adverse effects as keywords in electronic databases. Data show the association between the use of CLZ and uncommon adverse effects, including ischemic colitis, paralytic ileus, hematemesis, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudo-pheochromocytoma, periorbital edema, and parotitis, which are influenced by other variables including age, early diagnosis, and previous/current pharmacological therapies. Some of these adverse effects, although unpredictable, are often manageable if promptly recognized and treated. Others are serious and potentially life-threatening. However, an adequate knowledge of the drug, clinical vigilance, and rapid intervention can drastically reduce the morbidity and mortality related to CLZ treatment. PMID:26273202

  4. Clozapine use and sedentary lifestyle as determinants of metabolic syndrome in outpatients with schizophrenia.

    PubMed

    Eskelinen, Saana; Sailas, Eila; Joutsenniemi, Kaisla; Holi, Matti; Suvisaari, Jaana

    2015-07-01

    Schizophrenia patients are in danger of developing metabolic syndrome (MetS) and its outcomes type 2 diabetes and cardiovascular disease. Antipsychotic treatment and adverse lifestyle increase the burden of metabolic problems in schizophrenia, but little is known about the role of patients' current psychiatric problems and living arrangements in MetS. This study aims to evaluate correlations between MetS, severity of psychiatric symptoms, living arrangements, health behaviour and antipsychotic medication in outpatients with schizophrenia spectrum disorders. A general practitioner and psychiatric nurses performed a comprehensive health examination for all consenting patients with schizophrenia spectrum disorders treated in a psychosis outpatient clinic. Examination comprised of an interview, a questionnaire, measurements, laboratory tests and a general clinical examination. Diagnosis of MetS was made according to International Diabetes Federation (IDF) definition. Correlations were calculated and logistic regression analysis performed with SAS. 276 patients (men n = 152, mean age ± standard deviation = 44.9 ± 12.6 years) participated in the study; 58.7% (n = 162) of them had MetS according to the IDF definition. Clozapine use doubled the risk of MetS (OR = 2.04, 95% CI 1.09-3.82, P = 0.03), whereas self-reported regular physical activity decreased the risk significantly (OR = 0.32, 95% CI 0.18-0.57, P < 0.001). We found no correlations between MetS and living arrangements or current severity of psychiatric symptoms. MetS was alarmingly common in our sample. Even moderate physical activity was associated with decreased risk of MetS. Promotion of a physically active lifestyle should be one of the targets in treatment of schizophrenia, especially in patients using clozapine.

  5. Treatment options for chronic pancreatitis.

    PubMed

    Issa, Yama; Bruno, Marco J; Bakker, Olaf J; Besselink, Marc G; Schepers, Nicolien J; van Santvoort, Hjalmar C; Gooszen, Hein G; Boermeester, Marja A

    2014-09-01

    This Review covers the latest developments in the treatment options for chronic pancreatitis. Pain is the most frequent and dominant symptom in patients with chronic pancreatitis, which ranges from severe disabling continuous pain to mild pain attacks and pain-free periods. Conventional treatment strategies and recent changes in the treatment of pain in patients with chronic pancreatitis are outlined. The different treatment options for pain consist of medical therapy, endoscopy or surgery. Their related merits and drawbacks are discussed. Finally, novel insights in the field of genetics and microbiota are summarized, and future perspectives are discussed.

  6. Pharmacological interventions for clozapine-induced hypersalivation

    PubMed Central

    Syed, Rebecca; Au, Katie; Cahill, Caroline; Duggan, Lorna; He, Yanling; Udu, Victor; Xia, Jun

    2014-01-01

    Background Clozapine is widely used for people with schizophrenia. Although agranulocytosis, weight gain, and cardiac problems are serious problems associated with its use, hypersalivation, sometimes of a gross and socially unacceptable quantity, is also common (30-80%). Objectives To determine the clinical effects of pharmacological interventions for clozapine-induced hypersalivation. Search methods We searched the Cochrane Schizophrenia Group Trials Register (March 2007), inspected references of all identified studies for further trials, contacted relevant pharmaceutical companies, drug approval agencies and authors of trials. Selection criteria We included randomised controlled trials comparing pharmacological interventions, at any dose and by any route of administration, for clozapine-induced hypersalivation. Data collection and analysis We extracted data independently. For dichotomous data (homogenous) we calculated relative risk (RR) with 95% confidence intervals (CI) and numbers needed to treat (NNT) on an intention-to-treat basis. We calculated weighted mean difference (WMD) for continuous data. Main results Of the 15 trials identified, 14 were conducted in China and 14 in hospitals. The quality of reporting was poor with no studies clearly describing allocation concealment and much data were missing or unusable. All results are vulnerable to considerable bias. Most frequently the primary outcome was the diameter of the wet patch on the pillow. Antimuscarinics (astemizole, diphenhydramine, propantheline, doxepin) were the most commonly evaluated drugs. For the outcome of ‘no clinically important improvement’ astemizole and diphenhydramine were more effective than placebo (astemizole: n=97, 2 RCTs, RR 0.61 CI 0.47 to 0.81 NNT 3 CI 2 to 5; diphenhydramine: n=131, 2 RCTs, RR 0.43 CI 0.31 to 0.58, NNT 2 CI 1.5 to 2.5), but the doses of astemizole used were those that can cause toxicity. Data involving propantheline were heterogeneous (I2= 86.6%), but both

  7. Atypical antipsychotics in the treatment of early-onset schizophrenia

    PubMed Central

    Hrdlicka, Michal; Dudova, Iva

    2015-01-01

    Atypical antipsychotics (AAPs) have been successfully used in early-onset schizophrenia (EOS). This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least. PMID:25897226

  8. Double activity imaging reveals distinct cellular targets of haloperidol, clozapine and dopamine D(3) receptor selective RGH-1756.

    PubMed

    Kovács, K J; Csejtei, M; Laszlovszky, I

    2001-03-01

    Acute administration of typical (haloperidol) and atypical (clozapine) antipsychotics results in distinct and overlapping regions of immediate-early gene expression in the rat brain. RGH-1756 is a recently developed atypical antipsychotic with high affinity to dopamine D(3) receptors that results in a unique pattern of c-Fos induction. A single injection of either antipsychotic results in c-fos mRNA expression that peaks around 30 min after drug administration, while the maximum of c-Fos protein induction is seen 2 h after challenge. The transient and distinct temporal inducibility of c-fos mRNA and c-Fos protein was exploited to reveal and compare cellular targets of different antipsychotic drugs by concomitant localization of c-fos mRNA and c-Fos immunoreactivity in brain sections of rats that were timely challenged with two different antipsychotics. Double activity imaging revealed that haloperidol, clozapine and RGH-1756 share cellular targets in the nucleus accumbens, where 40% of all labeled neurons displayed both c-fos mRNA and c-Fos protein. Haloperidol activates cells in the caudate putamen, while clozapine-responsive, single labeled neurons were dominant in the prefrontal cortex and major island of Calleja. RGH-1756 targets haloperidol-sensitive cells in the caudate putamen, but cells that are activated by clozapine and RGH-1756 in the major island of Calleja are different.

  9. Comparison of hippocampal G protein activation by 5-HT(1A) receptor agonists and the atypical antipsychotics clozapine and S16924.

    PubMed

    Newman-Tancredi, A; Rivet, J-M; Cussac, D; Touzard, M; Chaput, C; Marini, L; Millan, M J

    2003-09-01

    This study employed [(35)S]guanosine 5'- O-(3-thiotriphosphate) ([(35)S]GTPgammaS) binding to compare the actions of antipsychotic agents known to stimulate cloned, human 5-HT(1A) receptors with those of reference agonists at postsynaptic 5-HT(1A) receptors. In rat hippocampal membranes, the following order of efficacy was observed (maximum efficacy, E(max), values relative to 5-HT=100): (+)8-OH-DPAT (85), flesinoxan (62), eltoprazine (60), S14506 (59), S16924 (48), buspirone (41), S15535 (22), clozapine (22), ziprasidone (21), pindolol (7), p-MPPI (0), WAY100,635 (0), spiperone (0). Despite differences in species and tissue source, the efficacy and potency (pEC(50)) of agonists (with the exception of clozapine) correlated well with those determined previously at human 5-HT(1A) receptors expressed in Chinese hamster ovary (CHO) cells. In contrast, clozapine was more potent at hippocampal membranes. The selective antagonists p-MPPI and WAY100,635 abolished stimulation of binding by (+)8-OH-DPAT, clozapine and S16924 (p-MPPI), indicating that these actions were mediated specifically by 5-HT(1A) receptors. Clozapine and S16924 also attenuated 5-HT- and (+)8-OH-DPAT-stimulated [(35)S]GTPgammaS binding, consistent with partial agonist properties. In [(35)S]GTPgammaS autoradiographic studies, 5-HT-induced stimulation, mediated through 5-HT(1A) receptors, was more potent in the septum (pEC(50) approximately 6.5) than in the dentate gyrus of the hippocampus (pEC(50) approximately 5) suggesting potential differences in coupling efficiency or G protein expression. Though clozapine (30 and 100 microM) did not enhance [(35)S]GTPgammaS labelling in any structure, S16924 (10 micro M) modestly increased [(35)S]GTPgammaS labelling in the dentate gyrus. On the other hand, both these antipsychotic agents attenuated 5-HT (10 microM)-stimulated [(35)S]GTPgammaS binding in the dentate gyrus and septum. In conclusion, clozapine, S16924 and ziprasidone act as partial agonists for G

  10. Impact of apolipoprotein A5 (APOA5) polymorphisms on serum triglyceride levels in schizophrenic patients under long-term atypical antipsychotic treatment.

    PubMed

    Hong, Chen-Jee; Chen, Tzu-Ting; Bai, Ya Mei; Liou, Ying-Jay; Tsai, Shih-Jen

    2012-01-01

    Schizophrenic patients treated with clozapine or olanzapine often develop hypertriglyceridemia. The apolipoprotein A5 gene (APOA5), which affects VLDL production and lipolysis, has been implicated in the triglyceride (TG) metabolism. This study examined the association of common APOA5 genetic variants and TG levels in chronically institutionalized schizophrenic patients, on a stable dose of atypical antipsychotic (clozapine, olanzapine or risperidone. The TG levels in 466 schizophrenic patients treated with clozapine (n = 182), olanzapine (n = 89) or risperidone (n = 195) were measured. Patients were genotyped for the three APOA5 single nucleotide polymorphisms (SNPs) rs662799 (-1131T > C), rs651821 (3A > G) and rs2266788 (1891T > C). A gene × drug interaction with TG levels was observed. In single-marker-based analysis, the minor alleles of the two polymorphisms (-1131C and -3G) were observed to be associated with increased TGs in patients treated with risperidone, but not with clozapine or olanzapine. Haplotype analysis further revealed that carriers of the haplotype constructed with the three minor alleles had higher TG levels than those who did not carry this haplotype in patients taking risperidone (CGC((+/+)) vs. = 125.4 ± 59.1 vs. 82.2 ± 65.8, P = 0.015; CGC((-/+ )) vs. CGC((-/-)) = 113.7 ± 80.4 vs. 82.2 ± 65.8, P = 0.012). Our findings extend and add new information to the existing data regarding the association between APOA5 and TG regulation during long-term atypical antipsychotic treatment.

  11. Clozapine and glycinamide prevent MK-801-induced deficits in the novel object recognition (NOR) test in the domestic rabbit (Oryctolagus cuniculus).

    PubMed

    Hoffman, Kurt L; Basurto, Enrique

    2014-09-01

    Studies in humans indicate that acute administration of sub-anesthetic doses of ketamine, an NMDA receptor antagonist, provokes schizophrenic-like symptoms in healthy volunteers, and exacerbates existing symptoms in individuals with schizophrenia. These and other findings suggest that NMDA receptor hypofunction might participate in the pathophysiology of schizophrenia, and have prompted the development of rodent pharmacological models for this disorder based on acute or subchronic treatment with NMDA receptor antagonists, as well as the development of novel pharmacotherapies based on increasing extrasynaptic glycine concentrations. In the present study, we tested whether acute hyperlocomotory behavior and/or deficits in the novel object recognition (NOR) task, induced in male rabbits by the acute subcutaneous (s.c.) administration of MK-801 (0.025 and 0.037 mg/kg s.c., respectively), were prevented by prior administration of the atypcial antipsychotic, clozapine (0.2mg/kg, s.c.), or the glycine pro-drug glycinamide (56 mg/kg, s.c.). We found that clozapine fully prevented the MK-801-induced hyperlocomotion, and both clozapine and glycinamide prevented MK-801-induced deficits in the NOR task. The present results show that MK-801-induced hyperlocomotion and deficits in the NOR task in the domestic rabbit demonstrate predictive validity as an alternative animal model for symptoms of schizophrenia. Moreover, these results indicate that glycinamide should be investigated in pre-clinical models of neuropsychiatric disorders such as schizophrenia, obsessive compulsive disorder and anxiety disorders, where augmentation of extrasynaptic glycine concentrations may have therapeutic utility. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Treatment of Chronic Cough.

    PubMed

    Soni, Resha S; Ebersole, Barbara; Jamal, Nausheen

    2017-01-01

    Objective Chronic cough remains a challenging condition, especially in cases where it persists despite comprehensive medical management. For these particular patients, there appears to be an emerging role for behavior modification therapy. We report a series of patients with refractory chronic cough to assess if there is any benefit of adding behavioral therapy to their treatment regimen. Study Design A case series with planned chart review of patients treated for chronic cough. Setting The review was performed with an outpatient electronic health record system at a tertiary care center. Subjects and Methods The charts of all patients treated for chronic cough by a single laryngologist over a 30-month period were analyzed. Patients' response to treatment and rate of cough improvement were assessed for those with refractory chronic cough who underwent behavior modification therapy. Results Thirty-eight patients with chronic cough were initially treated empirically for the most common causes of cough, of which 32% experienced improvement. Nineteen patients who did not significantly improve with medical management underwent behavior modification therapy with a speech-language pathologist. Of these patients, 84% experienced resolution or marked improvement of their symptoms. Conclusion Behavioral therapy may be underutilized in practice and could lead to improvement of otherwise recalcitrant cough.

  13. Early treatment resistance in a Latin-American cohort of patients with schizophrenia.

    PubMed

    Mena, Cristian; Gonzalez-Valderrama, Alfonso; Iruretagoyena, Barbara; Undurraga, Juan; Crossley, Nicolas A

    2018-03-08

    Failure to respond to antipsychotic medication in schizophrenia is a common clinical scenario with significant morbidity. Recent studies have highlighted that many patients present treatment-resistance from disease onset. We here present an analysis of clozapine prescription patterns, used as a real-world proxy marker for treatment-resistance, in a cohort of 1195 patients with schizophrenia from a Latin-American cohort, to explore the timing of emergence of treatment resistance and possible subgroup differences. Survival analysis from national databases of clozapine monitoring system, national disease notification registers, and discharges from an early intervention ward. Echoing previous studies, we found that around 1 in 5 patients diagnosed with schizophrenia were eventually prescribed clozapine, with an over-representation of males and those with a younger onset of psychosis. The annual probability of being prescribed clozapine was highest within the first year (probability of 0.11, 95% confidence interval of 0.093-0.13), compared to 0.018 (0.012-0.024) between years 1 and 5, and 0.006 (0-0.019) after 5years. Age at psychosis onset, gender, dose of clozapine used, and compliance with hematological monitoring at 12months, was not related to the onset of treatment resistance. A similar pattern was observed in a subgroup of 230 patients discharged from an early intervention ward with a diagnosis of non-affective first episode of psychosis. Our results highlight that treatment resistance is frequently present from the onset of psychosis. Future studies will shed light on the possible different clinical and neurobiological characteristics of this subtype of psychosis. Copyright © 2018. Published by Elsevier B.V.

  14. Sedative effect of Clozapine is a function of 5-HT2A and environmental novelty.

    PubMed

    Joshi, Radhika S; Quadros, Rolen; Drumm, Michael; Ain, Rupasri; Panicker, Mitradas M

    2017-01-01

    Antipsychotic drugs are the mainstay in the treatment of schizophrenia and bipolar disorder. However, antipsychotics often exhibit sedation or activity suppression among many other side effects, and the factors that influence them remain poorly understood. We now show, using a 5-HT 2A knockout (Htr2a -/- ) mouse, that environmental circumstances can affect suppression of activity induced by the atypical antipsychotic- Clozapine. We observed that Htr2a -/- mice were more resistant to Clozapine-induced suppression of activity (CISA) and this behaviour was dependent on the environment being 'novel'. In their 'home' environment, at identical doses the mice exhibited CISA. Interestingly, the effect of genotype and environmental novelty on CISA could not be extended to the other antipsychotics that were tested, i.e. Haloperidol and Risperidone. Haloperidol-induced activity suppression was independent of context and genotype. Whereas context affected Risperidone-induced activity suppression only in the Htr2a +/+ mice. Furthermore, we observed that caffeine, a stimulant, elicited resistance to CISA similar to that seen in the 'novel' context. Our study establishes a previously unknown interaction between the environmental context, 5-HT 2A and CISA and emphasises the role of non-pharmacological factors such as environment on the effects of the drug, which seem antipsychotic-specific. Our findings should advance the understanding of the side effects of individual antipsychotics and the role of environment to overcome side effects such as sedation. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  15. The incidence of clozapine-induced leukopenia in patients with schizophrenia at Srinagarind Hospital.

    PubMed

    Maskasame, Sarin; Krisanaprakornkit, Thawatchai; Khiewyoo, Jiraporn

    2007-10-01

    Define the incidence of clozapine-induced leukopenia, neutropenia, and agranulocytosis in patients with schizophrenia at Srinagarind Hospital. A descriptive study was done by retrospective reviews of the medical records of schizophrenic outpatients at psychiatric clinic in Srinagarind Hospital who had received clozapine from January 1st, 2003 to December 31st, 2005. The demographic data, incidence rate, and incidence density of leukopenia, neutropenia, and agranulocytosis were collected. One hundred and seventeen medical records were reviewed, 65 patients met the inclusion criteria. One patient developed neutropenia. The incidence rate of neutropenia was 1.5% and the incidence density of neutropenia was 0.01/year. No leukopenia or agranulocytosis was found in the present study. The complete blood counts were not obtained regularly due to the problems of patient's adherence and variations in practice among the physicians. Neutropenia is uncommon. No leukopenia and agranulocytosis were found. According to variations of incidence reports among different studies, the monitoring of white blood count should be continued.

  16. Postnatal iron-induced motor behaviour alterations following chronic neuroleptic administration in mice.

    PubMed

    Fredriksson, A; Eriksson, P; Archer, T

    2006-02-01

    C57/BL6 mice were administered either 7.5 mg Fe(2+)/kg or vehicle (saline) postnatally on days 10-12 after birth. From 61 days of age onwards for 21 days, groups of mice were administered either clozapine (1 or 5 mg/kg, s.c.) or haloperidol (1 mg/kg, s.c.) or vehicle (Tween-80). Twenty-four hours after the final injection of either neuroleptic compound or vehicle, spontaneous motor activity was measured over a 60-min interval. Following this, each animal was removed, injected apomorphine (1 mg/kg, s.c.) and replaced in the same test chamber. It was found that postnatal administration of Fe(2+) at the 7.5 mg/kg dose level reduced activity during the initial 20-min periods (0-20 and 20-40 min) and then induced hyperactivity during the final 20-min period over all three parameters of activity. Subchronic treatment with the higher, 5 mg/kg, dose of clozapine abolished or attenuated the hypoactivity in by postnatal Fe(2+) during the 1(st) two 20-min periods over all three parameters of activity. Subchronic treatment with the higher, 5 mg/kg, dose of clozapine abolished or attenuated the hyperactivity in by postnatal Fe(2+) during the 3(rd) and final 20-min period. Subchronic administration of haloperidol, without postnatal iron, increased the level of both locomotion (1(st) 20 min) and rearing (2(nd) 20 min) activity. Postnatal administration of Fe(2+) at the 7.5 mg/kg dose increased the levels of both locomotion and rearing, but not total activity, following administration of apomorphine (1 mg/kg). Subchronic administration of clozapine, at both the 1 and 5 mg/kg doses, reduced the increased locomotor activity caused by postnatal Fe(2+), whereas clozapine, 5 mg/kg, elevated further the postnatal Fe(2+)-induced increased in rearing. Subchronic administration of clozapine, at both the 1 and 5 mg/kg doses, and haloperidol, 1 mg/kg, increased the level of locomotor following administration of apomorphine (1 mg/kg) in mice treated postnatally with vehicle, whereas only

  17. [Physical treatment modalities for chronic leg ulcers].

    PubMed

    Dissemond, J

    2010-05-01

    An increasing numbers of physical treatment options are available for chronic leg ulcer. In this review article, compression therapy, therapeutic ultrasound, negative pressure therapy, extracorporeal shock wave therapy, electrostimulation therapy, electromagnetic therapy, photodynamic therapy, water-filtered infrared-A-radiation and hydrotherapy are discussed in terms of their practical applications and the underlying evidence. With the exception of compression therapy for most of these treatments, good scientific data are not available. However this is a widespread problem in the treatment of chronic wounds. Nevertheless, several of the described methods such as negative pressure therapy represent one of the gold standards in practical treatment of patients with chronic leg ulcers. Although the use of physical treatment modalities may improve healing in patients with chronic leg ulcers, the diagnosis and treatment of the underlying causes are essential for long-lasting success.

  18. New developments in the diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome.

    PubMed

    Pontari, Michel; Giusto, Laura

    2013-11-01

    To describe new developments in the diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome (CPPS). Symptoms in men with chronic prostatitis/CPPS appear to cluster into a group with primarily pelvic or localized disease, and a group with more systemic symptoms. Several other chronic pain conditions can be associated with chronic prostatitis/CPPS, including irritable bowel syndrome, fibromyalgia, and chronic fatigue syndrome. Markers of neurologic inflammation and autoimmune disease parallel changes in symptoms after treatment. Treatment options include new alpha-blockers, psychological intervention, and prostate-directed therapy. The areas of acupuncture and pelvic floor physical therapy/myofascial release have received increased recent attention and appear to be good options in these patients. Future therapy may include antibodies to mediators of neurogenic inflammation and even treatment of bacteria in the bowel. The diagnosis of chronic prostatitis/CPPS must include conditions traditionally outside the scope of urologic practice but important for the care of men with chronic pelvic pain. The treatment is best done using multiple simultaneous therapies aimed at the different aspects of the condition.

  19. Endoscopic treatment of chronic radiation proctopathy.

    PubMed

    Wilson, Sydney A; Rex, Douglas K

    2006-09-01

    Chronic radiation proctopathy is a complication of pelvic radiation therapy. The acute phase of radiation injury to the rectum occurs during or up to 3 months following radiation. Acute radiation injury can continue into a chronic phase or chronic radiation proctopathy may develop after a latent period of several months or years. Symptoms associated with the condition include diarrhea, rectal pain, bleeding, tenesmus, and stricture formation. Of the various symptoms, only bleeding from radiation-induced telangiectasias is amenable to endoscopic therapy. This paper summarizes the findings of experts in the field on endoscopic treatment of bleeding from chronic radiation proctopathy. Medical management is generally ineffective in controlling bleeding from chronic radiation proctopathy. Surgical intervention has a high incidence of morbidity. Promising advances have been made in endoscopic therapy, including formalin, neodymium/yttrium aluminum garnet, argon and potassium titanyl phosphate laser treatments, as well as argon plasma coagulation. Argon plasma coagulation presents an effective, efficient, inexpensive and reasonably safe noncontact method for destruction of radiation telangiectasias. Based on currently available data and trends, argon plasma coagulation is the favored treatment for bleeding from chronic radiation proctopathy.

  20. ["Catatonic dilemma". Therapy with lorazepam and clozapine].

    PubMed

    Lausberg, H; Hellweg, R

    1998-09-01

    We are reporting on a patient with a schizoaffective disorder (ICD 10:F25.1), whose catatonic symptoms deteriorated while receiving high-potency neuroleptic drugs in combination with anticholinergic medication. Initially there was a "catatonic dilemma", i.e. it was not possible to differentiate between the morbigenous and pharmacogenic (malignant neuroleptic syndrome) etiology of the catatonic symptoms. Catatonic symptoms were successfully treated with a combination of lorazepam and clozapine. The severe catatonic syndrome was found to be a neuroleptic-induced deterioration of a primary morbogenous catatonic syndrome. Thus, this case also suggests that the malignant neuroleptic syndrome and neuroleptic non-responsive catatonia may not be two different disease entities but that catatonia under neuroleptic medication is caused by the interaction of individual disposition, morbigenous and pharmacogenic factors.

  1. Effective physical treatment for chronic low back pain.

    PubMed

    Maher, C G

    2004-01-01

    It is now feasible to adopt an evidence-based approach when providing physical treatment for patients with chronic LBP. A summary of the efficacy of a range of physical treatments is provided in Table 1. The evidence-based primary care options are exercise, laser, massage, and spinal manipulation; however, the latter three have small or transient effects that limit their value as therapies for chronic LBP. In contrast, exercise produces large reductions in pain and disability, a feature that suggests that exercise should play a major role in the management of chronic LBP. Physical treatments, such as acupuncture, backschool, hydrotherapy, lumbar supports, magnets, TENS, traction, ultrasound, Pilates therapy, Feldenkrais therapy, Alexander technique, and craniosacral therapy are either of unknown value or ineffective and so should not be considered. Outside of primary care, multidisciplinary treatment or functional restoration is effective; however, the high cost probably means that these programs should be reserved for patients who do not respond to cheaper treatment options for chronic LBP. Although there are now effective treatment options for chronic LBP, it needs to be acknowledged that the problem of chronic LBP is far from solved. Though treatments can provide marked improvements in the patient's condition, the available evidence suggests that the typical chronic LBP patient is left with some residual pain and disability. Developing new, more powerful treatments and refining the current group of known effective treatments is the challenge for the future.

  2. First-line treatment of chronic myeloid leukaemia.

    PubMed

    O'Dwyer, Michael

    2010-02-01

    Since the introduction of imatinib just over a decade ago, there has been a dramatic change in the treatment and prognosis of early chronic phase chronic myeloid Leukaemia (CML). This review article focuses on recent advances, culminating in the approval of nilotinib by the US Food and Drug Administration for the treatment of adult patients with newly diagnosed CML in the chronic phase.

  3. First-line treatment of chronic myeloid leukaemia

    PubMed Central

    O'Dwyer, Michael

    2010-01-01

    Since the introduction of imatinib just over a decade ago, there has been a dramatic change in the treatment and prognosis of early chronic phase chronic myeloid Leukaemia (CML). This review article focuses on recent advances, culminating in the approval of nilotinib by the US Food and Drug Administration for the treatment of adult patients with newly diagnosed CML in the chronic phase. PMID:23556068

  4. Matrix-assisted laser desorption/ionization imaging mass spectrometry for direct measurement of clozapine in rat brain tissue.

    PubMed

    Hsieh, Yunsheng; Casale, Roger; Fukuda, Elaine; Chen, Jiwen; Knemeyer, Ian; Wingate, Julia; Morrison, Richard; Korfmacher, Walter

    2006-01-01

    Matrix-assisted laser desorption/ionization hyphenated with quadrupole time-of-flight (QTOF) mass spectrometry (MS) has been used to directly determine the distribution of pharmaceuticals in rat brain tissue slices which might unravel their disposition for new drug development. Clozapine, an antipsychotic drug, and norclozapine were used as model compounds to investigate fundamental parameters such as matrix and solvent effects and irradiance dependence on MALDI intensity but also to address the issues with direct tissue imaging MS technique such as (1) uniform coating by the matrix, (2) linearity of MALDI signals, and (3) redistribution of surface analytes. The tissue sections were coated with various matrices on MALDI plates by airspray deposition prior to MS detection. MALDI signals of analytes were detected by monitoring the dissociation of the individual protonated molecules to their predominant MS/MS product ions. The matrices were chosen for tissue applications based on their ability to form a homogeneous coating of dense crystals and to yield greater sensitivity. Images revealing the spatial localization in tissue sections using MALDI-QTOF following a direct infusion of (3)H-clozapine into rat brain were found to be in good correlation with those using a radioautographic approach. The density of clozapine and its major metabolites from whole brain homogenates was further confirmed using fast high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) procedures. Copyright (c) 2006 John Wiley & Sons, Ltd.

  5. Intersection of chronic pain treatment and opioid analgesic misuse: causes, treatments, and policy strategies

    PubMed Central

    Wachholtz, Amy; Gonzalez, Gerardo; Boyer, Edward; Naqvi, Zafar N; Rosenbaum, Christopher; Ziedonis, Douglas

    2011-01-01

    Treating chronic pain in the context of opioid misuse can be very challenging. This paper explores the epidemiology and potential treatments for chronic pain and opioid misuse and identifies educational and regulation changes that may reduce diversion of opioid analgesics. We cover the epidemiology of chronic pain and aberrant opioid behaviors, psychosocial influences on pain, pharmacological treatments, psychological treatments, and social treatments, as well as educational and regulatory efforts being made to reduce the diversion of prescription opioids. There are a number of ongoing challenges in treating chronic pain and opioid misuse, and more research is needed to provide strong, integrated, and empirically validated treatments to reduce opioid misuse in the context of chronic pain. PMID:24474854

  6. Metabolic effects of adjunctive aripiprazole in clozapine-treated patients with schizophrenia

    PubMed Central

    Fan, Xiaoduo; Borba, Christina P.C.; Copeland, Paul; Hayden, Doug; Freudenreich, Oliver; Goff, Donald C.; Henderson, David C.

    2015-01-01

    Objective This study examined the effects of adjunctive aripiprazole therapy on metabolism in clozapine-treated patients with schizophrenia. Method In an 8-week randomized, double-blind, placebo-controlled study, subjects received either aripiprazole (15mg/day) or placebo. At baseline and week 8, metabolic parameters were assessed by the frequently sampled intravenous glucose tolerance test, nuclear magnetic resonance spectroscopy and whole-body dual-energy X-ray absorptiometry (DXA). Results Thirty subjects completed the study (16 in the aripiprazole group and 14 in the placebo group). Glucose effectiveness measured by the frequently sampled intravenous glucose tolerance test improved significantly in the aripiprazole group (0.003 ± 0.006 versus −0.005 ± 0.007/min, P = 0.010). The aripiprazole group showed significant reductions in both plasma low-density lipoprotein (LDL) levels (−15.1 ± 19.8 vs. 4.4 ± 22.5 mg/dl, P = 0.019) and LDL particle numbers (−376 ± 632 vs. −36 ± 301 nM, P= 0.035). Further, there was a significant reduction in lean mass (−1125 ± 1620 vs. 607 ± 1578 g, P= 0.011) measured by whole-body DXA scan in the aripiprazole group. All values were expressed as mean ± standard deviation, aripiprazole vs. placebo. Conclusion Adjunctive therapy with aripiprazole may have some metabolic benefits in clozapine-treated patients with schizophrenia. PMID:22943577

  7. Chronic orchialgia: Review of treatments old and new

    PubMed Central

    Tojuola, Bayo; Layman, Jeffrey; Kartal, Ibrahim; Gudelogul, Ahmet; Brahmbhatt, Jamin; Parekattil, Sijo

    2016-01-01

    Introduction: Chronic orchialgia is historically and currently a challenging disease to treat. It is a diagnostic and therapeutic challenge for physicians. Conservative therapy has served as the first line of treatment. For those who fail conservative therapy, surgical intervention may be required. We aim to provide a review of currently available surgical options and novel surgical treatment options. Methods: A review of current literature was performed using PubMed. Literature discussing treatment options for chronic orchialgia were identified. The following search terms were used to identify literature that was relevant to this review: Chronic orchialgia, testicular pain, scrotal content pain, and microsurgical denervation of the spermatic cord (MDSC). Results: The incidence of chronic orchialgia has been increasing over time. In the USA, it affects up to 100,000 men per year due to varying etiologies. The etiology of chronic orchialgia can be a confounding problem. Conservative therapy should be viewed as the first line therapy. Studies have reported poor success rates. Current surgical options for those who fail conservative options include varicocelectomy, MDSC, epididymectomy, and orchiectomy. Novel treatment options include microcryoablation of the peri-spermatic cord, botox injection, and amniofix injection. Conclusion: Chronic orchialgia has been and will continue to be a challenging disease to treat due to its multiple etiologies and variable treatment outcomes. Further studies are needed to better understand the problem. Treatment options for patients with chronic orchialgia are improving. Additional studies are warranted to better understand the long-term durability of this treatment options. PMID:26941490

  8. Effect of depression treatment on chronic pain outcomes.

    PubMed

    Teh, Carrie Farmer; Zaslavsky, Alan M; Reynolds, Charles F; Cleary, Paul D

    2010-01-01

    To examine the effect of depression treatment on medical and social outcomes for individuals with chronic pain and depression. People with chronic pain and depression have worse health outcomes than those with chronic pain alone. Little is known about the effectiveness of depression treatment for this population. Propensity score-weighted analyses, using both waves (1997-1998 and 2000-2001) of the National Survey of Alcohol, Drug, and Mental Health Problems, were used to examine the effect of a) any depression treatment and b) minimally adequate depression treatment on persistence of depression symptoms, depression severity, pain severity, overall health, mental health status, physical health status, social functioning, employment status, and number of workdays missed. Analyses were limited to those who met Composite International Diagnostic Interview Short-Form criteria for major depressive disorder, reported having at least one chronic pain condition, and completed both interviews (n = 553). Receiving any depression treatment was associated with higher scores on the mental component summary of the Medical Outcomes Study Short Form-12, indicating better mental health (difference = 2.65 points, p = .002) and less interference of pain on work (odds ratio = 0.57, p = .02). Among those receiving treatment, minimal adequacy of treatment was not significantly associated with better outcomes. Depression treatment improves mental health and reduces the effects of pain on work among those with chronic pain and depression. Understanding the effect of depression treatment on outcomes for this population is important for employers, healthcare providers treating this population, and policymakers working in this decade of pain control and research to improve care for chronic pain sufferers.

  9. Effects of Antipsychotic Drugs Haloperidol and Clozapine on Visual Responses of Retinal Ganglion Cells in a Rat Model of Retinitis Pigmentosa.

    PubMed

    Jensen, Ralph J

    2016-12-01

    In the P23H rat model of retinitis pigmentosa, the dopamine D2 receptor antagonists sulpiride and eticlopride appear to improve visual responses of retinal ganglion cells (RGCs) by increasing light sensitivity of RGCs and transforming abnormal, long-latency ON-center RGCs into OFF-center cells. Antipsychotic drugs are believed to mediate their therapeutic benefits by blocking D2 receptors. This investigation was conducted to test whether haloperidol (a typical antipsychotic drug) and clozapine (an atypical antipsychotic drug) could similarly alter the light responses of RGCs in the P23H rat retina. Extracellular recordings were made from RGCs in isolated P23H rat retinas. Responses of RGCs to flashes of light were evaluated before and during bath application of a drug. Both haloperidol and clozapine increased light sensitivity of RGCs on average by ∼0.3 log unit. For those ON-center RGCs that exhibit an abnormally long-latency response to the onset of a small spot of light, both haloperidol and clozapine brought out a short-latency OFF response and markedly reduced the long-latency ON response. The selective serotonin 5-HT2A antagonist MDL 100907 had similar effects on RGCs. The effects of haloperidol on light responses of RGCs can be explained by its D2 receptor antagonism. The effects of clozapine on light responses of RGCs on the other hand may largely be due to its 5-HT2A receptor antagonism. Overall, the results suggest that antipsychotic drugs may be useful in improving vision in patients with retinitis pigmentosa.

  10. Cryosurgical treatment of professional chronic radiodermatitis.

    PubMed

    Conejo-Mir, J S; Moreno, J C; Camacho, F

    1997-06-01

    Chronic x-ray dermatitis in professionals is a frequent problem for doctors in our country due to the fact that many of them widely used radiotherapy without any protection 15-20 years ago. Surgery has been the most accepted treatment, though it generally decreases hand function. Up to now, cryosurgery was not usually considered as a possible treatment if the lesions were located on fingers. In this study, the advantages of cryosurgery for the treatment of professional chronic radiodermatitis with incipient pretumoral lesions are emphasized. Cryosurgery was performed on six patients affected with chronic professional radiodermatitis that showed keratomas and ulcerations, using both spray (keratomas) and a probe 0.5 cm in diameter (ulcerations, in situ squamous cell carcinoma). Nerve block anesthesia with mepivacaine 1% was used in all cases. Before the treatment, all suspected lesions were biopsied; if invasive squamous cell carcinoma was revealed in the dermatopathological study, the patient was rejected. Variables such as blister and necrosis formation, pain, and achromatic, sensibility, and mobility disorders were studied. The follow-up period was 2 years. Immediate postoperative results showed great pain and blistering in all cases. Residual achromias were observed early postoperatively in all cases, but were repigmented 1 year after therapy in four cases (66%). Sensory alterations (hypo- and hyperthesias) were found in four cases (66%) 1 month after treatment, although this complication was not observed 6 months after treatment. Finger mobility was perfect in all cases 2 months after treatment, and there was no recurrence in any case after 2 years of follow-up. We believe cryosurgery must be considered as an excellent treatment for professional chronic radiodermatitis with keratomas, ulcerations, and incipient squamous cell carcinomas. Its use may prevent further dramatic surgical treatment, like amputations, allowing the preservation of finger function.

  11. [Antipsychotic Treatment of the Adult Patient in the Acute Phase of Schizophrenia].

    PubMed

    Bohórquez Peñaranda, Adriana; Gómez Restrepo, Carlos; García Valencia, Jenny; Jaramillo González, Luis Eduardo; de la Hoz, Ana María; Arenas, Álvaro; Tamayo Martínez, Nathalie

    2014-01-01

    To determine the efficacy and safety of different antipsychotic drugs in the management of patients diagnosed with schizophrenia in the acute phase. To formulate evidence-based recommendations on the antipsychotic (AP) drug management strategies for the treatment of the adult diagnosed with schizophrenia in the acute phase. Clinical practice guidelines were prepared, using the guidelines of the Methodology Guide of the Ministry of Health and Social Protection, in order to identify, synthesise, and evaluate the evidence and formulate recommendations as regards the management and follow-up of adult patients diagnosed with schizophrenia. The evidence of the NICE 82 guideline was adopted and updated, which answered the question on the management of the acute phase of adults with a diagnosis of schizophrenia. The evidence and its level were presented to the Guideline Development Group (GDG) in order to formulate recommendations following the methodology proposed by the GRADE approach. Clozapine, olanzapine, risperidone, ziprasidone, amisulpride, paliperidone, haloperidol, quetiapine, and aripiprazole were more effective than placebo for the majority of psychotic symptoms and the abandonment of treatment, but asenapine was not. Paliperidone, risperidone, quetiapine, clozapine, and olanzapine showed significant increases in weight compared to placebo. Haloperidol, risperidone, ziprasidone, and paliperidone had a higher risk of extrapyramidal symptoms than placebo. There was a significant risk of sedation or drowsiness with, risperidone, haloperidol, ziprasidone, quetiapine, olanzapine, and clozapine in the comparisons with placebo. Of the results of the comparisons between AP, it was shown that clozapine and paliperidone had a clinically significant effect compared to haloperidol and quetiapine, respectively. Olanzapine and risperidone had a lower risk of abandoning the treatment in general, and due to adverse reactions in two comparisons of each one, haloperidol was the

  12. Plasma levels of mature brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) in treatment-resistant schizophrenia treated with clozapine.

    PubMed

    Yamamori, Hidenaga; Hashimoto, Ryota; Ishima, Tamaki; Kishi, Fukuko; Yasuda, Yuka; Ohi, Kazutaka; Fujimoto, Michiko; Umeda-Yano, Satomi; Ito, Akira; Hashimoto, Kenji; Takeda, Masatoshi

    2013-11-27

    Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. Peripheral BDNF levels in patients with schizophrenia have been widely reported in the literature. However, it is still controversial whether peripheral levels of BDNF are altered in patients with schizophrenia. The peripheral BDNF levels previously reported in patients with schizophrenia were total BDNF (proBDNF and mature BDNF) as it was unable to specifically measure mature BDNF due to limited BDNF antibody specificity. In this study, we examined whether peripheral levels of mature BDNF were altered in patients with treatment-resistant schizophrenia. Matrix metalloproteinase-9 (MMP-9) levels were also measured, as MMP-9 plays a role in the conversion of proBDNF to mature BDNF. Twenty-two patients with treatment-resistant schizophrenia treated with clozapine and 22 age- and sex-matched healthy controls were enrolled. The plasma levels of mature BDNF and MMP-9 were measured using ELISA kits. No significant difference was observed for mature BDNF however, MMP-9 was significantly increased in patients with schizophrenia. The significant correlation was observed between mature BDNF and MMP-9 plasma levels. Neither mature BDNF nor MMP-9 plasma levels were associated clinical variables. Our results do not support the view that peripheral BDNF levels are associated with schizophrenia. MMP-9 may play a role in the pathophysiology of schizophrenia and serve as a biomarker for schizophrenia. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  13. Effect of Depression Treatment on Chronic Pain Outcomes

    PubMed Central

    Teh, Carrie Farmer; Zaslavsky, Alan; Reynolds, Charles F.; Cleary, Paul D.

    2011-01-01

    Objective People with chronic pain and depression have worse health outcomes than those with chronic pain alone. Little is known about the effectiveness of depression treatment for this population. We examined the effect of depression treatment on medical and social outcomes for individuals with chronic pain and depression Methods Propensity score weighted analyses using both waves (1997-1998 and 2000-2001) of the National Survey of Alcohol, Drug, and Mental Health Problems were used to examine the effect of (1) any depression treatment and (2) minimally adequate depression treatment on persistence of depression symptoms, depression severity, pain severity, overall health, mental health status, physical health status, social functioning, employment status, and number of work days missed. Analyses were limited to those who met CIDI-SF criteria for major depressive disorder, reported having at least one chronic pain condition, and completed both interviews (n=553). Results Receiving any depression treatment was associated with higher scores on the mental component summary of the MOS SF-12, indicating better mental health (difference = 2.65 points, p=0.002) and less interference of pain on work (OR=0.57, p=0.02). Among those receiving treatment, minimal adequacy of treatment was not significantly associated with better outcomes. Conclusions Depression treatment improves mental health and reduces the effects of pain on work among those with chronic pain and depression. Understanding the effect of depression treatment on outcomes for this population is important for employers, healthcare providers treating this population, and policymakers working in this Decade of Pain Control and Research to improve care for chronic pain sufferers. PMID:19875633

  14. Computers in the treatment of chronic aphasia.

    PubMed

    Katz, Richard C

    2010-02-01

    Computers and related technology can increase the amount of treatment received by adults with chronic aphasia. Computers used in treatment, however, are only valuable to the patient if the intervention is efficacious. Real and potential applications of computer technology are discussed in the context of three roles of computerized aphasia treatment for adults with chronic aphasia. Pertinent studies regarding Phases 1 and 2 are briefly described. The only Phase 3 study of efficacy of computerized aphasia treatment is more fully described and its implications discussed.

  15. Chronic proctalgia and chronic pelvic pain syndromes: New etiologic insights and treatment options

    PubMed Central

    Chiarioni, Giuseppe; Asteria, Corrado; Whitehead, William E

    2011-01-01

    This systematic review addresses the pathophysiology, diagnostic evaluation, and treatment of several chronic pain syndromes affecting the pelvic organs: chronic proctalgia, coccygodynia, pudendal neuralgia, and chronic pelvic pain. Chronic or recurrent pain in the anal canal, rectum, or other pelvic organs occurs in 7% to 24% of the population and is associated with impaired quality of life and high health care costs. However, these pain syndromes are poorly understood, with little research evidence available to guide their diagnosis and treatment. This situation appears to be changing: A recently published large randomized, controlled trial by our group comparing biofeedback, electrogalvanic stimulation, and massage for the treatment of chronic proctalgia has shown success rates of 85% for biofeedback when patients are selected based on physical examination evidence of tenderness in response to traction on the levator ani muscle-a physical sign suggestive of striated muscle tension. Excessive tension (spasm) in the striated muscles of the pelvic floor appears to be common to most of the pelvic pain syndromes. This suggests the possibility that similar approaches to diagnostic assessment and treatment may improve outcomes in other pelvic pain disorders. PMID:22110274

  16. Atypical antipsychotic (clozapine) self-poisoning in late pregnancy presenting with absent fetal heart rate variability without acidosis and delayed peristalsis in the newborn baby: a case report.

    PubMed

    Novikova, N; Chitnis, M; Linder, V; Hofmeyr, G J

    2009-08-01

    A case of an attempted suicide with atypical antipsychotic (clozapine) in late pregnancy is reported. Toxic effects of clozapine in the mother as well as in the fetus and newborn were observed. It should be remembered as a rare cause of unexplained loss of consciousness in pregnant women, a cause of abnormalities on fetal cardiotocogram as well as a cause of delayed peristalsis in a newborn baby.

  17. Diagnosis, treatment, and nursing care of patients with chronic leukemia.

    PubMed

    Breed, Cheryl D

    2003-05-01

    To provide an update on the impact of new information about the molecular biology of chronic leukemia and new treatment modalities available to patients. Published articles, books, and research studies. There has been significant progress in the diagnosis and management of chronic myeloid and chronic lymphocytic leukemia. New therapies provide more options for patients and longer treatment periods. With increasing treatment options and longer survival, patients with chronic myelogenous or chronic lymphocytic leukemia need increased education, support, and assistance with symptom management. Nurses caring for these patients must remain knowledgeable about new treatments and their management.

  18. [Treatment motivation in patients with chronic cardiorenal syndrome].

    PubMed

    Efremova, E V; Shutov, A M; Borodulina, E O

    2015-01-01

    To study treatment motivation in patients with chronic heart failure (CHF) and in those with CHF concurrent with chronic kidney disease (CKD). A total of 203 patients (130 men and 73 women; mean age, 61.8±9.6 years) with CHF diagnosed and assessed in accordance with the National Guidelines of the All-Russian Research Society of Cardiology and the Heart Failure Society for the diagnosis and treatment of CHF (third edition, 2009) were examined. CKD was diagnosed according to the 2012 National Guidelines of the Research Nephrology Society of Russia. A group of patients with chronic cardiorenal syndrome (CRS) included those with CHF and CKD with a glomerular filtration rate (GFR) of <60 ml/min/1.73 m2. The clinical course of CHF, personality profile, and motivation for non-drug and drug treatments were assessed in patients with chronic CRS. CFR was 67.7±17.2 ml/min/1.73 m2; chronic CRS was observed in 89 (44%) patients. Psychological functioning assessment showed that the patients with chronic CRS as compared with those with CHF without CKD had high anxiety and maladaptive disease attitudes. CHF treatment motivation (compliance with lifestyle modification and medication) was proved inadequate and detected only in 31 (15.3%) patients with CHF regardless of the presence of CKD. The specific features of psychological functioning, which affected treatment motivation, were seen in patients with chronic CRS: those who were lowly motivated had a euphoric attitude towards their disease (p=0.03); those who were satisfactorily motivated showed an emotive accentuation of character (p=0.002). The presence of CKD aggravates the clinical course of CHF and negatively affects the psychological functioning of patients with CHF. The patients with chronic CRS are characterized by a low level of motivation for both drug and non-drug treatments, which should be taken into account when managing this cohort of patients.

  19. Regulation of Brain Glucose Metabolic Patterns by Protein Phosphorlyation and Drug Therapy

    DTIC Science & Technology

    2007-03-30

    chlorpromazine and haloperidol revolutionized the treatment of mental illness the sedating and neuroleptic side effects produced by "typical...demonstrated in rodents chronically treated with haloperidol and clozapine. We also demonstrate significantly higher levels of lactate in the postmortem...lactate levels in the cerebellum of patients with schizophrenia (n = 35) and control subjects (n = 42) and in rats chronically treated with haloperidol

  20. Conservative treatment of chronic pancreatitis.

    PubMed

    Löhr, J-Matthias; Haas, Stephen L; Lindgren, Fredrik; Enochsson, Lars; Hedström, Aleksandra; Swahn, Fredrik; Segersvärd, Ralf; Arnelo, Urban

    2013-01-01

    Chronic pancreatitis is a progressive inflammatory disease giving rise to several complications that need to be treated accordingly. Because pancreatic surgery has significant morbidity and mortality, less invasive therapy seems to be an attractive option. This paper reviews current state-of-the-art strategies to treat chronic pancreatitis without surgery and the current guidelines for the medical therapy of chronic pancreatitis. Endoscopic therapy of complications of chronic pancreatitis such as pain, main pancreatic duct strictures and stones as well as pseudocysts is technically feasible and safe. The long-term outcome, however, is inferior to definitive surgical procedures such as resection or drainage. On the other hand, the medical therapy of pancreatic endocrine and exocrine insufficiency is well established and evidence based. Endoscopic therapy may be an option to bridge for surgery and in children/young adolescents and those unfit for surgery. Pain in chronic pancreatitis as well as treatment of pancreatic exocrine insufficiency follows established guidelines. Copyright © 2013 S. Karger AG, Basel.

  1. Preparation of magnetic ODS-PAN thin-films for microextraction of quetiapine and clozapine in plasma and urine samples followed by HPLC-UV detection.

    PubMed

    Li, Dan; Zou, Juan; Cai, Pei-Shan; Xiong, Chao-Mei; Ruan, Jin-Lan

    2016-06-05

    In this study, conventional thin-film microextraction (TFME) was endowed with magnetic by introducing superparamagnetic SiO2@Fe3O4 nanoparticles in thin-films. Novel magnetic octadecylsilane (ODS)-polyacrylonitrile (PAN) thin-films were prepared by spraying, and used for the microextraction of quetiapine and clozapine in plasma and urine samples, followed by the detection of HPLC-UV. The influencing factors on the extraction efficiency of magnetic ODS-PAN TFME, including pH, extraction time, desorption solvent, desorption time, and ion strength were investigated systematically. Under the optimal conditions, both analytes showed good linearity over ranges of 0.070-9.000μgmL(-1) and 0.012-9.000μgmL(-1) in plasma and urine samples, respectively, with correlation coefficients (R(2)) above 0.9990. Limits of detection (LODs) for quetiapine in plasma and urine samples were 0.013 and 0.003μgmL(-1), respectively. LODs for clozapine in plasma and urine samples were 0.015 and 0.003μgmL(-1), respectively. The relative standard deviations (RSDs) for quetiapine and clozapine were less than 9.23%. After the validation, the protocol was successfully applied for the determination of quetiapine and clozapine in patients' plasma and urine samples with satisfactory recoveries between 99-110%. The proposed magnetic ODS-PAN TFME was very simple, fast and easy to handle. It showed high potential as a powerful pretreatment technology for routine therapeutic drug monitoring (TDM) in plasma and urine samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Cytogenetic Effects of Chronic Methylphenidate Treatment and Chronic Social Stress in Adults with Attention-Deficit/Hyperactivity Disorder.

    PubMed

    Kittel-Schneider, S; Spiegel, S; Renner, T; Romanos, M; Reif, A; Reichert, S; Heupel, J; Schnetzler, L; Stopper, H; Jacob, C

    2016-07-01

    Methylphenidate (MPH) is widely used to treat childhood and adult attention-deficit/hyperactivity disorder (ADHD). However, there are still safety concerns about side effects in long-term treatment. The aim of this study was to assess cytogenetic effects of chronic MPH treatment in adult ADHD and to find out if chronic social stress is attenuated by medication and to investigate whether chronic psychosocial stress leads to mutagenic effects by itself. Lymphocytes for micronucleus assay and saliva samples for cortisol measurement were collected from adult ADHD patients and healthy controls. Stress exposure of the last 3 months was assessed by TICS (Trier Inventory for Chronic Stress). We could not detect an influence of MPH treatment on cytogenetic markers. ADHD patients displayed significantly higher chronic stress levels measured by TICS compared to healthy controls which were influenced by duration of MPH treatment. ADHD patients also showed significantly lower basal cortisol levels. We could corroborate that there are neither cytogenetic effects of chronic stress nor of chronic MPH intake even after several years of treatment. © Georg Thieme Verlag KG Stuttgart · New York.

  3. The association between rehabilitation programs and metabolic syndrome in chronic inpatients with schizophrenia.

    PubMed

    Lin, Yi-Chun; Lai, Chien-Liang; Chan, Hung-Yu

    2017-12-02

    The correlation between different rehabilitation programs and the prevalence of metabolic syndrome in people with schizophrenia is unclear. We tested the association in chronic inpatients with schizophrenia of a psychiatric hospital in Taiwan. Patients with schizophrenia and age from 20 to 65 years old were included. The criteria of metabolic syndrome were according to the adapted Adult Treatment Protocol for Asians. According to different types of rehabilitations, patients were divided into work group, occupational therapy group and daily activities group. A total of 359 chronic inpatients with schizophrenia were recruited. Participants had a mean age of 45.9 years and the prevalence of metabolic syndrome was 37.3%. There was a significantly higher prevalence of metabolic syndrome in the work group than in the daily activity group (adjusted odds ratio (aOR) = 1.91, 95% CI = 1.019-3.564, p < 0.05) after adjusted related confounders. Other factors associated with higher prevalence of metabolic syndrome included old age, female gender, low psychotic symptoms severity and clozapine user. This study identified a high prevalence of metabolic syndrome in chronic inpatients with schizophrenia especially in patients with good occupational function. Further investigation of the relationship between the occupational function and metabolic syndrome is necessary for chronic inpatients with schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Chronic Myelogenous Leukemia Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Chronic myelogenous leukemia treatments include tyrosine kinase inhibitors, high-dose therapy with allogeneic transplantation, and other medications. Get detailed information about chronic myelogenous leukemia (CML) treatment options in this summary for clinicians.

  5. Practical Guidelines for the Use of New Generation Antipsychotic Drugs (except Clozapine) in Adult Individuals with Intellectual Disabilities

    ERIC Educational Resources Information Center

    de Leon, Jose; Greenlee, Brian; Barber, Jack; Sabaawi, Mohamed; Singh, Nirbhay N.

    2009-01-01

    New generation antipsychotic (NGA) drugs introduced to the US market after clozapine (aripiprazole, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone) are frequently used in individuals with intellectual disabilities (ID). However, there is very limited research to fully establish evidence-based or personalized medicine approaches…

  6. Treatment of chronic extensor tendons lesions of the fingers.

    PubMed

    Bellemère, P

    2015-09-01

    Chronic finger extensor apparatus injuries are the result of the initial acute treatment having failed or being flawed. Because of their chronic nature, these injuries present various amounts of tendon retraction, tendon callus lengthening, peritendinous scar adhesions, static and dynamic imbalances with the flexor apparatus and intrinsic muscles, and joint contractures. This article will review the anatomy of the extensor mechanism and then will outline by location, the various clinical pictures that are secondary to chronic tendon injury. The clinical presentation of these injuries can be highly variable but their symptomatology and treatment are very specific. Of the possible therapeutic strategies for chronic mallet finger with or without associated swan-neck deformity, chronic boutonniere deformity, chronic sagittal band injuries, old ruptures on the dorsum of the wrist and traumatic defects in multiple tissues, conservative treatment is often the main element. Secondary surgical repair is not free of complications, and the results are often lacking. Rehabilitation and orthotic bracing are an integral part of the management of these injuries, no matter which treatment method is being considered. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  7. [New guidelines on chronic pancreatitis : interdisciplinary treatment strategies].

    PubMed

    Lerch, M M; Bachmann, K A; Izbicki, J R

    2013-02-01

    Chronic pancreatitis is a common disorder associated with significant morbidity and mortality. Interdisciplinary consensus guidelines have recently updated the definitions and diagnostic criteria for chronic pancreatitis and provide a critical assessment of therapeutic procedures. Diagnostic imaging relies on endoscopic ultrasound (EUS) as the most sensitive technique, whereas computed tomography (CT) and magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) remain a frequent preoperative requirement. Endoscopic retrograde cholangiopancreatography (ERCP) is now used mostly as a therapeutic procedure except for the differential diagnosis of autoimmune pancreatitis. Complications of chronic pancreatitis, such as pseudocysts, duct stricture and intractable pain can be treated with endoscopic interventions as well as open surgery. In the treatment of pseudocysts endoscopic drainage procedures now prevail while pain treatment has greater long-term effectiveness following surgical procedures. Currently, endocopic as well as surgical treatment of chronic pancreatitis require an ever increasing degree of technical and medical expertise and are provided increasingly more often by interdisciplinary centres. Surgical treatment is superior to interventional therapy regarding the outcome of pain control and duodenum-preserving pancreatic head resection is presently the surgical procedure of choice.

  8. Chronic constipation: new diagnostic and treatment approaches

    PubMed Central

    Levenick, John M.; Crowell, Michael

    2012-01-01

    Chronic constipation is a highly prevalent disorder that affects approximately 15% of the US population. Chronic constipation refers to patients who have had symptoms for more than 6 months. In clinical practice, chronic constipation is often used interchangeably with the term functional constipation. This is best defined using the Rome III criteria, which involves an evaluation of stool frequency in addition to symptoms of straining, feelings of incomplete evacuation, and the need to use manual maneuvers to assist with stool evacuation. Symptoms can be burdensome, leading to a reduction in patients’ quality of life. As a national healthcare issue, chronic constipation is also important because it imposes a significant economic impact on the healthcare system. A number of treatment options are currently available, both over-the-counter and by prescription, although not all patients respond to these therapies. This review will focus on new medical treatment options for the management of chronic constipation, and the safety and efficacy of these agents will be reviewed. In addition, the efficacy of new diagnostic tests to evaluate colonic motility and anorectal function are described. PMID:22778789

  9. Validation of an algorithm-based definition of treatment resistance in patients with schizophrenia.

    PubMed

    Ajnakina, Olesya; Horsdal, Henriette Thisted; Lally, John; MacCabe, James H; Murray, Robin M; Gasse, Christiane; Wimberley, Theresa

    2018-02-19

    Large-scale pharmacoepidemiological research on treatment resistance relies on accurate identification of people with treatment-resistant schizophrenia (TRS) based on data that are retrievable from administrative registers. This is usually approached by operationalising clinical treatment guidelines by using prescription and hospital admission information. We examined the accuracy of an algorithm-based definition of TRS based on clozapine prescription and/or meeting algorithm-based eligibility criteria for clozapine against a gold standard definition using case notes. We additionally validated a definition entirely based on clozapine prescription. 139 schizophrenia patients aged 18-65years were followed for a mean of 5years after first presentation to psychiatric services in South-London, UK. The diagnostic accuracy of the algorithm-based measure against the gold standard was measured with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). A total of 45 (32.4%) schizophrenia patients met the criteria for the gold standard definition of TRS; applying the algorithm-based definition to the same cohort led to 44 (31.7%) patients fulfilling criteria for TRS with sensitivity, specificity, PPV and NPV of 62.2%, 83.0%, 63.6% and 82.1%, respectively. The definition based on lifetime clozapine prescription had sensitivity, specificity, PPV and NPV of 40.0%, 94.7%, 78.3% and 76.7%, respectively. Although a perfect definition of TRS cannot be derived from available prescription and hospital registers, these results indicate that researchers can confidently use registries to identify individuals with TRS for research and clinical practices. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Chronic inflammatory demyelinating polyneuropathy after treatment with interferon-alpha.

    PubMed

    Hirotani, Makoto; Nakano, Hitoshi; Ura, Shigehisa; Yoshida, Kazuto; Niino, Masaaki; Yabe, Ichiro; Sasaki, Hidenao

    2009-01-01

    Interferon-alpha (IFN-alpha), though widely used for the treatment of chronic viral hepatitis, may be associated with the occurrence of autoimmune disorders. In this case report, a patient with chronic hepatitis C virus infection had chronic inflammatory demyelinating polyneuropathy (CIDP) after the initiation of IFN-alpha therapy. The neurological symptoms of this patient continued to progress even though the treatment with IFN-alpha had been withdrawn; the symptoms improved dramatically following treatment with intravenous immunoglobulin. This case may therefore provide an important clue to understand the immune mechanism of CIDP and IFN-alpha.

  11. Ziconotide for treatment of severe chronic pain.

    PubMed

    Schmidtko, Achim; Lötsch, Jörn; Freynhagen, Rainer; Geisslinger, Gerd

    2010-05-01

    Pharmacological management of severe chronic pain is difficult to achieve with currently available analgesic drugs, and remains a large unmet therapeutic need. The synthetic peptide ziconotide has been approved by the US Food and Drug Administration and the European Medicines Agency for intrathecal treatment of patients with severe chronic pain that is refractory to other treatment modalities. Ziconotide is the first member in the new drug class of selective N-type voltage-sensitive calcium-channel blockers. The ziconotide-induced blockade of N-type calcium channels in the spinal cord inhibits release of pain-relevant neurotransmitters from central terminals of primary afferent neurons. By this mechanism, ziconotide can effectively reduce pain. However, ziconotide has a narrow therapeutic window because of substantial CNS side-effects, and thus treatment with ziconotide is appropriate for only a small subset of patients with severe chronic pain. We provide an overview of the benefits and limitations of intrathecal ziconotide treatment and review potential future developments in this new drug class. Copyright 2010 Elsevier Ltd. All rights reserved.

  12. Evaluation of treatment with carboxymethylcellulose on chronic venous ulcers*

    PubMed Central

    Januário, Virginia; de Ávila, Dione Augusto; Penetra, Maria Alice; Sampaio, Ana Luisa Bittencourt; Noronha Neta, Maria Isabel; Cassia, Flavia de Freire; Carneiro, Sueli

    2016-01-01

    BACKGROUND: Among the chronic leg ulcers, venous ulcers are the most common and constitute a major burden to public health. Despite all technology available, some patients do not respond to established treatments. In our study, carboxymethylcellulose was tested in the treatment of refractory chronic venous ulcers. OBJECTIVE: To evaluate the efficacy of carboxymethylcellulose 20% on the healing of chronic venous ulcers refractory to conventional treatments. METHODS: This is an analytical, pre-experimental study. Thirty patients were included with refractory venous ulcers, and applied dressings with carboxymethylcellulose 20% for 20 weeks. The analysis was based on measurement of the area of ulcers, performed at the first visit and after the end of the treatment. RESULTS: There was a reduction of 3.9 cm2 of lesion area (p=0.0001), corresponding to 38.8% (p=0.0001). There was no interruption of treatment and no increase in lesion area in any patient. CONCLUSIONS: Carboxymethylcellulose 20% represents a low cost and effective therapeutic alternative for the treatment of refractory chronic venous ulcers. However, controlled studies are necessary to prove its efficacy. PMID:26982773

  13. Stem cell treatment for chronic lung diseases.

    PubMed

    Tzouvelekis, Argyris; Ntolios, Paschalis; Bouros, Demosthenes

    2013-01-01

    Chronic lung diseases such as idiopathic pulmonary fibrosis and cystic fibrosis or chronic obstructive pulmonary disease and asthma are leading causes of morbidity and mortality worldwide with a considerable human, societal and financial burden. In view of the current disappointing status of available pharmaceutical agents, there is an urgent need for alternative more effective therapeutic approaches that will not only help to relieve patient symptoms but will also affect the natural course of the respective disease. Regenerative medicine represents a promising option with several fruitful therapeutic applications in patients suffering from chronic lung diseases. Nevertheless, despite relative enthusiasm arising from experimental data, application of stem cell therapy in the clinical setting has been severely hampered by several safety concerns arising from the major lack of knowledge on the fate of exogenously administered stem cells within chronically injured lung as well as the mechanisms regulating the activation of resident progenitor cells. On the other hand, salient data arising from few 'brave' pilot investigations of the safety of stem cell treatment in chronic lung diseases seem promising. The main scope of this review article is to summarize the current state of knowledge regarding the application status of stem cell treatment in chronic lung diseases, address important safety and efficacy issues and present future challenges and perspectives. In this review, we argue in favor of large multicenter clinical trials setting realistic goals to assess treatment efficacy. We propose the use of biomarkers that reflect clinically inconspicuous alterations of the disease molecular phenotype before rigid conclusions can be safely drawn. Copyright © 2013 S. Karger AG, Basel.

  14. Psychological Neuromodulatory Treatments for Young People with Chronic Pain

    PubMed Central

    Miró, Jordi; Castarlenas, Elena; de la Vega, Rocío; Roy, Rubén; Solé, Ester; Tomé-Pires, Catarina; Jensen, Mark P.

    2016-01-01

    The treatment of young people with chronic pain is a complex endeavor. Many of these youth do not obtain adequate relief from available interventions. Psychological neuromodulatory treatments have been shown to have potential benefit for adults with chronic pain. Here, we review and summarize the available information about the efficacy of three promising psychological neuromodulatory treatments—neurofeedback, meditation and hypnosis—when provided to young people with chronic pain. A total of 16 articles were identified and reviewed. The findings from these studies show that hypnotic treatments are effective in reducing pain intensity for a variety of pediatric chronic pain problems, although research suggests variability in outcomes as a function of the specific pain problem treated. There are too few studies evaluating the efficacy of neurofeedback or meditation training in young people with chronic pain to draw firm conclusions regarding their efficacy. However, preliminary data indicate that these treatments could potentially have positive effects on a variety of outcomes (e.g., pain intensity, frequency of pain episodes, physical and psychological function), at least in the short term. Clinical trials are needed to evaluate the effects of neurofeedback and meditation training, and research is needed to identify the moderators of treatment benefits as well as better understand the mechanisms underlying the efficacy of all three of these treatments. The findings from such research could enhance overall treatment efficacy by: (1) providing an empirical basis for better patient-treatment matching; and (2) identifying specific mechanisms that could be targeted with treatment. PMID:27929419

  15. Neuromodulatory treatments for chronic pain: efficacy and mechanisms

    PubMed Central

    Jensen, Mark P.; Day, Melissa A.; Miró, Jordi

    2017-01-01

    Chronic pain is common, and the available treatments do not provide adequate relief for most patients. Neuromodulatory interventions that modify brain processes underlying the experience of pain have the potential to provide substantial relief for some of these patients. The purpose of this Review is to summarize the state of knowledge regarding the efficacy and mechanisms of noninvasive neuromodulatory treatments for chronic pain. The findings provide support for the efficacy and positive side-effect profile of hypnosis, and limited evidence for the potential efficacy of meditation training, noninvasive electrical stimulation procedures, and neurofeedback procedures. Mechanisms research indicates that hypnosis influences multiple neurophysiological processes involved in the experience of pain. Evidence also indicates that mindfulness meditation has both immediate and long-term effects on cortical structures and activity involved in attention, emotional responding and pain. Less is known about the mechanisms of other neuromodulatory treatments. On the basis of the data discussed in this Review, training in the use of self-hypnosis might be considered a viable ‘first-line’ approach to treat chronic pain. More-definitive research regarding the benefits and costs of meditation training, noninvasive brain stimulation and neurofeedback is needed before these treatments can be recommended for the treatment of chronic pain. PMID:24535464

  16. Neuromodulatory treatments for chronic pain: efficacy and mechanisms.

    PubMed

    Jensen, Mark P; Day, Melissa A; Miró, Jordi

    2014-03-01

    Chronic pain is common, and the available treatments do not provide adequate relief for most patients. Neuromodulatory interventions that modify brain processes underlying the experience of pain have the potential to provide substantial relief for some of these patients. The purpose of this Review is to summarize the state of knowledge regarding the efficacy and mechanisms of noninvasive neuromodulatory treatments for chronic pain. The findings provide support for the efficacy and positive side-effect profile of hypnosis, and limited evidence for the potential efficacy of meditation training, noninvasive electrical stimulation procedures, and neurofeedback procedures. Mechanisms research indicates that hypnosis influences multiple neurophysiological processes involved in the experience of pain. Evidence also indicates that mindfulness meditation has both immediate and long-term effects on cortical structures and activity involved in attention, emotional responding and pain. Less is known about the mechanisms of other neuromodulatory treatments. On the basis of the data discussed in this Review, training in the use of self-hypnosis might be considered a viable 'first-line' approach to treat chronic pain. More-definitive research regarding the benefits and costs of meditation training, noninvasive brain stimulation and neurofeedback is needed before these treatments can be recommended for the treatment of chronic pain.

  17. Chronic constipation: Current treatment options

    PubMed Central

    Liu, Louis Wing Cheong

    2011-01-01

    Chronic constipation is a common functional gastrointestinal disorder that affects patients of all ages. In 2007, a consensus group of 10 Canadian gastroenterologists developed a set of recommendations pertaining to the management of chronic constipation and constipation-dominant irritable bowel syndrome. Since then, tegaserod has been withdrawn from the Canadian market. A new, highly selective serotonin receptor subtype 4 agonist, prucalopride, has been examined in several large, randomized, placebo-controlled trials demonstrating its efficacy and safety in the management of patients with chronic constipation. Additional studies evaluating the use of stimulant laxatives, polyethylene glycol and probiotics in the management of chronic constipation have also been published. The present review summarizes the previous recommendations and new evidence supporting different treatment modalities – namely, diet and lifestyle, bulking agents, stool softeners, osmotic and stimulant laxatives, prucalopride and probiotics in the management of chronic constipation. A brief summary of lubiprostone and linaclotide is also presented. The quality of evidence is presented by adopting the Grading of Recommendations, Assessment, Development and Evaluation system. Finally, a management pyramid for patients with chronic constipation is proposed based on the quality of evidence, impact of each modality on constipation and on general health, and their availabilities in Canada. PMID:22114754

  18. Clozapine and olanzapine but not risperidone impair the pre-frontal striatal system in relation to egocentric spatial orientation in a Y-maze.

    PubMed

    Castro, Cibele Canal; Dos Reis-Lunardelli, Eleonora Araujo; Schmidt, Werner J; Coitinho, Adriana Simon; Izquierdo, Iván

    2007-11-01

    Many studies indicate a dissociation between two forms of orientation: allocentric orientation, in which an organism orients on the basis of cues external to the organism, and egocentric spatial orientation (ESO) by which an organism orients on the basis of proprioceptive information. While allocentric orientation is mediated primarily by the hippocampus and its afferent and efferent connections, ESO is mediated by the prefronto-striatal system. Striatal lesions as well as classical neuroleptics, which block dopamine receptors, act through the prefronto-striatal system and impair ESO. The purpose of the present study was to determine the effects of the atypical antipsychotics clozapine, olanzapine and risperidone which are believed to exert its antipsychotic effects mainly by dopaminergic, cholinergic and serotonergic mechanisms. A delayed-two-alternative-choice-task, under conditions that required ESO and at the same time excluded allocentric spatial orientation was used. Clozapine and olanzapine treated rats made more errors than risperidone treated rats in the delayed alternation in comparison with the controls. Motor abilities were not impaired by any of the drugs. Thus, with regard to the delayed alternation requiring ESO, clozapine and olanzapine but not risperidone affects the prefronto-striatal system in a similar way as classical neuroleptics does.

  19. What's New in Chronic Lymphocytic Leukemia Research and Treatment?

    MedlinePlus

    ... Lymphocytic Leukemia (CLL) About Chronic Lymphocytic Leukemia What's New in Chronic Lymphocytic Leukemia Research and Treatment? Research ... help researchers learn more about how CLL develops. New drugs for chronic lymphocytic leukemia Dozens of new ...

  20. Treatment patterns of schizophrenia based on the data from seven Central and Eastern European Countries.

    PubMed

    Szkultecka-Dębek, Monika; Miernik, Katarzyna; Stelmachowski, Jarosław; Jakovljević, Miro; Jukić, Vlado; Aadamsoo, Kaire; Janno, Sven; Bitter, István; Tolna, Judit; Jarema, Marek; Jankovic, Slobodan; Pecenak, Jan; Vavrusova, Livia; Tavčar, Rok; Walczak, Jacek; Talbot, Darren; Augustyńska, Joanna

    2016-09-01

    The aim is to analyze how schizophrenia is pharmacologically treated in seven CEE countries: Croatia, Estonia, Hungary, Poland, Serbia, Slovakia and Slovenia. Psychiatrists from selected centers in each of participating countries were asked to complete a pre-defined questionnaire on their current clinical practice. Information on protocols and resource utilization in schizophrenia treatment was included and derived from randomly selected patient medical records. Expert opinions on country-wide treatment patterns were additionally sought. This sub-analysis focuses on pharmacological treatment patterns in the last six months and over the course of the disease. 961 patients' data show that during last six months the most commonly prescribed medications were oral atypical antipsychotics: olanzapine (n=268), clozapine (n=234) and risperidone (n=160). The most frequently prescribed atypical antipsychotics over course of disease were: risperidone (54.5%), olanzapine (52.4%) and clozapine (35.1%), along with haloperidol (39.3%). Experts reported risperidone (four countries) and olanzapine (three countries) as first-line treatment, with the same two medications prescribed as second-line treatment. Clozapine was the most reported medication for refractory patients. Approximately 22% of patients received polypharmacy with antipsychotics in at least one period over the disease course. Mean time since diagnosis was 13.1 years and on average 4.8 treatment courses received during that period. Anxiolytics (70%), antidepressants (42%), mood-stabilizers (27%) were also prescribed, with diazepam (35.4%), sertraline (10.5%), valproic acid (17.5%) the most commonly reported, respectively, in each group. The most frequently reported treatment change was switch from one oral atypical antipsychotic to another (51%). Oral atypical antipsychotics, mostly older drugs (risperidone, olanzapine, clozapine), were most commonly prescribed for schizophrenia treatment in participating countries

  1. Evaluation of the performance of a point-of-care method for total and differential white blood cell count in clozapine users.

    PubMed

    Bui, H N; Bogers, J P A M; Cohen, D; Njo, T; Herruer, M H

    2016-12-01

    We evaluated the performance of the HemoCue WBC DIFF, a point-of-care device for total and differential white cell count, primarily to test its suitability for the mandatory white blood cell monitoring in clozapine use. Leukocyte count and 5-part differentiation was performed by the point-of-care device and by routine laboratory method in venous EDTA-blood samples from 20 clozapine users, 20 neutropenic patients, and 20 healthy volunteers. From the volunteers, also a capillary sample was drawn. Intra-assay reproducibility and drop-to-drop variation were tested. The correlation between both methods in venous samples was r > 0.95 for leukocyte, neutrophil, and lymphocyte counts. The correlation between point-of-care (capillary sample) and routine (venous sample) methods for these cells was 0.772; 0.817 and 0.798, respectively. Only for leukocyte and neutrophil counts, the intra-assay reproducibility was sufficient. The point-of-care device can be used to screen for leukocyte and neutrophil counts. Because of the relatively high measurement uncertainty and poor correlation with venous samples, we recommend to repeat the measurement with a venous sample if cell counts are in the lower reference range. In case of clozapine therapy, neutropenia can probably be excluded if high neutrophil counts are found and patients can continue their therapy. © 2016 John Wiley & Sons Ltd.

  2. A two-hit model of suicide-trait-related behaviors in the context of a schizophrenia-like phenotype: Distinct effects of lithium chloride and clozapine.

    PubMed

    Deslauriers, Jessica; Belleville, Karine; Beaudet, Nicolas; Sarret, Philippe; Grignon, Sylvain

    2016-03-15

    Schizophrenia patients show a high rate of premature mortality due to suicide. The pathophysiological mechanisms of these suicidal behaviors in schizophrenia do not appear to involve serotonergic neurotransmission as found in the general population. Our aim was to develop an in vivo model of schizophrenia presenting suicide-trait-related behaviors such as aggressiveness, impulsivity, anxiety and helplessness. We opted for a two-hit model: C57BL/6 dams were injected with polyI:C on gestational day 12. The pups were submitted to social isolation for 4weeks after weaning. During the last week of social isolation and 30min before behavioral testing, the mice received vehicle, lithium chloride or clozapine. Lithium chloride is well known for its suicide preventive effects in the non-schizophrenic population, while clozapine is the antipsychotic with the best-established suicide preventive effect. The two-hit model induced several schizophrenia-related and suicide-trait-related behaviors in male, but not female, mice. Additionally, lithium chloride improved prepulse inhibition, aggressiveness, impulsivity and anxiety-like behavior in socially isolated mice only, whereas clozapine prevented behavioral abnormalities mainly in mice prenatally exposed to polyI:C and submitted to isolated rearing. The distinct effects of lithium chloride and clozapine suggested that mice prenatally exposed to polyI:C and submitted to social isolation presented a distinct phenotype from that of mice submitted to social isolation only. Because diagnosing suicidal risk in patients is a challenge for psychiatrists given the lack of specific clinical predictors, our in vivo model could help in gaining a better understanding of the mechanisms underlying suicidal behavior in the context of schizophrenia. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Cardiac transcriptional response to acute and chronic angiotensin II treatments.

    PubMed

    Larkin, Jennie E; Frank, Bryan C; Gaspard, Renee M; Duka, Irena; Gavras, Haralambos; Quackenbush, John

    2004-07-08

    Exposure of experimental animals to increased angiotensin II (ANG II) induces hypertension associated with cardiac hypertrophy, inflammation, and myocardial necrosis and fibrosis. Some of the most effective antihypertensive treatments are those that antagonize ANG II. We investigated cardiac gene expression in response to acute (24 h) and chronic (14 day) infusion of ANG II in mice; 24-h treatment induces hypertension, and 14-day treatment induces hypertension and extensive cardiac hypertrophy and necrosis. For genes differentially expressed in response to ANG II treatment, we tested for significant regulation of pathways, based on Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Microarray Pathway Profiler (GenMAPP) databases, as well as functional classes based on Gene Ontology (GO) terms. Both acute and chronic ANG II treatments resulted in decreased expression of mitochondrial metabolic genes, notably those for the electron transport chain and Krebs-TCA cycle; chronic ANG II treatment also resulted in decreased expression of genes involved in fatty acid metabolism. In contrast, genes involved in protein translation and ribosomal activity increased expression following both acute and chronic ANG II treatments. Some classes of genes showed differential response between acute and chronic ANG II treatments. Acute treatment increased expression of genes involved in oxidative stress and amino acid metabolism, whereas chronic treatments increased cytoskeletal and extracellular matrix genes, second messenger cascades responsive to ANG II, and amyloidosis genes. Although a functional linkage between Alzheimer disease, hypertension, and high cholesterol has been previously documented in studies of brain tissue, this is the first demonstration of induction of Alzheimer disease pathways by hypertension in heart tissue. This study provides the most comprehensive available survey of gene expression changes in response to acute and chronic ANG II treatment, verifying

  4. Endoscopic versus surgical drainage treatment of calcific chronic pancreatitis.

    PubMed

    Jiang, Li; Ning, Deng; Cheng, Qi; Chen, Xiao-Ping

    2018-04-21

    Endoscopic therapy and surgery are both conventional treatments to remove pancreatic duct stones that developed during the natural course of chronic pancreatitis. However, few studies comparing the effect and safety between surgery drainage and endoscopic drainage (plus Extracorporeal Shock Wave Lithotripsy, ESWL).The aim of this study was to compare the benefits between endoscopic and surgical drainage of the pancreatic duct for patients with calcified chronic pancreatitis. A total of 86 patients were classified into endoscopic/ESWL (n = 40) or surgical (n = 46) treatment groups. The medical records of these patients were retrospectively analyzed. Pain recurrence and hospital stays were similar between the endoscopic/ESWL treatment and surgery group. However, endoscopic/ESWL treatment yielded significantly lower medical expense and less complications compared with the surgical treatment. In selective patients, endoscopic/ESWL treatment could achieve comparable efficacy to the surgical treatment. With lower medical expense and less complications, endoscopic/ESWL treatment would be much preferred to be the initial treatment of choice for patients with calcified chronic pancreatitis. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  5. Contemporary treatment options for chronic prostatitis/chronic pelvic pain syndrome.

    PubMed

    Ismail, M; Mackenzie, K; Hashim, H

    2013-07-01

    The prostate gland, about the size a walnut, forms part of the male reproductive system and sits directly underneath the bladder surrounding the urethra. It is a fibromuscular exocrine gland that secretes a complex proteolytic fluid which constitutes one-third of the volume of the seminal fluid. Prostatitis refers to a group of disorders that affect the prostate and cause genitourinary pain, dysuria, urinary frequency and sexual dysfunction. The prevalence of prostatitis in the United States has been estimated to be around 9%, while the worldwide prevalence ranges from 2 to 10%, and 15% of men experience prostatitis-like symptoms at some point in their lives. There are a number of treatments which have been used for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), with only a small amount of high-level evidence. The current recommended treatment for CP/CPPS is predominantly a multimodal approach using a combination of antibiotics, α-blockers, antimuscarinic and anti-inflammatory drugs. The response to treatment and improvement in symptoms is very variable; therefore, as the evidence evolves, it is likely that treatment will become symptom specific rather than a generic, 'one strategy fits all' treatment for CP/CPPS. Copyright 2013 Prous Science, S.A.U. or its licensors. All rights reserved.

  6. Psychopharmacological treatment of aggression in schizophrenic patients.

    PubMed

    Brieden, T; Ujeyl, M; Naber, D

    2002-05-01

    Aggressive behavior is frequently observed in schizophrenic patients. More than 50 % of all psychiatric patients and 10 % of schizophrenic patients show aggressive symptoms varying from threatening behavior and agitation to assault. The pharmacological treatment of acute, persisting and repetitive aggression is a serious problem for other patients and staff members. Not only is violent behavior from mentally ill patients the most detrimental factor in their stigmatization, aggression is also a considerable direct source of danger for the patients themselves. Based on rather limited evidence, a wide variety of medications for the pharmacological treatment of aggression has been recommended: typical and atypical antipsychotics, benzodiazepines, mood stabilizers, beta-blockers and selective serotonin reuptake inhibitors (SSRIs). Most clinical information on treating aggression has been collected for atypical neuroleptics, particularly for clozapine. Several retrospective and open studies indicate its efficacy. Treatment duration of 6 months is recommended to induce a stable reduction of physical and verbal aggression. Severe side effects have very rarely been seen. At the moment, clozapine seems to be the first choice in aggression treatment. Within the last few years, about 10 articles were published showing that this is the most effective antiaggressive agent in the treatment of aggression and agitation in psychiatric patients, independent of psychiatric diagnosis. However, clozapine, like all the other substances used, does not have an established indication for the treatment of aggressive symptoms. Noncompliance with medication makes it difficult to choose the right preparation for the medication: tablets, liquids, intramuscular injections and readily soluble "FDDFs" are available. Ethical, juridical and methodological problems prevent controlled studies from establishing a reference in the treatment of aggression in mentally ill patients. This review summarizes

  7. Effect of Shodhana Treatment on Chronic Toxicity and Recovery of Aconite

    PubMed Central

    Sarkar, P.K.; Prajapati, P.K.; Shukla, V.J.; Ravishankar, B.

    2012-01-01

    Aconite is one of the poisonous plants used therapeutically in practice of Ayurveda after proper treatment called as ‘Shodhana’. To determine the effect of Shodhana treatment on chronic toxicity and to assess the effect of recovery period after chronic toxicity of aconite. Raw aconite (RV), urine treated aconite (SM), and milk treated aconite (SD) were administered in 6.25 mg/kg dose in Charles Foster strain albino rats for 90 days for chronic toxicity. Six rats from each were kept for another 30 days without test drugs treatment to observe recovery from chronic toxicity. RV was found to be highly toxic in chronic exposure, SM had no apparent toxicity, but SD had mild toxicity in kidney. The toxicities of RV and SD were reversible, but sudden withdrawal of SM caused adverse effects, suggestive of tapering withdrawal. Shodhana treatments remove toxic effects from raw aconite. Chronic toxicity of aconite is reversible. Confirmed the arrangement of abstract PMID:22736901

  8. [Use of decamethoxine in the complex treatment of chronic bronchitis].

    PubMed

    Iukhimets, V A; Pilipchuk, V N

    1990-02-01

    Seventy-two patients with chronic bronchitis were examined and divided into 3 groups. Group I consisted of patients with chronic catarrhal bronchitis (CCB) group II of those with chronic purulent bronchitis (CPB), group III of subjects with bronchitis associated with purulent destructive pulmonary diseases. All the patients received combined treatment with decamethoxin as an antibacterial modality. It was found that decamethoxin promotes elimination of the infection of the bronchial secretion in 60% of chronic bronchitis suffers, the incidence of microorganisms resistent to several antibiotics reduced 2-fold. Local use of decamethoxin as an antibacterial and antiinflammatory drug in multimodality treatment of chronic purulent bronchitis proved highly effective.

  9. Effects of acute and chronic cilazapril treatment in spontaneously hypertensive rats

    PubMed Central

    Fischli, W.; Hefti, F.; Clozel, J.-P.

    1989-01-01

    1 The effects of acute and chronic treatment with cilazapril, a new ACE inhibitor, on peripheral vasculature and renal excretory function were assessed in spontaneously hypertensive rats. Regional blood flow and cardiac output were measured by the radio-active microspheres technique. 2 Acute treatment (3 mg kg-1 intravenously) reduced mean arterial blood pressure from 171 ± 7 to 140 241 ± 7 mm Hg (P < 0.001), chronic treatment (1 × 10 mg kg-1 day-1 orally for 9 weeks) from 191 ± 5 to 122 ± 3 mm Hg P < 0.001). With both kinds of treatments cardiac output was unchanged. Heart rate was slightly decreased (-9%, P < 0.05) with chronic treatment. Acutely, the main effect of cilazapril was a decrease of the renal vascular resistance (-41%, P < 0.001) associated with an increase of the fraction of the cardiac output distributed to the kidney (+46%, P < 0.001). Chronically, cilazapril decreased regional vascular resistance in most of the peripheral vascular beds except the heart. 3 With a high dose of cilazapril (10 mg kg-1 orally) both acute and chronic treatment increased diuresis (+107% and +92%, P < 0.001) and natriuresis (+124% and +111%, P < 0.001) with a slight increase in kaliuresis. However, with a low dose (1 mg kg-1 orally) the kidneys responded only to chronic treatment. 4 It is concluded that chronic treatment with cilazapril decreases arterial blood pressure more than acute treatment. This effect seems to be due to a greater peripheral vasodilation. In addition, diuretic and natriuretic effects of cilazapril probably contribute to blood pressure reduction. PMID:2527529

  10. The effects of antipsychotic switching on diabetes in chronic schizophrenia.

    PubMed

    Arnoldy, R; Curtis, J; Samaras, K

    2014-03-01

    People with severe mental illness have a 20-year life-expectancy shortfall. The majority of antipsychotic medications are associated with obesity and heightened diabetes risk. People with severe mental illness less frequently achieve benchmarked diabetes care, often attributed to poor adherence, lower clinical attendance and documented medical biases in treatment. This case is presented to highlight the profound effect medication change can have on diabetes control. A 56-year-old man with a 42-year history of schizophrenia had required clozapine treatment for the preceding 14 years. Type 2 diabetes and obesity occurred within 4 years of clozapine instigation. Glycaemic control had been continuously poor, despite frequent contact with diabetes services and multiple medications, including insulin at a dose exceeding 200 IU daily. Request for consideration of antipsychotic review and close interaction with the psychiatry team was initiated at the diabetes outpatient clinic. A gradual medication switch from clozapine to aripiprazole was associated with a reduction in HbA(1c) from 80 to 50 mmol/mol (9.5 to 6.7%) over 4 months, associated with a weight loss of 10 kg. Over the ensuing 2 years, the improvement in HbA(1c) has endured, with total weight loss of 13 kg and halving of insulin requirements. This case illustrates the benefits of engagement between endocrinologists and psychiatrists to achieve the shared goal of improved physical health in severe mental illness. Greater interdisciplinary collaboration will help bridge the life-expectancy gap in severe mental illness and may assist in preventing disabling diabetes complications in this vulnerable patient group. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

  11. Two distinct patterns of treatment resistance: clinical predictors of treatment resistance in first-episode schizophrenia spectrum psychoses.

    PubMed

    Lally, J; Ajnakina, O; Di Forti, M; Trotta, A; Demjaha, A; Kolliakou, A; Mondelli, V; Reis Marques, T; Pariante, C; Dazzan, P; Shergil, S S; Howes, O D; David, A S; MacCabe, J H; Gaughran, F; Murray, R M

    2016-11-01

    Clozapine remains the only evidence-based antipsychotic for treatment-resistant schizophrenia (TRS). The ability to predict which patients with their first onset of schizophrenia would subsequently meet criteria for treatment resistance (TR) could help to diminish the severe functional disability which may ensue if TR is not recognized and correctly treated. This is a 5-year longitudinal assessment of clinical outcomes in a cohort of 246 first-episode schizophrenia spectrum patients recruited as part of the NIHR Genetics and Psychosis (GAP) study conducted in South London from 2005 to 2010. We examined the relationship between baseline demographic and clinical measures and the emergence of TR. TR status was determined from a review of electronic case records. We assessed for associations with early-, and late-onset TR, and non-TR, and differences between those TR patients treated with clozapine and those who were not. Seventy per cent (n = 56) of TR patients, and 23% of the total study population (n = 246) were treatment resistant from illness onset. Those who met criteria for TR during the first 5 years of illness were more likely to have an early age of first contact for psychosis (<20 years) [odds ratio (OR) 2.49, 95% confidence interval (CI) 1.25-4.94] compared to those with non-TR. The relationship between an early age of first contact (<20 years) and TR was significant in patients of Black ethnicity (OR 3.71, 95% CI 1.44-9.56); and patients of male gender (OR 3.13 95% CI 1.35-7.23). For the majority of the TR group, antipsychotic TR is present from illness onset, necessitating increased consideration for the earlier use of clozapine.

  12. [Latex ligation in treatment of chronic hemorrhoids].

    PubMed

    Ektov, V N; Somov, K A

    2015-01-01

    We analyzed the results of treatment of 432 patients with chronic hemorrhoids using different variants of latex ligation. New technique including ligation of mucosa and submucosa of low-ampullar rectum providing ligation of hemorrhoidalvessels, lifting and recto-anal repair is developed and suggested. This method is advisable to use in case of chronic internal hemorrhoids stages I and II. The authors recommend simultaneous combined ligation of mucosa of low-ampullar rectum and internal hemorrhoids for stages III and IV. Different variants of latex ligation with external hemorrhoids excision were used in 103 patients. Pointed variants of latex ligation preserve important advantages including mini-invasiveness, simplicity and wide availability, low cost. Good remote results were obtained after these procedures in 87.3% of observations. Suggested tactics extends use of latex ligation and increases its effectiveness in treatment of different stages and forms of chronic hemorrhoids.

  13. Lubiprostone: a novel treatment for chronic constipation.

    PubMed

    Lacy, Brian E; Levy, L Campbell

    2008-01-01

    Chronic constipation is highly prevalent, reduces patients' quality of life, and imposes a significant health care burden on society. Lifestyle modifications and over-the-counter agents improve symptoms of constipation in some patients, however many patients have persistent symptoms and require the use of prescription medications. Three prescription medications are currently Food and Drug Administration (FDA) approved and available for the treatment of chronic constipation in adults. This review will focus on lubiprostone, the newest medication available for the treatment of chronic constipation. Lubiprostone is a bicyclic fatty acid metabolite analogue ofprostaglandin E1. It activates specific chloride channels in the gastrointestinal tract to stimulate intestinal fluid secretion, increase gastrointestinal transit, and improve symptoms of constipation. This article will provide a brief overview on chloride channel function in the gastrointestinal tract, describe the structure, function, and pharmacokinetics of lubiprostone, and discuss the safety and efficacy of this new medication.

  14. A Double Blind, Placebo- controlled Trial of Rosiglitazone for Clozapine induced Glucose Metabolism Impairment in patients with Schizophrenia

    PubMed Central

    Henderson, David C.; Fan, Xiaoduo; Sharma, Bikash; Copeland, Paul M.; Borba, Christina P; Boxill, Ryan; Freudenreich, Oliver; Cather, Corey; Evins, A. Eden; Goff, Donald C.

    2014-01-01

    Objective The primary purpose of this eight week double blind, placebo-controlled trial of rosiglitazone 4 mg/day was to examine its effect on insulin sensitivity index (SI) and glucose utilization (SG) in clozapine-treated schizophrenia subjects with insulin resistance. Methods Eighteen subjects were randomized and accessed with a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) at the baseline and week 8 to estimate SG, and SI. Results Controlling for the baseline, comparing the rosiglitazone group to placebo group, there was a non-significant improvement of SG (0.016± 0.006 to 0.018± 0.008, effect size= 0.23, p= 0.05) with a trend of improvement in SI in the rosiglitazone group (4.6± 2.8 to 7.8± 6.7, effect size= 0.18, p= 0.08). There was a significant reduction in small low-density-lipoprotein cholesterol (LDL-C)- particle number (987± 443 to 694± 415, effect size= 0.30, p= 0.04). Conclusion Rosiglitazone may have a role in addressing the insulin resistance and lipid abnormalities associated with clozapine. PMID:19183127

  15. The stability of amitriptyline N-oxide and clozapine N-oxide on treated and untreated dry blood spot cards.

    PubMed

    Temesi, David; Swales, John; Keene, Warren; Dick, Samuel

    2013-03-25

    Procedures for drug monitoring based on Dried Blood Spot (DBS) sampling are gaining acceptance for an increasing number of clinical and preclinical applications, where ease of use, small sample requirement, and improved sample stability have been shown to offer advantages over blood tube sampling. However, to-date, the vast majority of this work has described the analysis of well characterized drugs. Using amitriptyline, clozapine, and their potentially labile N-oxide metabolites as model compounds, we consider the merits of using DBS for discovery pharmacokinetic (PK) studies where the metabolic fate of test compounds are often unknown. Both N-oxide metabolites reverted to parent compound under standard drying (2hr) and extraction conditions. Card type significantly affected the outcome, with 14% and 22% degradation occurring for clozapine-N-oxide and amitriptyline-N-oxide on a brand of untreated DBS cards, compared to 59 and 88% on a brand of treated DBS cards. Enrichment of the parent compound ex vivo leads to overestimation of circulating blood concentration and inaccurate determination of the PK profile. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Catatonia in Psychotic Patients: Clinical Features and Treatment Response

    PubMed Central

    England, Mary L.; Öngür, Dost; Konopaske, Glenn T.; Karmacharya, Rakesh

    2012-01-01

    We report clinical features and treatment response in 25 patients with catatonia admitted to an inpatient psychiatric unit specializing in psychotic disorders. ECT, benzodiazepines, and clozapine had beneficial effects on catatonic features, while typical antipsychotics resulted in clinical worsening. PMID:21677256

  17. [Efficiency of multidisciplinary treatment of chronic pain with locomotor disability].

    PubMed

    Collado Cruz, A; Torres i Mata, X; Arias i Gassol, A; Cerdà Gabaroi, D; Vilarrasa, R; Valdés Miyar, M; Muñoz-Gómez, J

    2001-10-13

    Disabling chronic pain is especially devastating among working population and, in many cases, it does not respond to conventional therapies. In chronic pain, the importance of psychosocial and occupational factors, in addition to biological ones, has prompted the development of successful multidisciplinary treatment programmes in various countries. We assessed the outcome of a multidisciplinary therapeutic program for work-disabled selected patients with chronic pain refractory to conventional treatment. The study included 70 patients (58 women, mean age [SD]: 42 [9]years) with chronic pain and sick leave (mean [SD]: 7 [4] months of work disability) diagnosed with fibromyalgia (51%), chronic low back pain (16%), regional myofascial pain (15%), cervicocraneal syndrome (3%), anquilosing spondylitis (3%), and other conditions(12%). All patients had received previous pharmacological treatment,physical therapy and/or other measures (surgery in 12% cases)without improvement. All patients underwent an intensive multidisciplinary treatment of 4 weeks' duration including medical techniques for pain control, cognitive-behavioural therapy, physical therapy,and occupational therapy. Average follow-up was 10 (4) months(1-24 months) post-discharge. Significant improvements were observed with regard to all relevant variables, as reflected in pre and post-discharge measures: pain(Visual-Analogue Scale 1-10 cm): 7.4 (1.5) versus 3.2 (2) (p <0.01); anxiety (HARS), 19 (7) versus 14 (8) (p < 0.01); depression(BDI), 16 (8) versus 10 (8) (p < 0.01); functional ability(HAQ), 1.6 (0.4) versus 0.6 (0.5) (p < 0.001). At discharge,73% of patients returned to work. In addition, 69% of treated patients maintained the acquired improvement and their employment status at the end of follow-up. Multidisciplinary treatment of chronic pain with special attention to work return is useful for selected patients with a disabling chronic pain syndrome refractory to conventional treatment.

  18. [Application of cryogenic stimulation in treatment of chronic wounds].

    PubMed

    Vinnik, Iu S; Karapetian, G E; Iakimov, S V; Sychev, A G

    2008-01-01

    The authors have studied alterations occurring both in the ultrastructure of the cell matrix and in the microcirculatory bed of the chronic wound after local exposure to cryoagent. The up-to-date effective methods including laser Doppler flowmetry were used followed by correct statistical processing of the data obtained. The cryogenic stimulation of the wound was shown to result in considerably improved perfusion of the microcirculatory bed, epithelization and remodeling of the scar. It allowed transformation of a chronic process into acute and thus led to considerably accelerated process of regeneration. The developed method of cryogenic treatment of the chronic wound was used in 35 patients, allowed quicker healing of the chronic wounds and made ambulatory treatment of the patients 3 weeks shorter.

  19. Treatment of chronic plantar fasciopathy with extracorporeal shock waves (review)

    PubMed Central

    2013-01-01

    There is an increasing interest by doctors and patients in extracorporeal shock wave therapy (ESWT) for chronic plantar fasciopathy (PF), particularly in second generation radial extracorporeal shock wave therapy (RSWT). The present review aims at serving this interest by providing a comprehensive overview on physical and medical definitions of shock waves and a detailed assessment of the quality and significance of the randomized clinical trials published on ESWT and RSWT as it is used to treat chronic PF. Both ESWT and RSWT are safe, effective, and technically easy treatments for chronic PF. The main advantages of RSWT over ESWT are the lack of need for any anesthesia during the treatment and the demonstrated long-term treatment success (demonstrated at both 6 and 12 months after the first treatment using RSWT, compared to follow-up intervals of no more than 12 weeks after the first treatment using ESWT). In recent years, a greater understanding of the clinical outcomes in ESWT and RSWT for chronic PF has arisen in relationship not only in the design of studies, but also in procedure, energy level, and shock wave propagation. Either procedure should be considered for patients 18 years of age or older with chronic PF prior to surgical intervention. PMID:24004715

  20. The diagnosis and treatment of chronic migraine

    PubMed Central

    2015-01-01

    Migraine is the most common disabling brain disorder. Chronic migraine, a condition characterized by the experience of migrainous headache on at least 15 days per month, is highly disabling. Patients with chronic migraine present to primary care, are often referred for management to secondary care, and make up a large proportion of patients in specialist headache clinics. Many patients with chronic migraine also have medication overuse, defined as using a compound analgesic, opioid, triptan or ergot derivative on at least 10 days per month. All doctors will encounter patients with chronic headaches. A basic working knowledge of the common primary headaches, and a rational manner of approaching the patient with these conditions, allows a specific diagnosis of chronic migraine to be made quickly and safely, and by making this diagnosis one opens up a substantial number of acute and preventive treatment options. This article discusses the current state of management of chronic migraine. PMID:25954496

  1. [Thought and method of classic formulae in treatment of chronic cough].

    PubMed

    Su, Ke-Lei; Zhang, Ye-Qing

    2018-06-01

    Chronic cough is a common clinical disease with complex etiology, which is easily misdiagnosed and mistreated. Chronic cough guideline has been developed based on the modern anatomical etiology classification, and it may improve the level of diagnosis and treatment. Common causes of chronic cough are as follows: cough variant asthma, upper airway cough syndrome, eosinophilic bronchitis, gastroesophageal reflux-related cough, post-infectious cough, etc. There is a long history and rich experience in treatment of cough in traditional Chinese medicine which is characterized by syndrome differentiation. The four elements of pathogenesis for chronic cough include wind, phlegm, fire, and deficiency. Classic formula is widely used in the treatment of chronic cough, and the focus is on prescriptions corresponding to syndromes. This article attempts to explore the thought and method of classic formulae in treatment of chronic cough based on three perspectives: differentiation of etiology, pathogenesis and formula-syndrome. Three medical cases are selected at last in order to prove its correction. Copyright© by the Chinese Pharmaceutical Association.

  2. Effect of 'chronic' versus 'acute' ketamine administration and its 'withdrawal' effect on behavioural alterations in mice: implications for experimental psychosis.

    PubMed

    Chatterjee, Manavi; Ganguly, Surajit; Srivastava, Mukesh; Palit, Gautam

    2011-01-01

    Lack of appropriate animal models simulating core behavioural aspects of human psychosis is a major limitation in schizophrenia research. The use of drugs, that is believed to act through N-methyl d-aspartate receptor, has been demonstrated to mimic relatively broader range of behavioural symptoms in putative animal models. Our goal in this study has been to further evaluate one such drug, ketamine in mice and characterize some selective behavioural phenotypes associated with the drug dosage, treatment period and withdrawal effects to extend the understanding of this model. Our results indicate that acute treatment of ketamine (100 mg/kg, i.p.) induced hyperlocomotory response and reduced the 'transfer-latency time' in passive avoidance test but did not have any effect in the forced swim test (negative symptoms). In contrast, chronic administration of ketamine not only produced significant 'hyperactivity' response but also enhanced the immobility period in animals during the forced swim test and reduced the latency period in the passive avoidance test. Further, these behavioural alterations persisted at least for 10 days after the withdrawal of ketamine treatment. These observations were substantiated by using standard typical and atypical antipsychotic drugs, haloperidol (0.25 mg/kg, i.p.), clozapine (10 mg/kg, i.p.) and risperidone (0.025 mg/kg, i.p.). Therefore, the present study suggests that the chronic treatment with ketamine has the potential of exhibiting changes in broader range of behavioural domains than the acute treatment. Hence, animals chronically treated with ketamine might serve as a useful tool to study the underlying pathogenic mechanisms associated with some symptoms in schizophrenia and other psychiatric disorders. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Medium-level laser in chronic tinnitus treatment.

    PubMed

    Dejakum, K; Piegger, J; Plewka, C; Gunkel, A; Thumfart, W; Kudaibergenova, S; Goebel, G; Kral, F; Freysinger, W

    2013-01-01

    The purpose of this study was to evaluate the effect of medium-level laser therapy in chronic tinnitus treatment. In a prospective double-blind placebo-controlled trial, either active laser (450 mW, 830 nm combined Ga-Al-As diode laser) or placebo irradiation was applied through the external acoustic meatus of the affected ear towards the cochlea. Fourty-eight patients with chronic tinnitus were studied. The main outcome was measured using the Goebel tinnitus questionnaire, visual analogue scales measuring the perceived loudness of tinnitus, the annoyance associated with tinnitus, and the degree of attention paid to tinnitus as well as psycho-acoustical matches of tinnitus pitch and loudness. The results did show only very moderate temporary improvement of tinnitus. Moreover, no statistically relevant differences between laser and placebo group could be found. We conclude that medium-level laser therapy cannot be regarded as an effective treatment of chronic tinnitus in our therapy regime considering the limited number of patients included in our study.

  4. Lubiprostone: a novel treatment for chronic constipation

    PubMed Central

    Lacy, Brian E; Levy, L Campbell

    2008-01-01

    Chronic constipation is highly prevalent, reduces patients’ quality of life, and imposes a significant health care burden on society. Lifestyle modifications and over-the-counter agents improve symptoms of constipation in some patients, however many patients have persistent symptoms and require the use of prescription medications. Three prescription medications are currently Food and Drug Administration (FDA) approved and available for the treatment of chronic constipation in adults. This review will focus on lubiprostone, the newest medication available for the treatment of chronic constipation. Lubiprostone is a bicyclic fatty acid metabolite analogue of prostaglandin E1. It activates specific chloride channels in the gastrointestinal tract to stimulate intestinal fluid secretion, increase gastrointestinal transit, and improve symptoms of constipation. This article will provide a brief overview on chloride channel function in the gastrointestinal tract, describe the structure, function, and pharmacokinetics of lubiprostone, and discuss the safety and efficacy of this new medication. PMID:18686757

  5. Review of the treatment options for chronic constipation.

    PubMed

    Johanson, John F

    2007-05-02

    Constipation is a common gastrointestinal motility disorder that is often chronic, negatively affects patients' daily lives, and is associated with high healthcare costs. There is a considerable range of treatment modalities available for patients with constipation; however, the clinical evidence supporting their use varies widely. Nonpharmacologic modalities, such as increased exercise or fluid intake and bowel habit training, are generally recommended as first-line approaches, but data on the effectiveness of these measures are limited. The clinical benefits of various traditional pharmacologic agents (many of which are available over the counter, such as laxatives and fiber supplements) remain unclear. Although these modalities may benefit some patients with temporary constipation, their efficacy in patients for whom constipation is chronic is less well defined. Some studies suggest benefit with psyllium, polyethylene glycol, and lactulose; however, the use of other agents, such as calcium polycarbophil, methylcellulose, bran, magnesium hydroxide, and stimulant laxatives, is not supported by strong clinical evidence. More recently, newer agents have been approved for the treatment of patients with chronic constipation on the basis of comprehensive clinical investigation programs. Tegaserod, with its well-established clinical profile, and lubiprostone, the latest addition to the treatment armamentarium, represent the new generation of therapies for chronic constipation. This article reviews the efficacy and safety of traditional therapies used in the management of the multiple symptoms associated with chronic constipation and discusses recently approved and emerging therapies for this disorder.

  6. Current diagnosis and treatment of chronic subdural haematomas

    PubMed Central

    Iliescu, IA

    2015-01-01

    A developed society is usually also characterized by an elderly population, which has a continuous percentage growth. This population frequently presents a cumulus of medical pathologies. With the development of the medication and surgical treatment of different affections, the life span has increased and the pathology of an old patient has diversified as far as the cumulus of various pathological diseases in the same person is concerned. Chronic subdural pathologies represent an affection frequently met in neurosurgery practice. Any neurosurgeon, neurologist and not only, has to be aware of the possibility of the existence of a chronic subdural haematoma, especially when the patient is old and is subjected to an anticoagulant or antiaggregant treatment, these 2 causes being by far the etiological factors most frequently met in chronic subdural haematomas. With an adequate diagnosis and treatment, usually surgical, the prognosis is favorable. Although the surgical treatment presents a categorical indication in most of the cases, the fact that there are many surgical techniques, a great relapse rate, as well as the numerous studies, which try to highlight the efficiency of a technique as compared to another, demonstrate that the treatment of these haematomas is far from reaching a consensus among the neurosurgeons. The latest conservatory treatment directions are still being studied and need many years to be confirmed. Abbreviations: CT = computerized tomography, MRI = magnetic resonance imaging PMID:26351527

  7. Hydrogen Treatment Protects Mice Against Chronic Pancreatitis by Restoring Regulatory T Cells Loss.

    PubMed

    Chen, Luguang; Ma, Chao; Bian, Yun; Li, Jing; Wang, Tiegong; Su, Li; Lu, Jianping

    2017-01-01

    Chronic pancreatitis is an inflammatory disease of the pancreas characterized by progressive tissue destruction and fibrogenesis. The development of chronic pancreatitis is associated with immune cell dysregulation. Currently, the specific and effective treatment of chronic pancreatitis remains absent. By using an L-arginine induced chronic pancreatitis mouse model, we tested the therapeutic potential of hydrogen, a strong hydroxyl radicals scavenger, in the chronic pancreatitis model. Tissue inflammation, damage and fibrosis were analyzed on HE, TUNEL, MPO, and sirius staining. Pancreas levels of MDA content, SOD activity, TNF-α , IL-10 cytokine expression and serum amylase and lipase activity were determined by ELISA and absorbance assay. Apoptosis, T cells subtype proportion and intracellular level of reactive oxygen species (ROS) were analyzed by flow cytometry. Tregs adoptive transfer and CD25 neutralization were used to validate the role of Tregs in chronic pancreatitis. We found that hydrogen treatment significantly improved multiple symptoms of chronic pancreatitis. The number of Tregs was reduced in chronic pancreatitis mice, while hydrogen treatment restored the Treg loss by L-arginine administrations. Depletion of Tregs abolished the protective effect of hydrogen treatment in chronic pancreatitis. In vitro study showed that hydrogen blocked ROS generation in Tregs and promoted Tregs survival. Hydrogen treatment showed reliable benefits in controlling the severity of chronic pancreatitis. Our study supported that hydrogen could be used as a novel treatment in chronic pancreatitis patient in the future. © 2017 The Author(s). Published by S. Karger AG, Basel.

  8. Effectiveness of surgical treatment in chronic migraine.

    PubMed

    Amaya-Blas, Francisco Javier; Mecott, Gabriel A; Marfil-Rivera, Alejandro; Tamayo-Esquivel, María de Lourdes; García-Pérez, Mauricio Manuel; Chacón-Moreno, Hernán; Pérez-Porras, Sergio; Coutiño, Rosa; Castro-Góvea, Yanko

    2018-01-01

    Migraine affects more than 35 million people in the United States of America, and 10% of the population in the world. The purpose of this study was to evaluate the effectiveness of surgical treatment in chronic migraine with frontal or occipital trigger areas. We designed a pilot, proof of concept, and prospective study to analyze the effectiveness of surgical release of trigger nerves in severe frontal or occipital chronic migraines. The study was approved by the Ethics and Investigation Committee of Hospital Universitario Dr. José Eleuterio González (Monterrey, N.L., Mexico). We included patients diagnosed with chronic migraine by the neurology service of Hospital Universitario Dr. José Eleuterio González that attended our consult from March to December 2012. The patients were assessed by the MIDAS questionnaire and the diagnosis confirmed by injecting 2% lidocaine in the trigger sites. We realized a superior palpebral approach in frontal migraines to resection the glabellar muscles and an occipital approach to free the greater occipital nerve bilaterally. We evaluated complete and partial clinical response measuring the frequency, intensity, and duration of migraine episodes. We included three patients with Stage IV (severe incapacitating) frontal or occipital chronic migraines. Two were occipital trigger sites and one frontal. We obtained complete clinical response in two patients and a partial response in one. Pain intensity decreased in all patients. Surgical treatment is effective in Stage IV (severe incapacitating) frontal or occipital trigger chronic migraines. Copyright: © 2018 Permanyer.

  9. Cost-effectiveness of benign Wirsung duct strictures treatment in chronic pancreatitis.

    PubMed

    Łaski, Dariusz; Hać, Stanisław; Marek, Iwona; Kobiela, Jarosław; Kostro, Justyna; Adrych, Krystian; Śledziński, Zbigniew

    2018-03-01

    Chronic pancreatitis (CP) is an important problem for modern medicine, the healthcare system (Poland - NFZ) and the national insurance system (Poland - ZUS). The chronic nature of the disease, the lack of targeted treatment and the low mortality rate lead to an accumulation of patients who demand expensive treatment, both conservative and invasive. Rising costs in health care are forcing the need for a more cost-effective method of treatment. The primary aim of this study was to perform a retrospective calculation of costs in both surgical and endoscopic treatment, hospital stay, healthcare, and public insurance of patients suffering from chronic pancreatitis. Parallel quality of life analysis was performed. It was possible to develop a cost-effective therapeutic algorithm for patients with an uncomplicated stricture of Wirsung's duct within the Polish health care system. In Poland, the hospital costs of endoscopic treatment of patients with chronic pancreatitis were higher than those of the surgical treatment group despite both resulting in a similar life quality. From a cost-effectiveness perspective, it was shown that surgical intervention is a more cost-effective therapy than endotherapy. Furthermore, patients with benign stricture of the main pancreatic duct in chronic pancreatitis should not be treated with endotherapy for longer than 12 months.

  10. Cost-effectiveness of benign Wirsung duct strictures treatment in chronic pancreatitis

    PubMed Central

    Hać, Stanisław; Marek, Iwona; Kobiela, Jarosław; Kostro, Justyna; Adrych, Krystian; Śledziński, Zbigniew

    2018-01-01

    Introduction Chronic pancreatitis (CP) is an important problem for modern medicine, the healthcare system (Poland – NFZ) and the national insurance system (Poland – ZUS). The chronic nature of the disease, the lack of targeted treatment and the low mortality rate lead to an accumulation of patients who demand expensive treatment, both conservative and invasive. Rising costs in health care are forcing the need for a more cost-effective method of treatment. Aim The primary aim of this study was to perform a retrospective calculation of costs in both surgical and endoscopic treatment, hospital stay, healthcare, and public insurance of patients suffering from chronic pancreatitis. Parallel quality of life analysis was performed. It was possible to develop a cost-effective therapeutic algorithm for patients with an uncomplicated stricture of Wirsung’s duct within the Polish health care system. Results In Poland, the hospital costs of endoscopic treatment of patients with chronic pancreatitis were higher than those of the surgical treatment group despite both resulting in a similar life quality. Conclusions From a cost-effectiveness perspective, it was shown that surgical intervention is a more cost-effective therapy than endotherapy. Furthermore, patients with benign stricture of the main pancreatic duct in chronic pancreatitis should not be treated with endotherapy for longer than 12 months. PMID:29643954

  11. Visually induced analgesia during massage treatment in chronic back pain patients.

    PubMed

    Löffler, A; Trojan, J; Zieglgänsberger, W; Diers, M

    2017-11-01

    Previous findings suggest that watching sites of experimental and chronic pain can exert an analgesic effect. Our present study investigates whether watching one's back during massage increases the analgesic effect of this treatment in chronic back pain patients. Twenty patients with chronic back pain were treated with a conventional massage therapy. During this treatment, patients received a real-time video feedback of their own back. Watching a neutral object, a video of another person of the same sex being massaged, a picture of the own back, and keeping one's eyes closed were used as controls. These conditions were presented in randomized order on five separate days. All conditions yielded significant decreases in habitual pain intensity. The effect of real-time video feedback of the own back on massage treatment was the strongest and differed significantly from the effect of watching a neutral object, but not from the other control conditions, which may have induced slight effects of their own. Repeated real-time video feedback may be useful during massage treatment of chronic pain. This study shows that inducing visual induced analgesia during massage treatment can be helpful in alleviating chronic pain. © 2017 European Pain Federation - EFIC®.

  12. New developments in diagnosis and non-surgical treatment of chronic pancreatitis.

    PubMed

    Inui, Kazuo; Yoshino, Junji; Miyoshi, Hironao; Yamamoto, Satoshi; Kobayashi, Takashi

    2013-12-01

    Chronic pancreatitis is progressive and irreversible, leading to digestive and absorptive disorders by destruction of the exocrine pancreas and to diabetes mellitus by destruction of the endocrine pancreas. When complications such as pancreatolithiasis and pseudocyst occur, elevated pancreatic ductal pressure exacerbates pain and induces other complications, worsening the patient's general condition. Combined treatment with extracorporeal shock-wave lithotripsy and endoscopic lithotripsy is a useful, minimally invasive, first-line treatment approach that can preserve pancreatic exocrine function. Pancreatic duct stenosis elevates intraductal pressure and favor both pancreatolithiasis and pseudocyst formation, making effective treatment vitally important. Endoscopic treatment of benign pancreatic duct stenosis stenting frequently decreases pain in chronic pancreatitis. Importantly, stenosis of the main pancreatic duct increases risk of stone recurrence after treatment of pancreatolithiasis. Recently, good results were reported in treating pancreatic duct stricture with a fully covered self-expandable metallic stent, which shows promise for preventing stone recurrence after lithotripsy in patients with pancreatic stricture. Chronic pancreatitis has many complications including pancreatic carcinoma, pancreatic atrophy, and loss of exocrine and endocrine function, as well as frequent recurrence of stones after treatment of pancreatolithiasis. As early treatment of chronic pancreatitis is essential, the new concept of early chronic pancreatitis, including characteristics findings in endoscopic ultrasonograms, is presented. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  13. Topical treatments for chronic plaque psoriasis.

    PubMed

    Mason, Anne R; Mason, James; Cork, Michael; Dooley, Gordon; Edwards, Gladys

    2009-04-15

    Chronic plaque psoriasis is the most common type of psoriasis and is characterised by redness, thickness and scaling. First line management of chronic plaque psoriasis is with topical treatments, including vitamin D analogues, topical corticosteroids, tar-based preparations, dithranol, salicylic acid and topical retinoids. To compare the effectiveness, tolerability and safety of topical treatments for chronic plaque psoriasis with placebo; to compare vitamin D analogues with other topical treatments. The Cochrane Skin Group's Trials Register was searched (2004/12). To update an unpublished 2002 review we also searched CENTRAL in The Cochrane Library (Issue 1,2005); MEDLINE (to 2005/02); EMBASE (to 2005/08); Science Citation Index (to 2005); Biosis (to 2005); Dissertation Abstracts (all publication years); Inside Conferences (all publication years); SIGLE (to 2005); National Research Register (all projects with a start date of 2001 to 2005); metaRegister of Current Controlled Trials. Randomised trials comparing treatments against placebo or against vitamin D analogues in people with chronic plaque psoriasis. One author extracted study data and assessed study quality. A second author checked these data. We routinely contacted triallists and companies for missing data. We extracted data on withdrawals and adverse events. The review included 131 RCTs with 21,448 participants. Vitamin D was significantly more effective than placebo, although there was a wide variation in effect size with the standardised mean difference (SMD) ranging from -0.82 (95% CI -1.34 to -0.29) to -1.90 (95% CI -2.09 to -1.71). With one exception, all corticosteroids performed better than placebo, with potent corticosteroids (SMD: -0.95 (95% CI: -1.11 to -0.80; I(2): 61.1%; 17 studies; 2386 participants)) having smaller benefits than very potent corticosteroids (SMD: -1.29 (95% CI: -1.45 to -1.13; I(2): 53.2%; 11 studies; 1571 participants)). Dithranol and tazarotene performed better than placebo

  14. The role of insomnia in the treatment of chronic fatigue.

    PubMed

    Kallestad, Håvard; Jacobsen, Henrik B; Landrø, Nils Inge; Borchgrevink, Petter C; Stiles, Tore C

    2015-05-01

    The definition of Chronic Fatigue Syndrome (CFS) overlaps with definitions of insomnia, but there is limited knowledge about the role of insomnia in the treatment of chronic fatigue. To test if improvement of insomnia during treatment of chronic fatigue was associated with improved outcomes on 1) fatigue and 2) cortisol recovery span during a standardized stress exposure. Patients (n = 122) with chronic fatigue received a 3.5-week inpatient return-to-work rehabilitation program based on Acceptance and Commitment Therapy, and had been on paid sick leave>8 weeks due their condition. A physician and a psychologist examined the patients, assessed medication use, and SCID-I diagnoses. Patients completed self-report questionnaires measuring fatigue, pain, depression, anxiety, and insomnia before and after treatment. A subgroup (n = 25) also completed the Trier Social Stress Test for Groups (TSST-G) before and after treatment. Seven cortisol samples were collected during each test and cortisol spans for the TSST-G were calculated. A hierarchical regression analysis in nine steps showed that insomnia improvement predicted improvement in fatigue, independently of age, gender, improvement in pain intensity, depression and anxiety. A second hierarchical regression analysis showed that improvement in insomnia significantly predicted the cortisol recovery span after the TSST-G independently of improvement in fatigue. Improvement in insomnia severity had a significant impact on both improvement in fatigue and the ability to recover from a stressful situation. Insomnia severity may be a maintaining factor in chronic fatigue and specifically targeting this in treatment could increase treatment response. Copyright © 2014. Published by Elsevier Inc.

  15. New perspectives for chronic pain treatment: a patent review (2010-2016).

    PubMed

    Pina, Lícia T S; Gouveia, Daniele N; Costa, Janara S; Quintans, Jullyana S S; Quintans-Júnior, Lucindo J; Barreto, Rosana S S; Guimarães, Adriana G

    2017-07-01

    Chronic pain is a major problem of public health worldwide and is responsible for the increase in health costs. The therapeutic options available in the market for the treatment of chronic pain are often rather ineffective due to; the high number of adverse reactions, tolerance and dependence, reducing the quality of life, pharmacotherapy adherence and functional capacity. Hence, several studies have been conducted in the search for new treatment alternatives for chronic pain syndromes. Areas covered: This review brings together the therapeutic patents published over the past six years reporting the discovery of new drugs for the treatment of chronic pain, based on the perspective that these compounds are candidates for the management of chronic pain conditions. Expert opinion: Over the past 6 years, several pharmaceutical companies, as well as universities and researchers, have synthesized a series of compounds, which have been shown to be effective in controlling chronic pain in preclinical studies. These findings nurture the hope of discovering new therapeutic options for chronic pain. However, such studies are in early stages and there is a long and hard path to be followed until these compounds can become chemical entities available to the public.

  16. Advances in surgical treatment of chronic pancreatitis.

    PubMed

    Ni, Qingqiang; Yun, Lin; Roy, Manish; Shang, Dong

    2015-02-08

    The incidence of chronic pancreatitis (CP) is between 2 and 200 per 100,000 persons and shows an increasing trend year by year. India has the highest incidence of CP in the world at approximately 114 to 200 per 100,000 persons. The incidence of CP in China is approximately 13 per 100,000 persons. The aim of this review is to assist surgeons in managing patients with CP in surgical treatment. We conducted a PubMed search for "chronic pancreatitis" and "surgical treatment" and reviewed relevant articles. On the basis of our review of the literature, we found that CP cannot be completely cured. The purpose of surgical therapy for CP is to relieve symptoms, especially pain; to improve the patient's quality of life; and to treat complications. Decompression (drainage), resection, neuroablation and decompression combined with resection are commonly used methods for the surgical treatment of CP. Before developing a surgical regimen, surgeons should comprehensively evaluate the patient's clinical manifestations, auxiliary examination results and medical history to develop an individualized surgical treatment regimen.

  17. Medium-Level Laser in Chronic Tinnitus Treatment

    PubMed Central

    Dejakum, K.; Piegger, J.; Plewka, C.; Gunkel, A.; Thumfart, W.; Kudaibergenova, S.; Goebel, G.; Kral, F.; Freysinger, W.

    2013-01-01

    The purpose of this study was to evaluate the effect of medium-level laser therapy in chronic tinnitus treatment. In a prospective double-blind placebo-controlled trial, either active laser (450 mW, 830 nm combined Ga-Al-As diode laser) or placebo irradiation was applied through the external acoustic meatus of the affected ear towards the cochlea. Fourty-eight patients with chronic tinnitus were studied. The main outcome was measured using the Goebel tinnitus questionnaire, visual analogue scales measuring the perceived loudness of tinnitus, the annoyance associated with tinnitus, and the degree of attention paid to tinnitus as well as psycho-acoustical matches of tinnitus pitch and loudness. The results did show only very moderate temporary improvement of tinnitus. Moreover, no statistically relevant differences between laser and placebo group could be found. We conclude that medium-level laser therapy cannot be regarded as an effective treatment of chronic tinnitus in our therapy regime considering the limited number of patients included in our study. PMID:24294604

  18. Challenges in the Treatment of Chronic Wounds

    PubMed Central

    Frykberg, Robert G.; Banks, Jaminelli

    2015-01-01

    Significance: Chronic wounds include, but are not limited, to diabetic foot ulcers, venous leg ulcers, and pressure ulcers. They are a challenge to wound care professionals and consume a great deal of healthcare resources around the globe. This review discusses the pathophysiology of complex chronic wounds and the means and modalities currently available to achieve healing in such patients. Recent Advances: Although often difficult to treat, an understanding of the underlying pathophysiology and specific attention toward managing these perturbations can often lead to successful healing. Critical Issues: Overcoming the factors that contribute to delayed healing are key components of a comprehensive approach to wound care and present the primary challenges to the treatment of chronic wounds. When wounds fail to achieve sufficient healing after 4 weeks of standard care, reassessment of underlying pathology and consideration of the need for advanced therapeutic agents should be undertaken. However, selection of an appropriate therapy is often not evidence based. Future Directions: Basic tenets of care need to be routinely followed, and a systematic evaluation of patients and their wounds will also facilitate appropriate care. Underlying pathologies, which result in the failure of these wounds to heal, differ among various types of chronic wounds. A better understanding of the differences between various types of chronic wounds at the molecular and cellular levels should improve our treatment approaches, leading to better healing rates, and facilitate the development of new more effective therapies. More evidence for the efficacy of current and future advanced wound therapies is required for their appropriate use. PMID:26339534

  19. Diagnosis and treatment of chronic constipation – a European perspective

    PubMed Central

    Tack, J; Müller-Lissner, S; Stanghellini, V; Boeckxstaens, G; Kamm, M A; Simren, M; Galmiche, J-P; Fried, M

    2011-01-01

    Background Although constipation can be a chronic and severe problem, it is largely treated empirically. Evidence for the efficacy of some of the older laxatives from well-designed trials is limited. Patients often report high levels of dissatisfaction with their treatment, which is attributed to a lack of efficacy or unpleasant side-effects. Management guidelines and recommendations are limited and are not sufficiently current to include treatments that became available more recently, such as prokinetic agents in Europe. Purpose We present an overview of the pathophysiology, diagnosis, current management and available guidelines for the treatment of chronic constipation, and include recent data on the efficacy and potential clinical use of the more newly available therapeutic agents. Based on published algorithms and guidelines on the management of chronic constipation, secondary pathologies and causes are first excluded and then diet, lifestyle, and, if available, behavioral measures adopted. If these fail, bulk-forming, osmotic, and stimulant laxatives can be used. If symptoms are not satisfactorily resolved, a prokinetic agent such as prucalopride can be prescribed. Biofeedback is recommended as a treatment for chronic constipation in patients with disordered defecation. Surgery should only be considered once all other treatment options have been exhausted. PMID:21605282

  20. Predicting balance improvements following STARS treatments in chronic ankle instability participants.

    PubMed

    Wikstrom, Erik A; McKeon, Patrick O

    2017-04-01

    Sensory Targeted Ankle Rehabilitation Strategies that stimulate sensory receptors improve postural control in chronic ankle instability participants. However, not all participants have equal responses. Therefore, identifying predictors of treatment success is needed to improve clinician efficiency when treating chronic ankle instability. Therefore, the purpose was to identify predictors of successfully improving postural control in chronic ankle instability participants. Secondary data analysis. Fifty-nine participants with self-reported chronic ankle instability participated. The condition was defined as a history of at least two episodes of "giving way" within the past 6 months; and limitations in self-reported function as measured by the Foot and Ankle Ability Measure. Participants were randomized into three treatment groups (plantar massage, ankle joint mobilization, calf stretching) that received 6, 5-min treatment sessions over a 2-week period. The main outcome measure was treatment success, defined as a participant exceeding the minimal detectable change score for a clinician-oriented single limb balance test. Participants with ≥3 balance test errors had a 73% probability of treatment success following ankle joint mobilizations. Participants with a self-reported function between limb difference <16.07% and who made >2.5 errors had a 99% probability of treatment success following plantar massage. Those who sustained ≥11 ankle sprains had a 94% treatment success probability following calf stretching. Self-reported functional deficits, worse single limb balance, and number of previous ankle sprains are important characteristics when determining if chronic ankle instability participants will have an increased probability of treatment success. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  1. Diagnosis and treatment of chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: a consensus guideline.

    PubMed

    Rees, Jon; Abrahams, Mark; Doble, Andrew; Cooper, Alison

    2015-10-01

    To improve awareness and recognition of chronic bacterial prostatitis (CBP) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) among non-specialists and patients. To provide guidance to healthcare professionals treating patients with CBP and CP/CPPS, in both non-specialist and specialist settings. To promote efficient referral of care between non-specialists and specialists and the involvement of the multidisciplinary team (MDT). The guideline population were men with CBP or CP/CPPS (persistent or recurrent symptoms and no other urogenital pathology for ≥3 of the previous 6 months). Consensus recommendations for the guidelines were based on a search to identify literature on the diagnosis and management of CBP and CP/CPPS (published between 1999 and February 2014). A Delphi panel process was used where high-quality, published evidence was lacking. CBP and CP/CPPS can present with a wide range of clinical manifestations. The four main symptom domains are urogenital pain, lower urinary tract symptoms (LUTS - voiding or storage symptoms), psychological issues and sexual dysfunction. Patients should be managed according to their individual symptom pattern. Options for first-line treatment include antibiotics, α-adrenergic antagonists (if voiding LUTS are present) and simple analgesics. Repeated use of antibiotics, such as quinolones, should be avoided if there is no obvious symptomatic benefit from infection control or cultures do not support an infectious cause. Early use of treatments targeting neuropathic pain and/or referral to specialist services should be considered for patients who do not respond to initial measures. An MDT approach (urologists, pain specialists, nurse specialists, specialist physiotherapists, general practitioners, cognitive behavioural therapists/psychologists, and sexual health specialists) is recommended. Patients should be fully informed about the possible underlying causes and treatment options, including an explanation of

  2. Traditional Chinese medicinal herbs for the treatment of idiopathic chronic fatigue and chronic fatigue syndrome.

    PubMed

    Adams, Denise; Wu, Taixiang; Yang, Xunzhe; Tai, Shusheng; Vohra, Sunita

    2009-10-07

    Chronic fatigue is increasingly common. Conventional medical care is limited in treating chronic fatigue, leading some patients to use traditional Chinese medicine therapies, including herbal medicine. To assess the effectiveness of traditional Chinese medicine herbal products in treating idiopathic chronic fatigue and chronic fatigue syndrome. The following databases were searched for terms related to traditional Chinese medicine, chronic fatigue, and clinical trials: CCDAN Controlled Trials Register (July 2009), MEDLINE (1966-2008), EMBASE (1980-2008), AMED (1985-2008), CINAHL (1982-2008), PSYCHINFO (1985-2008), CENTRAL (Issue 2 2008), the Chalmers Research Group PedCAM Database (2004), VIP Information (1989-2008), CNKI (1976-2008), OCLC Proceedings First (1992-2008), Conference Papers Index (1982-2008), and Dissertation Abstracts (1980-2008). Reference lists of included studies and review articles were examined and experts in the field were contacted for knowledge of additional studies. Selection criteria included published or unpublished randomized controlled trials (RCTs) of participants diagnosed with idiopathic chronic fatigue or chronic fatigue syndrome comparing traditional Chinese medicinal herbs with placebo, conventional standard of care (SOC), or no treatment/wait lists. The outcome of interest was fatigue. 13 databases were searched for RCTs investigating TCM herbal products for the treatment of chronic fatigue. Over 2400 references were located. Studies were screened and assessed for inclusion criteria by two authors. No studies that met all inclusion criteria were identified. Although studies examining the use of TCM herbal products for chronic fatigue were located, methodologic limitations resulted in the exclusion of all studies. Of note, many of the studies labelled as RCTs and conducted in China did not utilize rigorous randomization procedures. Improvements in methodology in future studies is required for meaningful synthesis of data.

  3. Treatment of Chronic Migraine with OnabotulinumtoxinA: Mode of Action, Efficacy and Safety.

    PubMed

    Szok, Délia; Csáti, Anett; Vécsei, László; Tajti, János

    2015-07-17

    Chronic migraine is a common, highly disabling, underdiagnosed and undertreated entity of migraine. It affects 0.9%-2.2% of the general adult population. The present paper overviews the preclinical and clinical data regarding the therapeutic effect of onabotulinumtoxinA in chronic migraineurs. A literature search was conducted in the database of PubMed up to 20 May 2015 for articles related to the pathomechanism of chronic migraine, the mode of action, and the efficacy, safety and tolerability of onabotulinumtoxinA for the preventive treatment of chronic migraine. The pathomechanism of chronic migraine has not been fully elucidated. The mode of action of onabotulinumtoxinA in the treatment of chronic migraine is suggested to be related to the inhibition of the release of calcitonin gene-related peptide and substance P in the trigeminovascular system. Randomized clinical trials demonstrated that long-term onabotulinumtoxinA fixed-site and fixed-dose (155-195 U) intramuscular injection therapy was effective and well tolerated for the prophylactic treatment of chronic migraine. Chronic migraine is a highly devastating entity of migraine. Its exact pathomechanism is unrevealed. Two-third of chronic migraineurs do not receive proper preventive medication. Recent clinical studies revealed that onabotulinumtoxinA was an efficacious and safe treatment for chronic migraine.

  4. Treatment of Chronic Migraine with OnabotulinumtoxinA: Mode of Action, Efficacy and Safety

    PubMed Central

    Szok, Délia; Csáti, Anett; Vécsei, László; Tajti, János

    2015-01-01

    Background: Chronic migraine is a common, highly disabling, underdiagnosed and undertreated entity of migraine. It affects 0.9%–2.2% of the general adult population. The present paper overviews the preclinical and clinical data regarding the therapeutic effect of onabotulinumtoxinA in chronic migraineurs. Methods: A literature search was conducted in the database of PubMed up to 20 May 2015 for articles related to the pathomechanism of chronic migraine, the mode of action, and the efficacy, safety and tolerability of onabotulinumtoxinA for the preventive treatment of chronic migraine. Results: The pathomechanism of chronic migraine has not been fully elucidated. The mode of action of onabotulinumtoxinA in the treatment of chronic migraine is suggested to be related to the inhibition of the release of calcitonin gene-related peptide and substance P in the trigeminovascular system. Randomized clinical trials demonstrated that long-term onabotulinumtoxinA fixed-site and fixed-dose (155–195 U) intramuscular injection therapy was effective and well tolerated for the prophylactic treatment of chronic migraine. Conclusions: Chronic migraine is a highly devastating entity of migraine. Its exact pathomechanism is unrevealed. Two-third of chronic migraineurs do not receive proper preventive medication. Recent clinical studies revealed that onabotulinumtoxinA was an efficacious and safe treatment for chronic migraine. PMID:26193319

  5. Chronic lithium treatment rectifies maladaptive dopamine release in the nucleus accumbens.

    PubMed

    Can, Adem; Frost, Douglas O; Cachope, Roger; Cheer, Joseph F; Gould, Todd D

    2016-11-01

    Chronic lithium treatment effectively reduces behavioral phenotypes of mania in humans and rodents. The mechanisms by which lithium exerts these actions are poorly understood. Pre-clinical and clinical evidence have implicated increased mesolimbic dopamine (DA) neurotransmission with mania. We used fast-scan cyclic voltammetry to characterize changes in extracellular DA concentrations in the nucleus accumbens (NAc) core evoked by 20 and 60 Hz electrical stimulation of the ventral tegmental area (VTA) in C57BL6/J mice treated either acutely or chronically with lithium. The effects of chronic lithium treatment on the availability of DA for release were assessed by depleting readily releasable DA using short inter-train intervals, or administering d-amphetamine acutely to mobilize readily releasable DA. Chronic, but not acute, lithium treatment decreased the amplitude of DA responses in the NAc following 60 Hz pulse train stimulation. Neither lithium treatment altered the kinetics of DA release or reuptake. Chronic treatment did not impact the progressive reduction in the amplitude of DA responses when, using 20 or 60 Hz pulse trains, the VTA was stimulated every 6 s to deplete DA. Specifically, the amplitude of DA responses to 60 Hz pulse trains was initially reduced compared to control mice, but by the fifth pulse train, there was no longer a treatment effect. However, chronic lithium treatment attenuated d-amphetamine-induced increases in DA responses to 20 Hz pulse trains stimulation. Our data suggest that long-term administration of lithium may ameliorate mania phenotypes by normalizing the readily releasable DA pool in VTA axon terminals in the NAc. Read the Editorial Highlight for this article on Page 520. © 2016 International Society for Neurochemistry.

  6. [Magneto- laser-phoresis with heparin in the treatment of patients with chronic pharyngitis].

    PubMed

    Portenko, G M; Grafskaia, N A

    2002-01-01

    The results of treatment of various forms of chronic pharyngitis by magnetolaserophoresis (MLP) with heparin show that MLP is more effective in hypertrophic chronic pharyngitis. It is emphasized that when planning treatment of chronic pharyngitis one should take into consideration the state of the gastrointestinal tract.

  7. [Treatment of chronic recurrent vulvovaginal candidiasis with fluconazole (fungolon--Actavis)].

    PubMed

    Borisov, I; Kolarov, G; Bobcheva, S; Ivanova, A

    2005-01-01

    The object of the study was to evaluate the efficacy of peroral administration of Fluconazole (Fungolon caps. 50 mg - "Actavis") in dose 150 mg (3 caps. x 50 mg) once weekly for a period of 6 months. 50 female patients of reproductive age with chronic vulvovaginal candidiasis caused by C. albicans with three or more recurrences per year were enrolled in an open trial prospective study and 42 women were evaluated before and after treatment. Clinical improvement was observed in 81% of the patients after treatment Microbiological cure was observed in 86% of the patients (36/42). Positive cultures for C. albicans after treatment had 6 patients. Four of these 6 patients had duration of the chronic candidiasis for more than 3 years. Side effects during the treatment were not significant and might not be directly correlated with the administration of fluconazole. There was no cessation of therapy due to side effects. 53.3% of the patients accepted positively the long duration of therapy while 30% found the long duration of treatment a major inconvenience. Fluconazole is easily administrated well tolerated and is suitable for the long treatment of chronic vulvovaginal candididasis.

  8. Effectiveness of an Extended Yoga Treatment for Women with Chronic Posttraumatic Stress Disorder

    PubMed Central

    Price, Maggi; Musicaro, Regina; Turner, Jennifer; Suvak, Michael; Emerson, David; van der Kolk, Bessel

    2017-01-01

    Abstract Background: Yoga has been found to be an effective posttraumatic stress disorder (PTSD) treatment for a variety of trauma survivors, including females with chronic PTSD. Aim/Purpose: The current study builds on extant research by examining an extended trauma-sensitive yoga treatment for women with chronic PTSD. The study sought to optimize the results of a treatment protocol examined in a recent randomized controlled trial with a shorter duration and without assignment or monitoring of home practice. Materials and Methods: The authors examined a 20-week trauma-sensitive yoga treatment in a non-randomized single-group treatment feasibility study for women with chronic treatment-resistant PTSD (N = 9). The authors examined PTSD and dissociation symptom reduction over several assessment periods. Results: The results indicate that participants experienced significant reductions in PTSD and dissociative symptomatology above and beyond similar treatments of a shorter duration. Conclusions: The findings suggest that more intensive trauma-sensitive yoga treatment characterized by longer duration and intentional assignment and monitoring of home practice may be more advantageous for individuals with severe and chronic PTSD. The implications of the findings for the potentially more substantial role of yoga as an intervention for a subset of adults with chronic treatment-resistant PTSD are discussed. PMID:28121466

  9. Effectiveness of an Extended Yoga Treatment for Women with Chronic Posttraumatic Stress Disorder.

    PubMed

    Price, Maggi; Spinazzola, Joseph; Musicaro, Regina; Turner, Jennifer; Suvak, Michael; Emerson, David; van der Kolk, Bessel

    2017-04-01

    Yoga has been found to be an effective posttraumatic stress disorder (PTSD) treatment for a variety of trauma survivors, including females with chronic PTSD. Aim/Purpose: The current study builds on extant research by examining an extended trauma-sensitive yoga treatment for women with chronic PTSD. The study sought to optimize the results of a treatment protocol examined in a recent randomized controlled trial with a shorter duration and without assignment or monitoring of home practice. The authors examined a 20-week trauma-sensitive yoga treatment in a non-randomized single-group treatment feasibility study for women with chronic treatment-resistant PTSD (N = 9). The authors examined PTSD and dissociation symptom reduction over several assessment periods. The results indicate that participants experienced significant reductions in PTSD and dissociative symptomatology above and beyond similar treatments of a shorter duration. The findings suggest that more intensive trauma-sensitive yoga treatment characterized by longer duration and intentional assignment and monitoring of home practice may be more advantageous for individuals with severe and chronic PTSD. The implications of the findings for the potentially more substantial role of yoga as an intervention for a subset of adults with chronic treatment-resistant PTSD are discussed.

  10. Surgical Treatment for Chronic Pelvic Pain

    PubMed Central

    1998-01-01

    The source of chronic pelvic pain may be reproductive organ, urological, musculoskeletal - neurological, gastrointestinal, or myofascial. A psychological component almost always is a factor, whether as an antecedent event or presenting as depression as result of the pain. Surgical interventions for chronic pelvic pain include: 1) resection or vaporization of vulvar/vestibular tissue for human papillion virus (HPV) induced or chronic vulvodynia/vestibulitis; 2) cervical dilation for cervix stenosis; 3) hysteroscopic resection for intracavitary or submucous myomas or intracavitary polyps; 4) myomectomy or myolysis for symptomatic intramural, subserosal or pedunculated myomas; 5) adhesiolysis for peritubular and periovarian adhesions, and enterolysis for bowel adhesions, adhesiolysis for all thick adhesions in areas of pain as well as thin ahesions affecting critical structures such as ovaries and tubes; 6) salpingectomy or neosalpingostomy for symptomatic hydrosalpinx; 7) ovarian treatment for symptomatic ovarian pain; 8) uterosacral nerve vaporization for dysmenorrhea; 9) presacral neurectomy for disabling central pain primarily of uterine but also of bladder origin; 10) resection of endometriosis from all surfaces including removal from bladder and bowel as well as from the rectovaginal septal space. Complete resection of all disease in a debulking operation is essential; 11) appendectomy for symptoms of chronic appendicitis, and chronic right lower quadrant pain; 12) uterine suspension for symptoms of collision dyspareunia, pelvic congestion, severe dysmenorrhea, cul-desac endometriosis; 13) repair of all hernia defects whether sciatic, inguinal, femoral, Spigelian, ventral or incisional; 14) hysterectomy if relief has not been achieved by organ-preserving surgery such as resection of all endometriosis and presacral neurectomy, or the central pain continues to be disabling. Before such a radical step is taken, MRI of the uterus to confirm presence of adenomyosis

  11. Periodic catatonia with long-term treatment: a case report.

    PubMed

    Chen, Ruei-An; Huang, Tiao-Lai

    2017-09-29

    Periodic catatonia has long been a challenging diagnosis and there are no absolute guidelines for treatment when precipitating factors are also unclear. We report a schizophrenia patient with periodic catatonia with a 15-year treatment course. A possible correlation between decreased daylight exposure and periodic attacks has been observed. We describe a 49-year-old woman with periodic catatonia associated with schizophrenia with 15 years of follow-up. The patient was treated with the antipsychotics risperidone, haloperidol, loxapine and quetiapine, but catatonia still relapsed once per year during the first few years of her disease course. The treatment was consequently been switched to clozapine due to fluctuated psychotic illness, and a longer duration of remittance was achieved. Lorazepam-diazepam protocol was used for rapid relief of catatonic symptoms, and was able to significantly shorten the duration of the symptoms. In addition, we observed a possible correlation between catatonic episodes and decreased daylight exposure during the 15-year duration. Successful treatment of acute periodic catatonia was achieved with a lorazepam-diazepam protocol, and the patient remained in remission for a longer duration under clozapine treatment. Besides, the possibility of decreased daylight exposure acting as a precipitating factor was observed during our 15 years of follow-up.

  12. Chronic Myeloproliferative Neoplasms Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Chronic Myeloproliferative Neoplasms (MPN) treatment varies widely depending on the specific diagnosis. Treatment options may include observation, phlebotomy, steroids, chemotherapy, immunotherapy, and stem cell transplant. Get detailed information about MPNs in this summary for clinicians.

  13. Chronic Lymphocytic Leukemia Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Chronic lymphocytic leukemia (CLL) treatment options can include observation, steroids, chemotherapy, targeted therapy, and/or stem cell transplant. Get detailed information about newly diagnosed and recurrent CLL and available treatment modalities in this summary for clinicians.

  14. BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia.

    PubMed

    Cuellar, Sandra; Vozniak, Michael; Rhodes, Jill; Forcello, Nicholas; Olszta, Daniel

    2017-01-01

    The management of chronic myeloid leukemia with BCR-ABL1 tyrosine kinase inhibitors has evolved chronic myeloid leukemia into a chronic, manageable disease. A patient-centered approach is important for the appropriate management of chronic myeloid leukemia and optimization of long-term treatment outcomes. The pharmacist plays a key role in treatment selection, monitoring drug-drug interactions, identification and management of adverse events, and educating patients on adherence. The combination of tyrosine kinase inhibitors with unique safety profiles and individual patients with unique medical histories can make managing treatment difficult. This review will provide up-to-date information regarding tyrosine kinase inhibitor-based treatment of patients with chronic myeloid leukemia. Management strategies for adverse events and considerations for drug-drug interactions will not only vary among patients but also across tyrosine kinase inhibitors. Drug-drug interactions can be mild to severe. In instances where co-administration of concomitant medications cannot be avoided, it is critical to understand how drug levels are impacted and how subsequent dose modifications ensure therapeutic drug levels are maintained. An important component of patient-centered management of chronic myeloid leukemia also includes educating patients on the significance of early and regular monitoring of therapeutic milestones, emphasizing the importance of adhering to treatment in achieving these targets, and appropriately modifying treatment if these clinical goals are not being met. Overall, staying apprised of current research, utilizing the close pharmacist-patient relationship, and having regular interactions with patients, will help achieve successful long-term treatment of chronic myeloid leukemia in the age of BCR-ABL1 tyrosine kinase inhibitors.

  15. Pain Volatility and Prescription Opioid Addiction Treatment Outcomes in Patients with Chronic Pain

    PubMed Central

    Worley, Matthew J.; Heinzerling, Keith G.; Shoptaw, Steven; Ling, Walter

    2015-01-01

    The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (N = 149) who received buprenorphine-naloxone (BUP-NLX) and counseling for 12 weeks in an outpatient, multi-site clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least two of the previous three weeks. Pain severity significantly declined over time during treatment (b = − 0.36, p < .001). Patients with greater pain volatility were less likely to have a good treatment outcome (OR = 0.55, p < .05), controlling for baseline pain severity and rate of change in pain over time. A one standard deviation increase in pain volatility was associated with a 44% reduction in the probability of endpoint abstinence. The significant reduction in subjective pain during treatment provides observational support for the analgesic effects of BUP-NLX in patients with chronic pain and opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk for returning to opioid use by the conclusion of an intensive treatment with BUP-NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain. PMID:26302337

  16. Pain volatility and prescription opioid addiction treatment outcomes in patients with chronic pain.

    PubMed

    Worley, Matthew J; Heinzerling, Keith G; Shoptaw, Steven; Ling, Walter

    2015-12-01

    The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (n = 149) who received buprenorphine/naloxone (BUP/NLX) and counseling for 12 weeks in an outpatient, multisite clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least 2 of the previous 3 weeks. Pain severity significantly declined over time during treatment (b = -0.36, p < .001). Patients with greater pain volatility were less likely to have a good treatment outcome (odds ratio = 0.55, p < .05), controlling for baseline pain severity and rate of change in pain over time. A 1 standard deviation increase in pain volatility was associated with a 44% reduction in the probability of endpoint abstinence. The significant reduction in subjective pain during treatment provides observational support for the analgesic effects of BUP/NLX in patients with chronic pain and opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk of returning to opioid use by the conclusion of an intensive treatment with BUP/NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  17. Topical antimicrobial agents for the treatment of chronic wounds.

    PubMed

    Ousey, Karen; McIntosh, Caroline

    2009-09-01

    Chronic wounds are commonly observed in acute and community settings. The management of chronic wounds represents a significant proportion of health-care resources and makes up a substantial amount of contact time with community-based nurses spending approximately 25% to 50% of their time treating wounds. Chronic wounds often exhibit increased bacterial burden that can negatively impact upon patients, reduce their quality of life and substantially increase treatment costs for health care providers. Antibiotic resistance has become a major medical and public health problem, and interest has been generated in the use of topical therapies to manage wound infection. This article presents an overview of the historical use of honey, silver and iodine for the treatment of infected wounds progressing through to modern day use and the current evidence base for the use of these antimicrobial agents in the management of infected wounds.

  18. Discontinuing treatment in children with chronic, critical illnesses.

    PubMed

    Mahon, M M; Deatrick, J A; McKnight, H J; Mohr, W K

    2000-03-01

    Decisions about optimal treatment for critically ill children are qualitatively different from those related to adults. Technological advances over the past several decades have resulted in myriad treatment options that leave many children chronically, critically ill. These children are often technology dependent. With new technologies and new patient populations comes the responsibility to understand how, when, and why these technologies are applied and when technology should not be used or should be withdrawn. Much has been written about ethical decision making in the care of chronically, critically ill adults and newborns. In this article, relevant factors about the care of children older than neonates are described: standards, decision makers, age of the child, and pain management. A case study is used as a mechanism to explore these issues. Dimensions of futility, discontinuing aggressive treatment, and a consideration of benefits and burdens are integrated throughout the discussion to inform nurse practitioner practice.

  19. Extracorporeal shock wave treatment for chronic rotator cuff tendonitis (shoulder pain).

    PubMed

    Ho, C

    2007-01-01

    (1) Electrohydraulic, electromagnetic, or piezoelectric devices are used to translate energy into acoustic waves during extracorporeal shock wave treatment (ESWT) for chronic rotator cuff tendonitis (shoulder pain). The acoustic waves may help to accelerate the healing process of chronic rotator cuff tendonitis via an unknown mechanism. (2) ESWT, which is performed as an outpatient procedure, is intended to alleviate the pain due to chronic rotator cuff tendonitis. (3) Limited evidence from a German study indicates that the cost of ESWT for rotator cuff tendonitis is one-fifth to one-seventh the cost of surgical treatment, with longer recovery time and time off work in the surgical treatment group accounting for about two-thirds of the overall cost. (4) The evidence reviewed for this bulletin supports the use of high-energy ESWT for chronic calcific rotator cuff tendonitis, but not for non-calcific rotator cuff tendonitis. High-quality RCTs with larger sample sizes are needed to provide stronger evidence.

  20. [Current alternatives in the surgical treatment of chronic pancreatitis--a review article].

    PubMed

    Kat'uchová, Jana; Radonak, Jozef

    2011-01-01

    Chronic pancreatitis is characterized as an inflammatory process affecting the pancreas that causes progressive destruction of the gland and fibrosis, with subsequent endocrine and exocrine insufficiency. The most common cause of chronic pancreatitis is alcohol use in combination with nicotine. Manifestations are persistent or recurrent painful attacks. The only parameter of successful treatment of chronic pancreatitis is a relieve from long-lasting pain and improvement of the quality of life. Surgical treatment options include drainage operations on the pancreas, pancreatic resection or a combination of both. With optimal surgical treatment performed and good patient's compliance, operations for chronic pancreatitis have low number of post-operative complications and relatively good long-term results. The continued consumption of alcohol and drugs bring about worse outcomes, sometimes even a complete failure of therapy. Chronic pancreatitis also has considerable socio-economic consequences. Due to the persisting pain and frequent hospitalization it can lead to long-term disability and early retirement predominantly in young patients.

  1. Update of Inpatient Treatment for Refractory Chronic Daily Headache.

    PubMed

    Lai, Tzu-Hsien; Wang, Shuu-Jiun

    2016-01-01

    Chronic daily headache (CDH) is a group of headache disorders, in which headaches occur daily or near-daily (>15 days per month) and last for more than 3 months. Important CDH subtypes include chronic migraine, chronic tension-type headache, hemicrania continua, and new daily persistent headache. Other headaches with shorter durations (<4 h/day) are usually not included in CDH. Common comorbidities of CDH are medication overuse headache and various psychiatric disorders, such as depression and anxiety. Indications of inpatient treatment for CDH patients include poor responses to outpatient management, need for detoxification for overuse of specific medications (particularly opioids and barbiturates), and severe psychiatric comorbidities. Inpatient treatment usually involves stopping acute pain, preventing future attacks, and detoxifying medication overuse if present. Multidisciplinary integrated care that includes medical staff from different disciplines (e.g., psychiatry, clinical psychology, and physical therapy) has been recommended. The outcomes of inpatient treatment are satisfactory in terms of decreasing headache intensity or frequency, withdrawal from medication overuse, reducing disability, and improving life quality, although long-term relapse is not uncommon. In conclusion, inpatient treatment may be useful for select patients with refractory CDH and should be incorporated in a holistic headache care program.

  2. Atypical antipsychotic clozapine reversed deficit on prepulse inhibition of the acoustic startle reflex produced by microinjection of DOI into the inferior colliculus in rats.

    PubMed

    de Oliveira, Rodolpho Pereira; Nagaishi, Karen Yuriko; Barbosa Silva, Regina Cláudia

    2017-05-15

    Dysfunctions of the serotonergic system have been suggested to be important in the neurobiology of schizophrenia. Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. PPI is the normal reduction in the startle response caused by a low intensity non-startling stimulus (prepulse) which is presented shortly before the startle stimulus (pulse). The hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI), a 5-hydroxytryptamine(HT) 2 receptor agonist disrupted PPI in rats. The inferior colliculus (IC) is a critical nucleus of the auditory pathway mediating acoustic PPI. The activation of the IC by the acoustic prepulse reduces startle magnitude. The present study investigated the role of serotonergic transmission in the IC on the expression of acoustic PPI. For that we investigated whether 5-HT2A receptor activation or blockade would affect this response. Unilateral microinjection of DOI (10μg/0.3μl) into the IC disrupted PPI, while microinjection of the 5-HT2A receptor antagonist ritanserin (4μg/0.3μl), into this structure did not alter PPI. We also examined the ability of the atypical antipsychotic clozapine (5.0mg/kg; I.P.) to reverse the disruption of PPI produced by unilateral microinjections of DOI into the IC of rats. Pretreatment with clozapine blocked DOI-induced disruption of PPI. Altogether, these results suggest that serotonin-mediated mechanisms of the IC are involved in the expression of PPI in rodents and that this response is sensitive to atypical antipsychotic clozapine. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Surgical and endoscopic treatment of pain in chronic pancreatitis: a multidisciplinary update.

    PubMed

    Issa, Y; van Santvoort, H C; van Goor, H; Cahen, D L; Bruno, M J; Boermeester, M A

    2013-01-01

    Chronic pancreatitis is an inflammatory disease of the pancreas with abdominal pain as the most prominent symptom. Adequate treatment of patients with chronic pancreatitis remains a major challenge, mainly because of the lack of evidence-based treatment protocols. The primary goal of treatment is to achieve long-term pain relief, control of the complications associated with the disease, and to restore the quality of life. Currently, a conservative step-up approach is often used for the treatment of pain; progression to severe and intractable pain is considered necessary before invasive treatment is considered. Recent studies, however, suggest that surgical intervention should not be considered only as last-resort treatment, since it can mitigate disease progression, achieve excellent pain control, and preserve pancreatic function. In this review, we present a state-of-the art overview of endoscopic and surgical treatment options for patients with painful chronic pancreatitis, and elaborate on the timing of surgery. Copyright © 2013 S. Karger AG, Basel.

  4. Is exercise an alternative treatment for chronic insomnia?

    PubMed Central

    Passos, Giselle Soares; Poyares, Dalva Lucia Rollemberg; Santana, Marcos Gonçalves; Tufik, Sergio; de Mello, Marco Túlio

    2012-01-01

    The purposes of this systematic/critical review are: 1) to identify studies on the effects of exercise on chronic insomnia and sleep complaints in middle-aged and older adults and to compare the results of exercise with those obtained with hypnotic medications and 2) to discuss potential mechanisms by which exercise could promote sleep in insomniac patients. We identified studies from 1983 through 2011 using MEDLINE, SCOPUS and Web of Science. For systematic analyses, only studies assessing the chronic effects of exercise on sleep in people with sleep complaints or chronic insomnia were considered. We used the following keywords when searching for articles: insomnia, sleep, sleep complaints, exercise and physical activity. For a critical review, studies were selected on the effects of exercise and possible mechanisms that may explain the effects of exercise on insomnia. We identified five studies that met our inclusion criteria for systematic review. Exercise training is effective at decreasing sleep complaints and insomnia. Aerobic exercise has been more extensively studied, and its effects are similar to those observed after hypnotic medication use. Mechanisms are proposed to explain the effects of exercise on insomnia. There is additional documented evidence on the antidepressant and anti-anxiety effects of exercise. Exercise is effective to decrease sleep complaints and to treat chronic insomnia. Exercise presented similar results when compared with hypnotics; however, prospective studies comparing the effects of exercise with medical and non-medical treatments are warranted before including exercise as a first-line treatment for chronic insomnia are necessary. PMID:22760906

  5. Treatment and follow up of children with chronic hepatitis C in Albania

    PubMed Central

    2012-01-01

    Background Treatment of Hepatitis C in children has a better outcome than in adults, and for this reason the treatment had different views. However, in pediatric age hepatitis C is seen to have an evolution towards chronicity. Today is a normal option to treat chronic hepatitis C as early as possible according to certain criteria. The aim of this study is to show the results of treatment with interferon and ribavirin and the follow-up of children diagnosed with chronic hepatitis C in our service. Patients and methods This is a prospective study which has included children 3 up to 15 years old (13 boys and 4 girls) diagnosed with chronic hepatitis C. All patients underwent a certain protocol, including liver biopsy prior to treatment. Treatment consisted in use for 48 weeks of INF α-2b, 3 MIU/m2 three times a week s/c and ribavirin 15 mg/kg orally divided bid. Two patients were treated with PEGINF α-2b with dose 1.5 mcg/kg once a week s/c and ribavirin 15 mg/kg. After the treatment all patients have stayed under our control for an average period of 24 weeks. Results At the end of the treatment we detected a patient with HCV-RNA positive. End Treatment Viral Response was 94%. Six months later we found three patients who showed relapse of disease. Sustained Viral Response was approximately 83% Conclusion The combination therapy of interferon with Ribavirin in treatment of children with chronic hepatitis C provides a higher SVR when treatment is initiated at the earliest stages of hepatic changes. Side effects of therapy are insignificant in comparison with results obtained PMID:22244498

  6. Pharmacokinetic interactions of herbal medicines for the treatment of chronic hepatitis.

    PubMed

    Hsueh, Tun-Pin; Lin, Wan-Ling; Tsai, Tung-Hu

    2017-04-01

    Chronic liver disease is a serious global health problem, and an increasing number of patients are seeking alternative medicines or complementary treatment. Herbal medicines account for 16.8% of patients with chronic liver disease who use complementary and alternative therapies. A survey of the National Health Insurance Research Database in Taiwan reported that Long-Dan-Xie-Gan-Tang, Jia-Wei-Xia-Yao-San, and Xiao-Chai-Hu-Tang (Sho-saiko-to) were the most frequent formula prescriptions for chronic hepatitis used by traditional Chinese medicine physicians. Bioanalytical methods of herbal medicines for the treatment of chronic hepatitis were developed to investigate pharmacokinetics properties, but multicomponent herbal formulas have been seldom discussed. The pharmacokinetics of herbal formulas is closely related to efficacy, efficiency, and patient safety of traditional herbal medicines. Potential herbal formula-drug interactions are another essential issue during herbal formula administration in chronic hepatitis patients. In a survey with the PubMed database, this review article evaluates the existing evidence-based data associated with the documented pharmacokinetics profiles and potential herbal-drug interactions of herbal formulas for the treatment of chronic hepatitis. In addition, the existing pharmacokinetic profiles were further linked with clinical practice to provide insight for the safety and specific use of traditional herbal medicines. Copyright © 2016. Published by Elsevier B.V.

  7. [The use of eurespal for the treatment of chronic laryngitis].

    PubMed

    Riabova, M A

    2011-01-01

    The author provides a rationale for the use of eurespal for the treatment of chronic laryngitis based on the pathogenetic concept of pathological condition. The results of a clinical study designed to evaluate the efficiency and safety of eurespal therapy in patients with chronic laryngitis are presented.

  8. The Relationship Between Posttraumatic Stress Disorder and Chronic Pain in People Seeking Treatment for Chronic Pain: The Mediating Role of Psychological Flexibility.

    PubMed

    Åkerblom, Sophia; Perrin, Sean; Rivano Fischer, Marcelo; McCracken, Lance M

    2018-06-01

    The symptoms of posttraumatic stress disorder (PTSD) and chronic pain are thought to interact to increase the severity and impact of both conditions, but the mechanisms by which they interact remain unclear. This study examines the relationship between PTSD and chronic pain and whether indices of Psychological Flexibility mediate the relationship between these 2 conditions. Standardized self-report measures of PTSD, pain severity, pain interference, depression, and psychological flexibility (pain-related acceptance, committed action, cognitive fusion, and values-based action) were obtained from 315 people seeking treatment for chronic pain who also reported at least 1 traumatic experience. People seeking treatment for chronic pain and reporting symptoms consistent with a current diagnosis of PTSD had significantly higher levels of pain severity, pain interference, depression, and cognitive fusion and lower levels of pain-related acceptance and committed action than those reporting symptoms below the diagnostic threshold for PTSD. Pain-related acceptance, committed action, cognitive fusion, and depression mediated the relationship between PTSD and pain severity/interference, with pain-related acceptance being the strongest mediator from the Psychological Flexibility model. Processes from the Psychological Flexibility model were identified as mediators of the relationship between PTSD and chronic pain in people seeking treatment for chronic pain. The Psychological Flexibility model may be useful as an overarching model to help understand the relationship between PTSD and chronic pain. It is possible that targeting pain-related acceptance, committed action, and cognitive fusion (among other processes) in the treatment of chronic pain may produce corresponding improvements in comorbid symptoms of PTSD when these are present and may reduce impacts of PTSD on outcomes of chronic pain. Conversely, targeting of these processes in the treatment of PTSD may produce similar

  9. Spinal cord stimulation: Current applications for treatment of chronic pain.

    PubMed

    Vannemreddy, Prasad; Slavin, Konstantin V

    2011-01-01

    Spinal cord stimulation (SCS) is thought to relieve chronic intractable pain by stimulating nerve fibers in the spinal cord. The resulting impulses in the fibers may inhibit the conduction of pain signals to the brain, according to the pain gate theory proposed by Melzack and Wall in 1965 and the sensation of pain is thus blocked. Although SCS may reduce pain, it will not eliminate it. After a period of concern about safety and efficacy, SCS is now regaining popularity among pain specialists for the treatment of chronic pain. The sympatholytic effect of SCS is one of its most interesting therapeutic properties. This effect is considered responsible for the effectiveness of SCS in peripheral ischemia, and at least some cases of complex regional pain syndrome. The sympatholytic effect has also been considered part of the management of other chronic pain states such as failed back surgery syndrome, phantom pain, diabetic neuropathy, and postherpetic neuralgia. In general, SCS is part of an overall treatment strategy and is used only after the more conservative treatments have failed. The concept of SCS has evolved rapidly following the technological advances that have produced leads with multiple contact electrodes and battery systems. The current prevalence of patients with chronic pain requiring treatment other than conventional medical management has significantly increased and so has been the need for SCS. With the cost benefit analysis showing significant support for SCS, it may be appropriate to offer this as an effective alternative treatment for these patients.

  10. Diagnosis and treatment of chronic acquired demyelinating polyneuropathies.

    PubMed

    Latov, Norman

    2014-08-01

    Chronic neuropathies are operationally classified as primarily demyelinating or axonal, on the basis of electrodiagnostic or pathological criteria. Demyelinating neuropathies are further classified as hereditary or acquired-this distinction is important, because the acquired neuropathies are immune-mediated and, thus, amenable to treatment. The acquired chronic demyelinating neuropathies include chronic inflammatory demyelinating polyneuropathy (CIDP), neuropathy associated with monoclonal IgM antibodies to myelin-associated glycoprotein (MAG; anti-MAG neuropathy), multifocal motor neuropathy (MMN), and POEMS syndrome. They have characteristic--though overlapping--clinical presentations, are mediated by distinct immune mechanisms, and respond to different therapies. CIDP is the default diagnosis if the neuropathy is demyelinating and no other cause is found. Anti-MAG neuropathy is diagnosed on the basis of the presence of anti-MAG antibodies, MMN is characterized by multifocal weakness and motor conduction blocks, and POEMS syndrome is associated with IgG or IgA λ-type monoclonal gammopathy and osteosclerotic myeloma. The correct diagnosis, however, can be difficult to make in patients with atypical or overlapping presentations, or nondefinitive laboratory studies. First-line treatments include intravenous immunoglobulin (IVIg), corticosteroids or plasmapheresis for CIDP; IVIg for MMN; rituximab for anti-MAG neuropathy; and irradiation or chemotherapy for POEMS syndrome. A correct diagnosis is required for choosing the appropriate treatment, with the aim of preventing progressive neuropathy.

  11. Unemployment risk among individuals undergoing medical treatment for chronic diseases.

    PubMed

    Nakaya, N; Nakamura, T; Tsuchiya, N; Tsuji, I; Hozawa, A; Tomita, H

    2016-03-01

    Chronic diseases increase the risk of unemployment even in non-disaster settings; therefore, in post-disaster settings, special attention needs to be paid to the employment status of those suffering from chronic diseases. To examine the association between chronic disease and the risk of unemployment in a disaster area. This cross-sectional study was conducted in Shichigahama Town, Miyagi, north-eastern Japan, where had been severely inundated by the 2011 tsunami. Logistic regression analyses were used to evaluate the association between undergoing medical treatment for a combination of chronic diseases (stroke, cancer, myocardial infarction and angina) and unemployment risk. Confounders such as psychological distress and levels of daily life activity were considered. Among the 2588 individuals studied, there was a statistically significant association between undergoing medical treatment for chronic disease and the risk of unemployment [odds ratio (OR) = 1.7, 95% confidence interval (CI) 1.02-2.7, P < 0.05]. In participants with a lower degree of psychological distress and better levels of daily life activity (n = 1967), no significant associations were observed (OR = 1.1, 95% CI 0.6-2.1). Conversely, in 536 participants with a higher degree of psychological distress and/or poorer levels of daily life activity, statistically significant associations were found (OR = 2.6, 95% CI 1.01-6.6, P < 0.05). The association between undergoing medical treatment for chronic disease and unemployment risk was observed only in participants with a higher degree of psychological distress and/or poorer levels of daily life activity. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Recovery from dispositional and pharmacodynamic tolerance after chronic pentobarbital treatment.

    PubMed

    Okamoto, M; Rao, S N; Reyes, J; Rifkind, A B

    1985-10-01

    Recovery characteristics of dispositional and pharmacodynamic tolerances produced by chronic Na-pentobarbital treatment were studied. To study dispositional tolerance, the rate of disappearance of pentobarbital from blood was estimated by sequential blood sampling before and after chronic treatment and during 15 days of withdrawal after chronic treatment. Pentobarbital half-life values were compared with four representative cytochrome P-450-mediated hepatic microsomal mixed-function oxidase reactions: aminopyrine demethylase, benzo(a)pyrene hydroxylase, 7-ethoxycoumarin deethylase and 7-ethoxyresorufin deethylase and with the concentration of cytochrome P-450 in sequentially biopsied liver samples. Pharmacodynamic tolerance was evaluated by measuring the increase in pentobarbital blood concentration required to produce predetermined central nervous system functional depression ratings. The recovery from dispositional tolerance was more rapid than the recovery from pharmacodynamic tolerance. Thus, whereas cytochrome P-450 levels and pentobarbital elimination rates were increased to close to twice pretreatment values by chronic treatment, by about 2 week post-withdrawal the values had normalized. In contrast, pharmacodynamic tolerance persisted after no residual dispositional tolerance remained. The neuronal functions most sensitive to barbiturate (i.e., sedation and loss of fine motor coordination) exhibited a greater degree of pharmacodynamic tolerance than other functions; hence the recovery of these neuronal functions took a longer period of time for their recovery. However, the rates of recovery of pharmacodynamic tolerance at all levels of central nervous system function seemed relatively constant indicating that there are uniform readaptation mechanisms for all the central nervous systems functions.

  13. Reversal of social deficits by subchronic oxytocin in two autism mouse models

    PubMed Central

    Teng, Brian L.; Nikolova, Viktoriya D.; Riddick, Natallia V.; Agster, Kara L.; Crowley, James J.; Baker, Lorinda K.; Koller, Beverly H.; Pedersen, Cort A.; Jarstfer, Michael B.; Moy, Sheryl S.

    2016-01-01

    Social deficits are a hallmark feature of autism spectrum disorder (ASD) and related developmental syndromes. Although there is no standard treatment for social dysfunction, clinical studies have identified oxytocin as a potential therapeutic with prosocial efficacy. We have previously reported that peripheral oxytocin treatment can increase sociability and ameliorate repetitive stereotypy in adolescent mice from the C58/J model of ASD-like behavior. In the present study, we determined that prosocial oxytocin effects were not limited to the adolescent period, since C58/J mice, tested in adulthood, demonstrated significant social preference up to 2 weeks following subchronic oxytocin treatment. Oxytocin was also evaluated in adult mice with underexpression of the N-methyl-D-aspartate receptor NR1 subunit (encoded by Grin1), a genetic model of autism- and schizophrenia- like behavior. Subchronic oxytocin had striking prosocial efficacy in male Grin1 knockdown mice; in contrast, chronic regimens with clozapine (66 mg/kg/day) or risperidone (2 mg/kg/day) failed to reverse deficits in sociability. Neither the subchronic oxytocin regimen, nor chronic treatment with clozapine or risperidone, reversed impaired prepulse inhibition in the Grin1 knockdown mice. Overall, these studies demonstrate oxytocin can enhance sociability in mouse models with divergent genotypes and behavioral profiles, adding to the evidence that this neurohormone could have therapeutic prosocial efficacy across a spectrum of developmental disorders. PMID:26748053

  14. [Chronic urticaria in childhood : Rational diagnostics and treatment].

    PubMed

    Ott, H

    2017-07-01

    Chronic urticaria (CU) is defined by episodes of urticaria with or without angioedema, which recur daily or nearly daily over more than 6 weeks. Sudden manifestations of CU with or without known causes are termed chronic spontaneous urticaria, which is differentiated from chronic inducible urticaria. The differential diagnoses of CU in childhood range from self-limiting dermatoses to severe systemic diseases. Further targeted steps are taken to detect potential trigger factors or underlying illnesses only if suspicion arises on anamnestic grounds and CU is best treated in accordance with international guidelines. First-line therapy consists of non-sedating H 1 -antihistamines at approved or even higher doses. If symptoms persist, additional treatment with omalizumab, cyclosporine or montelukast can be initiated after careful individual consideration.

  15. Chronic total coronary occlusion: treatment results.

    PubMed

    Kirk Christensen, Martin; Freeman, Phillip Fischer; Rasmussen, Jeppe Groendal; Villadsen, Anton Boel; Raungaard, Bent; Eggert Jensen, Svend; Thuesen, Leif

    2017-08-01

    To describe the clinical and procedural coronary chronic total occlusion (CTO) treatment results in a Nordic PCI centre during the implementation of a CTO treatment program. In a retrospective registry study, we assessed; (1) indication for the procedure, (2) Canadian Cardiovascular Society angina pectoris score (CCS)/New York Heart Association (NYHA) heart failure score, (3) lesion complexity and (4) adverse events during hospital stay and three months following the index procedure. The study cohort included 503 patients (594 lesions). From 2010 to 2013 96% of procedures were performed with antegrade wire-escalation technique and 4% performed using retrograde techniques, from 2013-2016 the corresponding numbers were 83% and 17.0%. The procedural success rate was 69%, increasing from 64% before to 72% (p = .06) after routinely using the retrograde approach. No individual patient characteristic, lesion variable or score was strongly associated with procedural success or failure. There were 4% serious procedure related complications. In patients with PCI of a CTO lesion only, 87% were in CCS or NYHA functional class ≥2 before the index procedure vs. 22% at follow-up. Routine use of retrograde techniques tended to increase the procedural success rate. Clinical results after three months were acceptable, but the complication rate was higher than for non-CTO PCI. Individual patient and lesion characteristics had a low predictability for procedural success. Therefore, clinical symptoms, objective signs of myocardial ischemia and procedural risk should be focus points in coronary chronic total occlusion treatment strategies.

  16. [Factors that influence treatment adherence in chronic disease patients undergoing hemodialysis].

    PubMed

    Maldaner, Cláudia Regina; Beuter, Margrid; Brondani, Cecília Maria; Budó, Maria de Lourdes Denardin; Pauletto, Macilene Regina

    2008-12-01

    The following bibliographical research wanted to identify the main factors that influence adherence to treatment in chronic disease. The study focused on patients undergoing hemodialysis, as well as on the support nurses require for the promotion of health education among individuals with low treatment adherence. The identification of bibliographical sources was conducted at Health Virtual Library and Scientific Electronic Library Online (SciELO) data bases. Some printed magazines were also used. The results indicated nine factors influencing treatment adherence or non-adherence: team trust, support nets, educational level; accepting disease, treatment side effects, lack of access to medicines, long-term treatment, complex therapeutic approach, and lack of symptoms. It is advisable that nurses take into account these factors when dealing with chronic-disease patients that present low treatment adherence, getting family and multidisciplinary team support seeking treatment adherence.

  17. The effect of acupuncture treatment for insomnia in chronic hemodialysis patients

    NASA Astrophysics Data System (ADS)

    Widjaja, J. A.; Simadibrata, C.; Srilestari, A.; Marbun, M. B. H.

    2017-08-01

    Insomnia is a problem often experienced by patients on chronic dialysiswhich reduces their quality of life. Current management of insomnia with this specific group of patients has yet to produce optimum results. In this study, we explored the roleof acupuncture as a treatment for symptoms of insomnia in patients on chronic dialysis. Twenty-eight hemodialysis patients suffering from insomnia were divided randomly into two groups, an acupuncture group (n = 15) who received acupuncture treatment at the points HT7 Shenmen, PC6 Neiguan, GV20 Baihui, and EX-HN1 Sishenchong, anda control group (n = 13) who underwenta sham procedure in which a needle was inserted into an elastic bandage at the same points. The acupuncture treatment was done during hemodialysis twice a week for five weeks. PSQI scores and the WHOQOL-BREF were assessed before treatment, after the fifth treatment, and at the end of the treatment. Significant differences were found in the PSQI score ((4.20±2.27 vs. 11.23±3.37) p = 0.000) and in the WHOQOL-BREF ((94.53±10.08 vs. 82.69±11.90) p = 0.008) between the acupuncture group and the control group by the end of the period of treatment. Acupuncture treatment effectively improved the quality of sleep and the quality of life for these chronic hemodialysis patients.

  18. Surgical treatment of chronic pancreatitis--a 14 years experience.

    PubMed

    Stroescu, C; Dima, S; Scarlat, A; Ivanov, B; Bouaru, O; Ionescu, M; Vasilescu, C; Popescu, I

    2010-01-01

    Operative treatment of chronic pancreatitis is indicated for patients with intractable pain after failed medical and endoscopic treatment, or in the presence of complications of the disease. This study evaluates a single-center experience with operative management of chronic pancreatitis over a period of time of 14 years, regarding indication, surgical technique, early and late results. The records of 265 consecutive patients who underwent surgery for chronic pancreatitis between 1995 and 2008 were retrospectively reviewed and analyzed. Long-term outcomes were assessed by patient survey, with a median follow-up of 40 months. 265 patients underwent 275 operations for chronic pancreatitis with the main indication abdominal pain (46.8%), followed by suspected malignancy in 24.8% and recurrent episodes of acute pancreatitis in 18.6%. Resection procedures 54.5% (150), drainage procedures 1.09% (3), bypass and denervation procedures 44.36% (122) and exploratory laparotomy 3.27% (9) were performed with an overall morbidity of 22% and an in-hospital mortality rate of 2.64%. After a median follow-up of 40 months survival information was available for 137 patients (51.69%) with a 5-and actuarial survival rate of 74.7% and quality of life improvement in most patients, especially in the resected group. Our results suggest that in chronic pancreatitis the type of surgery has to be individualized in each patient (resection VS drainage) and organ preserving operations are safe and effective in providing long-term pain relief and in treating CP-related complications

  19. Treatment of Chronic Enterovirus Encephalitis With Fluoxetine in a Patient With X-Linked Agammaglobulinemia.

    PubMed

    Gofshteyn, Jacqueline; Cárdenas, Ana María; Bearden, David

    2016-11-01

    Enterovirus may result in a devastating chronic encephalitis in immunocompromised patients, particularly in patients with X-linked agammaglobulinemia. Prognosis for patients with chronic enterovirus encephalitis is poor, almost invariably resulting in mortality without specific treatment. There are currently no approved antiviral agents for enterovirus, but the antidepressant drug fluoxetine has been identified through library-based compound screening as a potential anti-enteroviral agent in vitro. However, use of fluoxetine has not previously been studied in humans with enteroviral disease. A five year old boy with X-linked agammaglobulinemia presented with progressive neurological deterioration and was found to have chronic enterovirus encephalitis by brain biopsy. He failed to respond to standard treatment with high dose intravenous immunoglobulin, but showed stabilization and improvement following treatment with fluoxetine. This is the first report to describe the use of fluoxetine as a potential therapy for chronic enterovirus infection. Further investigation of fluoxetine as a treatment option for chronic enterovirus encephalitis is necessary. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Chronic Treatment With Aripiprazole Prevents Development of Dopamine Supersensitivity and Potentially Supersensitivity Psychosis

    PubMed Central

    Tadokoro, Shigenori; Okamura, Naoe; Sekine, Yoshimoto; Kanahara, Nobuhisa; Hashimoto, Kenji; Iyo, Masaomi

    2012-01-01

    Background: Long-term treatment of schizophrenia with antipsychotics is crucial for relapse prevention, but a prolonged blockade of D2 dopamine receptors may lead to the development of supersensitivity psychosis. We investigated the chronic effects of aripiprazole (ARI) on dopamine sensitivity. Methods: We administered ARI (1.5 mg/kg/d), haloperidol (HAL; 0.75 mg/kg/d), or vehicle (VEH) via minipump for 14 days to drug-naive rats or to rats pretreated with HAL (0.75 mg/kg/d) or VEH via minipump for 14 days. On the seventh day following treatment cessation, we examined the effects of the treatment conditions on the locomotor response to methamphetamine and on striatal D2 receptor density (N = 4-10/condition/experiment). Results: Chronic treatment with HAL led to significant increases in locomotor response and D2 receptor density, compared with the effects of chronic treatment with either VEH or ARI; there were no significant differences in either locomotor response or D2 density between the VEH- and ARI-treated groups. We also investigated the effects of chronic treatment with HAL, ARI, or VEH preceded by HAL or VEH treatment on locomotor response and D2 density. ANOVA analysis indicated that the rank ordering of groups for both locomotor response and D2 density was HAL-HAL > HAL-VEH > HAL-ARI > VEH-VEH. Conclusions: Chronic treatment with ARI prevents development of dopamine supersensitivity and potentially supersensitivity psychosis, suggesting that by reducing excessive sensitivity to dopamine and by stabilizing sensitivity for an extended period of time, ARI may be helpful for some patients with treatment-resistant schizophrenia. PMID:21402722

  1. Extracorporeal shock wave treatment for chronic plantar fasciitis (heel pain).

    PubMed

    Ho, C

    2007-01-01

    (1) Electrohydraulic, electromagnetic, or piezoelectric devices are used to translate energy into acoustic waves during extracorporeal shock wave treatment (ESWT) for chronic plantar fasciitis (or heel pain). These waves may help to accelerate the healing process via an unknown mechanism. (2) ESWT, which is performed as an outpatient procedure, is intended to alleviate the pain due to chronic plantar fasciitis. (3) Results from randomized controlled trials have been conflicting. Six trials reported data that favour ESWT over placebo or conservative treatment for efficacy outcomes, while three trials showed no significant difference between the ESWT group and the placebo group. (4) The lack of convergent findings from randomized trials of ESWT for chronic plantar fasciitis suggests uncertainty about its effectiveness. The evidence reviewed in this bulletin does not support the use of this technology for this condition.

  2. Pharmacokinetic monitoring of chronic treatment with digoxin from Primary Health Care.

    PubMed

    García-Iranzo, Emma M; Rodríguez-Lucena, Francisco J; Matoses-Chirivella, Carmen; García-Monsalve, Ana; Murcia-López, Ana Cristina; Navarro-Ruiz, Andrés

    2017-07-01

    The serum digoxin concentration (SDC) should be between 0.8 and 2 ng/ml. The objective is to assess the pharmacokinetic monitoring of SDC performed from primary healthcare (PH) in patients with chronic treatment. Cross-sectional retrospective study of patients with chronic treatment with digoxin belonging to the department of a General University Hospital.Data were analized: age, sex, diagnosis, number of serum digoxin concentration determinations, date and origin of the request for monitoring, analytical result and pharmacokinetic assessment are collected. 624 patients are undergoing chronic treatment with digoxin, 68% women, mean age 78.4 (39-98) years. 308 (49.4%) patients haven't analytical determination of SDC (Group 1), 183 (29.3%) patients have a SDC occasionally performed with a request from specialist care (Group 2) and 133 (21,3%) patients have CSD performed with a request from primary healthcare doctors, with an average of 2.42 monitoring per patient and year (Group 3). These are those patients who have pharmacokinetic monitoring of chronic treatment with digoxin. Of the group 2.25 (13.6%) patientes were hospital admission from emergency department for presenting digitalis intoxication with CSD>2 ng/ml, and 39 (21.3%) patients for low dosing with CSD<0.5 ng/ml. Group 3.4 (3%) patients presented digitalis intoxication and 5 (3.8%) for insufficient dosing. A small proportion of patients undergoing chronic treatment with digoxin are under pharmacokinetic monitoring and a reduction in complications derived from inappropriate CSD compared to those not under pharmacokinetic follow-up is observed. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  3. Long-term opioid treatment of chronic nonmalignant pain: unproven efficacy and neglected safety?

    PubMed Central

    Kissin, Igor

    2013-01-01

    Background For the past 30 years, opioids have been used to treat chronic nonmalignant pain. This study tests the following hypotheses: (1) there is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective; and (2) the main problem associated with the safety of such treatment – assessment of the risk of addiction – has been neglected. Methods Scientometric analysis of the articles representing clinical research in this area was performed to assess (1) the quality of presented evidence (type of study); and (2) the duration of the treatment phase. The sufficiency of representation of addiction was assessed by counting the number of articles that represent (1) editorials; (2) articles in the top specialty journals; and (3) articles with titles clearly indicating that the addiction-related safety is involved (topic-in-title articles). Results Not a single randomized controlled trial with opioid treatment lasting >3 months was found. All studies with a duration of opioid treatment ≥6 months (n = 16) were conducted without a proper control group. Such studies cannot provide the consistent good-quality evidence necessary for a strong clinical recommendation. There were profound differences in the number of addiction articles related specifically to chronic nonmalignant pain patients and to opioid addiction in general. An inadequate number of chronic pain-related publications were observed with all three types of counted articles: editorials, articles in the top specialty journals, and topic-in-title articles. Conclusion There is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective. The above identified signs indicating neglect of addiction associated with the opioid treatment of chronic nonmalignant pain were present. PMID:23874119

  4. Comparative Effectiveness of Treatments for Chronic Low Back Pain: A Multiple Treatment Comparison Analysis.

    PubMed

    Rihn, Jeffrey A; Radcliff, Kristen; Norvell, Daniel C; Eastlack, Robert; Phillips, Frank M; Berland, Daniel; Sherry, Ned; Freedman, Mitchell; Vaccaro, Alexander R

    2017-06-01

    A systematic review and network meta-analysis. To determine current treatment options of chronic low back pain (LBP) as defined by randomized controlled trials (RCTs) and to compare effectiveness of those treatments using a mixed-treatment comparison (MTC). It is important to provide an evidence-based assessment of the treatment options that exist for LBP. A systematic search of RCTs was conducted in MEDLINE and the Cochrane Collaboration Library from 1990 to 2014. From the selected studies, we extracted preoperative and postoperative ODI and VAS back pain scores, additional surgeries, and complications. Standard and network meta-analytic techniques were used. Twelve RCTs were included in the analysis: 5 total disk replacement (TDR) versus fusion; 1 TDR versus exercise and cognitive behavioral therapy (CBT); 5 fusion versus exercise and CBT; and 1 fusion versus physical therapy (PT). On the basis of MTC, with respect to ODI change scores, the pooled mean difference favoring fusion over exercise and CBT was 2.0 points (95% CI, -1.2 to 4.8). The pooled mean difference favoring TDR over exercise and CBT was 6.4 points (95% CI, 3.2-9.3). The pooled mean difference favoring fusion over PT was 8.8 points (95% CI, 4.1-13.6). The pooled mean differences favoring TDR over fusion was 4.4 points (95% CI, 2.37-6.63). For PT versus structured exercise with CBT, the pooled mean difference favoring exercise with CBT over PT was 6.8 points (95% CI, 1.5-12.8). For TDR versus PT, the pooled mean difference favoring TDR over PT was 13.2 points (95% CI, 8.0-18.4). Additional surgery rates were similar between treatment options. All 4 treatments provided some benefit to patients with chronic LBP. According to the MTC analysis, TDR may be the most effective treatment and PT the least effective treatment for chronic LBP. This review is based on a limited number of RCT studies and does not support any 1 treatment modality for all patients.

  5. [Efficiency of etiologic correction of concomitant ascaridosis in the complex treatment of chronic pancreatitis].

    PubMed

    Babinets', L S; Droniak, Iu V; Pliashko, K O; Babinets', A I

    2014-11-01

    The of antihelmintic preparation albendazole using in the complex treatment of patients with chronic pancreatitis with the concomitant ascaridosis was promote regression of clinical demonstration of basic and concomitant diseases (P < 0.05). Options of coprogram and the structural state of pancreas from data of ultrasonography in marks by Marseille-Cambridge classification of chronic pancreatitis, after the conducted treatment became the better (P < 0.05), that established expedience of the use of albendazole in complex treatment of patients with a chronic pancreatitis with a concomitant ascaridosis.

  6. Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis

    PubMed Central

    Rummel-Kluge, Christine; Komossa, Katja; Schwarz, Sandra; Hunger, Heike; Schmid, Franziska; Lobos, Claudia Asenjo; Kissling, Werner; Davis, John M; Leucht, Stefan

    2010-01-01

    Objective The metabolic side effects of second-generation antipsychotics (SGA) are serious and have not been compared head to head in a meta-analysis. We conducted a meta-analysis of studies comparing the metabolic side effects of the following SGAs head-to-head: amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, zotepine. Method We searched the register of the Cochrane schizophrenia group (last search May 2007), supplemented by MEDLINE and EMBASE (last search January 2009) for randomized, blinded studies comparing the above mentioned SGA in the treatment of schizophrenia or related disorders. At least three reviewers extracted the data independently. The primary outcome was weight change. We also assessed changes of cholesterol and glucose. The results were combined in a meta-analysis. Results We included 48 studies with 105 relevant arms. Olanzapine produced more weight gain than all other second-generation antipsychotics except for clozapine where no difference was found. Clozapine produced more weight gain than risperidone, risperidone more than amisulpride, and sertindole more than risperidone. Olanzapine produced more cholesterol increase than aripiprazole, risperidone and ziprasidone. (No differences with amisulpride, clozapine and quetiapine were found). Quetiapine produced more cholesterol increase than risperidone and ziprasidone. Olanzapine produced more increase in glucose than amisulpride, aripiprazole, quetiapine, risperidone and ziprasidone; no difference was found with clozapine. Conclusions Some SGAs lead to substantially more metabolic side effects than other SGAs. When choosing an SGA for an individual patient these side effects with their potential cause of secondary diseases must be weighed against efficacy and characteristics of the individual patient. PMID:20692814

  7. Chronic Morphine Treatment Reduces Recovery from Opioid Desensitization

    PubMed Central

    Dang, Vu C.; Williams, John T.

    2013-01-01

    Tolerance and dependence result from long-term exposure to opioids, and there is growing evidence linking acute receptor desensitization to these more long-term processes. Receptor desensitization encompasses a series of events leading to the loss of receptor function and internalization. This study examines the onset and recovery from desensitization in locus ceruleus neurons recorded in brain slices taken from animals that have been chronically treated with morphine. After chronic morphine treatment, desensitization was altered as follows. First, the rate of desensitization was increased. Second, recovery from desensitization was always incomplete, even after a brief (1–2 min) exposure to agonist. This contrasts with experiments in controls in which recovery from desensitization, after a brief exposure to agonist, was complete within 25 min. Finally, morphine-6-β-D-glucuronide, a metabolite of morphine that was ineffective at causing desensitization in controls, induced significant desensitization in slices from morphine-treated animals. When brain slices from controls were treated with inhibitors of PKC or monensin, agents known to compromise G-protein-coupled receptor resensitization, desensitization was increased, and recovery was significantly reduced. These results indicate that receptor resensitization maintains signaling during periods of intense and sustained stimulation. After chronic morphine treatment, desensitization is potentiated, and receptor resensitization is compromised. PMID:15342737

  8. Chronic morphine treatment reduces recovery from opioid desensitization.

    PubMed

    Dang, Vu C; Williams, John T

    2004-09-01

    Tolerance and dependence result from long-term exposure to opioids, and there is growing evidence linking acute receptor desensitization to these more long-term processes. Receptor desensitization encompasses a series of events leading to the loss of receptor function and internalization. This study examines the onset and recovery from desensitization in locus ceruleus neurons recorded in brain slices taken from animals that have been chronically treated with morphine. After chronic morphine treatment, desensitization was altered as follows. First, the rate of desensitization was increased. Second, recovery from desensitization was always incomplete, even after a brief (1-2 min) exposure to agonist. This contrasts with experiments in controls in which recovery from desensitization, after a brief exposure to agonist, was complete within 25 min. Finally, morphine-6-beta-D-glucuronide, a metabolite of morphine that was ineffective at causing desensitization in controls, induced significant desensitization in slices from morphine-treated animals. When brain slices from controls were treated with inhibitors of PKC or monensin, agents known to compromise G-protein-coupled receptor resensitization, desensitization was increased, and recovery was significantly reduced. These results indicate that receptor resensitization maintains signaling during periods of intense and sustained stimulation. After chronic morphine treatment, desensitization is potentiated, and receptor resensitization is compromised.

  9. Topical treatments for chronic plaque psoriasis.

    PubMed

    Mason, Anne R; Mason, James; Cork, Michael; Dooley, Gordon; Hancock, Helen

    2013-03-28

    Chronic plaque psoriasis is the most common type of psoriasis, and it is characterised by redness, thickness, and scaling. First-line management of chronic plaque psoriasis is with topical treatments, including vitamin D analogues, topical corticosteroids, tar-based preparations, dithranol, salicylic acid, and topical retinoids. To compare the effectiveness, tolerability, and safety of topical treatments for chronic plaque psoriasis, relative to placebo, and to similarly compare vitamin D analogues (used alone or in combination) with other topical treatments. We updated our searches of the following databases to February 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2011, Issue 2), MEDLINE (from 1948), EMBASE (from 1980), Science Citation Index (from 2008), Conference Proceedings Citation Index - Science (from 2008), BIOSIS (from 1993), Dissertation Abstracts via DialogClassic (all publication years), and Inside Conferences (all publication years).We identified ongoing and unpublished studies from the UK Clinical Research Network Study Portfolio and the metaRegister of Controlled Trials. We checked the bibliographies of published studies and reviews for further references to relevant trials, and we contacted trialists and companies for information about newly published studies.A separate search for adverse effects was undertaken in February 2011 using MEDLINE and EMBASE (from 2005).Final update searches for both RCTs and adverse effects were undertaken in August 2012. Although it has not been possible to incorporate RCTs and adverse effects studies identified through these final searches within this review, we will incorporate these into the next update. Randomised trials comparing active topical treatments against placebo or against vitamin D analogues (used alone or in combination) in people with chronic plaque psoriasis. One author extracted study data and assessed study quality. A second author checked these data. We

  10. Efficacy of itraconazole in the treatment of patients with chronic cough whose sputa yield basidiomycetous fungi-fungus-associated chronic cough (FACC).

    PubMed

    Ogawa, Haruhiko; Fujimura, Masaki; Takeuchi, Yasuo; Makimura, Koichi

    2009-05-01

    This controlled study was performed to clarify the therapeutic benefit of itraconazole for the treatment of patients with chronic cough, wherein a sputum culture yielded basidiomycetous (BM) fungi. Of the 171 patients who visited our hospital for the diagnosis and treatment of chronic cough, BM was detected in the sputum of 39 patients. Informed consents were obtained from 21 patients who were subsequently enrolled in this trial. After the administration of the standard therapy, all the patients were enrolled in a randomized placebo-controlled study with 2 weeks of treatment with a low dose of itraconazole (50 mg/day) (n = 10) in comparison with a corresponding period of treatment with matched placebo (ambroxol hydrochloride 45 mg/day) (n = 11). Coughing was assessed using subjective cough symptom scale and capsaicin cough challenging. The treatment with itraconazole, but not placebo (p = 0.17), was associated with a significant improvement in the cough scale (p = 0.0051); moreover, the improvement achieved with itraconazole was significant (p < 0.001) when compared with that of the placebo. Low-dose itraconazole was shown to be an effective antitussive in patients with chronic cough in which sputum examination yielded BM fungi. The 21 patients described here entailed the following manifestations: (1) chronic cough; (2) the presence of environmental fungi, particularly basidiomycetous (BM) fungi, in the sputum; and (3) good clinical response to antifungal drugs. These clinical features may constitute a unique disease concept called fungus-associated chronic cough (FACC).

  11. Healthcare professionals' perceptions of psychological treatment for chronic pain in Singapore: challenges, barriers, and the way forward.

    PubMed

    Yang, Su-Yin; Bogosian, Angeliki; Moss-Morris, Rona; McCracken, Lance M

    2016-08-01

    There are very few studies on healthcare providers' experiences of delivering treatment for chronic pain in a Southeast Asian setting. The aims of this study are to understand the experiences of professionals delivering treatment for people with chronic pain in Singapore and identify possible barriers to psychological treatment for this condition within the broader experiences of these professionals. Healthcare professionals with at least 1-year experience treating chronic pain were recruited and purposefully sampled. Fifteen inductive semi-structured interviews were conducted to explore healthcare professionals' experiences of treating people with chronic pain. Interviews were transcribed verbatim and analysed using thematic analysis. Four main themes were identified: 'System Barriers', 'Core Beliefs and management of Chronic Pain', 'Engaging Patients in treatment' and 'Creating Awareness for Chronic Pain Management'. Professionals trained in a multidisciplinary approach to pain management were seen as rare. Professionals who could refer patients for psychological treatment do not refer due to costs, and their perception that patients may lack understanding of such a treatment. Reducing barriers in the access to psychological treatment in settings like Singapore will require a multifaceted approach. Implications for Rehabilitation A multifaceted approach is required to reduce barriers to psychological treatment for chronic pain in settings like Singapore. Educating healthcare professionals on the need for a multidisciplinary approach to chronic pain could help in reducing misconceptions and increase understanding of the benefits of psychological approaches. Utilizing both media and technological platforms as a means to facilitate psychological treatment uptake for chronic pain may be a way forward for a technological savvy generation.

  12. Psychosocial factors and adherence to drug treatment in patients on chronic haemodialysis.

    PubMed

    Huertas-Vieco, María P; Pérez-García, Rafael; Albalate, Marta; de Sequera, Patricia; Ortega, Mayra; Puerta, Marta; Corchete, Elena; Alcázar, Roberto

    2014-11-17

    The daily pill burden in hemodialysis patients is one of the highest reported to date in any chronic disease. The adherence to prescribed treatment has implications on the quality of life, the survival of patients, and the economic cost of their treatment, this being a priority public health issue. To evaluate the adherence to pharmacological treatment examining, among the possible causes of non-adherence, psychosocial factors such as depression, anxiety, cognitive impairment and social support. Transversal-observational study of thirty five patients that suffer from chronic renal disease and who are on manteinance hemodialysis, evaluated by self-reported measures. Non-adherent patients have significant higher depression index than adherent patients. Anxiety, cognitive impairment and social support do not show a significant relation with the degree of adherence or compliance with farmacological treatment. These results suggest that psychological intervention in chronic haemodialysis patients with a severe depression index could increase the degree of fulfillment and general well-being of renal patients.

  13. [Therapeutic bacterial vaccine Immunovac in complex treatment of patients with chronic pyoderma].

    PubMed

    Sorokina, E V; Masiukova, S A; Kurbatova, E A; Egorova, N B

    2010-01-01

    Assessment of therapeutic effect and immunologic parameters during use of Immunovac vaccine for complex treatment of chronic forms of pyoderma. Ninety-five patients with different clinical forms of chronic pyoderma (furunculosis, hydradenitis, chronic ulcerative and ulcerative-vegetans pyoderma, folliculitis, impetigo etc.) were studied. Fifty-nine patients received immunotherapy with Immunovac vaccine together with basic therapy and 36 patients comprised control group treated only with basic therapy. Studied immunologic parameters were as follows: assessment of functional activity of lymphocytes, determination of lymphocyte subpopulations by flow cytometry, total immunoglobulins classes A, G, M by radial immunoduffusion, affinity of antibodies by enzyme immunoassay, levels of IFNalpha and IFNgamma. Use of Immunovac vaccine in complex treatment of patients with chronic forms of pyoderma enhanced clinical effect of basic therapy, which expressed in decrease of severity and frequency of disease relapses irrespective to clinical form and severity of pyoderma. Therapeutic effect during use of Immunovac vaccine amounted 84.7%, whereas in control group it was 41.6% after 12 months of follow-up. Increase of functional activity of neutrophils, subpopulation of lymphocytes with markers CD4+, CD8+, CD72+, affinity of antibodies as well as induced production of IFNalpha and IFNgamma was revealed. Correction of immunologic parameters correlated with positive results of patients treatment. Inclusion of bacterial polycomponent vaccine Immunovac in complex treatment of patients with chronic pyoderma promotes enhancement of therapeutic effect of basic therapy and correction of immunologic parameters.

  14. Chronic corticosterone treatment enhances extinction-induced depression in aged rats.

    PubMed

    Huston, Joseph P; Komorowski, Mara; de Souza Silva, Maria A; Lamounier-Zepter, Valéria; Nikolaus, Susanne; Mattern, Claudia; Müller, Christian P; Topic, Bianca

    2016-11-01

    Withdrawal and avoidance behavior are common symptoms of depression and can appear as a consequence of absence of reward, i.e. extinction-induced depression (EID). This is particularly relevant for the aged organism subjected to pronounced loss of former rewards. Avoidance of the former site of reward and increased withdrawal into a distant compartment accompany extinction of food-rewarded behavior in rodent models. During extinction, behavioral markers for re-learning dissociate from indicators of extinction-induced depression. Here we examined the effect of a chronic treatment with corticosterone (CORT), a well-known inducer of depression-related behavior, on EID in adult and aged rats. Adult (3-4months) and aged (18months) male rats were treated with CORT via drinking water for 3weeks prior to extinction of a cued food-reward task. CORT treatment increased the distance from the site of reward and decreased goal tracking behavior during extinction, especially in the aged rats. Plasma hormone levels measured before and after restraint stress showed a decline in basal ACTH- and CORT-levels after chronic CORT treatment in aged animals. The treatment significantly impaired the HPA-axis activation after acute stress in both, adult and aged animals, alike. Altogether, these findings show an enhancement of EID after chronic CORT treatment in the aged organism, which may be mediated by an impaired HPA-axis sensitivity. These findings may have special relevance for the investigation of human geriatric depression. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Lubiprostone: a chloride channel activator for treatment of chronic constipation.

    PubMed

    Ambizas, Emily M; Ginzburg, Regina

    2007-06-01

    To review lubiprostone's pharmacology, pharmacokinetics, efficacy, and safety in the treatment of chronic constipation. A literature search was conducted using PubMed/MEDLINE (1966-January 2007), IngentaConnect, and International Pharmaceutical Abstracts (1977-January 2007). Key words used included lubiprostone, Amitiza, and chronic constipation. All articles identified from the data sources that were published in English were evaluated. Lubiprostone is a chloride channel activator approved by the Food and Drug Administration for the treatment of chronic constipation. A randomized, double-blind, parallel-group, placebo-controlled study evaluating the effect of lubiprostone on gastric function showed slowed gastric emptying and increased small bowel and colonic transit time. Peak plasma concentration was shown to be around 1.14 hours, with a majority of the drug excreted in the urine within 48 hours. Phase III trials have noted that most patients with chronic constipation have a spontaneous bowel movement within 24 hours after taking lubiprostone. The most common adverse events in these trials were nausea, diarrhea, abdominal pain, and headache. Lubiprostone use has not been studied in the pediatric population. Lubiprostone may be a reasonable alternative for use in patients who either fail or are intolerant of standard therapy for chronic constipation. Head-to-head comparison studies with conventional therapy are needed to contrast clinical efficacy and safety of this medication.

  16. Treatment of Substance Abusing Patients with Comorbid Psychiatric Disorders

    PubMed Central

    Kelly, Thomas M.; Daley, Dennis C.; Douaihy, Antoine B.

    2011-01-01

    Objective To update clinicians on the latest in evidence-based treatments for substance use disorders (SUD) and non-substance use disorders among adults and suggest how these treatments can be combined into an evidence based process that enhances treatment effectiveness in comorbid patients. Method Articles were extracted from Pubmed using the search terms “dual diagnosis,” “comorbidity” and “co-occurring” and were reviewed for evidence of effectiveness for pharmacologic and psychotherapeutic treatments of comorbidity. Results Twenty-four research reviews and 43 research trials were reviewed. The preponderance of the evidence suggests that antidepressants prescribed to improve substance-related symptoms among patients with mood and anxiety disorders are either not highly effective or involve risk due to high side-effect profiles or toxicity. Second-generation antipsychotics are more effective for treatment of schizophrenia and comorbid substance abuse and current evidence suggests clozapine, olanzapine and risperidone are among the best. Clozapine appears to be the most effective of the antipsychotics for reducing alcohol, cocaine and cannabis abuse among patients with schizophrenia. Motivational interviewing has robust support as a highly effective psychotherapy for establishing a therapeutic alliance. This finding is critical since retention in treatment is essential for maintaining effectiveness. Highly structured therapy programs that integrate intensive outpatient treatments, case management services and behavioral therapies such as Contingency Management (CM) are most effective for treatment of severe comorbid conditions. Conclusions Creative combinations of psychotherapies, behavioral and pharmacological interventions offer the most effective treatment for comorbidity. Intensity of treatment must be increased for severe comorbid conditions such as the schizophrenia/cannabis dependence comorbidity due to the limitations of pharmacological

  17. Older people's experiences of patient-centered treatment for chronic pain: a qualitative study.

    PubMed

    Teh, Carrie F; Karp, Jordan F; Kleinman, Arthur; Reynolds Iii, Charles F; Weiner, Debra K; Cleary, Paul D

    2009-04-01

    Older adults with chronic pain who seek treatment often are in a health care environment that emphasizes patient-directed care, a change from the patriarchal model of care to which many older adults are accustomed. To explore the experiences of older adults seeking treatment for chronic pain, with respect to patient-directed care and the patient-provider relationship. In-depth interviews with 15 Caucasian older adults with chronic pain who had been evaluated at a university-based pain clinic. All interviews were audiotaped and the transcripts were analyzed using a grounded theory based approach. Older adults with chronic pain vary in their willingness to be involved in their treatment decisions. Many frequently participate in decisions about their pain treatment by asking for or refusing specific treatments, demanding quality care, or operating outside of the patient-provider relationship to manage pain on their own. However, others prefer to let their provider make the decisions. In either case, having a mutually respectful patient-provider relationship is important to this population. Specifically, participants described the importance of "being heard" and "being understood" by providers. As some providers switch from a patriarchal model of care toward a model of care that emphasizes patient activation and patient-centeredness, the development and cultivation of valued patient-provider relationships may change. While it is important to encourage patient involvement in treatment decisions, high-quality, patient-centered care for older adults with chronic pain should include efforts to strengthen the patient-provider relationship by attending to differences in patients' willingness to engage in patient-directed care and emphasizing shared decision-making.

  18. Reinstitution of neuroleptic treatment with molindone in a patient with a history of neuroleptic malignant syndrome.

    PubMed

    Slack, T; Stoudemire, A

    1989-09-01

    The decision to reinstitute neuroleptic treatment in patients with a history of neuroleptic treatment is fraught with hazards. A case is reported in which neuroleptic treatment was successfully reintroduced with molindone after previous bouts of neuroleptic malignant syndrome (NMS) with trifluoperazine and thioridazine. Molindone may represent an alternative neuroleptic to consider in patients with a history of NMS, although all neuroleptics including clozapine and molindone may potentially precipitate this syndrome.

  19. Are cannabinoids an effective treatment for chronic non-cancer pain?

    PubMed

    Allende-Salazar, Rubén F; Rada, Gabriel

    2017-06-14

    The use of cannabinoids has been proposed as an analgesic for different painful conditions, especially for chronic pain refractory to usual treatment. However, its real efficacy and safety remains controversial. We sought to determine whether cannabinoids are an effective treatment for chronic non-cancer pain. To answer this question, we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We identified 37 systematic reviews including 41 studies overall, of which 32 were randomized trials relevant for the question of interest. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded it is not clear whether cannabinoids decrease pain in patients with chronic non-cancer pain because the certainty of available evidence is very low. On the other hand, they are associated with significant adverse effects.

  20. An autoradiographic analysis of cholinergic receptors in mouse brain after chronic nicotine treatment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pauly, J.R.; Marks, M.J.; Gross, S.D.

    1991-09-01

    Quantitative autoradiographic procedures were used to examine the effects of chronic nicotine infusion on the number of central nervous system nicotinic cholinergic receptors. Female DBA mice were implanted with jugular cannulas and infused with saline or various doses of nicotine (0.25, 0.5, 1.0 or 2.0 mg/kg/hr) for 10 days. The animals were then sacrificed and the brains were removed and frozen in isopentane. Cryostat sections were collected and prepared for autoradiographic procedures as previously described. Nicotinic cholinergic receptors were labeled with L-(3H)nicotine or alpha-(125I)bungarotoxin; (3H)quinuclidinyl benzilate was used to measure muscarinic cholinergic receptor binding. Chronic nicotine infusion increased the numbermore » of sites labeled by (3H)nicotine in most brain areas. However, the extent of the increase in binding as well as the dose-response curves for the increase were widely different among brain regions. After the highest treatment dose, binding was increased in 67 of 86 regions measured. Septal and thalamic regions were most resistant to change. Nicotinic binding measured by alpha-(125I)bungarotoxin also increased after chronic treatment, but in a less robust fashion. At the highest treatment dose, only 26 of 80 regions were significantly changes. Muscarinic binding was not altered after chronic nicotine treatment. These data suggest that brain regions are not equivalent in the mechanisms that regulate alterations in nicotinic cholinergic receptor binding after chronic nicotine treatment.« less

  1. Treatment of central sensitization in patients with 'unexplained' chronic pain: what options do we have?

    PubMed

    Nijs, Jo; Meeus, Mira; Van Oosterwijck, Jessica; Roussel, Nathalie; De Kooning, Margot; Ickmans, Kelly; Matic, Milica

    2011-05-01

    Central sensitization accounts for chronic 'unexplained' pain in a wide variety of disorders, including chronic whiplash-associated disorders, temporomandibular disorders, chronic low back pain, osteoarthritis, fibromyalgia, chronic fatigue syndrome and chronic tension-type headache among others. Given the increasing evidence supporting the clinical significance of central sensitization in those with unexplained chronic pain, the awareness is growing that central sensitization should be a treatment target in these patients. This article provides an overview of the treatment options available for desensitizing the CNS in patients with chronic pain due to central sensitization. It focuses on those strategies that specifically target pathophysiological mechanisms known to be involved in central sensitization. In addition, pharmacological options, rehabilitation and neurotechnology options are discussed. Acetaminophen, serotonin-reuptake inhibitor drugs, selective and balanced serototin and norepinephrine-reuptake inhibitor drugs, the serotonin precursor tryptophan, opioids, N-methyl-d-aspartate (NMDA)-receptor antagonists, calcium-channel alpha(2)delta (a2δ) ligands, transcranial magnetic stimulation, transcutaneous electric nerve stimulation (TENS), manual therapy and stress management each target central pain processing mechanisms in animals that - theoretically - desensitize the CNS in humans. To provide a comprehensive treatment for 'unexplained' chronic pain disorders characterized by central sensitization, it is advocated to combine the best evidence available with treatment modalities known to target central sensitization. © 2011 Informa UK, Ltd

  2. Chronic Pain: How Challenging Are DDIs in the Analgesic Treatment of Inpatients with Multiple Chronic Conditions?

    PubMed

    Siebenhuener, Klarissa; Eschmann, Emmanuel; Kienast, Alexander; Schneider, Dominik; Minder, Christoph E; Saller, Reinhard; Zimmerli, Lukas; Blaser, Jürg; Battegay, Edouard; Holzer, Barbara M

    2017-01-01

    Chronic pain is common in multimorbid patients. However, little is known about the implications of chronic pain and analgesic treatment on multimorbid patients. This study aimed to assess chronic pain therapy with regard to the interaction potential in a sample of inpatients with multiple chronic conditions. We conducted a retrospective study with all multimorbid inpatients aged ≥18 years admitted to the Department of Internal Medicine of University Hospital Zurich in 2011 (n = 1,039 patients). Data were extracted from the electronic health records and reviewed. We identified 433 hospitalizations of patients with chronic pain and analyzed their combinations of chronic conditions (multimorbidity). We then classified all analgesic prescriptions according to the World Health Organization (WHO) analgesic ladder. Furthermore, we used a Swiss drug-drug interactions knowledge base to identify potential interactions between opioids and other drug classes, in particular coanalgesics and other concomitant drugs. Chronic pain was present in 38% of patients with multimorbidity. On average, patients with chronic pain were aged 65.7 years and had a mean number of 6.6 diagnoses. Hypertension was the most common chronic condition. Chronic back pain was the most common painful condition. Almost 90% of patients were exposed to polypharmacotherapy. Of the chronic pain patients, 71.1% received opioids for moderate to severe pain, 43.4% received coanalgesics. We identified 3,186 potential drug-drug interactions, with 17% classified between analgesics (without coanalgesics). Analgesic drugs-related DDIs, in particular opioids, in multimorbid patients are often complex and difficult to assess by using DDI knowledge bases alone. Drug-multimorbidity interactions are not sufficiently investigated and understood. Today, the scientific literature is scarce for chronic pain in combination with multiple coexisting medical conditions and medication regimens. Our work may provide useful

  3. Effect of growth hormone treatment on the adult height of children with chronic renal failure. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

    PubMed

    Haffner, D; Schaefer, F; Nissel, R; Wühl, E; Tönshoff, B; Mehls, O

    2000-09-28

    Growth hormone treatment stimulates growth in short children with chronic renal failure. However, the extent to which this therapy increases final adult height is not known. We followed 38 initially prepubertal children with chronic renal failure treated with growth hormone for a mean of 5.3 years until they reached their final adult height. The mean (+/-SD) age at the start of treatment was 10.4+/-2.2 years, the mean bone age was 7.1+/-2.3 years, and the mean height was 3.1+/-1.2 SD below normal. Fifty matched children with chronic renal failure who were not treated with growth hormone served as controls. The children treated with growth hormone had sustained catch-up growth, whereas the control children had progressive growth failure. The mean final height of the growth hormone-treated children was 165 cm for boys and 156 cm for girls. The mean final adult height of the growth hormone-treated children was 1.6+/-1.2 SD below normal, which was 1.4 SD above their standardized height at base line (P< 0.001). In contrast, the final height of the untreated children (2.1+/-1.2 SD below normal) was 0.6 SD below their standardized height at base line (P<0.001). Although prepubertal bone maturation was accelerated in growth hormone-treated children, treatment was not associated with a shortening of the pubertal growth spurt. The total height gain was positively associated with the initial target-height deficit and the duration of growth hormone therapy and was negatively associated with the percentage of the observation period spent receiving dialysis treatment. Long-term growth hormone treatment of children with chronic renal failure induces persistent catch-up growth, and the majority of patients achieve normal adult height.

  4. Treatment of a Case Example with PTSD and Chronic Pain

    ERIC Educational Resources Information Center

    Shipherd, Jillian C.

    2006-01-01

    This commentary reviews the case of GH, a survivor of a road traffic collision, who has chronic pain and posttraumatic stress disorder (PTSD). The case formulation, assessment strategy, and treatment plan are informed by the relevant experimental literature and empirically supported treatments using a cognitive behavioral perspective. Given this…

  5. Antihypertensive mechanisms of chronic captopril or N-acetylcysteine treatment in L-NAME hypertensive rats.

    PubMed

    Zicha, Josef; Dobesová, Zdenka; Kunes, Jaroslav

    2006-12-01

    Hypertension due to chronic inhibition of NO synthase (NOS) by Nomega-nitro-L-arginine methyl ester (L-NAME) administration is characterized by both impaired NO-dependent vasodilation and enhanced sympathetic vasoconstriction. The aim of our study was to evaluate changes in the participation of major vasoactive systems in L-NAME-treated rats which were subjected to simultaneous antihypertensive (captopril) or antioxidant (N-acetylcysteine, NAC) treatment. Three-month-old Wistar males treated with L-NAME (60 mg/kg/day) for 5 weeks were compared to rats in which L-NAME treatment was combined with simultaneous chronic administration of captopril or NAC. Basal blood pressure (BP) and its acute responses to consecutive i.v. injections of captopril (10 mg/kg), pentolinium (5 mg/kg), L-NAME (30 mg/kg), tetraethylammonium (TEA, 16 mg/kg) and nitroprusside (NP, 20 microg/kg) were determined in conscious rats at the end of the study. The development of L-NAME hypertension was prevented by captopril treatment, whereas NAC treatment caused only a moderate BP reduction. Captopril treatment normalized the sympathetic BP component and significantly reduced residual BP (measured at full NP-induced vasodilation). In contrast, chronic NAC treatment did not modify the sympathetic BP component or residual BP, but significantly enhanced NO-dependent vasodilation. Neither captopril nor NAC treatment influenced the compensatory increase of TEA-sensitive vasodilation mediated by endothelium-derived hyperpolarizing factor in L-NAME-treated rats. Chronic captopril treatment prevented L-NAME hypertension by lowering of sympathetic tone, whereas chronic NAC treatment attenuated L-NAME hypertension by reduction in the vasodilator deficit due to enhanced NO-dependent vasodilation.

  6. Treatment expectancy affects the outcome of cognitive-behavioral interventions in chronic pain.

    PubMed

    Goossens, Mariëlle E J B; Vlaeyen, Johan W S; Hidding, Alita; Kole-Snijders, Ank; Evers, Silvia M A A

    2005-01-01

    Patients' initial beliefs about the success of a given pain treatment are shown to have an important influence on the final treatment outcome. The aims of the paper are to assess determinants of patients' treatment expectancy and to examine the extent to which treatment expectancy predicts the short-term and long-term outcome of cognitive-behavioral treatment of chronic pain. This study employs the data of 2 pooled randomized clinical trials evaluating the effectiveness of cognitive-behavioral interventions for 171 patients with fibromyalgia and chronic low back pain. Pretreatment and posttreatment expectancy were measured by a short questionnaire, which was based on the procedure by Borkovec and Nau. Four composite outcome variables (pain coping and control, motoric behavior, negative affect, and quality of life) were measured before and after the intervention and at 12 months follow-up. Furthermore, several patient characteristics were taken into account. Patients with higher treatment expectancies significantly received less disability compensation and were less fearful. A regression model of 3 factors (better pain coping and control, active and positive interpretation of pain, and less disability compensation) significantly explained 10% of the variance in pretreatment expectancy. Pretreatment expectancy significantly predicted each of the 4 outcome measures immediately after treatment and at 12 months follow-up. This study corroborates the importance of treatment expectation before entering a cognitive-behavioral intervention in patients with chronic musculoskeletal pain.

  7. [Lengthening temporalis myoplasty in treatment of chronic facial paralysis].

    PubMed

    Bonde, Alexander; Wolthers, Mette Stueland

    2017-11-06

    Introducing the lengthening temporalis myoplasty (LTM), a newly implemented surgical treatment of chronic facial paralysis. LTM is a single-stage operation where the temporalis muscle is transposed for dynamic smile reconstruction, hereby serving as an alternative to the more complex two-stage microvascular functional muscle transplantation. This case report demonstrates how LTM can be used to treat patients, who are not motivated or suitable for extensive surgery. The introduction of this technique aims to help a larger number of patients with chronic facial paralysis.

  8. [Treatment of chronic bovine endometritis and factors for treatment success].

    PubMed

    Feldmann, M; Tenhagen genannt Emming, S; Hoedemaker, M

    2005-01-01

    In a controlled field trial, 178 dairy cows with chronic endometritis and at least 21 days in lactation were randomly assigned to four different treatment groups: prostaglandin F2alpha intramuscularly (PG, 5 mg dinoprost (5 ml Dinolytic), n = 51), intrauterine antibiotics (AB; 400 mg ampicillin + 800 oxacillin (20 ml Totocillin), n = 49), intrauterine antiseptics (AS; 100 ml 4% Lotagen, n = 50); control (C, no initial treatment, n = 28). Before treatment, uterine swabs for bacteriologic examination and blood samples for determination of serum progesterone concentrations were collected. Two weeks following the first treatment, cows were reexamined. In case no clinical cure was diagnosed, treatment was repeated and control cows were treated for the first time with one of the three treatments mentioned above. The four treatment groups did not differ with respect to the clinical cure or reproductive performance. Therefore, factors that might have an influence on clinical cure and fertility were evaluated. With increasing duration of lactation, the clinical cure after a single treatment increased significantly over all treatment groups from 59.5% (treatment before day 42 postpartum) to 79.6% (treatment following day 42 postpartum) (P < 0.05). Within the PG group, a statistically significantly higher cure rate after a single treatment and first service conception rate and a lower pregnancy index were obtained when the treatment was performed following day 42 postpartum (P < 0.05). This was not the case in the other treatment groups. A retarded involution of the uterus based on the size had a negative effect on clinical cure over all groups (first treatment clinical cure: 68.2% (small uteri) vs 44.4% (large uteri); P < 0.05). Within groups, this effect was also detected, but only as a trend (P > 0.05). Isolation of Arcanobacterium (A.) pyogenes negatively influenced first treatment clinical cure over all treatment groups (79.0% vs 31.5%) and within treatment groups (P < 0

  9. Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain

    PubMed Central

    Berta, Temugin; Qadri, Yawar; Tan, Ping-Heng; Ji, Ru-Rong

    2018-01-01

    Introduction Currently the treatment of chronic pain is inadequate and compromised by debilitating central nervous system side effects. Here we discuss new therapeutic strategies that target dorsal root ganglia (DRGs) in the peripheral nervous system for a better and safer treatment of chronic pain. Areas covered The DRGs contain the cell bodies of primary sensory neurons including nociceptive neurons. After painful injuries, primary sensory neurons demonstrate maladaptive molecular changes in DRG cell bodies and in their axons. These changes result in hypersensitivity and hyperexcitability of sensory neurons (peripheral sensitization) and are crucial for the onset and maintenance of chronic pain. We discuss the following new strategies to target DRGs and primary sensory neurons as a means of alleviating chronic pain and minimizing side effects: inhibition of sensory neuron-expressing ion channels such as TRPA1, TRPV1, and Nav1.7, selective blockade of C- and Aβ-afferent fibers, gene therapy, and implantation of bone marrow stem cells. Expert opinion These peripheral pharmacological treatments, as well as gene and cell therapies, aimed at DRG tissues and primary sensory neurons can offer better and safer treatments for inflammatory, neuropathic, cancer, and other chronic pain states. PMID:28480765

  10. Sublingual buprenorphine is effective in the treatment of chronic pain syndrome.

    PubMed

    Malinoff, Herbert L; Barkin, Robert L; Wilson, Geoffrey

    2005-01-01

    Many patients with chronic pain have less than optimal therapeutic outcomes after prolonged treatment with opiate analgesics. Worsening of pain perception, functional capacity, and mood often result. Medical detoxification is often undertaken in this situation. Ninety-five consecutive patients (49 men and 46 women; age range, 26-84) with chronic noncancer pain (maldynia) were referred by local pain clinics for detoxification from long-term opiate analgesic (LTOA) therapy. All patients had failed treatment as manifest by increasing pain levels, worsening functional capacity, and, in 8%, the emergence of opiate addiction. Length of prior LTOA therapy ranged from 1.5 to 27 years (mean, 8.8 years). After a minimum of 12 hours of abstinence from all opiate analgesics, patients were given low doses of sublingual (SL) buprenorphine or buprenorphine/naloxone (Reckitt Benckiser). Maintenance dosing was individualized to treat chronic pain. Daily SL dose of buprenorphine ranged from 4 to 16 mg (mean, 8 mg) in divided doses. Mean duration of treatment is 8.8 months (range, 2.4-16.6 months). At clinic appointments, patients were assessed for pain reports, functional capacity, and mood inventory. Eighty-six percent of patients experienced moderate to substantial relief of pain accompanied by both improved mood and functioning. Patient and family satisfaction was robust. Only 6 patients discontinued therapy secondary to side effects and/or exacerbation of pain. In this open-label study, SL buprenorphine and buprenorphine/naloxone were well tolerated and safe and appeared to be effective in the treatment of chronic pain patients refractory to LTOA.

  11. Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity

    PubMed Central

    Sacchi, Silvia; Novellis, Vito De; Paolone, Giovanna; Nuzzo, Tommaso; Iannotta, Monica; Belardo, Carmela; Squillace, Marta; Bolognesi, Paolo; Rosini, Elena; Motta, Zoraide; Frassineti, Martina; Bertolino, Alessandro; Pollegioni, Loredano; Morari, Michele; Maione, Sabatino; Errico, Francesco; Usiello, Alessandro

    2017-01-01

    D-aspartate levels in the brain are regulated by the catabolic enzyme D-aspartate oxidase (DDO). D-aspartate activates NMDA receptors, and influences brain connectivity and behaviors relevant to schizophrenia in animal models. In addition, recent evidence reported a significant reduction of D-aspartate levels in the post-mortem brain of schizophrenia-affected patients, associated to higher DDO activity. In the present work, microdialysis experiments in freely moving mice revealed that exogenously administered D-aspartate efficiently cross the blood brain barrier and stimulates L-glutamate efflux in the prefrontal cortex (PFC). Consistently, D-aspartate was able to evoke L-glutamate release in a preparation of cortical synaptosomes through presynaptic stimulation of NMDA, mGlu5 and AMPA/kainate receptors. In support of a potential therapeutic relevance of D-aspartate metabolism in schizophrenia, in vitro enzymatic assays revealed that the second-generation antipsychotic olanzapine, differently to clozapine, chlorpromazine, haloperidol, bupropion, fluoxetine and amitriptyline, inhibits the human DDO activity. In line with in vitro evidence, chronic systemic administration of olanzapine induces a significant extracellular release of D-aspartate and L-glutamate in the PFC of freely moving mice, which is suppressed in Ddo knockout animals. These results suggest that the second-generation antipsychotic olanzapine, through the inhibition of DDO activity, increases L-glutamate release in the PFC of treated mice. PMID:28393897

  12. Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments

    PubMed Central

    Herradón, Esperanza; González, Cristina; Uranga, José A.; Abalo, Raquel; Martín, Ma I.; López-Miranda, Visitacion

    2017-01-01

    In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week). Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations. PMID:28533750

  13. Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments.

    PubMed

    Herradón, Esperanza; González, Cristina; Uranga, José A; Abalo, Raquel; Martín, Ma I; López-Miranda, Visitacion

    2017-01-01

    In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week). Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations.

  14. Chronic fatigue syndrome: aetiology, diagnosis and treatment

    PubMed Central

    Avellaneda Fernández, Alfredo; Pérez Martín, Álvaro; Izquierdo Martínez, Maravillas; Arruti Bustillo, Mar; Barbado Hernández, Francisco Javier; de la Cruz Labrado, Javier; Díaz-Delgado Peñas, Rafael; Gutiérrez Rivas, Eduardo; Palacín Delgado, Cecilia; Rivera Redondo, Javier; Ramón Giménez, José Ramón

    2009-01-01

    Chronic fatigue syndrome is characterised by intense fatigue, with duration of over six months and associated to other related symptoms. The latter include asthenia and easily induced tiredness that is not recovered after a night's sleep. The fatigue becomes so severe that it forces a 50% reduction in daily activities. Given its unknown aetiology, different hypotheses have been considered to explain the origin of the condition (from immunological disorders to the presence of post-traumatic oxidative stress), although there are no conclusive diagnostic tests. Diagnosis is established through the exclusion of other diseases causing fatigue. This syndrome is rare in childhood and adolescence, although the fatigue symptom per se is quite common in paediatric patients. Currently, no curative treatment exists for patients with chronic fatigue syndrome. The therapeutic approach to this syndrome requires a combination of different therapeutic modalities. The specific characteristics of the symptomatology of patients with chronic fatigue require a rapid adaptation of the educational, healthcare and social systems to prevent the problems derived from current systems. Such patients require multidisciplinary management due to the multiple and different issues affecting them. This document was realized by one of the Interdisciplinary Work Groups from the Institute for Rare Diseases, and its aim is to point out the main social and care needs for people affected with Chronic Fatigue Syndrome. For this, it includes not only the view of representatives for different scientific societies, but also the patient associations view, because they know the true history of their social and sanitary needs. In an interdisciplinary approach, this work also reviews the principal scientific, medical, socio-sanitary and psychological aspects of Chronic Fatigue Syndrome. PMID:19857242

  15. Pharmacological Approaches for Treatment-resistant Bipolar Disorder

    PubMed Central

    Poon, Shi Hui; Sim, Kang; Baldessarini, Ross J.

    2015-01-01

    Bipolar disorder is prevalent, with high risks of disability, substance abuse and premature mortality. Treatment responses typically are incomplete, especially for depressive components, so that many cases can be considered “treatment resistant.” We reviewed reports on experimental treatments for such patients: there is a striking paucity of such research, mainly involving small incompletely controlled trials of add-on treatment, and findings remain preliminary. Encouraging results have been reported by adding aripiprazole, bupropion, clozapine, ketamine, memantine, pramipexole, pregabalin, and perhaps tri-iodothyronine in resistant manic or depressive phases. The urgency of incomplete responses in such a severe illness underscores the need for more systematic, simpler, and better controlled studies in more homogeneous samples of patients. PMID:26467409

  16. [Efficacy of hyaluronic acid in the treatment of chronic gingivitis in children].

    PubMed

    Igić, Marija; Mihailović, Dragan; Kesić, Ljiljana; Apostolović, Mirjana; Kostadinović, Ljiljana; Janjić, Olivera Tricković; Milasin, Jelena

    2011-12-01

    Gingivitis is a common occurrence in children and may well be thought as a risk factor for the appearance and progression of the diseases of parodontal tissues. It is thus necessary to react in a timely and adequate fashion to prevent the disease to become serious and produce parodontopathy. The aim of the study was to establish the efficacy of hyaluronic acid in the treatment of chronic gingivitis in children. The study enrolled 130 children with permanent dentition. All of the examinees were divided into three groups: group I--50 patients with chronic gingivitis in which only the basic treatment was applied; group II--50 patients with chronic gingivitis in which hyaluronic acid was applied in addition to basic treatment; group III--30 examinees with healthy gingiva (control group). Assessment of oral hygiene and status of the gingiva and parodontium was done using the appropriate indexes before and after the treatment. Inflammation of the gingiva was monitored by way of cytomorphometric studies. The pretreatment values of the plaque index (PI) were high: in the group I PI was 1.94; in the group II PI was 1.68. After the treatment, the PI value was reduced to null in both groups (PI = 0). In the group III PI was 0.17. The bleeding index (B1) in the group I was 2.02 before and 0.32 after the treatment; the BI value in the group II was 1.74 before and 0.16 after the treatment. In the group III BI was 0. In the group I, the Community Periodontal Index of Treatment Needs (CPITN) was 1.66 before and 0.32 after the treatment; in the group II, the CPITN value was 1.5 before and 0.24 after the treatment. In the group III, the CPITN value was 0. In the group I, the size of the nuclei of the stratified squamous epithelium of the gingiva was reduced, although not so much as the nuclear size in the group II of examinees. CONCLUSION. Basic treatment is able to successfully treat chronic gingivitis in children. The use of hyaluronic acid together with the basic treatment can

  17. The evolution of the surgical treatment of chronic pancreatitis.

    PubMed

    Andersen, Dana K; Frey, Charles F

    2010-01-01

    To establish the current status of surgical therapy for chronic pancreatitis, recent published reports are examined in the context of the historical advances in the field. The basis for decompression (drainage), denervation, and resection strategies for the treatment of pain caused by chronic pancreatitis is reviewed. These divergent approaches have finally coalesced as the head of the pancreas has become apparent as the nidus of chronic inflammation. The recent developments in surgical methods to treat the complications of chronic pancreatitis and the results of recent prospective randomized trials of operative approaches were reviewed to establish the current best practices. Local resection of the pancreatic head, with or without duct drainage, and duodenum-preserving pancreatic head resection offer outcomes as effective as pancreaticoduodenectomy, with lowered morbidity and mortality. Local resection or excavation of the pancreatic head offers the advantage of lowest cost and morbidity and early prevention of postoperative diabetes. The late incidences of recurrent pain, diabetes, and exocrine insufficiency are equivalent for all 3 surgical approaches. Local resection of the pancreatic head appears to offer best outcomes and lowest risk for the management of the pain of chronic pancreatitis.

  18. [Chronic prostatitis: a new paradigm of treatment].

    PubMed

    Bozhedomov, V A

    2016-08-01

    This paper proposes health care recommendations for men with chronic prostatitis (CP) taking into account etiopathogenesis and the clinical presentation of the disease. The proposal is based on the experience of federal and regional clinics of urology and gynecology, respective departments for postgraduate education and on the analysis of scientific literature. It is shown that managing patients with CP requires consideration of factors beyond the traditional practice of urology. The author validates the need to use the modern prostatitis classification UPOINT instead of the traditional NIH NIDDK (1995) to increase the effectiveness of treatment. It is demonstrated that the concurrent use of medications and non-pharmacological treatments aimed at different aspects of the state improve the treatment effectiveness. Indications are refined for medical and non-pharmacological treatments: antibiotics, alpha-blockers, anticholinergic agents, analgesics, antidepressants, herbal remedies, pelvic floor physiotherapy, psychotherapy. The shortcomings and mistakes of existing guidelines/standards are analyzed.

  19. Safety of long-term clozapine administration. Frequency of cardiomyopathy and hyponatraemia: two cross-sectional, naturalistic studies.

    PubMed

    Serrano, Ana; Rangel, Nairy; Carrizo, Edgardo; Uzcátegui, Euderruh; Sandia, Ignacio; Zabala, Angélica; Fernández, Erika; Tálamo, Eduardo; Servigna, Mercedes; Prieto, Dexi; Connell, Lisette; Baptista, Trino

    2014-02-01

    The antipsychotic drug (APD) clozapine (CLZ) is under-prescribed because of concerns about its safety. We evaluated in separate protocols the frequency of cardiomyopathy and hyponatraemia, which are adverse drug effects, where few comparative studies are available. Cross-sectional studies in subjects treated for at least 3 consecutive months with the same drug were conducted. Cardiomyopathy: Patients undergoing treatment either with CLZ (n = 125) or with other typical or atypical APDs (n = 59) were examined by a cardiologist who also recorded echocardiograms and electrocardiograms in order to diagnose cardiomyopathy. Hyponatraemia: Fasting sodium levels were assessed in patients receiving any of the following treatments: CLZ (n = 88), other atypical APDs (n = 61), typical APDs (n = 23), typical + atypical APDs (n = 11), and other drugs/drug-free (n = 36). Cardiomyopathy: No case of cardiomyopathy was detected. The frequency of abnormal ventricular ejection fraction (< 55%) was similar in both treatment groups (p = 1). Hyponatraemia: The frequency of hyponatraemia (percentage; 95% CI) was: CLZ (3.4%; -0.7, 7.1); other atypical APDs (4.9%; -0.5, 10.3); typical APDs (26.1%; 8.2, 44.0); typical + atypical APDs (9.1%; -7.8, 26.0); other drugs/drug-free (0%). None of the CLZ hyponatraemia subjects were on monotherapy. Our results are at odds with previous studies of CLZ-associated cardiomyopathy. However, they must be compared to further cross-sectional or prospective studies because most published data come from either case reports or pharmacovigilance systems. The frequency of hyponatraemia during CLZ administration was similar to that observed with other atypical APDs, and it was significantly lower than that recorded with typical agents. These results, along with numerous case reports on the effects of CLZ in patients with polydipsia and water intoxication, point to a safe or even positive profile of CLZ on electrolytic regulation.

  20. Conversion Disorder, Functional Neurological Symptom Disorder, and Chronic Pain: Comorbidity, Assessment, and Treatment.

    PubMed

    Tsui, Patricia; Deptula, Andrew; Yuan, Derek Y

    2017-06-01

    This paper examines the overlap of conversion disorder with chronic pain conditions, describes ways to assess for conversion disorder, and provides an overview of evidence-based treatments for conversion disorder and chronic pain, with a focus on conversion symptoms. Conversion disorder is a significant problem that warrants further study, given that there are not many well-established guidelines. Accurate and timely assessment should help move treatment in a more fruitful direction and avoid unnecessary medical interventions. Advances in neuroimaging may also help further our understanding of conversion disorder. Creating a supportive environment and a collaborative treatment relationship and improving understanding of conversion symptoms appear to help individuals diagnosed with conversion disorder engage in appropriate treatments. Novel uses of earlier treatments, such as hypnosis and psychodynamic approaches, could potentially be beneficial and require a more vigorous and systematic study. There are treatments that produce significant improvements in functioning and reduction of physical symptoms from conversion disorder even for very severe cases. Hypnotherapy, cognitive behavioral therapy, and inpatient multidisciplinary treatment with intensive physiotherapy for severe cases have the most evidence to support reduction of symptoms. Components of treatment for conversion disorder overlap with treatments for chronic pain and can be used together to produce therapeutic effects for both conditions. Treatment needs to be tailored for each individual's specific symptoms.

  1. Antioxidant Phytochemicals for the Prevention and Treatment of Chronic Diseases.

    PubMed

    Zhang, Yu-Jie; Gan, Ren-You; Li, Sha; Zhou, Yue; Li, An-Na; Xu, Dong-Ping; Li, Hua-Bin

    2015-11-27

    Overproduction of oxidants (reactive oxygen species and reactive nitrogen species) in the human body is responsible for the pathogenesis of some diseases. The scavenging of these oxidants is thought to be an effective measure to depress the level of oxidative stress of organisms. It has been reported that intake of vegetables and fruits is inversely associated with the risk of many chronic diseases, and antioxidant phytochemicals in vegetables and fruits are considered to be responsible for these health benefits. Antioxidant phytochemicals can be found in many foods and medicinal plants, and play an important role in the prevention and treatment of chronic diseases caused by oxidative stress. They often possess strong antioxidant and free radical scavenging abilities, as well as anti-inflammatory action, which are also the basis of other bioactivities and health benefits, such as anticancer, anti-aging, and protective action for cardiovascular diseases, diabetes mellitus, obesity and neurodegenerative diseases. This review summarizes recent progress on the health benefits of antioxidant phytochemicals, and discusses their potential mechanisms in the prevention and treatment of chronic diseases.

  2. Factors associated with low adherence to medicine treatment for chronic diseases in Brazil

    PubMed Central

    Tavares, Noemia Urruth Leão; Bertoldi, Andréa Dâmaso; Mengue, Sotero Serrate; Arrais, Paulo Sergio Dourado; Luiza, Vera Lucia; Oliveira, Maria Auxiliadora; Ramos, Luiz Roberto; Farias, Mareni Rocha; Pizzol, Tatiane da Silva Dal

    2016-01-01

    ABSTRACT OBJECTIVE To analyze factors associated with low adherence to drug treatment for chronic diseases in Brazil. METHODS Analysis of data from Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM - Brazilian Survey on Access, Use and Promotion of Rational Use of Medicines), a population-based cross-sectional household survey, based on a probabilistic sample of the Brazilian population. We analyzed the association between low adherence to drug treatment measured by the Brief Medication Questionnaire and demographic, socioeconomic, health, care and prescription factors. We used Poisson regression model to estimate crude and adjusted prevalence ratios, their respective 95% confidence interval (95%CI) and p-value (Wald test). RESULTS The prevalence of low adherence to drug treatment for chronic diseases was 30.8% (95%CI 28.8-33.0). The highest prevalence of low adherence was associated with individuals: young adults; no education; resident in the Northeast and Midwest Regions of Brazil; paying part of the treatment; poor self-perceived health; three or more diseases; reported limitations caused by a chronic disease; using five drugs or more. CONCLUSIONS Low adherence to drug treatment for chronic diseases in Brazil is relevant, and regional and demographic differences and those related to patients’ health care and therapy regime require coordinated action between health professionals, researchers, managers and policy makers. PMID:27982378

  3. Failure-free survival after second-line systemic treatment of chronic graft-versus-host disease

    PubMed Central

    Storer, Barry E.; Lee, Stephanie J.; Carpenter, Paul A.; Sandmaier, Brenda M.; Flowers, Mary E. D.; Martin, Paul J.

    2013-01-01

    This study attempted to characterize causes of treatment failure, identify associated prognostic factors, and develop shorter-term end points for trials testing investigational products or regimens for second-line systemic treatment of chronic graft-versus-host disease (GVHD). The study cohort (312 patients) received second-line systemic treatment of chronic GVHD. The primary end point was failure-free survival (FFS) defined by the absence of third-line treatment, nonrelapse mortality, and recurrent malignancy during second-line treatment. Treatment change was the major cause of treatment failure. FFS was 56% at 6 months after second-line treatment. Lower steroid doses at 6 months correlated with subsequent withdrawal of immunosuppressive treatment. Multivariate analysis showed that high-risk disease at transplantation, lower gastrointestinal involvement at second-line treatment, and severe NIH global score at second-line treatment were associated with increased risks of treatment failure. These three factors were used to define risk groups, and success rates at 6 months were calculated for each risk group either without or with various steroid dose limits at 6 months as an additional criterion of success. These success rates could be used as the basis for a clinically relevant and efficient shorter-term end point in clinical studies that evaluate agents for second-line systemic treatment of chronic GVHD. PMID:23321253

  4. A Unified, Transdiagnostic Treatment for Adolescents With Chronic Pain and Comorbid Anxiety and Depression

    PubMed Central

    Allen, Laura B.; Tsao, Jennie C.I.; Seidman, Laura C.; Ehrenreich-May, Jill; Zeltzer, Lonnie K.

    2017-01-01

    Chronic pain disorders represent a significant public health concern, particularly for children and adolescents. High rates of comorbid anxiety and unipolar mood disorders often complicate psychological interventions for chronic pain. Unified treatment approaches, based on emotion regulation skills, are applicable to a broad range of emotional disorders and suggest the possibility of extending these interventions to chronic pain and pain-related dysfunction. This case report describes the use of a unified protocol for treatment of an adolescent boy with chronic daily headache and social anxiety and an adolescent girl with whole body pain and depression. Following weekly, 50-minute individual treatment sessions, the boy demonstrated notable improvement in emotional symptoms, emotion regulation skills, somatization, and functional disability. The girl showed some improvement on measures of anxiety and depression, although there appeared to be a worsening of pain symptoms and somatization. However, both patients demonstrated improvement over follow-up. This case study illustrates the potential utility of a unified treatment approach targeting pain and emotional symptoms from an emotion regulation perspective in an adolescent population. PMID:28824271

  5. New developments in endoscopic treatment of chronic pancreatitis.

    PubMed

    Didden, P; Bruno, M; Poley, J W

    2012-12-01

    The aim of endoscopic therapy of chronic pancreatitis (CP) is to treat pain by draining the pancreatic duct or managing loco-regional complications. Recent decennia were characterized by continuous improvement of endoscopic techniques and devices, resulting in a better clinical outcome. Novel developments now also provide the opportunity to endoscopically treat refractory CP-related complications. Especially suboptimal surgical candidates could potentially benefit from these new developments, consequently avoiding invasive surgery. The use of fully covered self-expandable metal stents (SEMS) has been explored in pancreatic and CP-related biliary duct strictures, resistant to conventional treatment with plastic endoprotheses. Furthermore, endosonography-guided transmural drainage of the main pancreatic duct via duct-gastrostomy is an alternative treatment option in selected cases. Pancreatic pseudocysts represent an excellent indication for endoscopic therapy with some recent case series demonstrating effective drainage with the use of a fully covered SEMS. Although results of these new endoscopic developments are promising, high quality randomized trials are required to determine their definite role in the management of chronic pancreatitis.

  6. [Cost-effectiveness of Antipsychotics in the Maintenance Treatment of Schizophrenia in Colombia].

    PubMed

    Quitian Reyes, Hoover; Arciniegas Barrera, Jair Alberto; Bohórquez Peñaranda, Adriana; Gómez Restrepo, Carlos

    2016-01-01

    Assess the cost-effectiveness of the antipsychotics for treatment of schizophrenia. A five-year Markov model was built form patients with schizophrenia on the stage of maintenance. Costs were taken from the perspective of the Colombian health care system (Sistema General de Seguridad Social en Salud). The effectiveness was measured in years of life under the same maintenance plan. The Markov model indicated clozapine as the as the most cost-effective alternative between the first line antipsychotics and haloperidol is it when comparing other antipsychotics. Clozapine it's the cost-effectiveness strategy among the first line of antipsychotics and haloperidol is it among the other antipsychotics. Strategies prioritizing the use of cost-effective antipsychotics could improve the resources allocation in the Colombian health care system. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  7. Chronic Pain: How Challenging Are DDIs in the Analgesic Treatment of Inpatients with Multiple Chronic Conditions?

    PubMed Central

    Siebenhuener, Klarissa; Eschmann, Emmanuel; Kienast, Alexander; Schneider, Dominik; Minder, Christoph E.; Saller, Reinhard; Zimmerli, Lukas; Blaser, Jürg; Battegay, Edouard

    2017-01-01

    Background Chronic pain is common in multimorbid patients. However, little is known about the implications of chronic pain and analgesic treatment on multimorbid patients. This study aimed to assess chronic pain therapy with regard to the interaction potential in a sample of inpatients with multiple chronic conditions. Methods and Findings We conducted a retrospective study with all multimorbid inpatients aged ≥18 years admitted to the Department of Internal Medicine of University Hospital Zurich in 2011 (n = 1,039 patients). Data were extracted from the electronic health records and reviewed. We identified 433 hospitalizations of patients with chronic pain and analyzed their combinations of chronic conditions (multimorbidity). We then classified all analgesic prescriptions according to the World Health Organization (WHO) analgesic ladder. Furthermore, we used a Swiss drug-drug interactions knowledge base to identify potential interactions between opioids and other drug classes, in particular coanalgesics and other concomitant drugs. Chronic pain was present in 38% of patients with multimorbidity. On average, patients with chronic pain were aged 65.7 years and had a mean number of 6.6 diagnoses. Hypertension was the most common chronic condition. Chronic back pain was the most common painful condition. Almost 90% of patients were exposed to polypharmacotherapy. Of the chronic pain patients, 71.1% received opioids for moderate to severe pain, 43.4% received coanalgesics. We identified 3,186 potential drug-drug interactions, with 17% classified between analgesics (without coanalgesics). Conclusions Analgesic drugs-related DDIs, in particular opioids, in multimorbid patients are often complex and difficult to assess by using DDI knowledge bases alone. Drug-multimorbidity interactions are not sufficiently investigated and understood. Today, the scientific literature is scarce for chronic pain in combination with multiple coexisting medical conditions and medication

  8. Free intra-osseous muscle transfer for treatment of chronic osteomyelitis.

    PubMed

    Lê Thua, Trung-Hau; Boeckx, Willy D; Zirak, Christophe; De Mey, Albert

    2015-06-10

    Chronic osteomyelitis is still a big reconstructive challenge. Even with standard care, therapeutic failures and recurrences are common. Multiple techniques of tissue transfer have increased the success rate. This study recommends free muscle transfers into the intramedullary bone cavities for treatment of chronic osteomyelitis. The review included 29 patients that were treated for chronic osteomyelitis. Osteomyelitis was located at the femur in four patients, the tibia in 22 patients, and the foot in three patients. Dead bone and scar tissue were replaced with durable free muscle flap with special attention to fill the dead space. The average age of these patients was 48.5 years old (range = 23-70 years old). The average duration of osteomyelitis was 8.2 years (range = 1-45 years). Gracilis was applied in 20 cases (69%), latissimus dorsi was used in five cases (17.2%), and rectus abdominis was performed in four cases (13.8%). There was one flap failure, one partial superficial flap necrosis, two arterial thrombosis, and one venous thrombosis. All the remaining 28 muscle flaps survived. From 1-10 years follow-up, there was one recurrence of the osteomyelitis in the distal end of the intra-medullary cavity of a femur after reconstructing using the gracilis flap. The present study demonstrated that free intramedullary muscle transfers are effective in providing a high rate of success in the treatment of chronic osteomyelitis. The secondary filling of the intramedullary cavity after extensive removal of all infected bony sequesters has proven to give a long-term arrest of chronic osteomyelitis.

  9. Comparative Effectiveness of Proactive Tobacco Treatment among Smokers with and without Chronic Lower Respiratory Disease.

    PubMed

    Melzer, Anne C; Clothier, Barbara A; Japuntich, Sandra J; Noorbaloochi, Siamak; Hammett, Patrick; Burgess, Diana J; Joseph, Anne M; Fu, Steven S

    2018-03-01

    Adults with chronic lower respiratory disease differ in their barriers to smoking cessation but also suffer from tobacco-related health concerns, which may motivate quit attempts. Few studies have examined differences in tobacco treatment response between smokers with and without chronic lower respiratory disease. We examined the effectiveness of a proactive outreach program for cessation among smokers with and without chronic lower respiratory disease. Subgroup analysis of the Veterans Victory over Tobacco Study, a pragmatic randomized controlled trial that demonstrated the effectiveness of proactive outreach and the choice of tobacco treatments compared with usual care. Smokers identified via the electronic medical record were proactively offered phone-based counseling and care coordination to receive medication from their Veterans Affairs providers or in-person care. We compared the response among those with and without an International Classification of Diseases, 9th Revision diagnosis of a chronic lower respiratory disease (chronic obstructive pulmonary disease, chronic bronchitis, emphysema, asthma). We used stratification by propensity scores to adjust for imbalanced covariates between groups with and without chronic lower respiratory disease within each treatment arm, using complete case analysis accounting for the stratified sampling by site. The study participants were predominantly older, white, male smokers. Overall, 19.6% had chronic lower respiratory disease. A total of 3,307 had outcome data with the following assignments to the intervention: proactive care: n = 1,272 without chronic lower respiratory disease, n = 301 with chronic lower respiratory disease; usual care: n = 1,387 without chronic lower respiratory disease, n = 347 with chronic lower respiratory disease. A total of 1,888 had both complete baseline and outcome data and were included in the primary analysis. In unadjusted analyses (n = 3,307), among individuals with

  10. [Treatment Strategy and Results of Carotid Endarterectomy in Chronic Renal Failure Patients].

    PubMed

    Murahashi, Takeo; Kamiyama, Kenji; Osato, Toshiaki; Watanabe, Toshiichi; Ogino, Tatsuya; Sugio, Hironori; Endo, Hideki; Takahira, Kazuki; Shindo, Koichiro; Takahashi, Shuhei; Nakamura, Hirohiko

    2017-02-01

    The number of patients receiving chronic dialysis treatment in Japan currently exceeds 300,000 people. Few reports have described carotid endarterectomy(CEA)for chronic renal failure patients because of the unacceptable rate of perioperative stroke and other morbidities. A strategy for and treatment results of CEA for chronic renal failure patients in our hospital are described herein. The present study included 6 patients who underwent CEA while receiving dialysis treatment between April 2011 and November 2014. Dialysis treatment was initiated due to diabetes in 4 patients and renal sclerosis in 2 patients. All the patients were men, with a mean age of 74.0 years. Two patients were symptomatic, and four were asymptomatic. In all the patients, heart vascular lesions and arteriosclerosis risk factors were present. Postoperatively, pneumonia transient cranial neuropathy, heart failure, and pneumonia in 1 case required extensive treatment. However, by the time of discharge from hospital, no cases had deteriorated compared with their pre-CEA state. The modified Rankin scale score on discharge was 0-2 for all the patients. CEA can be performed safely in patients receiving dialysis, but further operative procedures and careful postoperative management are likely to be needed for patients with CEA who are receiving dialysis.

  11. Sialendoscopy-assisted treatment for chronic obstructive parotitis related to Sjogren syndrome.

    PubMed

    Guo, Yong-Feng; Sun, Ning-Ning; Wu, Chuan-Bin; Xue, Lei; Zhou, Qing

    2017-03-01

    Chronic obstructive parotitis related to Sjogren syndrome is not uncommon, but it is rarely reported in the literature. The aim of this study was to describe our experience in the treatment of chronic obstructive parotitis related to Sjogren syndrome. Seventeen cases of chronic obstructive parotitis related to Sjogren syndrome treated with sialendoscopy from June 2014 to June 2015 at the Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, were retrospectively reviewed. The cohort underwent ultrasonography, salivary gland scintigraphy, and sialography before sialendoscopy. All patients were asked to complete a visual analogue scale (VAS) evaluation before and 6 months after surgery. A paired t test was conducted, and P < .05 was considered statistically significant. The 17 study patients (27 parotid glands) successfully underwent interventional sialendoscopy under local anesthesia. The mean preoperative VAS score was 6, and the mean VAS score 6 months after sialendoscopy was significantly lower at 4.5 (P < .05). Interventional sialendoscopy plays a significant role in the treatment of chronic obstructive parotitis related to Sjogren syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Chronic molindone treatment: relative inability to elicit dopamine receptor supersensitivity in rats.

    PubMed

    Meller, E

    1982-01-01

    Chronic treatment of rats with the antipsychotic drug molindone (2.5 mg/kg) did not elicit behavioral supersensitivity to apomorphine (AP) (0.25 mg/kg) or increased striatal 3H-spiroperidol binding, whereas treatment with haloperidol (0.5-1.0 mg/kg) produced manifestations of dopaminergic supersensitivity in both paradigms. Chronic treatment with a high dose of molindone (20 mg/kg) elicited a small, but significant increase in behavioral sensitivity to AP (57%) which was, however, significantly less than that produced by 1 mg/kg haloperidol (126%, P less than 0.01). Apparent tolerance to elevation of striatal and frontal cortical 3,4-dihydroxyphenylacetic acid (DOPAC) levels was obtained with chronic molindone treatment (5 or 20 mg/kg). None of the molindone doses used (2.5-50 mg/kg) increased striatal dopamine receptor binding. Scatchard analyses revealed no change in either maximal binding capacity (Bmax) or dissociation constant (Kd). A significant (P less than 0.001) correlation of receptor binding activity and stereotypy score was obtained for haloperidol-, but not molindone-treated rats. These results with molindone in an animal model of tardive dyskinesia suggest that this drug may have a lower potential for eliciting this disorder in humans.

  13. Periodontal treatment reduces chronic systemic inflammation in peritoneal dialysis patients.

    PubMed

    Siribamrungwong, Monchai; Yothasamutr, Kasemsuk; Puangpanngam, Kutchaporn

    2014-06-01

    Chronic systemic inflammation, a non traditional risk factor of cardiovascular diseases, is associated with increasing mortality in chronic kidney disease, especially peritoneal dialysis patients. Periodontitis is a potential treatable source of systemic inflammation in peritoneal dialysis patients. Clinical periodontal status was evaluated in 32 stable chronic peritoneal dialysis patients by plaque index and periodontal disease index. Hematologic, blood chemical, nutritional, and dialysis-related data as well as highly sensitive C-reactive protein were analyzed before and after periodontal treatment. At baseline, high sensitive C-reactive protein positively correlated with the clinical periodontal status (plaque index; r = 0.57, P < 0.01, periodontal disease index; r = 0.56, P < 0.01). After completion of periodontal therapy, clinical periodontal indexes were significantly lower and high sensitivity C-reactive protein significantly decreased from 2.93 to 2.21 mg/L. Moreover, blood urea nitrogen increased from 47.33 to 51.8 mg/dL, reflecting nutritional status improvement. Erythropoietin dosage requirement decreased from 8000 to 6000 units/week while hemoglobin level was stable. Periodontitis is an important source of chronic systemic inflammation in peritoneal dialysis patients. Treatment of periodontal diseases can improve systemic inflammation, nutritional status and erythropoietin responsiveness in peritoneal dialysis patients. © 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.

  14. Unconventional treatments for chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Rajabally, Yusuf A

    2017-10-01

    This article focuses on the unconventional treatments used in chronic inflammatory demyelinating polyneuropathy (CIDP). First line, evidence-based treatments for CIDP include corticosteroids, immunoglobulins and plasma exchanges. Several unproven treatments are however given in treatment-refractory disease or to reduce requirements in validated therapies for reasons of side effects/practical delivery/cost. Despite methodological issues, IFN-α, azathioprine and methotrexate have not been shown to be useful in randomized controlled trials. Cyclophosphamide, rituximab and, as final resort in highly selected cases, hematopoietic stem cell transplant may be options considered in severely disabled refractory patients. Debatably, azathioprine, methotrexate, cyclosporine and mycophenolate mofetil are still occasionally used, among others, in milder disease. Physical therapy may be of benefit in CIDP but is not systematically considered as an integral part of management strategies. Current literature relating to unconventional therapies in CIDP is reviewed here and the possible avenues that require consideration in severe refractory disease and less disabling forms are discussed.

  15. Effect of chronic diuretic treatment on the plasma renin-angiotensin-aldosterone system in essential hypertension.

    PubMed Central

    Lijnen, P; Fagard, R; Staessen, J; Amery, A

    1981-01-01

    1 Chronic treatment with a constant dose of hydrochlorothiazide or tienilic acid increases plasma renin activity (PRA) acutely to reach a maximum within the first week. 2 During chronic diuretic therapy from 1 month to 1 year, PRA remained elevated at a rather constant level, though this was somewhat lower than the maximum level reached after 1 week. 3 A significant (P less than 0.01) correlation (r = 0.74) between changes in plasma angiotensin II and renin activity provoked by chronic treatment for 3 months with hydrochlorothiazide and tienilic acid was found. 4 The increase in plasma aldosterone during chronic treatment with hydrochlorothiazide and tienilic acid (1000 mg) is related (r = 0.68; P less than 0.01) to the rise in plasma angiotensin II. PMID:7028060

  16. Deciding in the dark: advance directives and continuation of treatment in chronic critical illness.

    PubMed

    Camhi, Sharon L; Mercado, Alice F; Morrison, R Sean; Du, Qingling; Platt, David M; August, Gary I; Nelson, Judith E

    2009-03-01

    Chronic critical illness is a devastating syndrome for which treatment offers limited clinical benefit but imposes heavy burdens on patients, families, clinicians, and the health care system. We studied the availability of advance directives and appropriate surrogates to guide decisions about life-sustaining treatment for the chronically critically ill and the extent and timing of treatment limitation. Prospective cohort study. Respiratory Care Unit (RCU) in a large, tertiary, urban, university-affiliated, hospital. Two hundred three chronically critically ill adults transferred to RCU after tracheotomy for failure to wean from mechanical ventilation in the intensive care unit. None. We interviewed RCU caregivers and reviewed patient records to identify proxy appointments, living wills, or oral statements of treatment preferences, resuscitation directives, and withholding/withdrawal of mechanical ventilation, nutrition, hydration, renal replacement and vasopressors. Forty-three of 203 patients (21.2%) appointed a proxy and 33 (16.2%) expressed preferences in advance directives. Do not resuscitate directives were given for 71 patients (35.0%). Treatment was limited for 39 patients (19.2%). Variables significantly associated with treatment limitation were proxy appointment prior to study entry (time of tracheotomy/RCU transfer) (odds ratio = 6.7, 95% confidence interval [CI], 2.3-20.0, p = 0.0006) and palliative care consultation in the RCU (OR = 40.9, 95% CI, 13.1-127.4, p < 0.0001). Median (interquartile range) time to first treatment limitation was 39 (31.0-45.0) days after hospital admission and 13 (8.0-29.0) days after RCU admission. For patients dying after treatment limitation, median time from first limitation to death ranged from 3 days for mechanical ventilation and hydration to 7 days for renal replacement. Most chronically critically ill patients fail to designate a surrogate decision-maker or express preferences regarding life-sustaining treatments

  17. Treatment of Chronic Plantar Fasciitis With Percutaneous Latticed Plantar Fasciotomy.

    PubMed

    Yanbin, Xu; Haikun, Chu; Xiaofeng, Ji; Wanshan, Yang; Shuangping, Liu

    2015-01-01

    Plantar fasciitis, the most common cause of pain in the inferior heel, accounts for 11% to 15% of all foot symptoms requiring professional care among adults. The present study reports the results of a minimally invasive surgical treatment of chronic plantar fasciitis. All patients with plantar fasciitis who had undergone percutaneous latticed plantar fasciotomy at 3 clinical sites from March 2008 to March 2009 were included in the present study. The follow-up evaluations for this treatment were conducted using the Mayo clinical scoring system. We investigated 17 patients with recalcitrant chronic plantar fasciitis who had undergone this treatment within a follow-up period of ≥13 months. All procedures were performed in the clinic with the patient under local anesthesia. No wound infections or blood vessel or nerve damage occurred. At a mean follow-up period of 16.0 ± 2.29 (range 13 to 21) months, significant improvement was seen in the preoperative mean Mayo score (from 12.06 ± 2.54 to 89.76 ± 4.28, p < .001) and no patient had developed symptom recurrence. Also, none of the patients had developed complex regional pain syndrome. All patients were able to return to regular shoe wear by 3 weeks postoperatively. The technique of plantar fasciitis with percutaneous latticed plantar fasciotomy could be a promising treatment option for patients with recalcitrant chronic plantar fasciitis. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  18. Benzodiazepine sensitivity in panic disorder: effects of chronic alprazolam treatment.

    PubMed

    Cowley, D S; Roy-Byrne, P P; Radant, A; Ritchie, J C; Greenblatt, D J; Nemeroff, C B; Hommer, D W

    1995-04-01

    The aim of the current study was to determine the degree to which patients with panic disorder develop tolerance to subjective and physiological effects of benzodiazepine after chronic treatment with alprazolam. Response to acute administration of diazepam was assessed in 19 panic disorder patients receiving chronic treatment with alprazolam and 23 untreated panic disorder patients. At baseline in the laboratory, the two groups did not differ in peak saccadic eye movement velocity, saccade latency, short-term memory, plasma cortisol and growth hormone concentrations, heart rate, and self-rated levels of sedation and anxiety. Compared with untreated patients, alprazolam-treated patients displayed significantly less diazepam-induced change in peak saccadic velocity, saccade latency, growth hormone secretion, memory, and self-rated levels of sedation. There was no difference between groups in diazepam effects on plasma cortisol concentrations or self-rated anxiety. Within alprazolam-treated patients, diazepam-induced slowing of peak saccade velocity was significantly inversely correlated with illness severity, as measured by reported panic attacks per week and severity of phobic avoidance, but not with alprazolam dose, blood level, or duration of treatment. Because the alprazolam-treated group reported more panic attacks per week than the untreated panic patients, treated patients were divided into those who were asymptomatic versus those with continuing panic attacks. The subgroup of nine alprazolam-treated subjects who were asymptomatic also showed significantly less diazepam effects than the group of untreated panic disorder patients, suggesting that overall group differences were at least partially attributable to the development of tolerance to selected benzodiazepine effects with chronic alprazolam treatment.

  19. Chronic pain relief after the exposure of nitrous oxide during dental treatment: longitudinal retrospective study.

    PubMed

    Mattos Júnior, Francisco Moreira; Mattos, Rafael Villanova; Teixeira, Manoel Jacobsen; Siqueira, Silvia Regina Dowgan Tesseroli de; Siqueira, Jose Tadeu Tesseroli de

    2015-07-01

    The objective was to investigate the effect of nitrous/oxygen in chronic pain. Seventy-seven chronic pain patients referred to dental treatment with conscious sedation with nitrous oxide/oxygen had their records included in this research. Data were collected regarding the location and intensity of pain by the visual analogue scale before and after the treatment. Statistical analysis was performed comparing pre- and post-treatment findings. It was observed a remarkable decrease in the prevalence of pain in this sample (only 18 patients still had chronic pain, p < 0.001) and in its intensity (p < 0.001). Patients that needed fewer sessions received higher proportions of nitrous oxide/oxygen. Nitrous oxide may be a tool to be used in the treatment of chronic pain, and future prospective studies are necessary to understand the underlying mechanisms and the effect of nitrous oxide/oxygen in patients according to the pain diagnosis and other characteristics.

  20. Imatinib mesylate in chronic myeloid leukemia: frontline treatment and long-term outcomes.

    PubMed

    Stagno, Fabio; Stella, Stefania; Spitaleri, Antonio; Pennisi, Maria Stella; Di Raimondo, Francesco; Vigneri, Paolo

    2016-01-01

    The tyrosine kinase inhibitor Imatinib Mesylate has dramatically improved the clinical outcome of chronic myeloid leukemia (CML) patients in the chronic phase of the disease, generating unprecedented rates of complete hematologic and cytogenetic responses and sustained reductions in BCR-ABL transcripts. Here, we present an overview on the efficacy and safety of Imatinib and describe the most important clinical studies employing this drug for the frontline treatment of chronic phase CML. We also discuss recent reports describing the long-term outcome of patients receiving Imatinib for their disease. The imminent availability of generic forms of Imatinib coupled with the approval of expensive second-generation tyrosine kinase inhibitors underlines an unmet need for early molecular parameters that may distinguish CML patients likely to benefit from the drug from those that should receive alternative forms of treatment.

  1. THE REFRIGERATION TREATMENT OF CHRONIC OSTEOMYELITIS

    PubMed Central

    Bingham, Robert

    1951-01-01

    Systemic penicillin therapy plus refrigeration at the site of the lesion, with operation if necessary, was used in the treatment of chronic osteomyelitis. Nine patients with disease of long standing were treated. For three, bed rest, chemotherapy and refrigeration were sufficient. Surgical treatment in addition was carried out in six cases. Operations consisted of unroofing the abscess cavity, multiple drilling for sievelike perforation of the abscessed bone, and primary suture of the incision. Solutions of penicillin, 500 to 1,000 units per cubic centimeter, were used for local irrigation at the time of closure. In all cases the lesions healed and there was no recurrence within a period of two years. The period of hospitalization did not exceed 14 days in any case. Refrigeration of the infected area before and after operation reduced pain, swelling, infection and toxemia. PMID:14801722

  2. [Complex treatment of chronic periodontitis with balneopeloid therapy].

    PubMed

    Leonova, L E; Smelova, L Z; Pavlova, G A; Chernyshova, L E

    2013-01-01

    Complex investigation and treatment has been realized on 127 patients aged from 27 to 45 years with chronic generalized periodontitis. Patients were divided into two groups. In the fist group (68 patients) complex treatment included course of balneopeloid therapy with irrigation of high mineralized natural water (sanatorium "Tumentransgas" chink №1-95, Ugorsk) followed by application of sapropel mud (the Pake lake). The second group (59 patients) received only conventional periodontal treatment. Positive effect of balneopeloid therapy was identified, which was reflected in stabilizations of pathological process in the periodontal tissues in 78% of patients, as well as changes in physical and chemical properties of the oral gluid. Also the number of periodontopahogenic germs of gingival pockets was decreased.

  3. [Laser therapy and famotidine in complex restorative treatment of primary chronic gastroduodenitis].

    PubMed

    Filimonov, R M; Musaeva, O M

    2003-01-01

    Primary chronic gastroduodenitis (PCG) is one of the most frequent diseases of the gastrointestinal tract. Timely and efficient treatment of patients with PCG promotes ulcer prevention. In this connection, an urgent problem of restorative medicine is to develop medical programs with active introduction of pharmacophysiotherapeutic complexes, in particular, laser therapy and anti-secretory preparation (famotidine) that increase therapeutic efficacy of treatment of this disease. To this end, we give results of treatment of 50 patients with primary chronic gastroduodenitis (26 having undergone laser therapy only, and 24 having had a combination of laser therapy and famotidine), which demonstrated that the complex action method has a more adequate effect on pathogenetic components in this disease than monotherapy.

  4. Use of Placental Membranes for the Treatment of Chronic Diabetic Foot Ulcers

    PubMed Central

    Brantley, Jonathan N.; Verla, Thomas D.

    2015-01-01

    Significance: Chronic diabetic foot ulcers (DFUs) remain a challenge for physicians to treat. High mortality rates for DFU patients have pointed to the low effectiveness of standard care and lack of quality wound care products. The composition (collagen-rich tissue matrix and endogenous growth factors and cells) and functional properties (anti-inflammatory, anti-bacterial, and angiogenic) of placental membranes are uniquely suited to address the needs of chronic wounds. This led to the commercialization of placental membranes, which are now widely available to physicians as a new advanced wound treatment option. Recent Advances: Progress in tissue processing and preservation methods has facilitated the development of placental products for wounds. Currently, a variety of commercial placental products are available to physicians for the treatment of chronic DFUs and other wounds. This review summarizes the key factors that negatively impact DFU healing (including social factors, such as smoking, vascular deficiencies, hyperglycemia, and other metabolic abnormalities), describes the structure and biology of placental membranes, and overviews commercially available placental products for wounds and data from the most recent DFU clinical trials utilizing commercial placental membranes. Critical Issues: Although the effects of diabetes on wound healing are complex and not fully understood, some of the key factors and pathways that interfere with healing have been identified. However, a multidisciplinary approach for the assessment of patients with chronic DFUs and guidelines for selection of appropriate treatment modalities remain to be implemented. Future Directions: The biological properties of placental membranes show benefits for the treatment of chronic DFUs, but scientific and clinical data for commercially available placental products are limited. Therefore, we need (1) more randomized, controlled clinical trials for commercial placental products; (2) studies

  5. Prevalence of chronic pain, impact on daily life, and treatment practices in India.

    PubMed

    Dureja, Gur Prasad; Jain, Paramanand N; Shetty, Naresh; Mandal, Shyama Prasad; Prabhoo, Ram; Joshi, Muralidhar; Goswami, Subrata; Natarajan, Karthic Babu; Iyer, Rajagopalan; Tanna, D D; Ghosh, Pahari; Saxena, Ashok; Kadhe, Ganesh; Phansalkar, Abhay A

    2014-02-01

    Chronic pain is of concern to health professionals, patients, society, and negatively impacts quality of life (QoL). The present epidemiologic study identified point prevalence of chronic pain in India, impact on individual's QoL, unveiling current pain treatment practices, and levels of satisfaction with treatment. This epidemiological telephonic survey consisted of two questionnaires: screening questionnaire that assessed prevalence of pain, its frequency during the past week, intensity during last episode, sites of pain, and main causes, and in-depth questionnaire that evaluated demography, frequency, duration, and intensity of pain; impact of pain on QoL; respondent's perception regarding the attitude of their family, friends, and doctors toward their pain. A total of 5004 respondents were included from eight cities across India. The overall point prevalence of chronic pain was 13%, and the mean intensity of pain on NRS scale was 6.93. Respondents with chronic moderate and chronic severe pain were 37% and 63%, respectively. Pain in knees (32%), legs (28%), and joints (22%) was most prevalent. Respondents with chronic pain were no longer able to exercise, sleep, maintain relationships with friends and family, and maintain an independent lifestyle. About 32% of patients lost ≥4 hours of work in the past 3 months. Majority (68%) of respondents were treated for pain with over the counter (OTC) drugs, and most were taking NSAIDs (95%). A significant population of India suffers from chronic pain, and their QoL is affected leading to disability. A proportion of respondents receiving pain treatment were taking nonprescription medications with a majority of respondents on NSAIDs. A very few were consulting pain management specialists. © 2013 World Institute of Pain.

  6. From Ideas to Efficacy: The ORBIT Model for Developing Behavioral Treatments for Chronic Diseases

    PubMed Central

    Czajkowski, Susan M.; Powell, Lynda H.; Adler, Nancy; Naar-King, Sylvie; Reynolds, Kim D.; Hunter, Christine M.; Laraia, Barbara; Olster, Deborah H.; Perna, Frank M.; Peterson, Janey C.; Epel, Elissa; Boyington, Josephine E.; Charlson, Mary E.

    2015-01-01

    Objective Given the critical role of behavior in preventing and treating chronic diseases, it is important to accelerate the development of behavioral treatments that can improve chronic disease prevention and outcomes. Findings from basic behavioral and social science research hold great promise for addressing behaviorally-based clinical health problems, yet there is currently no established pathway for translating fundamental behavioral science discoveries into health-related treatments ready for Phase III efficacy testing. This article provides a systematic framework for guiding efforts to translate basic behavioral science findings into behavioral treatments for preventing and treating chronic illness. Methods The ORBIT model for behavioral treatment development is described as involving a flexible and progressive process, pre-specified clinically significant milestones for forward movement, and return to earlier stages for refinement and optimization. Results This article presents the background and rationale for the ORBIT model, a summary of key questions for each phase, a selection of study designs and methodologies well-suited to answering these questions, and pre-specified milestones for forward or backward movement across phases. Conclusions The ORBIT model provides a progressive, clinically-relevant approach to increasing the number of evidence-based behavioral treatments available to prevent and treat chronic diseases. PMID:25642841

  7. Mycophenolate sodium for the treatment of chronic non-infectious uveitis of childhood.

    PubMed

    Doycheva, Deshka; Zierhut, Manfred; Blumenstock, Gunnar; Sobolewska, Bianka; Voykov, Bogomil; Hohmann, Johanna; Spitzer, Martin S; Deuter, Christoph

    2016-08-01

    To assess the efficacy and tolerability of mycophenolate sodium (MPS) in the therapy of children with chronic non-infectious uveitis. Retrospective analysis of 23 children with chronic uveitis, treated with MPS, with a follow-up of at least 6 months. The main outcome measures were time to uveitis reactivation and corticosteroid-sparing effect under MPS treatment. The secondary outcome measures were best-corrected visual acuity (BCVA) and treatment-related side effects. From 23 patients included in the study, 2 patients had anterior uveitis, 19 had intermediate uveitis and 2 had panuveitis. The probability of reactivation-free survival after MPS initiation was estimated as 65% at both 1 and 2 years. The probability of discontinuing systemic corticosteroids after 1 year of treatment was 39% and after 2 years 51%. The probability to taper corticosteroids to a daily dosage of ≤0.1 mg/kg after 1 and 2 years was 62% and 85%, respectively. BCVA improved or remained stable in 96% of eyes after 1 year of therapy. Treatment-related side effects were found in nine children (rate: 0.17/patient-year). No therapy discontinuation because of side effects was needed. Our data suggest that MPS is useful and well tolerated in children with chronic uveitis. MPS seems to be an effective drug for the treatment of chronic non-infectious uveitis of childhood and may be preferred as a first-line steroid-sparing agent in this form of uveitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  8. Management of chronic hepatitis B infection: Current treatment guidelines, challenges, and new developments

    PubMed Central

    Tang, Ceen-Ming; Yau, Tung On; Yu, Jun

    2014-01-01

    Chronic hepatitis B (CHB) virus infection is a global public health problem, affecting more than 400 million people worldwide. The clinical spectrum is wide, ranging from a subclinical inactive carrier state, to progressive chronic hepatitis, cirrhosis, decompensation, and hepatocellular carcinoma. However, complications of hepatitis B virus (HBV)-related chronic liver disease may be reduced by viral suppression. Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon, entecavir, or tenofovir, but the optimal treatment for an individual patient is controversial. The indications for treatment are contentious, and increasing evidence suggests that HBV genotyping, as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response. The likelihood of achieving a sustained virological response is also increased by extending treatment duration, and using combination therapy. Hence the paradigm for treatment of CHB is constantly evolving. This article summarizes the different indications for treatment, and systematically reviews the evidence for the efficacy of various antiviral agents. It further discusses the shortcomings of current guidelines, use of rescue therapy in drug-resistant strains of HBV, and highlights the promising clinical trials for emerging therapies in the pipeline. This concise overview presents an updated practical approach to guide the clinical management of CHB. PMID:24876747

  9. Older People’s Experiences of Patient-Centered Treatment for Chronic Pain: A Qualitative Study

    PubMed Central

    Teh, Carrie F.; Karp, Jordan F.; Kleinman, Arthur; Reynolds, Charles F.; Weiner, Debra K.; Cleary, Paul D.

    2010-01-01

    Introduction Older adults with chronic pain who seek treatment often are in a health care environment that emphasizes patient-directed care, a change from the patriarchal model of care to which many older adults are accustomed. Objective To explore the experiences of older adults seeking treatment for chronic pain, with respect to patient-directed care and the patient–provider relationship. Design In-depth interviews with 15 Caucasian older adults with chronic pain who had been evaluated at a university-based pain clinic. All interviews were audiotaped and the transcripts were analyzed using a grounded theory based approach. Results Older adults with chronic pain vary in their willingness to be involved in their treatment decisions. Many frequently participate in decisions about their pain treatment by asking for or refusing specific treatments, demanding quality care, or operating outside of the patient–provider relationship to manage pain on their own. However, others prefer to let their provider make the decisions. In either case, having a mutually respectful patient–provider relationship is important to this population. Specifically, participants described the importance of “being heard” and “being understood” by providers. Conclusions As some providers switch from a patriarchal model of care toward a model of care that emphasizes patient activation and patient-centeredness, the development and cultivation of valued patient–provider relationships may change. While it is important to encourage patient involvement in treatment decisions, high-quality, patient-centered care for older adults with chronic pain should include efforts to strengthen the patient–provider relationship by attending to differences in patients’ willingness to engage in patient-directed care and emphasizing shared decision-making. PMID:19207235

  10. Surgical treatment of chronic pancreatitis in young patients.

    PubMed

    Zhou, Feng; Gou, Shan-Miao; Xiong, Jiong-Xin; Wu, He-Shui; Wang, Chun-You; Liu, Tao

    2014-10-01

    The main treatment strategies for chronic pancreatitis in young patients include therapeutic endoscopic retrograde cholangio-pancreatography (ERCP) intervention and surgical intervention. Therapeutic ERCP intervention is performed much more extensively for its minimally invasive nature, but a part of patients are referred to surgery at last. Historical and follow-up data of 21 young patients with chronic pancreatitis undergoing duodenum-preserving total pancreatic head resection were analyzed to evaluate the outcomes of therapeutic ERCP intervention and surgical intervention in this study. The surgical complications of repeated therapeutic ERCP intervention and surgical intervention were 38% and 19% respectively. During the first therapeutic ERCP intervention to surgical intervention, 2 patients developed diabetes, 5 patients developed steatorrhea, and 5 patients developed pancreatic type B pain. During the follow-up of surgical intervention, 1 new case of diabetes occurred, 1 case of steatorrhea recovered, and 4 cases of pancreatic type B pain were completely relieved. In a part of young patients with chronic pancreatitis, surgical intervention was more effective than therapeutic ERCP intervention on delaying the progression of the disease and relieving the symptoms.

  11. Increasing Neuroplasticity to Bolster Chronic Pain Treatment: A Role for Intermittent Fasting and Glucose Administration?

    PubMed

    Sibille, Kimberly T; Bartsch, Felix; Reddy, Divya; Fillingim, Roger B; Keil, Andreas

    2016-03-01

    Neuroplastic changes in brain structure and function are not only a consequence of chronic pain but are involved in the maintenance of pain symptoms. Thus, promotion of adaptive, treatment-responsive neuroplasticity represents a promising clinical target. Emerging evidence about the human brain's response to an array of behavioral and environmental interventions may assist in identifying targets to facilitate increased neurobiological receptivity, promoting healthy neuroplastic changes. Specifically, strategies to maximize neuroplastic responsiveness to chronic pain treatment could enhance treatment gains by optimization of learning and positive central nervous system adaptation. Periods of heightened plasticity have been traditionally identified with the early years of development. More recent research, however, has identified a wide spectrum of methods that can be used to "reopen" and enhance plasticity and learning in adults. In addition to transcranial direct current stimulation and transcranial magnetic stimulation, behavioral and pharmacological interventions have been investigated. Intermittent fasting and glucose administration are two propitious strategies, that are noninvasive, inexpensive to administer, implementable in numerous settings, and might be applicable across differing chronic pain treatments. Key findings and neurophysiological mechanisms are summarized, and evidence for the potential clinical contributions of these two strategies toward ameliorating chronic pain is presented. Neuroplastic changes are a defining feature of chronic pain and a complicating factor in treatment. Noninvasive strategies to optimize the brain's response to treatment interventions might improve learning and memory, increase the positive adaptability of the central nervous system, and enhance treatment outcomes. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  12. The Effect of Photodynamic Therapy in the Treatment of Chronic Periodontitis: A Review of Literature.

    PubMed

    Meimandi, Mansour; Talebi Ardakani, Mohammad Reza; Esmaeil Nejad, Azadeh; Yousefnejad, Parisa; Saebi, Khosro; Tayeed, Mohammad Hossein

    2017-01-01

    Introduction: Chronic periodontitis is the most common periodontal disease which is related to the chronic accumulation of bacterial plaque. Since mechanical methods are not sufficient in the treatment of this disease, administration of local/systemic antibiotic is recommended following mechanical debridement. However, side effects of antibiotics such as microbial resistance and patient allergy led to development of alternative methods. One of these suggested methods is the antimicrobial photodynamic therapy (aPDT). PDT is a local noninvasive treatment modality without the side effects caused by antibiotics. The aim of this study was to review the articles related to the application of PDT with laser in the treatment of chronic periodontitis. Review of literature: In the present review of literature, the authors used key words such as chronic periodontitis, laser and photodynamic therapy, and conducted a literature search via Google Scholar and PubMed for the period of 1990 to 2015. A total of 47 articles in English were found. The articles that were not associated with the topic of research and review articles were deleted and only clinical trials were evaluated. After reviewing 23 articles' abstracts, the full texts of 16 articles were analyzed. Conclusion: Considering the safety, the lack of side effects and general advantages like more patient compliance, the PDT treatment with scaling and root planing (SRP) is recommended as an efficient adjunctive modality for the treatment of localized chronic periodontitis especially during the maintenance phase in non-surgical treatment.

  13. [RECOMMENDATION FOR EVALUATION AND TREATMENT OF CHRONIC URTICARIA - THE ISRAELI ASSOCIATION FOR ALLERGY AND CLINICAL IMMUNOLOGY].

    PubMed

    Levin Agmon, Nancy; Kessel, Aharon; Maoz Segal, Ramit; Rottem, Menachem; Tal, Yuval; Confino-Cohen, Ronit; Tobi, Elias

    2017-06-01

    Chronic urticaria is a disease manifested by a pruritic rash lasting longer than 6 weeks that may severely affect quality of life and daily function. Chronic urticaria can be further divided into chronic spontaneous urticaria which appears without a trigger and chronic inducible urticaria which evolves following distinct physical triggers. These two clinical manifestations could coexist in the same patient. The pathogenesis of chronic urticaria is not fully elucidated, although it is considered an autoimmune disease in at least 50% patients that produce auto- IgG antibodies targeted against the high affinity Fc receptor and to a lesser extent against IgE itself. Auto-antibodies associated with different autoimmune diseases can be detected such as those directed at thyroid proteins. Urticaria tends to spontaneously resolve in 50% of patients within the first year while others will suffer from it for a much longer period of time. The treatment of chronic urticaria has dramatically progressed in the last decade, enabling reduction of systemic corticosteroid use which has been the cornerstone of treatment in the past. The recommended treatment for chronic urticaria is currently based on a stepwise approach that enables achieving disease control with a reasonably good quality of life. The first step of the treatment ladder consists of selective, new generation, anti-H1 histamine blockers, which do not cross the blood brain barrier, starting from the recommended dose (first line) and increasing up to four-fold (second line). The third line of treatment is the addition of immune modulators such as leukotriene receptor blockers (Singulair), anti-IgE biological therapy (Xolair), or cyclosporine. In this review we present the updates and considerations arising during evaluation and treatment of chronic urticaria. The need for specific tests, immunologist/allergologist evaluation, as well as treatment modalities taking into consideration the large body of evidence that has

  14. Chronic pain treatment with opioid analgesics: benefits versus harms of long-term therapy.

    PubMed

    Sehgal, Nalini; Colson, James; Smith, Howard S

    2013-11-01

    Chronic non-cancer pain (CNCP) is a disabling chronic condition with a high prevalence rate around the world. Opioids are routinely prescribed for treatment of chronic pain (CP). In the past two decades there has been a massive increase in the number of opioid prescriptions, prescribed daily opioid doses and overall opioid availability. Many more patients with CNCP receive high doses of long-acting opioids on a long-term basis. Yet CP and related disability rates remain high, and majority of the patients with CNCP are dissatisfied with their treatments. Intersecting with the upward trajectory in opioid use are the increasing trends in opioid related adverse effects, especially prescription drug abuse, addiction and overdose deaths. This complex situation raises questions on the relevance of opioid therapy in the treatment of CNCP. This article reviews current evidence on opioid effectiveness, the benefits and harms of long-term therapy in CNCP.

  15. Dental findings and treatment in consanguinity associated congenital chronic familial neutropenia.

    PubMed

    Buduneli, Nurcan; Cogulu, Dilsah; Kardesler, Levent; Kütükçüler, Necil

    2006-01-01

    The purpose of this report is to describe dental findings and treatment of an 11-year old male patient and a 5-year old female patient, children of first cousins, suffering from severe benign congenital chronic familial neutropenia. This case report emphazises the importance of differential diagnosis of immunodeficiencies including congenital chronic familial neutropenia in the background of severe periodontal diseases and/or diffuse carious lesions in children.

  16. Beyond interferon: rationale and prospects for newer treatment paradigms for chronic hepatitis C

    PubMed Central

    Cortez, Karoll J.

    2015-01-01

    Hepatitis C virus (HCV) infection results in a chronic carrier state in 80% of individuals infected with the virus and presently affects over 170 million people worldwide. Approximately 20% of those chronically infected will ultimately progress to develop cirrhosis and death due to end-stage liver disease or hepatocellular carcinoma (HCC). Unlike many other chronic viral infections, effective treatments for HCV are available. Cure from the infection is known as a sustained virologic response (SVR). SVR is associated with reversal of the long-term outcomes of chronic liver disease, decrease in incidence of HCC, and decrease HCV attributable mortality. The current FDA approved therapies for hepatitis C virus genotype 1 (GT-1) include pegylated interferon (PEG-IFN) and ribavirin (RBV) in combination with a directly acting antiviral agent (DAA). New therapeutic advances are being made aiming to simplify management, improve the tolerability of treatment, and shorten the duration of therapy. Moreover, treatment regimens that will effectively eradicate hepatitis C without the use of interferon formulations (IFN) are being developed. In this review, we report the transition of HCV therapeutics from an interferon-α based combination therapy to an all-oral, directly acting antiviral therapy. PMID:25553238

  17. Pharmacogenomics and Patient Treatment Parameters to Opioid Treatment in Chronic Pain: A Focus on Morphine, Oxycodone, Tramadol, and Fentanyl.

    PubMed

    Lloyd, Renae A; Hotham, Elizabeth; Hall, Catherine; Williams, Marie; Suppiah, Vijayaprakash

    2017-12-01

    Opioids are one of the most commonly prescribed medicines for chronic pain. However, their use for chronic pain has been controversial. The objective of this literature review was to identify the role of genetic polymorphisms on patient treatment parameters (opioid dose requirements, response, and adverse effects) for opioids used in malignant and nonmalignant chronic pain. The opioids that this review focuses on are codeine, morphine, oxycodone, tramadol, and fentanyl. A literature search of databases Medline and Embase was carried out, and studies up to April 2016 were included in this review. Studies were included based on a combination of key words: chronic pain and related terms, pharmacogenetics and related terms, and opioids and related terms. Among the 1,408 individual papers retrieved from the search in Medline and Embase, 32 original articles were included in this review, with none related to codeine. The 32 papers reported various study designs, opioids, and polymorphisms being studied for associations with treatment outcomes. This literature review reveals that variants in ABCB1, OPRM1, and COMT have been replicated for opioid dosing and variants in ABCB1 have been replicated for both treatment response and adverse effects. Currently, there are few validated studies to form a strong evidence base to support pharmacogenomics testing when initiating opioid therapy. However, the field of pharmacogenomics in chronic pain is likely to expand over the coming years, with the increasing number of treatment options available and larger cohorts being assembled in order to identify true associations. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  18. A multidisciplinary systematic review of the treatment for chronic idiopathic tinnitus.

    PubMed

    Zenner, Hans-Peter; Delb, Wolfgang; Kröner-Herwig, Birgit; Jäger, Burkhard; Peroz, Ingrid; Hesse, Gerhard; Mazurek, Birgit; Goebel, Gerhard; Gerloff, Christian; Trollmann, Regina; Biesinger, Eberhard; Seidler, Harald; Langguth, Berthold

    2017-05-01

    The majority of tinnitus patients are affected by chronic idiopathic tinnitus, and almost 60 different treatment modalities have been reported. The present study is a multidisciplinary systematic analysis of the evidence for the different forms of treatment for chronic tinnitus. The results are used to form the basis of an S3 guideline. A systematic search was carried out in PubMed and the Cochrane Library. The basis for presenting the level of evidence was the evidence classification of the Oxford Centre of Evidence-based Medicine. Whenever available, randomised controlled trials were given preference for discussing therapeutic issues. All systematic reviews and meta-analyses were assessed for their methodological quality, and effect size was taken into account. As the need for patient counselling is self-evident, specific tinnitus counselling should be performed. Due to the high level of evidence, validated tinnitus-specific, cognitive behavioural therapy is strongly recommended. In addition, auditory therapeutic measures can be recommended for the treatment of concomitant hearing loss and comorbidities; those should also be treated with drugs whenever appropriate. In particular, depression should be treated, with pharmacological support if necessary. If needed, psychiatric treatment should also be given on a case-by-case basis. With simultaneous deafness or hearing loss bordering on deafness, a CI can also be indicated. For auditory therapeutic measures, transcranial magnetic or direct current stimulation and specific forms of acoustic stimulation (noiser/masker, retraining therapy, music, and coordinated reset) for the treatment of chronic tinnitus the currently available evidence is not yet sufficient for supporting their recommendation.

  19. Early investigational antibiotics for the treatment of acute exacerbations of chronic bronchitis.

    PubMed

    Falagas, Matthew E; Georgiou, Maria

    2017-03-01

    Acute exacerbations in patients with chronic bronchitis are a leading cause of hospitalizations and death. Bacteria contribute significantly to such exacerbations. The aim of this review was to explore the potential role of investigational antibiotics in the treatment of these episodes. Areas covered: The available literature in PubMed database, in websites related to investigational drugs and in websites of the producing companies has been searched. The in vitro activity against pathogens involved in acute exacerbations of chronic bronchitis and the pharmacokinetic profile of antibiotics currently under development were taken into consideration for inclusion in the review. Expert opinion: Several novel antimicrobial agents have completed preclinical and Phase I studies and were well-tolerated. Further investigation is mandatory in order to evaluate their future in treatment of chronic bronchitis exacerbations and discover potential advantages compared to already approved antimicrobials.

  20. Behavioral treatment of chronic belching due to aerophagia in a normal adult.

    PubMed

    Cigrang, Jeffrey A; Hunter, Christine M; Peterson, Alan L

    2006-05-01

    Aerophagia, or excessive air swallowing, is a potential cause of belching, flatulence, bloating, and abdominal pain and may contribute to a worsening of gastrointestinal (GI) disorders. A limited number of published reports of aerophagia treatment indicate that behavioral methods may be of benefit. A case report is presented describing the behavioral treatment of chronic belching due to aerophagia in an adult female. The collaborative application of single-participant design research helped identify open-mouth, diaphragmatic breathing and minimized swallowing as an effective intervention. Belching frequency was reduced from an average rate of 18 per 5-min interval during the baseline period to 3 per 5-min period after treatment. Results were maintained at an 18-month follow-up. Recommendations for the use of a brief treatment protocol with adults referred for chronic belching or other GI complaints attributed to aerophagia are discussed.

  1. Virtual Reality Hypnosis In The Treatment Of Chronic Neuropathic Pain: A Case Report

    PubMed Central

    Oneal, Brent J.; Patterson, David R.; Soltani, Maryam; Teeley, Aubriana; Jensen, Mark P.

    2009-01-01

    This case report evaluates virtual reality hypnosis (VRH) in treating chronic neuropathic pain in a patient with a 5-year history of failed treatments. The patient participated in a 6-month trial of VRH, and her pain ratings of intensity and unpleasantness dropped on average 36% and 33%, respectively, over the course of 33 sessions. In addition, she reported both no pain and a reduction of pain for an average of 3.86 and 12.21 hours, respectively, after treatment sessions throughout the course of the VRH treatment. These reductions and the duration of treatment effects following VRH treatment were superior to those following a trial of standard hypnosis (non-VR) treatment. However, the pain reductions with VRH did not persist over long periods of time. The findings support the potential of VRH treatment for helping individuals with refractory chronic pain conditions. PMID:18726807

  2. Measuring chronic pain intensity among veterans in a residential rehabilitation treatment program.

    PubMed

    Randleman, Mary L; Douglas, Mary E; DeLane, Alice M; Palmer, Glen A

    2014-01-01

    The purpose of this study was to identify whether veterans with chronic pain, substance abuse, and posttraumatic stress disorder (PTSD) diagnoses residing in a Residential Rehabilitation Treatment Program (RRTP) perceived a higher level of pain than those veterans who had chronic pain but did not have active substance abuse issues or PTSD. A sample of veterans (n = 200) with chronic pain undergoing treatment for either chemical dependency and/or PTSD in an RRTP and a Surgical Specialty Care outpatient clinic at a Department of Veterans Affairs medical center took part in the study. Multiple analysis of variance and further univariate statistics were examined to determine the association between groups on the different scales. There was a considerable difference in terms of which group of veterans perceived a higher rate of pain even with the use of the same four pain assessment scales (i.e., Numeric Rating, Visual Analog, Faces, and Mankoski). Scores were significantly higher for the RRTP group than the Surgical Specialty Care group on all screening measures (p < .001). Veterans with chronic pain, substance abuse, and/or PTSD diagnoses residing in an RRTP tended to have a higher perception of chronic pain compared to those without substance abuse or PTSD diagnoses.

  3. BPC 157 counteracts QTc prolongation induced by haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats.

    PubMed

    Strinic, Dean; Belosic Halle, Zeljka; Luetic, Kresimir; Nedic, Ana; Petrovic, Igor; Sucic, Mario; Zivanovic Posilovic, Gordana; Balenovic, Dijana; Strbe, Sanja; Udovicic, Mario; Drmic, Domagoj; Stupnisek, Mirjana; Lovric Bencic, Martina; Seiwerth, Sven; Sikiric, Predrag

    2017-10-01

    Commonly, neuroleptics and prokinetics induce a prolonged QTc interval. In this study, stable gastric pentadecapeptide BPC 157 counteracts the prolongation of the QTc interval in Wistar rats that underwent daily administration of dopamine neuroleptics or prokinetics. Previously, in rats and mice, BPC 157 counteracted neuroleptic-induced catalepsy and gastric ulcers. To counteract neuroleptic- or prokinetic-induced prolongation of the QTc interval, rats were given a BPC 157 regimen once daily over seven days (10μg, 10ng/kg ip) immediately after each administrations of haloperidol (0.625, 6.25, 12.5, and 25.0mg/kg ip), fluphenazine (0.5, 5.0mg/kg ip), clozapine (1.0, 10.0mg/kg ip), quetiapine (1.0, 10.0mg/kg ip), sulpiride (1.6, 16.0mg/kg ip), metoclopramide (2.5, 25.0mg/kg ip) or (1.0, 10.0mg/kg ip). Controls simultaneously received saline (5ml/kg ip). To assess the ECG presentation before and after neuroleptic/prokinetic medication, the assessment was at 1, 2, 3, 4, 5, 10, 15, 20 and 30min (first administration) as well as at 30min, 60min and 24h (first administration and subsequent administrations) and the ECG recording started prior to drug administration. Since very early, a prolonged QTc interval has been continually noted with haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats as a central common effect not seen with domperidone. Consistent counteraction appears with the stable gastric pentadecapeptide BPC 157. Thus, BPC 157 rapidly and permanently counteracts the QTc prolongation induced by neuroleptics and prokinetics. Pentadecapeptide BPC 157 is suited for counteracting a prolonged QT interval. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Immune deficiency in chronic rhinosinusitis: screening and treatment

    PubMed Central

    Chiarella, Sergio E.; Grammer, Leslie C.

    2017-01-01

    Introduction Chronic rhinosinusitis (CRS) is a prevalent disease with a high annual cost of treatment. Immune deficiencies are more common in individuals with CRS and should be especially considered in those patients who are refractory to medical and surgical therapy. Areas covered We performed a literature search in PubMed of the terms “immunodeficiency” and “sinusitis” or “rhinosinusitis” from 2006 through March 2016. All abstracts were reviewed to determine if they pertained to human disease; relevant articles were evaluated in their entirety and included in this review. Expert commentary CRS is a common disease; in those patients with frequent exacerbations or who are refractory to treatment, an immunodeficiency evaluation should be considered. Treatment includes vaccination, antibiotic therapy, immunoglobulin replacement and surgery. PMID:27500811

  5. Acetyl-L-Carnitine Augmentation of Clozapine in Partial-Responder Schizophrenia: A 12-Week, Open-Label Uncontrolled Preliminary Study.

    PubMed

    Bruno, Antonio; Pandolfo, Gianluca; Crucitti, Manuela; Lorusso, Simona; Zoccali, Rocco Antonio; Muscatello, Maria Rosaria Anna

    This was the first 12-week, open-label, uncontrolled trial aimed at exploring the efficacy of acetyl-L-carnitine (ALC) add-on pharmacotherapy on clinical symptoms and cognitive functioning in 15 schizophrenia patients with suboptimal clinical response despite receiving clozapine (CLZ) monotherapy at the highest tolerated dosage. After clinical (Positive and Negative Symptoms Scale [PANSS]) and neuropsychological (Wisconsin Card Sorting Test, Stroop Color-Word Test, Verbal Fluency Test) assessments, patients received 1 g/d of ALC for 12 weeks. A final sample of 9 subjects completed the study. Acetyl-L-carnitine augmentation of CLZ significantly reduced only PANSS domains "positive" (P = 0.049); at end point, only 2 subjects (22.2% of the completers) reached a minimal improvement (25% reduction in PANSS total score). No significant differences emerged in cognitive performances at the end of the study; effect sizes were small in each explored cognitive dimension. The findings provide preliminary evidence that ALC added to ongoing CLZ treatment appeared to be ineffective to improve symptoms in schizophrenia patients who have failed to respond sufficiently to CLZ. Further trials with adequately powered methodology are needed to identify which augmentation strategies are more effective in schizophrenia patients showing a suboptimal response to CLZ.

  6. The efficacy of the Peginterferon treatment in chronic hepatitis HDV and compensate liver cirrhosis.

    PubMed

    Tugui, Letitia; Dumitru, M; Iacob, Speranta; Gheorghe, Liana; Preda, Carmen; Dinu, Ioana; Becheanu, G; Dumbrava, Mona; Nicolae, Ioana; Andrei, Adriana; Lupu, A; Diculescu, M

    2014-01-01

    To evaluate the efficiency of the treatment with Peginterferon alfa 2a 180 mcg/week, 48 weeks in patients with chronic hepatitis or compensated liver cirrhosis HDV and predictive factors of response to treatment. Prospective study that enrolled 50 patients with chronic hepatitis or compensated cirrhosis HDV between the 1st of January 2011 - 3st of December 2011. The diagnosis of chronic HDV infection was made based on the presence of detectable anti HDV IgG antibodies and HDV-RNA. Patients were evaluated at baseline by CBC, liver function tests, HBV profile, HDV RNA, and by liver biopsy/Fibrotest for evaluating fibrosis and necroinflammatory activity. At 24 weeks CBC (count blood cells), liver function tests, quantitative HBsAg and at 48 and 72 weeks biochemical tests, HDV RNA, HBV DNA, quantitative HBsAg, were performed. Adverse reactions to the treatment were recorded. SVR (sustained virologic response) was recorded in 12 patients (24%) and biochemical response in 28 patients (56%). SVR was correlated with low-grade fibrosis, age, the aminotransferase value and the value of HBsAg at the beginning of the treatment. In week 48 HDV RNA was undetectable in 20 patients (40%). The therapy was well tolerated, except two patients for whom the discontinuation of the treatment was decided for severe exacerbation of cytolysis, respectively hepatic decompensation. In a representative group of patients, the treatment with Peginterferon once again proves its efficacy in treating chronic HDV.

  7. Chronic illness histories of adults entering treatment for co-occurring substance abuse and other mental health disorders.

    PubMed

    Chesher, Nicholas J; Bousman, Chad A; Gale, Maiken; Norman, Sonya B; Twamley, Elizabeth W; Heaton, Robert K; Everall, Ian P; Judd, Patricia A

    2012-01-01

    Little is known about the medical status of individuals entering treatment for co-occurring substance abuse and other mental disorders (COD). We analyzed the medical histories of 169 adults entering outpatient treatment for CODs, estimating lifetime prevalence of chronic illness and current smoking, comparing these rates to the general population, and examining psychiatric and substance-related correlates of chronic illness. Results revealed significantly higher prevalence of hypertension, asthma, arthritis, and smoking compared to the general US population, and showed an association between chronic illness and psychiatric symptom distress and substance use severity. Findings support integration of chronic illness management into COD treatment.  Copyright © American Academy of Addiction Psychiatry.

  8. Periodontal treatment in patients with chronic kidney disease: a pilot study.

    PubMed

    Almeida, S; Figueredo, C M; Lemos, C; Bregman, R; Fischer, R G

    2017-04-01

    This pilot cohort study evaluated the effect of periodontal treatment on renal function, metabolic markers and asymmetric dimethylarginine (ADMA) in patients with pre-dialysis chronic kidney disease (CKD) presenting chronic periodontitis. Twenty-six patients with CKD and severe chronic periodontitis were selected. Periodontal parameters included plaque index, bleeding on probing, probing pocket depth and clinical attachment level. Estimated glomerular filtration rate (eGFR), triglycerides, total cholesterol, albumin and ADMA levels were evaluated at baseline, 90 and 180 d after periodontal therapy. eGFR was evaluated by the Modification of Diet in Renal Disease equation. All periodontal clinical parameters significantly improved (p < 0.05) 180 d after periodontal therapy. There was a significant improvement on the median values (25%; 75% percentiles) of eGFR from 34.6 (27; 44.7) mL/min/1.73 m 2 on baseline to 37.6 (29.7; 57) mL/min/1.73 m 2 on day 90, and to 37.6 (28.6; 56) mL/min/1.73 m 2 (p < 0.05) on day 180. ADMA levels significantly reduced 180 d after periodontal treatment. No significant differences were observed at the median values of metabolic markers comparing baseline and 180 d after periodontal treatment. The results point to a link of kidney disease with endothelium dysfunction and periodontitis, suggesting that periodontal treatment may be beneficial to the course of CKD. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Consensus statement AIGO/SICCR diagnosis and treatment of chronic constipation and obstructed defecation (Part II: Treatment)

    PubMed Central

    Bove, Antonio; Bellini, Massimo; Battaglia, Edda; Bocchini, Renato; Gambaccini, Dario; Bove, Vincenzo; Pucciani, Filippo; Altomare, Donato Francesco; Dodi, Giuseppe; Sciaudone, Guido; Falletto, Ezio; Piloni, Vittorio

    2012-01-01

    The second part of the Consensus Statement of the Italian Association of Hospital Gastroenterologists and Italian Society of Colo-Rectal Surgery reports on the treatment of chronic constipation and obstructed defecation. There is no evidence that increasing fluid intake and physical activity can relieve the symptoms of chronic constipation. Patients with normal-transit constipation should increase their fibre intake through their diet or with commercial fibre. Osmotic laxatives may be effective in patients who do not respond to fibre supplements. Stimulant laxatives should be reserved for patients who do not respond to osmotic laxatives. Controlled trials have shown that serotoninergic enterokinetic agents, such as prucalopride, and prosecretory agents, such as lubiprostone, are effective in the treatment of patients with chronic constipation. Surgery is sometimes necessary. Total colectomy with ileorectostomy may be considered in patients with slow-transit constipation and inertia coli who are resistant to medical therapy and who do not have defecatory disorders, generalised motility disorders or psychological disorders. Randomised controlled trials have established the efficacy of rehabilitative treatment in dys-synergic defecation. Many surgical procedures may be used to treat obstructed defecation in patients with acquired anatomical defects, but none is considered to be the gold standard. Surgery should be reserved for selected patients with an impaired quality of life. Obstructed defecation is often associated with pelvic organ prolapse. Surgery with the placement of prostheses is replacing fascial surgery in the treatment of pelvic organ prolapse, but the efficacy and safety of such procedures have not yet been established. PMID:23049207

  10. Arthroscopic treatment of chronic patellar tendinopathy in high-level athletes

    PubMed Central

    Alaseirlis, Dimosthenis Artemis; Konstantinidis, George Athanasios; Malliaropoulos, Nikolaos; Nakou, Lamprini Stefanos; Korompilias, Anastasios; Maffulli, Nicola

    2012-01-01

    Summary To present the results of arthroscopic treatment of patellar tendinopathy in high-level competition athletes. Eleven high-level athletes presented chronic patellar tendinopathy which did not respond to long term conservative treatment. Average age of the patients was 24.8 ±3.4 years old. All patients received an arthroscopic procedure with osteoplasty of the distal patellar pole, debridement of the underlying Hoffa fat pad and of the degenerated areas of the proximal posterior patella tendon and cauterization of the visible neo-vessels. Mean duration of follow-up was 17.4±4 months. Patients showed a major improvement in the Lysholm score from 49.9±5.2 to 92.5±7 and in the VISA P score from 41.2±5.2 to 86.8±14.9 on tenth post-operative week. All patients had returned to sports activities by the twelfth postoperative week. Arthroscopic treatment of chronic patellar tendinopathy found to be a minimal invasive and safe technique which produced satisfactory results. PMID:23738308

  11. Customizing treatment for chronic pain patients: who, what, and why.

    PubMed

    Turk, D C

    1990-12-01

    Despite advances in the understanding of pain mechanisms and innovative strategies to assess pain patients, there continues to be a substantial proportion of patients who do not appear to benefit from treatment interventions available. One possible explanation for these results is the tendency to treat chronic pain patients as a homogeneous group with generic treatments--adherence to "patient and treatment uniformity myths." Following from the traditional medical model, several attempts have been made to identify specific subgroups of patients exclusively on the basis of physical factors. In addition, a number of studies have attempted to empirically identify subgroups of pain patients using standard psychiatric assessment instruments (e.g., MMPI, SCL-90) and, recently, cognitive measures and measures of pain behaviors. These different approaches and the assessment instruments used are reviewed, and the limitations are described. Alternative strategies to classify subgroups of pain patients based on combinations of physical, psychosocial, and behavioral measures (i.e., multiaxial strategies) are presented. The efforts to classify homogeneous subgroups of chronic pain patients are reviewed, and the potential utility of customizing therapeutic interventions to patient characteristics is discussed.

  12. On the definition of chronic cough and current treatment pathways: an international qualitative study

    PubMed Central

    2014-01-01

    Background The pathogenesis of chronic cough is not well understood and treatment options are limited. In this study we sought to explore the current understanding and management of chronic cough across an international group of specialists. Methods This was an international study of cross sectional qualitative design. In depth interviews were carried out with “Respiratory Specialists” experienced in treating treating Chronic Obstructive Pulmonary Disease (COPD), idiopathic pulmonary fibrosis (IPF), idiopathic chronic cough (ICC) and/or lung cancer patients and with “Disease Experts” in the field of Chronic Cough. Participants in the study were recruited from the USA, UK, Germany, Ireland, Australia and Japan. Interviews with specialists were held at research facilities and with DEs over the telephone. These were preceded by the specialists completing case records of patients recently seen. All interviews were conducted by native speaking trained moderators using a semi-structured interview guide script. This was designed to elicit the definition of chronic cough, explore the unmet needs for each disease state, define therapy goals, identify patient phenotypes and give an overview of the treatment pathway. Results 76 specialists and 10 experts took part in the study. Over two thirds (70%) of respondents defined chronic cough as “cough lasting more than 8/12 weeks” (range 2 weeks to 2 years). Physicians emphasised three interdependent aspects of clinical assessment: impact on quality of life, type of cough (productive versus non-productive) and the underlying pathology. Specialists emphasised treating the underlying cause rather than the cough, this being most prominent in Japan. Experts as a group focussed on chronic cough independently. Evaluation of the respiratory system, GI tract and upper airway (ENT) for establishing an underlying cause was recommended. Type of cough (productive vs non-productive) and impact on quality of life influenced

  13. Pulsed radiofrequency treatment of articular branches of femoral and obturator nerves for chronic hip pain.

    PubMed

    Chye, Cien-Leong; Liang, Cheng-Loong; Lu, Kang; Chen, Ya-Wen; Liliang, Po-Chou

    2015-01-01

    Chronic hip pain is a common symptom experienced by many people. Often, surgery is not an option for patients with multiple comorbidities, and conventional drugs either have many side effects or are ineffective. Pulsed radiofrequency (PRF) is a new method in the treatment of pain. We attempt to compare the efficacy of PRF relative to conservative management for chronic hip pain. Between August 2011 and July 2013, 29 patients with chronic hip pain were divided into two groups (PRF and conservative treatment) according to consent or refusal to undergo PRF procedure. Fifteen patients received PRF of the articular branches of the femoral and obturator nerves, and 14 patients received conservative treatment. Visual analog scale (VAS), Oxford hip scores (OHS), and pain medications were used for outcome measurement before treatment and at 1 week, 4 weeks, and 12 weeks after treatment. At 1 week, 4 weeks, and 12 weeks after treatment initiation, improvements in VAS were significantly greater with PRF. Improvements in OHS were significantly greater in the PRF group at 1 week, 4 weeks, and 12 weeks. Patients in the PRF group also used less pain medications. Eight subjects in the conservative treatment group switched to the PRF group after 12 weeks, and six of them had >50% improvement. When compared with conservative treatment, PRF of the articular branches of the femoral and obturator nerves offers greater pain relief for chronic hip pain and can augment physical functioning.

  14. Reserve-building activities attenuate treatment burden in chronic illness: The mediating role of appraisal and social support

    PubMed Central

    Schwartz, Carolyn E; Zhang, Jie; Michael, Wesley; Eton, David T; Rapkin, Bruce D

    2018-01-01

    This study examines the importance of four psychosocial factors—personality, cognitive appraisal of quality of life, social support, and current reserve-building—in predicting treatment burden in chronically ill patients. Chronically ill patients (n = 446) completed web-based measures. Structural equation modeling was used to investigate psychosocial factors predicting treatment burden. Reserve-building activities indirectly reduced treatment burden by: (1) reducing health worries appraisals, (2) reducing financial difficulties, (3) increasing calm and peaceful appraisals, and (4) increasing perceived social support. These findings point to key behaviors that chronically ill people can use to attenuate their treatment burden. PMID:29785278

  15. Systematic Review of Multidisciplinary Chronic Pain Treatment Facilities

    PubMed Central

    Fashler, Samantha R.; Cooper, Lynn K.; Oosenbrug, Eric D.; Burns, Lindsay C.; Razavi, Shima; Goldberg, Lauren; Katz, Joel

    2016-01-01

    This study reviewed the published literature evaluating multidisciplinary chronic pain treatment facilities to provide an overview of their availability, caseload, wait times, and facility characteristics. A systematic literature review was conducted using PRISMA guidelines following a search of MEDLINE, PsycINFO, and CINAHL databases. Inclusion criteria stipulated that studies be original research, survey more than one pain treatment facility directly, and describe a range of available treatments. Fourteen articles satisfied inclusion criteria. Results showed little consistency in the research design used to describe pain treatment facilities. Availability of pain treatment facilities was scarce and the reported caseloads and wait times were generally high. A wide range of medical, physical, and psychological pain treatments were available. Most studies reported findings on the percentage of practitioners in different health care professions employed. Future studies should consider using more comprehensive search strategies to survey facilities, improving clarity on what is considered to be a pain treatment facility, and reporting on a consistent set of variables to provide a clear summary of the status of pain treatment facilities. This review highlights important information for policymakers on the scope, demand, and accessibility of pain treatment facilities. PMID:27445618

  16. Functional, histological structure and mastocytes alterations in rat urinary bladders following acute and [corrected] chronic cyclophosphamide treatment.

    PubMed

    Juszczak, K; Gil, K; Wyczolkowski, M; Thor, P J

    2010-08-01

    Neurogenic inflammation is linked to urinary bladder overactivity development. Cyclophosphamide (CYP) damages all mucosal defence lines of urinary bladder and induces cystitis with overactivity. The aim of this study was to estimate the effect of CYP on rat urinary bladder function, histological structure and mastocytes numbers following acute and chronic CYP treatment. Fourty two female rats were divided into four groups: I (control), II (acute cystitis), III (chronic cystitis), IV (sham group). Acute and chronic cystitis were induced by CYP in single dose and four doses (1(st), 3(rd), 5(th), 7(th) day), respectively. In group I-III the cystometric evaluation was performed. Sections of the bladder were stained with HE and toluidine blue for the detection of mastocytes. The severity of inflammation was examined according to mucosal abrasion, haemorrhage, leukocyte infiltration and oedema. Acute and chronic CYP treatment caused inflammatory macroscopic and microscopic changes (mucosal abrasion, haemorrhage, oedema) and increased infiltration of inflammatory cells in urinary bladder. Acute treatment induced the infiltration of mastocytes within bladder wall contrary to chronic one decrement. Acute treatment caused more severe mucosal abrasion, whereas chronic one revealed more developed haemorrhage changes. Additionally, cystometric evaluation revealed urinary bladder overactivity development in both types of cystitis. Basal pressure and detrusor overactivity index after acute treatment increased considerably in comparison with the increase obtained after chronic one. Our results proved that acute model of CYP-induced cystitis in rats is more credible for further evaluation of neurogenic inflammation response in pathogenesis of overactive bladder as compared to chronic one.

  17. Habit Reversal as a Treatment for Chronic Skin Picking: A Pilot Investigation

    ERIC Educational Resources Information Center

    Teng, Ellen J.; Woods, Douglas W.; Twohig, Michael P.

    2006-01-01

    The purpose of this study was to compare the effectiveness of habit reversal (HR) to a wait-list control as a treatment for chronic skin picking in adults. Twenty-five adults with a chronic skin-picking problem were randomly assigned to a wait-list control or HR group. At pretreatment, posttreatment, and a 3-month follow-up, self-reported skin…

  18. Duloxetine treatment adherence across mental health and chronic pain conditions

    PubMed Central

    Able, Stephen L; Cui, Zhanglin; Shen, Wei

    2014-01-01

    Purpose This study applied a uniform methodology for measuring and comparing duloxetine adherence in the treatment of multiple chronic medical conditions. Materials and methods Study patients 18–64 years of age initiating duloxetine therapy during 2008 were identified from a large managed care database. The study was restricted to patients with continuous health plan eligibility for 12 months pre- and post-duloxetine initiation. Study patients had ≥1 medical claim with an inpatient or outpatient diagnosis of one (and only one) of the following conditions: major depressive disorder (MDD); generalized anxiety disorder (GAD); fibromyalgia, diabetic peripheral neuropathic pain; or chronic musculoskeletal pain, as established in studies in patients with osteoarthritis and chronic lower back pain (CLBP). Patients initiating duloxetine who had two or more of the six studied conditions were not included in this study, thereby avoiding the need to differentiate between primary and secondary diagnoses from the claims records. Adherence rate was defined as the percentage of patients with a 365-day medication possession ratio ≥0.8. Results A total of 20,490 patients initiated duloxetine treatment during 2008 with a diagnosis of one of the studied conditions during the study period. The adherence rate in our sample was 34.6% and was highest among patients with MDD (37.3%) and lowest for patients with CLBP (29.9%). In general, adherence among patients with MDD and GAD was greater than among those with a chronic pain condition. Conclusion Adherence among newly initiated duloxetine patients varied modestly across the medical conditions for which it was used. After adjusting for potential confounders, differences between the mental conditions (MDD and GAD) and the chronic pain conditions (CLBP, osteoarthritis, and diabetic peripheral neuropathic pain) were statistically significant. These results may be useful in the determination of expectations of adherence, and how it may

  19. Current approach to the treatment of chronic myeloid leukaemia.

    PubMed

    Pasic, Ivan; Lipton, Jeffrey H

    2017-04-01

    Of all the cancers, chronic myeloid leukaemia (CML) has witnessed the most rapid evolution of the therapeutic milieu in recent decades. The introduction of tyrosine kinase inhibitors (TKIs) as a therapeutic option has profoundly changed patient experience and outcome. The availability of multiple new highly effective therapies has increasingly underscored the importance of a good understanding of the underlying pathophysiological basis in CML, as well as patient-specific factors in choosing the right treatment for every individual. The treatment of CML has migrated in many jurisdictions from the office of a highly specialized malignant hematologist to the general hematologist or even a general practitioner. The goal of this review is to offer an overview of the modern approach to the treatment of CML, with an emphasis on chronic phase (CP) CML, including both TKI-based therapies such as imatinib, dasatinib, nilotinib, bosutinib and ponatinib, and non-TKI medications, such as omacetaxine. We discuss evidence behind each drug, most common and material adverse reactions and outline how this information can be used in selecting the right drug for the right patient. We also discuss evidence as it relates to other therapies, including stem cell transplant (SCT), and patients in accelerated (AP) and blastic phase (BP). Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. [Clinical significance of calcitonin gene-related peptide level before and after treatment in patients with chronic periodontitis].

    PubMed

    Yan, Ying; Xiang, Xue-Rong; Wang, Chun; Ye, Guo; Fan, Xiao-Ping

    2016-08-01

    To explore the clinical significance of calcitonin gene-related peptide (CGRP) levels in patients with chronic periodontitis before and after treatment, and to detect the calcitonin gene-related peptide content in human venous blood. Thirty healthy controls and thirty patients with mild, moderate, severe periodontitis were enrolled from August 2014 to June 2015.CGRP level in the patients' peripheral blood was detected by ELISA. Three months after periodontal treatment, CGRP level in mild, moderate, severe periodontitis patients' peripheral blood was re-examined by ELISA. Then the correlation between calcitonin gene-related peptide and inflammation of chronic periodontitis was analyzed with SPSS 22.0 software package. The content of CGRP in healthy controls was significantly higher than that in patients with periodontitis. With the aggravation of periodontal inflammation, blood level of CGRP decreased gradually, and the lowest was in patients with severe periodontitis (P<0.01). Three months after periodontal treatment, CGRP content was significantly higher compared with that before treatment (P<0.05), but no significant difference was found in patients with different degree of periodontitis (P>0.05). The level of CGRP in venous blood decreased with the increasing severity of chronic periodontitis, and CGRP was negatively correlated with the degree of inflammation of chronic periodontitis. CGRP may be involved in the occurrence and development of chronic periodontitis. CGRP content in serum of patients with chronic periodontitis after treatment was significantly increased, CGRP may be used as the basis for clinical detection of chronic periodontitis.

  1. Shockwave therapy for the treatment of chronic proximal hamstring tendinopathy in professional athletes.

    PubMed

    Cacchio, Angelo; Rompe, Jan D; Furia, John P; Susi, Piero; Santilli, Valter; De Paulis, Fosco

    2011-01-01

    Chronic proximal hamstring tendinopathy is an overuse syndrome that is usually managed by nonoperative methods. Shockwave therapy has proved to be effective in many tendinopathies. Shockwave therapy may be more effective than other nonoperative treatments for chronic proximal hamstring tendinopathy. Randomized controlled clinical study; Level of evidence, 1. Forty professional athletes with chronic proximal hamstring tendinopathy were enrolled between February 1, 2004, and September 30, 2006. Patients were randomly assigned to receive either shockwave therapy, consisting of 2500 impulses per session at a 0.18 mJ/mm² energy flux density without anesthesia, for 4 weeks (SWT group, n = 20), or traditional conservative treatment consisting of nonsteroidal anti-inflammatory drugs, physiotherapy, and an exercise program for hamstring muscles (TCT group, n = 20). Patients were evaluated before treatment, and 1 week and 3, 6, and 12 months after the end of treatment. The visual analog scale (VAS) score for pain and Nirschl phase rating scale (NPRS) were used as primary outcome measures. The patients were observed for a mean of 10.7 months (range, 1-12 months). Six patients were lost to follow-up because they underwent a surgical intervention: 3 (all in TCT group) were lost at 3 months; 2 (1 in each group), at 6 months; and 1 (in the TCT group), at 12 months. Primary follow-up was at 3 months after the beginning of treatment. The VAS scores in the SWT and TCT groups were 7 points before treatment (P = .84), and 2 points and 5 points, respectively, 3 months after treatment (P < .001). The NPRS scores in the SWT and TCT groups were 5 points in either group before treatment (P = .48), and 2 points and 6 points, respectively, 3 months after treatment (P < .001). At 3 months after treatment, 17 of the 20 patients (85%) in the SWT group and 2 of the 20 patients (10%) in the TCT group achieved a reduction of at least 50% in pain (P < .001). There were no serious complications in

  2. Endoscopic lung volume reduction coil treatment in patients with chronic hypercapnic respiratory failure: an observational study.

    PubMed

    Simon, Marcel; Harbaum, Lars; Oqueka, Tim; Kluge, Stefan; Klose, Hans

    2017-01-01

    Endoscopic lung volume reduction coil (LVRC) treatment is an option for selected patients with severe emphysema. In the advanced stages, emphysema leads to respiratory failure: hypoxemia and eventually chronic hypercapnic respiratory failure. It can be hypothesized that LVRC treatment, a procedure targeting hyperinflation and thereby reducing ventilatory workload, may be especially beneficial in patients with chronic hypercapnic respiratory failure. This study was conducted to gain first insights into the effects and the safety of LVRC treatment in patients with emphysema and chronic hypercapnic respiratory failure. A retrospective observational study conducted in the Department of Respiratory Medicine at the University Medical Center Hamburg-Eppendorf, Germany on all patients with chronic hypercapnic respiratory failure in whom bilateral LVRC treatment was performed between 1 April 2012 and 30 September 2015. During the study period, bilateral LVRC treatment was performed in 10 patients with chronic hypercapnic respiratory failure. Compared with baseline, bilateral LVRC treatment led to a significant increase in mean forced expiratory volume in one second (FEV 1 ) from 0.5 ± 0.1 l to 0.6 ± 0.2 l ( p = 0.004), a decrease in residual volume (RV) from 6.1 ± 0.9 l to 5.6 ± 1.1 l ( p = 0.02) and a reduction in partial pressure of carbon dioxide in arterial blood (PaCO 2 ) from 53 ± 5 mmHg to 48 ± 4 mmHg ( p = 0.03). One case of hemoptysis requiring readmission to hospital was the only severe adverse event. LVRC treatment was safe and effective in patients with nonsevere chronic hypercapnic respiratory failure. It led not only to an improvement in lung function but also to a significant decrease in PaCO 2 .

  3. The surgical treatment of chronic pancreatitis: a clinical series of 17 cases.

    PubMed

    Vasile, D; Ilco, A; Popa, D; Belega, A; Pana, S

    2013-01-01

    Despite the fact that in the last few years, new invasive non-surgical therapies were introduced, surgical treatment of chronic pancreatitis still plays an important part.The aim of the study is to evaluate pain remission and quality of life after surgical approach. We present 17 cases of chronic pancreatitis that were operated between 2007-2011. Surgical treatment was decided for after the failure of pain control therapy (14 cases)and by the suspicion of cancer in the head of the pancreas (3 cases). Imaging data for all the cases, CT-CE and ERCP, guided us in choosing the right therapy. Surgical techniques performed were pancreatico-jejunostomy (PJ) in eleven cases and duodenopancreatectomy(DP) in six cases. Good pain control was achieved in 10 patients: 6-PJ and 4-DP. Moderate results were observed in 4 cases: 2-PJ and 2-DP. In 3 patients symptoms remained the same. There is no consensus over the surgical treatment in chronic pancreatitis. Surgical approach, strongly motivated and personalised for each patient is followed by good results. It is possible that in the future, limited resections become the therapy of choice, replacing classic ones. Celsius.

  4. Rationale and motivating factors for treatment-free remission in chronic myeloid leukemia.

    PubMed

    Caldemeyer, Lauren; Akard, Luke P

    2016-12-01

    With BCR-ABL1 tyrosine kinase inhibitors (TKIs), such as imatinib, nilotinib, dasatinib, bosutinib, and ponatinib, many patients with chronic myeloid leukemia in chronic phase (CML-CP) can expect to live near-normal life spans. Current treatment recommendations of the National Comprehensive Cancer Network and the European LeukemiaNet state that patients with CML-CP should remain on TKI therapy indefinitely. However, there is increasing evidence from clinical trials that some patients with sustained deep molecular responses may be able to achieve treatment-free remission (TFR), whereby they can suspend TKI therapy without losing previously achieved responses. With many patients achieving deep molecular responses to TKI therapy, there is growing interest in whether such patients can achieve TFR. In addition, adverse events (AEs) with long-term TKI therapy, including both the potential for later-emerging AEs and chronic, low-grade AEs, represent a major motivator for oncologists and their patients to investigate the feasibility of TFR. In this review, we provide an overview of data from TFR clinical trials, discuss the importance of achieving a deep molecular response to TKI treatment, and consider potential reasons for investigating TFR following TKI therapy.

  5. Diagnosis and treatment of patients with nonacid gastroesophageal reflux-induced chronic cough

    PubMed Central

    Xu, Xianghuai; Yu, Li; Chen, Qiang; Lv, Hanjing; Qiu, Zhongmin

    2015-01-01

    Gastroesophageal reflux (GER) is one of the most common causes of chronic cough, and chronic cough due to GER represents a subtype of GER-related diseases. Gastroesophageal reflux-induced chronic cough (GERC) can be divided into two subgroups based on the pH of the GER. Nonacid GERC is less common than acid GERC, and its diagnosis and treatment strategy have not been standardized. However, nonacid GERC usually presents with its unique set of characteristics and features upon diagnosis and treatment in the clinic. Although the underlying molecular mechanism of nonacid GERC is not fully understood, it is considered to be associated with reflux theory, reflex theory and airway hypersensitivity. Multi-channel intraluminal impedance combined with pH monitoring is a promising new technique that can detect both acid and nonacid reflux, and our findings as well as those of others have shown its usefulness in diagnosing nonacid GERC. Development of new diagnostic techniques has led to an increased rate of nonacid GERC diagnosis. We summarize our experience in the diagnosis and treatment of nonacid GERC and provide a guide for future therapeutic approaches. PMID:26759577

  6. Nonnarcotic analgesics and tricyclic antidepressants for the treatment of chronic nonmalignant pain.

    PubMed

    Richlin, D M

    1991-05-01

    Chronic nonmalignant pain is often characterized by multiple treatment failures, a pattern of maladaptive behavior, and depression. Often there is a history of inappropriate and excessive use of medications for pain. Prior and ongoing use of narcotics and sedatives acts to compound and aggravate the chronic pain syndrome. A first step in treatment is controlled withdrawal of these agents. Nonnarcotic analgesics, NSAIDs, and tricyclic antidepressants are commonly employed in patients with chronic pain. Effective use of these agents requires understanding of their pharmacokinetic and pharmacodynamic properties. Use of a fixed-time schedule is necessary to achieve an effective, sustained therapeutic response. Careful patient education and monitoring for side effects and toxicity are necessary, particularly in the elderly and patients with coexisting medical disorders. Incidence of side effects and toxicity may be reduced by choice of drug and modification of dosing regimen. Nonnarcotic analgesics, TCAs, and NSAIDs are seldom effective by themselves in resolving the pain and distress of patients with chronic nonmalignant pain. This is particularly true when maladaptive behavior coexists. A comprehensive multimodal pain management program encompassing additional pain-relieving strategies and behavior-modifying techniques should be considered and utilized in conjunction with medication.

  7. Attention management as a treatment for chronic pain.

    PubMed

    Elomaa, Minna M; de C Williams, Amanda C; Kalso, Eija A

    2009-11-01

    Attention management is often included in cognitive-behavioural treatments (CBT). The aim of this study was to evaluate the effects of attention management strategies in the treatment for chronic pain. The present pilot study consisted of six weekly 90-min treatment sessions and was based on a CBT attention management manual describing techniques such as attention diversion, imagery and mindfulness exercises. The intended outcomes were reduction in pain-related anxiety and hypervigilance to pain and decrease in pain impact of everyday life, measured by self-report. Information was collected at baseline, pre-treatment, post-treatment, and at 3 and 6 months follow-up. The results at the end of treatment, and at 3-month follow-up, show significant reductions in pain-related anxiety, hypervigilance and interference of pain (effect sizes 0.40-0.90). Reduction in pain-related interference and anxiety remained at the 6-month follow-up. The results indicate that attention control skills can be a useful method to reduce anxiety in the short term. Clinical implications of the results are discussed.

  8. [Advances in the treatment of chronic lymphocytic leukaemia].

    PubMed

    Mozas, Pablo; Delgado, Julio

    2016-11-18

    Chronic lymphocytic leukemia (CLL), a proliferation of mature B cells, is one of the most prevalent haematological malignancies. Progress has been made in its treatment during the last few decades, and chemoimmunotherapy based on fludarabine, cyclophosphamide and rituximab is considered the treatment of choice for patients with standard-risk CLL and good performance status. However, due to the characterization of high-risk biological subgroups and its presentation in elderly patients and/or with comorbidities, targeted therapies, such as B-cell receptor inhibitors, have been developed and approved during the last few years. The current review examines traditional therapeutic strategies and focuses on new small molecules that already represent promising elements of the CLL treatment landscape. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  9. N-acetylaspartate (NAA) levels in selected areas of the brain in patients with chronic schizophrenia treated with typical and atypical neuroleptics: a proton magnetic resonance spectroscopy (1H MRS) study.

    PubMed

    Szulc, Agata; Galińska, Beata; Tarasów, Eugeniusz; Kubas, Bozena; Dzienis, Wojciech; Konarzewska, Beata; Poplawska, Regina; Tomczak, Anna A; Czernikiewicz, Andrzej; Walecki, Jerzy

    2007-05-01

    NAA, marker of neurons integrity and viability, is one of the most important brain metabolites visible in 1H MRS. In most studies of schizophrenia, the decrease of NAA level was observed in the temporal, frontal lobes and in the thalamus. This finding was observed more often among chronic patients, what suggests the influence of disease duration or the effect of neuroleptic treatment. The aim of the present study was the comparison of NAA levels in brain of schizophrenic patients taking typical and atypical neuroleptics. We analyzed the NAA levels in selected brain areas in 58 schizophrenic patients and 21 healthy controls. 10 patients were treated with typical neuroleptics, 10 patients with clozapine, 17 received olanzapine and 21 - risperidone. 1H MRS was performed on a 1,5 MR scanner with PRESS sequence. Voxels of 2x2x2 cm were localized in the left frontal, left temporal lobe and left thalamus. There were no differences in NAA levels between patients on typical and atypical medications analyzed together and separately (olanzapine, clozapine and risperidone groups). We also did not find any differences between patients taking selected atypical neuroleptics and controls. The NAA level in the thalamus in the group of patients receiving typical antipsychotics was the lowest among all groups and differed significantly from healthy controls. The results of our study suggest that atypical neuroleptics may have favorable effect on NAA concentration in brain of schizophrenic patients. Decrease in NAA level in patients taking typical medication may be caused by the progression of the disease or by the direct action of these drugs.

  10. [Surgical treatment of chronic pancreatitis, 2010].

    PubMed

    Farkas, Gyula

    2011-04-01

    Chronic pancreatitis (CP) is a benign inflammatory process, which can cause enlargement of the pancreatic head accompanied by severe pain and weight loss, and often leads to a significant reduction in quality of life (QoL). Basically, the disease is characterised by pain and functional disorders which are initially treated with conservative therapy, but in case of complications (uncontrollable pain or obstruction) surgical treatment is required. This article reviews the relevant literature of CP treatment, in particular randomized controlled trials and meta-analyses were involved with a comparison of different surgical treatment options for the management of CP complications. Recent studies have demonstrated that surgical procedures are superior to endoscopic therapy as regards long-term results of QoL and pain control. There was no significant difference found in postoperative pain relief and overall mortality when duodenum-preserving pancreatic head resection (DPPHR) of Beger and its modification (duodenum and organ-preserving pancreatic head resection [DOPPHR]) were compared with pancreatoduodenectomy (PD), but hospital stay, weight gain, exocrine and endocrine insufficiency, and QoL were significantly better in the DPPHR and DOPPHR groups. DPPHR and PD seem to be equally effective in terms of postoperative pain relief and overall mortality. However, recent data suggest that DOPPHR is superior in the treatment of CP with regard to several peri- and postoperative outcome parameters and QoL. Therefore, this should be the preferable treatment option for CP complications.

  11. Clinical effectiveness and cost-effectiveness of treatments for patients with chronic pain.

    PubMed

    Turk, Dennis C

    2002-01-01

    Chronic pain is a prevalent and costly problem. This review addresses the question of the clinical effectiveness and cost-effectiveness of the most common treatments for patients with chronic pain. Representative published studies that evaluate the clinical effectiveness of pharmacological treatments, conservative (standard) care, surgery, spinal cord stimulators, implantable drug delivery systems (IDDSs), and pain rehabilitation programs (PRPs) are examined and compared. The cost-effectiveness of these treatment approaches is also considered. Outcome criteria including pain reduction, medication use, health care consumption, functional activities, and closure of disability compensation cases are examined. In addition to clinical effectiveness, the cost-effectiveness of PRPs, conservative care, surgery, spinal cord stimulators, and IDDSs are compared using costs to return a treated patient to work to illustrate the relative expenses for each of these treatments. There are limitations to the success of all the available treatments. The author urges caution in interpreting the results, particularly in comparisons between treatments and across studies, because there are broad differences in the pain syndromes and inclusion criteria used, the drug dosages, comparability of treatments, the definition of "chronic" used, the outcome criteria selected to determine success, and societal differences. None of the currently available treatments eliminates pain for the majority of patients. Pain rehabilitation programs provide comparable reduction in pain to alternative pain treatment modalities, but with significantly better outcomes for medication use, health care utilization, functional activities, return to work, closure of disability claims, and with substantially fewer iatrogenic consequences and adverse events. Surgery, spinal cord stimulators, and IDDSs appear to have substantial benefits on some outcome criteria for carefully selected patients. These modalities are

  12. Stochastic modelling to assess economic effects of treatment of chronic subclinical mastitis caused by Streptococcus uberis.

    PubMed

    Steeneveld, Wilma; Swinkels, Jantijn; Hogeveen, Henk

    2007-11-01

    Chronic subclinical mastitis is usually not treated during the lactation. However, some veterinarians regard treatment of some types of subclinical mastitis to be effective. The goal of this research was to develop a stochastic Monte Carlo simulation model to support decisions around treatment of chronic subclinical mastitis caused by Streptococcus uberis. Factors in the model included the probability of cure after treatment, probability of the cow becoming clinically diseased, transmission of infection to other cows, and physiological effects of the infection. Using basic input parameters for Dutch circumstances, the average economic costs per cow of an untreated chronic subclinical mastitis case caused by Str. uberis in a single quarter from day of diagnosis onwards was euro109. With treatment, the average costs were higher (euro120). Thus, for the average cow, treatment was not efficient economically. However, the risk of high costs was much higher when cows with chronic subclinical mastitis were not treated. A sensitivity analysis showed that profitability of treatment of chronic subclinical Str. uberis mastitis depended on farm-specific factors (such as economic value of discarded milk) and cow-specific factors (such as day of diagnosis, duration of infection, amount of transmission to other cows and cure rate). Therefore, herd level protocols are not sufficient and decision support should be cow specific. Given the importance of cow-specific factors, information from the current model could be applied to automatic decision support systems.

  13. A Couple-Based Psychological Treatment for Chronic Pain and Relationship Distress.

    PubMed

    Cano, Annmarie; Corley, Angelia M; Clark, Shannon M; Martinez, Sarah C

    2018-02-01

    Chronic pain impacts individuals with pain as well as their loved ones. Yet, there has been little attention to the social context in individual psychological treatment approaches to chronic pain management. With this need in mind, we developed a couple-based treatment, "Mindful Living and Relating," aimed at alleviating pain and suffering by promoting couples' psychological and relational flexibility skills. Currently, there is no integrative treatment that fully harnesses the power of the couple, treating both the individual with chronic pain and the spouse as two individuals who are each in need of developing greater psychological and relational flexibility to improve their own and their partners' health. Mindfulness, acceptance, and values-based action exercises were used to promote psychological flexibility. The intervention also targets relational flexibility, which we define as the ability to interact with one's partner, fully attending to the present moment, and responding empathically in a way that serves one's own and one's partner's values. To this end, the intervention also included exercises aimed at applying psychological flexibility skills to social interactions as well as emotional disclosure and empathic responding exercises to enhance relational flexibility. The case presented demonstrates that healthy coping with pain and stress may be most successful and sustainable when one is involved in a supportive relationship with someone who also practices psychological flexibility skills and when both partners use relational flexibility skills during their interactions.

  14. The Use of Breathing Exercises in the Treatment of Chronic, Nonspecific Low Back Pain.

    PubMed

    Anderson, Barton E; Bliven, Kellie C Huxel

    2017-09-01

    Clinical Scenario: Research has shown a link between poor core stability and chronic, nonspecific low back pain, with data to suggest that alterations in core muscle activation patterns, breathing patterns, lung function, and diaphragm mechanics may occur. Traditional treatment approaches for chronic, nonspecific low back pain focus on exercise and manual therapy interventions, however it is not clear whether breathing exercises are effective in treating back pain. Focused Clinical Question: In adults with chronic, nonspecific low back pain, are breathing exercises effective in reducing pain, improving respiratory function, and/or health related quality of life? Summary of Key Findings: Following a literature search, 3 studies were identified for inclusion in the review. All reviewed studies were critically appraised at level 2 evidence and reported improvements in either low back pain or quality of life following breathing program intervention. Clinical Bottom Line: Exercise programs were shown to be effective in improving lung function, reducing back pain, and improving quality of life. Breathing program frequencies ranged from daily to 2-3 times per week, with durations ranging from 4 to 8 weeks. Based on these results, athletic trainers and physical therapists caring for patients with chronic, nonspecific low back pain should consider the inclusion of breathing exercises for the treatment of back pain when such treatments align with the clinician's own judgment and clinical expertise and the patient's preferences and values. Strength of Recommendation: Grade B evidence exists to support the use of breathing exercises in the treatment of chronic, nonspecific low back pain.

  15. "I'm not abusing or anything": patient-physician communication about opioid treatment in chronic pain.

    PubMed

    Matthias, Marianne S; Krebs, Erin E; Collins, Linda A; Bergman, Alicia A; Coffing, Jessica; Bair, Matthew J

    2013-11-01

    To characterize clinical communication about opioids through direct analysis of clinic visits and in-depth interviews with patients. This was a pilot study of 30 patients with chronic pain, who were audio-recorded in their primary care visits and interviewed after the visit about their pain care and relationship with their physicians. Emergent thematic analysis guided data interpretation. Uncertainties about opioid treatment for chronic pain, particularly addiction and misuse, play an important role in communicating about pain treatment. Three patterns of responding to uncertainty emerged in conversations between patients and physicians: reassurance, avoiding opioids, and gathering additional information. Results are interpreted within the framework of Problematic Integration theory. Although it is well-established that opioid treatment for chronic pain poses numerous uncertainties, little is known about how patients and their physicians navigate these uncertainties. This study illuminates ways in which patients and physicians face uncertainty communicatively and collaboratively. Acknowledging and confronting the uncertainties inherent in chronic opioid treatment are critical communication skills for patients taking opioids and their physicians. Many of the communication behaviors documented in this study may serve as a model for training patients and physicians to communicate effectively about opioids. Published by Elsevier Ireland Ltd.

  16. [Choice of the method of surgical treatment of chronic pancreatitis].

    PubMed

    Vorobeĭ, A V; Shuleĭko, A Ch; Orlovskiĭ, Iu N; Vizhinis, Iu I; Butra, Iu V; Lagodich, N A

    2014-01-01

    An analysis of surgical treatment of 187 patients with chronic pancreatitis was made during 3-year period in the department of surgery clinic of Byelorussian Medical Academy of Post-Graduate Education. Drainage operations were performed on 28 patients, resection-drainage operations were carried out on 130 patients and resection operations had 19 patients. The laser beam technologies were successfully applied during operations on the pancreas in 43 patients. Postoperative complications (14.8%) were analyzed and structured. Methods of corrections and ways of prophylaxis of complication development were provided. On the basis of the complication analysis and new conception concerning peripheral pancreatic hypertension the authors offered the rational approaches to choice of operations on the pancreas in case of chronic pancreatitis. The authors developed the classification of pancreatoductolitiasis, pancreatic hypertension and a new strategy of surgical management of chronic pancreatitis.

  17. High-energy extracorporeal shock wave therapy as a treatment for chronic noninsertional Achilles tendinopathy.

    PubMed

    Furia, John P

    2008-03-01

    High-energy extracorporeal shock wave therapy has been shown to be an effective treatment for chronic insertional Achilles tendinopathy. The results of high-energy shock wave therapy for chronic noninsertional Achilles tendinopathy have not been determined. Shock wave therapy is an effective treatment for noninsertional Achilles tendinopathy. Case control study; Level of evidence, 3. Thirty-four patients with chronic noninsertional Achilles tendinopathy were treated with a single dose of high-energy shock wave therapy (shock wave therapy group; 3000 shocks; 0.21 mJ/mm(2); total energy flux density, 604 mJ/mm(2)). Thirty-four patients with chronic noninsertional Achilles tendinopathy were treated not with shock wave therapy but with additional forms of nonoperative therapy (control group). All shock wave therapy procedures were performed using regional anesthesia. Evaluation was by change in visual analog score and by Roles and Maudsley score. One month, 3 months, and 12 months after treatment, the mean visual analog scores for the control and shock wave therapy groups were 8.4 and 4.4 (P < .001), 6.5 and 2.9 (P < .001), and 5.6 and 2.2 (P < .001), respectively. At final follow-up, the number of excellent, good, fair, and poor results for the shock wave therapy and control groups were 12 and 0 (P < .001), 17 and 9 (P < .001), 5 and 17 (P < .001), and 0 and 8 (P < .001), respectively. A chi(2) analysis revealed that the percentage of patients with excellent ("1") or good ("2") Roles and Maudsley scores, that is, successful results, 12 months after treatment was statistically greater in the shock wave therapy group than in the control group (P < .001). Shock wave therapy is an effective treatment for chronic noninsertional Achilles tendinopathy.

  18. [Surgical treatment of pain in chronic pancreatitis].

    PubMed

    Stefanović, Dejan; Knezević, Srbislav; Djordjević, Zoran; Kerkez, Mirko; Bulajić, Predrag; Marković, Ljiljana

    2006-01-01

    The principal indication for surgical intervention in chronic pancreatitis is intractable pain. Depending upon the presence of dilated pancreatic ductal system, pancreatic duct drainage procedures and different kinds of pancreatic resections are applied. The objective of the study was to show the most appropriate procedure to gain the most possible benefits in dependence of type of pathohistological process in chronic pancreatitis. Our study included 58 patients with intractable pain caused by chronic pancreatitis of alcoholic genesis. The first group consisted of 30 patients with dilated pancreatic ductal system more than 10 mm. The second group involved 28 patients without dilated pancreatic ductal system. Pain relief, weight gain and glucose tolerance were monitored. All patients of Group I (30) underwent latero-lateral pancreaticojejunal--Puestow operation. 80% of patients had no pain after 6 month, 13.6% had rare pain and 2 patients, i.e. 6.4%, who continued to consume alcohol, had strong pain. Group II consisting of 28 patients was without dilated pancreatic ductal system. This group was subjected to various types of pancreatic resections. Whipple procedure (W) was done in 6 patients, pylorus preserving Whipple (PPW) in 7 cases, and duodenum preserving cephalic pancreatectomy (DPCP) was performed in 15 patients. Generally, 89.2% of patients had no pain 6 month after the operation. An average weight gain was 1.9 kg in W group, 2.8 kg in PPW group and 4.1 kg in DPCP group. Insulin-dependent diabetes was recorded in 66.6% in W group, 57.1% in PPW group and 0% in DPCP group. According to our opinion, DPCP may be considered the procedure of choice for surgical treatment of pain in chronic pancreatitis in patients without dilatation of pancreas ductal system because of no serious postoperative metabolic consequences.

  19. Hereditary chronic pancreatitis: implications for surgical treatment and follow-up.

    PubMed

    Cowles, R A; Eckhauser, F E; Knol, J A

    2001-02-01

    Hereditary pancreatitis is an uncommon cause of chronic pancreatitis in Western society. It should be suspected when chronic pancreatitis presents in young adults. The diagnosis is made when chronic pancreatitis is present in several members of the same family who are determined not to have other risk factors for chronic pancreatitis. Molecular research focusing on mutations in the trypsinogen gene has uncovered the genetic defects associated with hereditary pancreatitis, and this knowledge has suggested the possible pathophysiologic mechanism of this disease. Because patients with hereditary pancreatitis develop their disease early in life they are very likely to require treatment for complications. As in patients with chronic pancreatitis of other etiologies those with hereditary pancreatitis should be treated medically for acute exacerbations. When complications occur or when the disease causes intractable pain surgery is recommended. Surgical therapy is tailored to the patient's pancreatic anatomy based on endoscopic retrograde cholangiopancreatography or CT scan. The two patients described in this report underwent successful longitudinal pancreaticojejunostomy (Puestow procedure) with good results. Finally it has been shown that patients with hereditary pancreatitis are at increased risk for developing pancreatic adenocarcinoma. Although not widely used pancreatic cancer screening programs have been suggested for surveillance of these patients.

  20. Prevalence of neuroleptic-induced movement disorders in chronic schizophrenia inpatients.

    PubMed

    Janno, Sven; Holi, Matti; Tuisku, Katinka; Wahlbeck, Kristian

    2004-01-01

    Since most of the world's schizophrenia patients are treated with conventional antipsychotics, the authors evaluated various methods for establishing the prevalence of neuroleptic-induced movement disorders in these patients. DSM-IV criteria and established score thresholds on a movement disorder rating scale were used to identify cases of neuroleptic-induced movement disorder in a representative Estonian patient sample of 99 chronic institutionalized schizophrenia patients, 18-65 years old, treated with conventional neuroleptics (79.8%) or clozapine (20.2%). Neuroleptic-induced movement disorders according to DSM-IV criteria were found in 61.6% of the group: 31.3% had neuroleptic-induced akathisia, 23.2% had neuroleptic-induced parkinsonism, and 32.3% had neuroleptic-induced tardive dyskinesia. Prevalence rates for akathisia and tardive dyskinesia were similar when either DSM-IV criteria or rating scale scores were used, but the prevalence rate for parkinsonism was much lower per DSM-IV criteria than according to rating scale score. Nearly two-thirds of chronic schizophrenia patients suffered from a neuroleptic-induced movement disorder. Globally, extrapyramidal adverse effects still impose a huge burden on the majority of neuroleptic-treated individuals with schizophrenia. The discrepancy between the standard identification methods for neuroleptic-induced movement disorder indicate the need for further research.

  1. Behavioral Treatment of Chronic Insomnia in Older Adults: Does Nocturia Matter?

    PubMed Central

    Tyagi, Shachi; Resnick, Neil M.; Perera, Subashan; Monk, Timothy H.; Hall, Martica H.; Buysse, Daniel J.

    2014-01-01

    Objective: To evaluate the impact of nocturia on the therapeutic response of chronic insomnia to behavioral treatment in older adults. Methods: Secondary analysis of a randomized clinical trial designed to assess the efficacy of brief behavioral treatment of insomnia (BBTI) vs. an information-only control (IC) in 79 community-dwelling older adults with chronic insomnia. For the current analysis, participants were stratified into 2 groups: those with self-reported nocturia at baseline i.e., ≥ 1 void/night (N = 30; 16 IC, 14 BBTI) and those without nocturia (N = 49; 24 IC, 25 BBTI). We then determined the impact of BBTI on sleep, sleep quality, and nocturia as assessed by self-report, actigraphy, and polysomnography Results: Individuals without baseline nocturia responded well to BBTI with significant decrease in sleep latency, wake after sleep onset, and total sleep time assessed by sleep diary and actigraphy; these changes were significantly greater than those in the IC group. In comparison, changes in the same sleep parameters among participants with nocturia were not significantly different from the IC control. Although BBTI showed significant improvement in sleep quality in groups with and without nocturia (as assessed by PSQI and sleep diary), the effect size of these improvements was larger in those without nocturia than in those with nocturia (PSQI d = 0.82 vs. 0.53, diary sleep quality d = 0.83 vs. 0.51). Conclusions: These secondary analyses suggest that brief behavioral treatment of insomnia may be more efficacious in improving insomnia in participants without nocturia. Addressing nocturia may improve the efficacy of behavioral insomnia treatment. Citation: Tyagi S; Resnick NM; Perera S; Monk TH; Hall MH; Buysse DJ. Behavioral treatment of chronic insomnia in older adults: does nocturia matter? SLEEP 2014;37(4):681-687. PMID:24899759

  2. The association of personality trait on treatment outcomes in patients with chronic prostatitis/chronic pelvic pain syndrome: an exploratory study.

    PubMed

    Koh, Jun Sung; Ko, Hyo Jung; Wang, Sheng-Min; Cho, Kang Joon; Kim, Joon Chul; Lee, Soo-Jung; Pae, Chi-Un; Serretti, Alessandro

    2014-02-01

    This study investigated the association of personality traits with the baseline clinical characteristics and treatment outcomes of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Subjects were evaluated at baseline and at week 12 following routine treatment for CP/CPPS using the Korean version of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) to measure the severity of CP/CPPS; the Korean version of the Patient Health Questionnaire-9 (PHQ-9) to assess depression; the Korean version of the Patient Health Questionnaire-15 (PHQ-15) to evaluate somatization; and the Korean version of the EuroQol Questionnaire-5 Dimensions (EQ-5D), specifically the EQ-5D utility index and the EQ-5D visual analog scale (EQ-5D VAS), to assess quality of life (QoL). Personality traits including extraversion, agreeableness, conscientiousness, neuroticism, and openness were determined at baseline using the 44-item Big Five Inventory (BFI). The influence of personality traits on the clinical characteristics and treatment outcomes of patients with CP/CPPS was assessed using relevant statistical analyses. Neuroticism was associated with a significantly poorer treatment response and higher levels of depression and somatization. Extraversion, agreeableness, and conscientiousness had some influence on clinical characteristics but openness did not affect overall symptoms or the treatment response in patients with CP/CPPS. We found that neuroticism may be the most important personality trait associated with treatment response and the severity of depression and somatization in patients with CP/CPPS. However, our exploratory findings should be confirmed by additional studies with adequate power and improved designs. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. The impact of chronic pain on opioid addiction treatment: a systematic review protocol.

    PubMed

    Dennis, Brittany B; Bawor, Monica; Paul, James; Varenbut, Michael; Daiter, Jeff; Plater, Carolyn; Pare, Guillaume; Marsh, David C; Worster, Andrew; Desai, Dipika; Thabane, Lehana; Samaan, Zainab

    2015-04-16

    The consequences of opioid relapse among patients being treated with opioid substitution treatment (OST) are serious and can result in abnormal cardiovascular function, overdose, and mortality. Chronic pain is a major risk factor for opioid relapse within the addiction treatment setting. There exist a number of opioid maintenance therapies including methadone, buprenorphine, naltrexone, and levomethadyl acetate (LAAM), of which the mediating effects of pain on treatment attrition, substance use behavior, and social functioning may differ across therapies. We aim to 1) evaluate the impact of pain on the treatment outcomes of addiction patients being managed with OST and 2) identify the most recently published opioid maintenance treatment guidelines from the United States, Canada, and the UK to determine how the evidence is being translated into clinical practice. The authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Database of Systematic Reviews, ProQuest Dissertations and theses Database, Cochrane Central Register of Controlled Trials (CENTRAL), World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. We will search www. gov and the National Institute for Care and Excellence (NICE) databases to identify the most recently published OST guidelines. All screening and data extraction will be completed in duplicate. Provided the data are suitable, we will perform a multiple treatment comparison using Bayesian meta-analytic methods to produce summary statistics estimating the effect of chronic pain on all OSTs. Our primary outcome is substance use behavior, which includes opioid and non-opioid substance use. We will also evaluate secondary endpoints such as treatment retention, general physical health, intervention adherence, personal and social functioning, as well as psychiatric symptoms. This review will capture the experience of treatment

  4. Under one roof: identification, evaluation, and treatment of chronic hepatitis C in addiction care.

    PubMed

    Martin, Stephen A; Bosse, Jordon; Wilson, Amanda; Losikoff, Phyllis; Chiodo, Lisa

    2018-04-25

    For over a decade, the vast majority of new hepatitis C virus (HCV) infections have been among young people who inject drugs (PWID). Well-characterized gaps in chronic HCV diagnosis, evaluation, and treatment have resulted in fewer than 5% of PWID receiving HCV treatment. While interferon-based treatment may have intentionally been foregone during part of this time in anticipation of improved oral therapies, the overall pattern points to deficiencies and treatment exclusions in the health care system. Treatment for HCV with all-oral, highly effective direct-acting antiviral medication for 12 weeks or less is now the standard of care, putting renewed focus on effective delivery of care. We describe here both the need for and process of chronic HCV care under the roof of addiction medicine.

  5. Chronic Pruritus in the Absence of Skin Disease: Pathophysiology, Diagnosis and Treatment.

    PubMed

    Pereira, Manuel P; Kremer, Andreas E; Mettang, Thomas; Ständer, Sonja

    2016-08-01

    Chronic pruritus arises not only from dermatoses, but also, in up to half of cases, from extracutaneous origins. A multitude of systemic, neurological, psychiatric, and somatoform conditions are associated with pruritus in the absence of skin disease. Moreover, pruritus is a frequently observed side effect of many drugs. It is therefore difficult for physicians to make a correct diagnosis. Chronic pruritus patients frequently present to the dermatologist with skin lesions secondary to a long-lasting scratching behavior, such as lichenification and prurigo nodularis. A structured clinical history and physical examination are essential in order to evaluate the pruritus, along with systematic, medical history-adapted laboratory and radiological tests carried out according to the differential diagnosis. For therapeutic reasons, a symptomatic therapy should be promptly initiated parallel to the diagnostic procedures. Once the underlying factor(s) leading to the pruritus are identified, a targeted therapy should be implemented. Importantly, the treatment of accompanying disorders such as sleep disturbances or mental symptoms should be taken into consideration. Even after successful treatment of the underlying cause, pruritus may persist, likely due to chronicity processes including peripheral and central sensitization or impaired inhibition at spinal level. A vast arsenal of topical and systemic agents targeting these pathophysiological mechanisms has been used to deter further chronicity. The therapeutic options currently available are, however, still insufficient for many patients. Thus, future studies aiming to unveil the complex mechanisms underlying chronic pruritus and develop new therapeutic agents are urgently needed.

  6. Diabetic ketoacidosis and severe hypertriglyceridaemia as a consequence of an atypical antipsychotic agent.

    PubMed

    Hepburn, Kirsten; Brzozowska, Malgorzata Monika

    2016-08-09

    The atypical antipsychotic agent clozapine, although an effective treatment for schizophrenia, is linked with metabolic adverse effects. We report a case of diabetic ketoacidosis and very severe hypertriglyceridaemia associated with clozapine use, in a patient with type 2 diabetes mellitus, who was successfully treated with continuous insulin infusion and fluids. As clozapine proved to be the most efficacious in controlling the patient's psychotic symptoms, the patient has been continued on clozapine despite its known metabolic side effects. Importantly the patient has achieved satisfactory long-term lipid and glycaemic control. The current recommendations related to the metabolic care for patients treated with atypical antipsychotic agents as well as the mechanisms behind abnormal glucose and lipid regulation with clozapine therapy are discussed. 2016 BMJ Publishing Group Ltd.

  7. Treatment strategies for childhood noninfectious chronic uveitis: an update.

    PubMed

    Cantarini, Luca; Simonini, Gabriele; Frediani, Bruno; Pagnini, Ilaria; Galeazzi, Mauro; Cimaz, Rolando

    2012-01-01

    Uveitis is an inflammatory disorder involving inflammation of the uveal tract. It is classified as anterior, intermediate, posterior or panuveitis, depending on the part of eye affected by the inflammatory process. In children, noninfectious, chronic uveitis is a relatively uncommon but serious disease, with the potential for significant long-term complications and possible blindness. Although frequently associated with an underlying systemic disease, for example, juvenile idiopathic arthritis, a significant number of cases in children show no associated signs or symptoms and are labeled as idiopathic. We reviewed the available literature. Taking into account this evidence, an anti-inflammatory therapy based on an immunomodulatory approach seems a reasonable strategy for noninfectious chronic uveitis, in children as well as in adults. Due to a lack of controlled studies regarding uveitis in children, immunosuppressive strategy is supported only at evidence level III. Our aim is to review the currently available medical strategies for the treatment of childhood sight-threatening chronic uveitis. Uveitis in children can be severe. Methotrexate is the drug of choice for recalcitrant cases, and biologic therapies can be useful in selected situations.

  8. Current Treatment of Chronic Lymphocytic Leukemia.

    PubMed

    Jamroziak, Krzysztof; Puła, Bartosz; Walewski, Jan

    2017-01-01

    A number of new treatment options have recently emerged for chronic lymphocytic leukemia (CLL) patients, including the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, phosphatidylinositol-3-kinase (PI3K) delta isoform inhibitor idelalisib combined with rituximab, the Bcl-2 antagonist venetoclax, and the new anti-CD20 antibodies obinutuzumab and ofatumumab. Most of these agents are already included into treatment algorithms defined by international practice guidelines, but more clinical investigations are needed to answer still remaining questions. Ibrutinib was proven as a primary choice for patients with the TP53 gene deletion/mutation, who otherwise have no active treatment available. Idelalisib with rituximab is also an active therapy, but due to increased risk of serious infections, its use in first-line treatment is limited to patients for whom ibrutinib is not an option. A new indication for ibrutinib was recently approved for older patients with comorbidities, as an alternative to the already existing indication for chlorambucil with obinutuzumab. The use of kinase inhibitors is already well established in recurrent/refractory disease. Immunochemotherapy with fludarabine, cyclophosphamide, rituximab (FCR) remains a major first-line option for many CLL patients without the TP53 gene deletion/mutation, and who have no significant comorbidities or history of infections, and is particularly effective in patients with favorable features including mutated IGHV status. There are a number of issues regarding novel therapies for CLL that need further investigation such as optimum duration of treatment with kinase inhibitors, appropriate sequencing of novel agents, mechanisms of resistance to inhibitors and response to class switching after treatment failure, along with the potential role of combinations of targeted agents.

  9. A Unified, Transdiagnostic Treatment for Adolescents with Chronic Pain and Comorbid Anxiety and Depression

    ERIC Educational Resources Information Center

    Allen, Laura B.; Tsao, Jennie C. I.; Seidman, Laura C.; Ehrenreich-May, Jill; Zeltzer, Lonnie K.

    2012-01-01

    Chronic pain disorders represent a significant public health concern, particularly for children and adolescents. High rates of comorbid anxiety and unipolar mood disorders often complicate psychological interventions for chronic pain. Unified treatment approaches, based on emotion regulation skills, are applicable to a broad range of emotional…

  10. Chronic treatment with fluoxetine modulates vascular adrenergic responses by inhibition of pre- and post-synaptic mechanisms.

    PubMed

    Pereira, Camila A; Rodrigues, Fernanda L; Ruginsk, Silvia G; Zanotto, Camila Z; Rodrigues, José A; Duarte, Diego A; Costa-Neto, Claudio M; Resstel, Leonardo B; Carneiro, Fernando S; Tostes, Rita C

    2017-04-05

    Fluoxetine, a serotonin reuptake inhibitor (SSRI), has other effects in addition to blocking serotonin reuptake, including changes in the vasomotor tone. Whereas many studies focused on the acute effects of fluoxetine in the vasculature, its chronic effects are still limited. In the present study, we tested the hypothesis that chronic fluoxetine treatment modulates adrenergic vascular responses by interfering with post- and pre-synaptic mechanisms. Wistar rats were treated with vehicle (water) or chronic fluoxetine (10mg/kg/day) for 21 days. Blood pressure (BP) and heart rate were measured. Vascular reactivity was evaluated in perfused mesenteric arterial beds (MAB) and in mesenteric resistance arteries. Protein expression by western blot analysis or immunohistochemistry, β-arrestin recruitment by BRET and calcium influx by FLIPR assay. Fluoxetine treatment decreased phenylephrine (PE)-induced, but not electrical-field stimulation (EFS)-induced vasoconstriction. Fluoxetine-treated rats exhibited increased KCl-induced vasoconstriction, which was abolished by prazosin. Desipramine, an inhibitor of norepinephrine (NA) reuptake, increased EFS-induced vasoconstrictor response in vehicle-treated, but not in fluoxetine-treated rats. Chronic treatment did not alter vascular expression of α 1 adrenoceptor, phosphorylation of PKCα or ERK 1/2 and RhoA. On the other hand, vascular contractions to calcium (Ca 2+ ) as well as Ca 2+ influx in mesenteric arteries were increased, while intracellular Ca 2+ storage was decreased by the chronic treatment with fluoxetine. In vitro, fluoxetine decreased vascular contractions to PE, EFS and Ca 2+ , but did not change β-arrestin activity. In conclusion, chronic treatment with fluoxetine decreases sympathetic-mediated vascular responses by mechanisms that involve inhibition of NA release/reuptake and decreased Ca 2+ stores. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Understanding and treatment of chronic pancreatitis.

    PubMed

    Drewes, Asbjørn Mohr

    2013-11-14

    Chronic pancreatitis is characterized by an inflammatory process of the pancreas, which is replaced by fibrosis and progressive destruction. The three major clinical features of chronic pancreatitis are pain, maldigestion, and diabetes. Chronic pancreatitis has a profound impact on social life and employment patterns. In the current issue, different topics highlight experimental models of chronic pancreatitis and bridge findings from recent research to bedside. Although the disease is still difficult to treat the current papers represent useful guidelines on how to approach chronic pancreatitis in the clinical settings with the major aim to improve the patient's suffering and quality of life.

  12. The treatment of chronic intestinal ischemia.

    PubMed

    Illuminati, G; Caliò, F G; D'Urso, A; Papaspyropoulos, V; Mancini, P; Ceccanei, G; Vietri, F

    2004-01-01

    Due to the rarity of the condition, large and prospective series defining the optimal method of digestive arteries revascularization, for the treatment of chronic intestinal ischemia, are lacking. The aim of this consecutive sample clinical study was to test the hypothesis that flexible application of different revascularization methods, according to individual cases, will yield the best results in the management of chronic intestinal ischemia. Eleven patients, of a mean age of 57 years, underwent revascularization of 11 digestive arteries for symptomatic chronic mesenteric occlusive disease. Eleven superior mesenteric arteries and one celiac axis were revascularized. The revascularization techniques included retrograde bypass grafting in 7 cases, antegrade bypass grafting in 2, percutaneous arterial angioplasty in 1, and arterial reimplantation in one case. The donor axis for either reimplantation or bypass grafting was the infrarenal aorta in 4 cases, an infrarenal Dacron graft in 4, and the celiac aorta in one case. Grafting materials included 5 polytetrafluoroethylene (PTFE) and 3 Dacron grafts. Concomitant procedures included 3 aorto-ilio-femoral grafts and one renal artery revascularization. Mean follow-up length was 31 months. There was no operative mortality. Cumulative survival rate was 88.9% at 36 months (SE 12.1%). Primary patency rate was 90% at 36 months (SE 11.6%). The symptom free rate was 90% at 36 months (SE 11.6%). Direct reimplantation, antegrade and retrograde bypass grafting, all allow good mid-term results: the choice of the optimal method depends on the anatomic and general patients status. Associated infrarenal and renal arterial lesions can be safely treated in the same time of digestive revascularization. Angioplasty alone yields poor results and should be limited to patients at poor risk for surgery.

  13. Citric acid treatment of chronic nonhealing ulcerated tophaceous gout with bursitis.

    PubMed

    Nagoba, Basavaraj S; Punpale, Ajay; Poddar, Ashok; Suryawanshi, Namdev M; Swami, Ganesh A; Selkar, Sohan P

    2013-12-01

    The ulceration associated with gout tophi is very difficult to treat because of impaired and halted local inflammatory response resulting from the gout treatment regimen. We report chronic nonhealing tophaceous gout with bursitis in an 80-year-old male, not responding to conventional treatment modality for months together. This nonhealing ulcer was treated successfully with local application of 3% citric acid ointment for 22 days.

  14. Treatment of Unexplained Chronic Cough: CHEST Guideline and Expert Panel Report.

    PubMed

    Gibson, Peter; Wang, Gang; McGarvey, Lorcan; Vertigan, Anne E; Altman, Kenneth W; Birring, Surinder S

    2016-01-01

    Unexplained chronic cough (UCC) causes significant impairments in quality of life. Effective assessment and treatment approaches are needed for UCC. This systematic review of randomized controlled trials (RCTs) asked: What is the efficacy of treatment compared with usual care for cough severity, cough frequency, and cough-related quality of life in patients with UCC? Studies of adults and adolescents aged > 12 years with a chronic cough of > 8 weeks' duration that was unexplained after systematic investigation and treatment were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on by using the American College of Chest Physicians organization methodology. Eleven RCTs and five systematic reviews were included. The 11 RCTs reported data on 570 participants with chronic cough who received a variety of interventions. Study quality was high in 10 RCTs. The studies used an assortment of descriptors and assessments to identify UCC. Although gabapentin and morphine exhibited positive effects on cough-related quality of life, only gabapentin was supported as a treatment recommendation. Studies of inhaled corticosteroids (ICS) were affected by intervention fidelity bias; when this factor was addressed, ICS were found to be ineffective for UCC. Esomeprazole was ineffective for UCC without features of gastroesophageal acid reflux. Studies addressing nonacid gastroesophageal reflux disease were not identified. A multimodality speech pathology intervention improved cough severity. The evidence supporting the diagnosis and management of UCC is limited. UCC requires further study to establish agreed terminology and the optimal methods of investigation using established criteria for intervention fidelity. Speech pathology-based cough suppression is suggested as a treatment option for UCC. This guideline presents suggestions for diagnosis and treatment based on the best available evidence and

  15. Interferon-based treatment of chronic hepatitis C.

    PubMed

    Souvignet, Claude; Lejeune, Olivier; Trepo, Christian

    2007-01-01

    The treatment of patients with chronic hepatitis C has rapidly evolved in the past 10 years centered on the use of interferon alpha 2 as an antiviral and immunomodulatory agent against hepatitis C virus. Firstly used as a monotherapy associated with a deceiving long-term efficacy, interferon alpha was then combined with ribavirin, a nucleoside analog with large antiviral properties. Combination of both drugs dramatically improved the efficacy of treatment with 50% of patients reaching a sustained viral response, characterized by the final eradication of the virus from the infected individual. Surprisingly, this synergistic effect remains greatly unexplained. The third step consisted in the use of pegylated interferon in order to adapt its pharmacokinetics and to allow a better efficacy with a more tolerable dosing schedule: once weekly subcutaneous injection instead of thrice weekly. Pegylated interferon combined with ribavirin during 24-48 weeks of treatment is the current standard of care with nearly 60% of sustained virologic response, overall. Development of new forms of interferon alpha are on the way with promising preliminary results.

  16. Thiothixene in the treatment of geriatric patients with chronic organic brain syndrome.

    PubMed

    Rada, R T; Kellner, R

    1976-03-01

    Thiothixene was used in a four-week double-blind placebo-controlled study of 42 geriatric patients with chronic organic brain syndrome (psychotic or nonpsychotic). The results, according to several rating measures, showed no significant difference between placebo and thiothixene. Side effects were mild and few. These data support the safety of thiothixene therapy for geriatric patients; however, there is no conclusive evidence of its efficacy in the treatment of chronic organic brain syndrome.

  17. Tyrosine Kinase Inhibitor Treatment for Newly Diagnosed Chronic Myeloid Leukemia.

    PubMed

    Radich, Jerald P; Mauro, Michael J

    2017-08-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disorder that accounts for approximately 10% of new cases of leukemia. The introduction of tyrosine kinase inhibitors has led to a reduction in mortalities. Thus, the estimated prevalence of CML is increasing. The National Comprehensive Cancer Network and the European Leukemia Net guidelines incorporate frequent molecular monitoring of the fusion BCR-ABL transcript to ensure that patients reach and keep treatment milestones. Most patients with CML are diagnosed in the chronic phase, and approximately 10% to 30% of these patients will at some time in their course meet definition criteria of resistance to imatinib. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Increasing Neuroplasticity to Bolster Chronic Pain Treatment: A Role for Intermittent Fasting and Glucose Administration?

    PubMed Central

    Sibille, KT; Bartsch, F; Reddy, D; Fillingim, RB; Keil, A

    2016-01-01

    Neuroplastic changes in brain structure and function are not only a consequence of chronic pain but are involved in the maintenance of pain symptoms. Thus, promoting adaptive, treatment responsive neuroplasticity represents a promising clinical target. Emerging evidence about the human brain’s response to an array of behavioral and environmental interventions may assist in identifying targets to facilitate increased neurobiological receptivity, promoting healthy neuroplastic changes. Specifically, strategies to maximize neuroplastic responsiveness to chronic pain treatment could enhance treatment gains by optimizing learning and positive central nervous system (CNS) adaptation. Periods of heightened plasticity have been traditionally identified with the early years of development. More recent research however has identified a wide spectrum of methods that can be used to “re-open” and enhance plasticity and learning in adults. In addition to transcranial direct current stimulation and transcranial magnetic stimulation, behavioral and pharmacological interventions have been investigated. Intermittent fasting and glucose administration are two propitious strategies, which are non-invasive, inexpensive to administer, implementable in numerous settings, and may be applicable across differing chronic pain treatments. Key findings and neurophysiological mechanisms are summarized, providing evidence for the potential clinical contributions of these two strategies toward ameliorating chronic pain. PMID:26848123

  19. Chronic Mountain Sickness: Clinical Aspects, Etiology, Management, and Treatment

    PubMed Central

    Corante, Noemí

    2016-01-01

    Abstract Villafuerte, Francisco C., and Noemí Corante. Chronic mountain sickness: clinical aspects, etiology, management, and treatment. High Alt Med Biol. 17:61–69, 2016.—Millions of people worldwide live at a high altitude, and a significant number are at risk of developing Chronic Mountain Sickness (CMS), a progressive incapacitating syndrome caused by lifelong exposure to hypoxia. CMS is characterized by severe symptomatic excessive erythrocytosis (EE; Hb ≥19 g/dL for women and Hb ≥21 g/dL for men) and accentuated hypoxemia, which are frequently associated with pulmonary hypertension. In advanced cases, the condition may evolve to cor pulmonale and congestive heart failure. Current knowledge indicates a genetic predisposition to develop CMS. However, there are important risk factors and comorbidities that may trigger and aggravate the condition. Thus, appropriate medical information on CMS is necessary to provide adequate diagnosis and healthcare to high-altitude inhabitants. After reviewing basic clinical aspects of CMS, including its definition, diagnosis, and common clinical findings, we discuss aspects of its etiology, and address its epidemiology, risk factors, and treatment. PMID:27218284

  20. Advances in treatment of hyperkalemia in chronic kidney disease.

    PubMed

    Sarafidis, Pantelis A; Georgianos, Panagiotis I; Bakris, George L

    2015-01-01

    Hyperkalemia is a frequent electrolyte disorder associated with life-threatening cardiac arrhythmias and sudden death. Patients prone to hyperkalemia have chronic kidney disease (CKD) either alone or in conjunction with diabetes or heart failure (HF). Although agents inhibiting the renin-angiotensin-aldosterone-system (RAAS) are currently the first-line treatments toward cardio- and nephroprotection, their administration often leads to potassium elevation in such patients and results in high rates of treatment discontinuation. This article provides an overview of factors interfering with potassium homeostasis and discusses emerging potassium-lowering therapies for long-term management of hyperkalemia. In recent randomized clinical studies, two new oral potassium-exchanging compounds, patiromer and sodium zirconium cyclosilicate, were shown to effectively normalize elevated serum potassium and chronically maintain potassium homeostasis in hyperkalemic patients treated with RAAS blockers. Both agents exhibit good tolerability and were not associated with serious adverse effects. Although additional research is required, these drugs are promising for lowering the risk of incident hyperkalemia associated with RAAS blockade use in people with diabetes or HF who have CKD. They also provide the opportunity to test whether patients who could not previously receive RAAS blockade may benefit from their cardio- and renoprotective effects.

  1. Rilonacept in the treatment of chronic inflammatory disorders.

    PubMed

    McDermott, Michael F

    2009-06-01

    Rilonacept (IL-1 Trap/Arcalyst) is a long-acting interleukin-1 (IL-1) blocker developed by Regeneron Pharmaceuticals. Initially, Regeneron entered into a joint development effort with Novartis to develop rilonacept for the treatment of rheumatoid arthritis (RA) but this was discontinued following the review of phase II clinical data showing that IL-1 blockade appeared to have limited benefit in RA. In February 2008, Regeneron received Orphan Drug approval from the Food and Drug Administration for rilonacept in the treatment of two cryopyrin-associated periodic syndromes (CAPS) disorders, namely, familial cold-induced autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS), for children and adults 12 years and older. CAPS is a group of inherited inflammatory disorders consisting of FCAS, MWS, neonatal-onset multisystem inflammatory disease (NOMID), also known as chronic infantile neurologic, cutaneous and articular (CINCA) syndrome, all associated with heterozygous mutations in the NLRP3 (CIAS1) gene, which encodes the protein NLRP3 or cryopyrin. Prior to the discovery of the NLRP3 (CIAS1) mutations and the advent of IL-1-targeted therapy, treatment was aimed at suppressing inflammation but with limited success. The dramatic success of selective blockade of IL-1beta, initially with the IL-1 receptor antagonist (IL-1Ra; Kineret(R) or anakinra/ Amgen, Inc.), not only provided supportive evidence for the role of IL-1beta in CAPS but also demonstrated the efficacy of targeting IL-1beta for treatment of these conditions. A high-affinity protein called rilonacept has been produced by cytokine Trap technology and was developed by Regeneron. The desirable longer half-life of rilonacept offers potential alternatives to patients who do not tolerate daily injections very well or have difficulty with drug compliance. The initial evidence for the beneficial effects of rilonacept for MWS and FCAS suggests that it would also be a suitable treatment for CNICA/NOMID. It is

  2. Effectiveness of Aloe Vera Gel in Chronic Ulcers in Comparison with Conventional Treatments

    PubMed Central

    Avijgan, Majid; Kamran, Asghar; Abedini, Amin

    2016-01-01

    Background: Aloe Vera is one of the endemic plants in southern Iran, which has been mentioned in the textbooks of Persian medicine since 2500 years ago. The aim of this study was to compare the effectiveness and cost of Aloe Vera gel with conventional treatments in patients with chronic ulcers. Methods: This comparative study was conducted on 60 patients with chronic ulcers (more than 3 weeks) in Al-Zahra hospital (Isfahan, Iran) in 2015. The participants were divided into two groups of 30 patients per group. In one group, we used conventional treatment plus Aloe Vera gel and in the other group, only the conventional treatment was used. In the Aloe Vera group, we used Aloe Vera gel twice a day. The patients were followed-up a week after the treatment and then monthly for 3 months. Results: The male: female ratio was 1:1 in each group. The mean age of the Aloe Vera and control groups were 62.3±11.2 and 63.1±9.6, respectively. After three months follow-up, wound healing occurred in 28 (93.3%) patients in the Aloe Vera group and 14 (46.7%) patients in the control group (P<0.05). The overall mean time of wound healing was 31.25±11.2 and 63.2±20.4 in the Aloe Vera and control groups, respectively (P<0.05). The mean hospitalization time was 35.2±6.4 and 67.4±8.9 in the Aloe Vera and control groups, respectively (P<0.05). The average cost of Aloe Vera gel and conventional treatment per patient was $2 and $10 daily, respectively (P<0.05). Conclusion: Aloe Vera gel is a beneficial treatment and cost effective for patients with chronic ulcers. The use of Aloe Vera gel in chronic ulcer is recommended in developing countries to lessen the financial burden. PMID:27840496

  3. The role of pharmacogenetics in the treatment of chronic hepatitis C infection.

    PubMed

    Kawaguchi-Suzuki, Marina; Frye, Reginald F

    2014-02-01

    Hepatitis C virus (HCV) chronically infects 170 million people worldwide. Until recently, combination therapy with peginterferon-α (pegIFN) and ribavirin (RBV) has been the standard of care. However, for many patients, especially those infected with the most common HCV genotype 1 (HCV-1), this treatment has resulted in unsatisfactory treatment response rates. Many clinical factors, including pharmacogenetics, influence the treatment response rate. Genetic variation in the interleukin 28B (IL28B) gene is the major determinant of treatment response, a finding that has been replicated in multiple independent cohorts. This review focuses on the association between pharmacogenetics and conventional pegIFN/RBV therapy in patients infected with HCV non-genotype 1; patients reinfected with HCV after liver transplantation; and patients coinfected with HCV and human immunodeficiency virus. We also review the pharmacogenetic data for boceprevir and telaprevir triple therapy in patients with HCV-1 infection, as well as viral genomic polymorphisms and genetic variants that may protect against anemia. Pharmacogenetic information offers a personalized medicine approach to help clinicians and patients make better informed decisions to maximize response and minimize toxicity for the treatment of chronic HCV infection. © 2013 Pharmacotherapy Publications, Inc.

  4. Platelet-rich plasma efficacy versus corticosteroid injection treatment for chronic severe plantar fasciitis.

    PubMed

    Monto, Raymond Rocco

    2014-04-01

    Chronic plantar fasciitis is a common orthopedic condition that can prove difficult to successfully treat. In this study, autologous platelet-rich plasma (PRP), a concentrated bioactive blood component rich in cytokines and growth factors, was compared to traditional cortisone injection in the treatment of chronic cases of plantar fasciitis resistant to traditional nonoperative management. Forty patients (23 females and 17 males) with unilateral chronic plantar fasciitis that did not respond to a minimum of 4 months of standardized traditional nonoperative treatment modalities were prospectively randomized and treated with either a single ultrasound guided injection of 3 cc PRP or 40 mg DepoMedrol cortisone. American Orthopedic Foot and Ankle Society (AOFAS) hindfoot scoring was completed for all patients immediately prior to PRP or cortisone injection (pretreatment = time 0) and at 3, 6, 12, and 24 months following injection treatment. Baseline pretreatment radiographs and MRI studies were obtained in all cases to confirm the diagnosis of plantar fasciitis. The cortisone group had a pretreatment average AOFAS score of 52, which initially improved to 81 at 3 months posttreatment but decreased to 74 at 6 months, then dropped to near baseline levels of 58 at 12 months, and continued to decline to a final score of 56 at 24 months. In contrast, the PRP group started with an average pretreatment AOFAS score of 37, which increased to 95 at 3 months, remained elevated at 94 at 6 and 12 months, and had a final score of 92 at 24 months. PRP was more effective and durable than cortisone injection for the treatment of chronic recalcitrant cases of plantar fasciitis. Level I, prospective randomized comparative series.

  5. Successful treatment of chronic severe neutropenia with weekly recombinant granulocyte-colony stimulating factor.

    PubMed

    Fine, K D; Byrd, T D; Stone, M J

    1997-04-01

    Daily treatment for symptomatic chronic neutropenia with recombinant granulocyte-colony stimulating factor (rhG-CSF) filgrastim is costly and sometimes causes neutrophillia. We report the use of weekly filgrastim in a 40-year-old man with life-long symptomatic neutropenia. Baseline neutrophil counts were < 1 x 10(9)/l 60% of the time, and fell below 0.5 x 10(9)/l for 7d periods every 22 d. Following 1 year of weekly filgrastim treatment, the absolute neutrophil count was maintained > 1 x 10(9)/l (averaging 2 x 10(9)/l) and the frequency and severity of symptoms were reduced by 85%. Therefore the benefits of filgrastim for the treatment of at least one form of chronic severe neutropenia can be derived from weekly rather than daily doses.

  6. A Randomized Controlled Trial of Intensive Sleep Retraining (ISR): A Brief Conditioning Treatment for Chronic Insomnia

    PubMed Central

    Harris, Jodie; Lack, Leon; Kemp, Kristyn; Wright, Helen; Bootzin, Richard

    2012-01-01

    Study Objective: To investigate the effectiveness of intensive sleep retraining in comparison and combination with traditional behavioral intervention for chronic primary insomnia. Participants: Seventy-nine volunteers with chronic sleep-onset insomnia (with or without sleep maintenance difficulties) were randomly assigned either to intensive sleep retraining (ISR), stimulus control therapy (SCT), ISR plus SCT, or the control (sleep hygiene) treatment condition. Intervention: ISR treatment consisted of 50 sleep onset trials over a 25-h sleep deprivation period. Measurements and Results: Treatment response was assessed with sleep diary, activity monitoring, and questionnaire measures. The active treatment groups (ISR, SCT, ISR+SCT) all resulted in significant improvements in sleep onset latency and sleep efficiency, with moderate to large effect sizes from pre- to post-treatment. Wake time after sleep onset decreased significantly in the SCT and ISR+SCT groups. Total sleep time increased significantly in the ISR and ISR+SCT treatment groups. Participants receiving ISR (ISR, ISR+SCT) experienced rapidly improved SOL and TST during treatment, suggesting an advantage of rapid improvements in sleep in response to ISR. Although there were few statistically significant differences between groups on individual variables, ISR+SCT resulted in consistently larger effect sizes of change than other treatments, including questionnaire measures of sleep quality, sleep self-efficacy, and daytime functioning. The combination treatment group (ISR+SCT) showed trends to outperform other active treatment groups with fewer treatment dropouts, and a greater proportion of treatment responders with 61% reaching “good sleeper” status. Treatment gains achieved at post-treatment in the active treatment groups were largely maintained throughout follow-up periods to 6 months. Conclusion: This 25-hour intensive conditioning treatment for chronic insomnia can produce rapid improvements in

  7. Antipsychotic Treatment of Adolescent Dual Diagnosis Patients

    PubMed Central

    Price, Scott A.; Brahm, Nancy C.

    2011-01-01

    BACKGROUND A diagnosis of schizophrenia requires development of a pharmacotherapy regimen that balances many factors in the therapeutic decision-making process. Patient age and the presence or absence of comorbid chemical dependency represent two factors. Comorbid chemical dependency can have a profound impact on the successful treatment of schizophrenia, making patients with dual diagnoses of schizophrenia and chemical dependence a uniquely challenging population. There is little information regarding treatment of schizophrenia and chemical dependence in the pediatric population. Existing data from pediatric and adult populations may facilitate a well-guided and knowledgeable approach to treating pediatric dual diagnosis patients. METHODS A review of the literature for medication trials evaluating antipsychotic medication used to treat schizophrenia in childhood and adolescence as well as antipsychotic use in the treatment of the dual diagnoses of schizophrenia and chemical dependence was done. Databases for Ovid MEDLINE, PubMed, and PsycInfo were searched using the terms “addiction,” “adolescence,” “childhood,” “dual diagnosis,” “schizophrenia,” and “substance abuse.” Results were limited to English-language articles. RESULTS Seven articles were identified related to psychotic disorders and substance abuse in pediatric populations. Psychosis measurement instruments included the Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale, and Clinical Global Impression. Mean improvements were insignificant in most cases. Medication trials included clozapine, olanzapine, risperidone, and molindone. Trial safety concerns included metabolic effects, increased prolactin levels, and akathisia. One study with random assignment to olanzapine was discontinued early because of substantial weight gain without evidence of superior efficacy. Clozapine treatment was associated with more adverse drug events. CONCLUSION There is a great need for

  8. [Results of treatment with peginterferon plus ribavirin in patients with chronic hepatitis C].

    PubMed

    Pizarro, Carolina; Venegas, Mauricio; Hola, Karen; Smok, Gladys; Brahm, Javier

    2011-06-01

    The current treatment recommendation for chronic hepatitis C virus infection is the combination of peginterferon and ribavirin for 24 or 48 weeks, depending on the viral genotype. The aim of the therapy is to obtain a sustained virological response. To report our experience in the treatment of chronic hepatitis C. Analysis of 52 patients treated between September 2000 and June 2009. Patients with genotype 1 or 5 were treated with peginterferon alpha 2a (180 ug/week) and ribavirin (1000 mg/day for those weighing less than 75 kg and 1200 mg/day for those weighing more than 75 kg) during 48 weeks. Patients with genotypes 2 and 3 were treated for 24 weeks with the same dose of peginterferon and ribavirin 800 mg/day. Viral genotypes 1, 2, 3 and 5 were present in 81, 4, 11 and 4% of patients, respectively. Twenty four patients (46 %), 18 with genotype 1, achieved a sustained viral response. Age was the only variable that influenced the response to treatment. Approximately half of the patients with chronic hepatitis C, achieve a sustained viral response with peginterferon and ribavirin.

  9. Ceftriaxone-induced immune hemolytic anemia as a life-threatening complication of antibiotic treatment of 'chronic Lyme disease'.

    PubMed

    De Wilde, Maarten; Speeckaert, Marijn; Callens, Rutger; Van Biesen, Wim

    2017-04-01

    'Chronic Lyme disease' is a controversial condition. As any hard evidence is lacking that unresolved systemic symptoms, following an appropriately diagnosed and treated Lyme disease, are related to a chronic infection with the tick-borne spirochaetes of the Borrelia genus, the term 'chronic Lyme disease' should be avoided and replaced by the term 'post-treatment Lyme disease syndrome.' The improper prescription of prolonged antibiotic treatments for these patients can have an impact on the community antimicrobial resistance and on the consumption of health care resources. Moreover, these treatments can be accompanied by severe complications. In this case report, we describe a life-threatening ceftriaxone-induced immune hemolytic anemia with an acute kidney injury (RIFLE-stadium F) due to a pigment-induced nephropathy in a 76-year-old woman, who was diagnosed with a so-called 'chronic Lyme disease.'

  10. Proposal of a model for multidisciplinary treatment program of chronic migraine with medication overuse: preliminary study.

    PubMed

    Grazzi, L; Prunesti, A; Bussone, G

    2015-05-01

    The treatment of patients with chronic migraine associated with medication overuse is challenging in clinical practice; different strategies of treatment have been recently developed, multidisciplinary treatment approaches have been developed in academic headache centers. Education and support of patients are necessary to improve patients' adherence to pharmacological treatments as well as to non-pharmacological therapies. This study reports a clinical experience conducted at our Headache center with a group of female patients, suffering from chronic migraine complicated by medication overuse, treated by a multidisciplinary approach and followed for a period of 1 year after withdrawal. Results confirm the efficacy of a multifaceted treatment to manage this problematic category of patients.

  11. [Ketotifen treatment of chronic urticaria. An open study of therapeutically difficult courses].

    PubMed

    Taube, K M; Wozniak, K D; Lässig, W

    1985-12-01

    21 patients suffering from chronic urticaria were treated with Ketotifen (2 X 1 mg/d) for 4 weeks. The suppression of weals and pruritus, the side effects in comparison with antihistamines, as well as the effect after finishing therapy have been studied. Ketotifen has a good suppressing effect on weals and pruritus. The general tolerance of the preparation is good, as well. Thus Ketotifen may be regarded as an additional possibility concerning treatment of chronic urticaria.

  12. Comparison of Operant Behavioral and Cognitive-Behavioral Group Treatment for Chronic Low Back Pain.

    ERIC Educational Resources Information Center

    Turner, Judith A.; Clancy, Steve

    1988-01-01

    Assigned chronic low back pain patients to operant behavioral (OB) treatment, cognitive-behavioral (CB) treatment, or waiting-list (WL) condition. Both treatments resulted in decreased physical and psychosocial disability. OB patients' greater improvement leveled off at followup; CB patients continued to improve over the 12 months following…

  13. Customizing treatment of chronic fatigue syndrome and fibromyalgia: the role of perpetuating factors.

    PubMed

    Van Houdenhove, Boudewijn; Luyten, Patrick

    2008-01-01

    Syndromes characterized by chronic, medically unexplained fatigue, effort- and stress-intolerance, and widespread pain are highly prevalent in medicine. In chronic fatigue syndrome (CFS) and fibromyalgia (FM), various perpetuating factors may impair patients' quality of life and functioning and impede recovery. Although cognitive-behavioral and graded-exercise therapy are evidence-based treatments, the effectiveness and acceptability of therapeutic interventions in CFS/FM may largely depend on a customized approach taking the heterogeneity of perpetuating factors into account. Further research should clarify the aim and outcome of different treatment strategies in CFS/FM, as well as the underlying mechanisms of change, including those facilitating neurobiological recovery.

  14. Effect of non-surgical periodontal treatment on transferrin serum levels in patients with chronic periodontitis

    PubMed Central

    Shirmohamadi, Adileh; Chitsazi, Mohamad Taghi; Faramarzi, Masoumeh; Salari, Ashkan; Naser Alavi, Fereshteh; Pashazadeh, Nazila

    2016-01-01

    Background. Transferrin is a negative acute phase protein, which decreases during inflammation and infection. The aim of the present investigation was to evaluate changes in the transferrin serum levels subsequent to non-surgical treatment of chronic periodontal disease. Methods. Twenty patients with chronic periodontitis and 20 systemically healthy subjects without periodontal disease, who had referred to Tabriz Faculty of Dentistry, were selected. Transferrin serum levels and clinical periodontal parameters (pocket depth, clinical attachment level, gingival index, bleeding index and plaque index) were measured at baseline and 3 months after non-surgical periodontal treatment. Data were analyzed with descriptive statistical methods (means ± standard deviations). Independent samples t-test was used to compare transferrin serum levels and clinical variables between the test and control groups. Paired samples t-test was used in the test group for comparisons before and after treatment. Statistical significance was set at P < 0.05. Results. The mean transferrin serum level in patients with chronic periodontitis (213.1 ± 9.2 mg/dL) was significantly less than that in periodontally healthy subjects (307.8 ± 11.7 mg/dL). Three months after periodontal treatment, the transferrin serum level increased significantly (298.3 ± 7.6 mg/dL) and approached the levels in periodontally healthy subjects (P < 0.05). Conclusion. The decrease and increase in transferrin serum levels with periodontal disease and periodontal treatment, respectively, indicated an inverse relationship between transferrin serum levels and chronic periodontitis. PMID:27651883

  15. Effects of phencyclidine (PCP) and MK 801 on the EEGq in the prefrontal cortex of conscious rats; antagonism by clozapine, and antagonists of AMPA-, alpha(1)- and 5-HT(2A)-receptors.

    PubMed

    Sebban, Claude; Tesolin-Decros, Brigitte; Ciprian-Ollivier, Jorge; Perret, Laurent; Spedding, Michael

    2002-01-01

    1. The electroencephalographic (EEG) effects of the propsychotic agent phencyclidine (PCP), were studied in conscious rats using power spectra (0 - 30 Hz), from the prefrontal cortex or sensorimotor cortex. PCP (0.1 - 3 mg kg(-1) s.c.) caused a marked dose-dependent increase in EEG power in the frontal cortex at 1 - 3 Hz with decreases in power at higher frequencies (9 - 30 Hz). At high doses (3 mg kg(-1) s.c.) the entire spectrum shifted to more positive values, indicating an increase in cortical synchronization. MK 801 (0.05 - 0.1 mg kg(-1) i.p.) caused similar effects but with lesser changes in power. 2. In contrast, the non-competitive AMPA antagonists GYKI 52466 and GYKI 53655 increased EEG power over the whole power spectrum (1 - 10 mg kg(-1) i.p.). The atypical antipsychotic clozapine (0.2 mg kg(-1) s.c.) synchronized the EEG (peak 8 Hz). The 5-HT(2A)-antagonist, M100907, specifically increased EEG power at 2 - 3 Hz at low doses (10 and 50 microg kg(-1) s.c.), whereas at higher doses (0.1 mg kg(-1) s.c.) the profile resembled that of clozapine. 3. Clozapine (0.2 mg kg(-1) s.c. ), GYKI 53655 (5 mg kg(-1) i.p.), prazosin (0.05 and 0.1 mg kg(-1) i.p.), and M100907 (0.01 and 0.05 mg kg(-1) s.c.) antagonized the decrease in power between 5 and 30 Hz caused by PCP (1 mg kg(-1) s.c.), but not the increase in power at 1 - 3 Hz in prefrontal cortex.

  16. Treatment of Chronic Hepatitis C Virus Infection With Crushed Ledipasvir/Sofosbuvir Administered via a Percutaneous Endoscopic Gastrostomy Tube.

    PubMed

    Jindracek, Lauren; Stark, Jennifer

    2017-01-01

    Ledipasvir/sofosbuvir (Harvoni®) is a fixed-dose tablet indicated for the treatment of chronic hepatitis C virus (HCV) infection. There are currently no data available on the safety and efficacy of crushed ledipasvir/sofosbuvir tablets. This report describes the first documented case of successful treatment of chronic HCV infection in a patient crushing ledipasvir/sofosbuvir for administration via a percutaneous endoscopic gastrostomy (PEG) tube. The patient was treatment experienced and had evidence of compensated cirrhosis. Treatment duration was 24 weeks, and HCV RNA was undetectable 12 weeks after completion of treatment (SVR12) which is the accepted measure of a clinical cure. Issues may arise during or prior to starting HCV treatment that necessitate crushing tablets. Stopping or interrupting HCV treatment could lead to development of resistance or treatment failure. This is the first published case in which crushed ledipasvir/sofosbuvir administered via a PEG tube is documented as a safe and effective option for treatment of chronic HCV infection.

  17. The economic costs of chronic pain among a cohort of treatment seeking adolescents in the United States

    PubMed Central

    Groenewald, Cornelius B.; Essner, Bonnie S.; Wright, Davene; Fesinmeyer, Megan D.; Palermo, Tonya M.

    2014-01-01

    The aim of this study was to assess the economic cost of chronic pain among adolescents receiving interdisciplinary pain treatment. Information was gathered from 149 adolescents (ages 10-17) presenting for evaluation and treatment at interdisciplinary pain clinics in the United States. Parents completed a validated measure of family economic attributes, the Client Service Receipt Inventory, to report on health service use and productivity losses due to their child's chronic pain retrospectively over 12 months. Health care costs were calculated by multiplying reported utilization estimates by unit visit costs from the 2010 Medical Expenditure Panel Survey. The estimated mean and median costs per participant were $11,787 and $6,770 respectively. Costs were concentrated in a small group of participants, the top 5 % of those patients incurring the highest costs accounted for 30 % of total costs while the lower 75 % of participants accounted for only 34 % of costs. Total costs to society for adolescents with moderate to severe chronic pain were extrapolated to $19.5 billion annually in the U.S. The cost of childhood chronic pain presents a substantial economic burden to families and society. Future research should focus on predictors of increased health services use and costs in adolescents with chronic pain. Perspective This cost of illness study comprehensively estimates the economic costs of chronic pain in a cohort of treatment-seeking adolescents. The primary driver of costs was direct medical costs followed by productivity losses. Because of its economic impact, policy makers should invest resources in the prevention, diagnosis, and treatment of chronic pediatric pain. PMID:24953887

  18. [Chronic insomnia: treatment methods based on the current "3P" model of insomnia].

    PubMed

    Poluektov, M G; Pchelina, P V

    2015-01-01

    Authors consider one of the popular models of the pathogenesis of chronic insomnia--"3P" model. It explains the origin and course of insomnia on the basis of interaction of three factors: predisposing, precipitating and perpetuating. The role of each group of factors and its connection to the cerebral hyperarousal state is discussed. Different variants of cognitive-behavioral therapy and pharmacological treatment of chronic insomnia are described.

  19. Saw palmetto and finasteride in the treatment of category-III prostatitis/chronic pelvic pain syndrome.

    PubMed

    Yang, Jennifer; Te, Alexis E

    2005-07-01

    Chronic nonbacterial prostatitis/chronic pelvic pain syndrome is a common entity for which a standardized management has not been established. Patients often have a significant symptom complex and impact on quality of life, but very little is known about the efficacy of second- and third-line treatments, such as the use of herbal supplements. Many treatments studied in recent literature include antibiotics, alpha-blockade, anti-inflammatory agents, and cognitive behavioral interventions such as biofeedback and psychotherapy.

  20. Changing environments and alternative perspectives in evaluating the cost-effectiveness of new antipsychotic drugs.

    PubMed

    Rosenheck, Robert; Doyle, Jefferson; Leslie, Douglas; Fontana, Alan

    2003-01-01

    This article examines the ways in which changes in the treatment environment and in measurement perspectives can affect the evaluation of cost-effectiveness of new medications. In three studies we reexamined data from a clinical trial of haloperidol and clozapine conducted from 1993 to 1996. The results of the studies are as follows: Study 1 found that clozapine treatment was associated with significantly reduced inpatient costs, and increased outpatient costs, suggesting that as systems use less inpatient care and more outpatient care, more effective medications may increase, rather than decrease, costs in sicker patients. Study 2 found that while provider assessments and standard measures favored clozapine over haloperidol, patient responses showed little evidence of a clinical advantage for clozapine and a less favorable side-effect profile. Study 3 found that while annual drug costs in the published trial were estimated to be dollars 4,545 for a full year of clozapine treatment, atypical antipsychotic costs in 2000 were estimated to range from dollars 1,254 to dollars 3,016 in the Department of Veterans Affairs system, and from dollars 2,221 to dollars 8,147 in the private sector. In conclusion, cost-effectiveness, as evaluated in studies like CATIE, will increasingly need to be tied to service system contingencies, environments, and evaluation perspectives.