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Sample records for chronic clozapine treatment

  1. Subjective experiences of clozapine treatment by patients with chronic schizophrenia.

    PubMed

    Waserman, J; Criollo, M

    2000-05-01

    A 37-item survey covering a variety of somatopsychic domains was constructed to explore patients' subjective response to treatment with clozapine. The survey was administered to 130 patients with diagnoses of chronic schizophrenic or schizoaffective disorders who were on a stable clozapine regimen. The majority reported improvement in their level of satisfaction, quality of life, compliance with treatment, thinking, mood, and alertness. Most patients reported worsening in nocturnal salivation, and smaller numbers reported worsening in various gastrointestinal and urinary symptoms and weight gain. This general health survey highlights the patients' positive regard for clozapine, despite adverse bodily experiences. Subjective reports are a useful component of outcome measures of drug treatment.

  2. Leukocytosis after Clozapine Treatment in a Patient with Chronic Schizophrenia

    PubMed Central

    POLAT, Aslıhan; ÇAKIR, Uğur; GÜNDÜZ, Nermin

    2016-01-01

    Clozapine is an atypical antipsychotic drug that is approved by the US Food and Drug Administration (FDA) for the treatment of psychotic disorders. Agranulocytosis is a well-established side effect of clozapine; clozapine has also been associated with other blood dyscrasias like leukocytosis, albeit rarely. In this paper, we aim to report a case of possible clozapine-associated leukocytosis in a 41-year-old woman.

  3. Chronic treatment with clozapine, unlike haloperidol, does not induce changes in striatal D-2 receptor function in the rat.

    PubMed

    Rupniak, N M; Hall, M D; Mann, S; Fleminger, S; Kilpatrick, G; Jenner, P; Marsden, C D

    1985-08-01

    Comparison has been made of the effects on brain dopamine function of chronic administration of haloperidol or clozapine to rats for up to 12 months. In rats treated for 1-12 months with haloperidol (1.4-1.6 mg/kg/day), purposeless chewing jaw movements emerged. These movements were only observed after 12 months' treatment with clozapine (24-27 mg/kg/day). Apomorphine-induced (0.125-0.25 mg/kg) stereotyped behaviour was inhibited during 12 months treatment with haloperidol. Clozapine treatment was without effect. After 12 months, stereotypy induced by higher doses of apomorphine (0.5-1.0 mg/kg) was enhanced in haloperidol, but not clozapine, treated rats. Bmax for striatal 3H-spiperone binding was elevated throughout 12 months of haloperidol administration, but was not altered by clozapine treatment. Bmax for striatal 3H-NPA binding was only elevated after 12 months of haloperidol treatment; clozapine treatment was without effect. Bmax for 3H-piflutixol binding was not altered by haloperidol treatment, but was increased after 9 and 12 months of clozapine treatment. Dopamine (50 microM)-stimulated adenylate cyclase activity was inhibited after 1 month's haloperidol treatment but normal thereafter. Adenylate cyclase activity was not altered by chronic clozapine treatment. Striatal acetylcholine content was increased after 3 and 12 months of haloperidol or clozapine intake. These findings indicate that the chronic administration of the atypical neuroleptic clozapine does not produce changes in brain dopamine function which mirror those of the typical neuroleptic haloperidol. In particular, chronic administration of clozapine, unlike haloperidol, does not appear to induce striatal D-2 receptor supersensitivity. Unexpectedly, clozapine treatment, unlike haloperidol, altered D-1 receptor function.

  4. [Obsessive-Compulsive Symptoms in a Sample of Patients with Chronic Schizophrenia Under Clozapine Treatment].

    PubMed

    Schreiter, S; Hasan, A; Majic, T; Wullschleger, A; Schouler-Ocak, M; Bermpohl, F; Gutwinski, S

    2016-11-01

    Background: There is a high prevalence of obsessive-compulsive symptoms (OCS) in patients with schizophrenia. Antipsychotic treatment, especially duration and type of substance, is suspected to increase or even cause OCS. Methods: We examined in a naturalistic cross-sectional study the severity of OCS (Obsessive-Compulsive Inventory - Revised) and the incidence of obsessive-compulsive disorder (OCD) according to ICD-10 criteria in 70 patients with schizophrenia. 26 patients were treated with clozapine and 44 patients were treated with another second-generation antipsychotic (SGA). After group matching, the two groups did not differ significantly in age, gender, duration of illness, treatment duration with the current antipsychotic substance and chlorpromazine-equivalent dosage. Results: Patients treated with Clozapine showed a significantly higher rate of OCD (χ(2) = 7.304, p = 0.007) and a significantly higher severity of OCS (t = 2.216, p = 0.037) compared to patients treated with another SGA. For the whole sample, duration of treatment with the current antipsychotic medication correlated significantly (p = 0.033, r = 0.323) with the severity of OCS, controlled for duration of illness. However, there was no significant correlation between severity of OCS and duration of illness, controlled for duration of treatment with the current antipsychotic substance. Discussion: Our data suggest an interrelation between the development of OCS or OCD and antipsychotic treatment, especially clozapine. Thereby, duration of treatment is correlated with the severity of OCS, irrespective of the duration of illness.

  5. Clozapine enhances disruption of prepulse inhibition after sub-chronic dizocilpine- or phencyclidine-treatment in Wistar rats.

    PubMed

    Schwabe, Kerstin; Brosda, Jan; Wegener, Nico; Koch, Michael

    2005-02-01

    Sensitisation (i.e. progressive enhancement) of behavioural abnormalities induced by repeated treatment with non-competitive NMDA receptor antagonists in animals is considered an animal model for schizophrenia. Here, male Wistar rats were treated for 11 days with either dizocilpine (0.1 mg/kg), phencyclidine (PCP, 2 mg/kg), or saline and tested for prepulse inhibition (PPI) of the acoustic startle response (ASR). The aims of this study were twofold: First, we tested whether sensitisation of PPI deficits previously found in Sprague-Dawley rats were also found in Wistar rats, and, second, whether these effects can be ameliorated by the atypical antipsychotic clozapine. PPI is a paradigm for the assessment of sensorimotor gating (and its deficits) and is impaired in schizophrenic patients. After the sub-chronic treatment the rats were tested drug-free (day 12), and on the following days after drug challenge by PCP (2 mg/kg), combinations of PCP (2 mg/kg) and clozapine (5 and 10 mg/kg), or clozapine (5 mg/kg) alone. PPI was significantly reduced by both NMDA receptor antagonists. This effect was not further enhanced by the daily treatment. Startle magnitude was increased after eight days of dizocilpine-treatment only, indicating sensitisation of startle-potentiation by this drug. Testing the rats drug-free on day 12 revealed enhanced PPI and reduced startle (compared to the matching test on day 0) irrespective of previous treatment. Drug challenge with PCP (2 mg/kg) again reduced PPI in all groups. Clozapine (5 and 10 mg/kg) failed to antagonise the PPI-disruptive effects of PCP and even enhanced the PCP-induced PPI-deficits in rats pretreated with PCP or dizocilpine. These findings suggest: (1) that PPI and startle are influenced differently by non-competitive NMDA receptor antagonists, (2) that PCP and dizocilpine reduce PPI in Wistar rats, but do not lead to a sensitisation of this effect; and (3) that under the present schedule of treatments, the antipsychotic

  6. Cyproheptadine resembles clozapine in vivo following both acute and chronic administration in rats.

    PubMed

    Goudie, Andrew J; Cooper, Gillian D; Cole, Jon C; Sumnall, Harry R

    2007-03-01

    Cyproheptadine is a cheap, widely available anti-allergy drug with a broad receptor binding profile which resembles that of clozapine. In rats discriminating clozapine from vehicle cyproheptadine mimicked clozapine very closely. Acutely it induced full generalization in the absence of response suppression, as observed with clozapine. Chronic administration of clozapine and cyproheptadine induced tolerance and cross-tolerance respectively to the clozapine stimulus. This was characterized by circa 3.5-fold parallel shifts to the right in the clozapine generalization curves. Such tolerance and cross-tolerance was spontaneously reversible, suggesting that it was pharmacodynamic, and that clozapine and cyproheptadine induce similar neuroadaptations when administered chronically. Administration of chlordiazepoxide at a very high dose induced no cross-tolerance to the clozapine stimulus showing the pharmacological specificity of tolerance. The clozapine stimulus is a compound cue involving actions at various receptors, and various clozapine-like antipsychotic (APD) drugs generalize fully to it. These data demonstrate that in vivo cyproheptadine resembles clozapine both acutely and chronically. Our findings, in conjunction with other actions of cyproheptadine -- induction of weight gain, alleviation of clozapine withdrawal, anxiolytic actions, alleviation of 'typical' APD-induced motoric side effects, and some preliminary clinical findings -- suggest that further study of cyproheptadine in conjunction with a 'typical' APD for the possible treatment of schizophrenia is merited at both pre-clinical and clinical levels.

  7. Chronic clozapine treatment in female rats does not induce weight gain or metabolic abnormalities but enhances adiposity: implications for animal models of antipsychotic-induced weight gain.

    PubMed

    Cooper, G D; Harrold, J A; Halford, J C G; Goudie, A J

    2008-02-15

    The ability of clozapine to induce weight gain in female rats was investigated in three studies with progressively lowered doses of clozapine. In an initial preliminary high dose study, clozapine at 6 and 12 mg/kg (i.p., b.i.d.) was found to induce weight loss. In a subsequent intermediate dose study, we obtained no evidence for clozapine-induced weight gain despite using identical procedures and doses of clozapine (1-4 mg/kg, i.p., b.i.d.) with which we have observed olanzapine-induced weight gain, hyperphagia, enhanced adiposity and metabolic changes [Cooper G, Pickavance L, Wilding J, Halford J, Goudie A (2005). A parametric analysis of olanzapine-induced weight gain in female rats. Psychopharmacology; 181: 80-89.]. Instead, clozapine induced weight loss without alteration in food intake and muscle mass or changes in levels of glucose, insulin, leptin and prolactin. However, these intermediate doses of clozapine enhanced visceral adiposity and elevated levels of adiponectin. In a final study, low doses of clozapine (0.25-0.5 mg/kg, i.p, b.i.d.) induced weight loss. These data demonstrate that clozapine-induced weight gain can be much more difficult to observe in female rats than olanzapine-induced weight gain. Moreover, these findings contrast with clinical findings with clozapine, which induces substantial weight gain in humans. Clozapine-induced enhanced adiposity appears to be easier to observe in rats than weight gain. These findings, along with other preclinical studies, suggest that enhanced adiposity can be observed in the absence of antipsychotic-induced weight gain and hyperphagia, possibly reflecting a direct drug effect on adipocyte function independent of drug-induced hyperphagia [e.g. Minet-Ringuet J, Even P, Valet P, Carpene C, Visentin V, Prevot D, Daviaud D, Quignard-Boulange A, Tome D, de Beaurepaire R (2007). Alterations of lipid metabolism and gene expression in rat adipocytes during chronic olanzapine treatment. Molecular Psychiatry; 12: 562

  8. Acute and chronic effects of clozapine on cholinergic transmission in cultured mouse superior cervical ganglion neurons.

    PubMed

    Saur, Taixiang; Cohen, Bruce M; Ma, Qi; Babb, Suzann M; Buttner, Edgar A; Yao, Wei-Dong

    Cholinergic dysfunction contributes to cognitive deficits in schizophrenia. The atypical antipsychotic clozapine improves cognition in patients with schizophrenia, possibly through modulation of the cholinergic system. However, little is known about specific underlying mechanisms. We investigated the acute and chronic effects of clozapine on cholinergic synaptic transmission in cultured superior cervical ganglion (SCG) neurons. Spontaneous excitatory postsynaptic currents (sEPSCs) were detected and were reversibly inhibited by the nicotinic receptor antagonist d-tubocurarine, confirming that the synaptic responses were primarily mediated by nicotinic receptors. Bath application of clozapine at therapeutic concentrations rapidly and reversely inhibited both the amplitude and frequency of sEPSCs in a concentration-dependent manner, without changing either rise or decay time, suggesting that clozapine effects have both presynaptic and postsynaptic origins. The acute effects of clozapine on sEPSCs were recapitulated by chronic treatment of SCG cultures with similar concentrations of clozapine, as clozapine treatment for 4 d reduced the frequency and amplitude of sEPSCs without affecting their kinetics. Cell survival analysis indicated that SCG neuron cell counts after chronic clozapine treatment were comparable to the control group. These results demonstrate that therapeutic concentrations of clozapine suppress nicotinic synaptic transmission in SCG cholinergic synapses, a simple in vitro preparation of cholinergic transmission.

  9. Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia.

    PubMed

    Kinoshita, Makoto; Numata, Shusuke; Tajima, Atsushi; Yamamori, Hidenaga; Yasuda, Yuka; Fujimoto, Michiko; Watanabe, Shinya; Umehara, Hidehiro; Shimodera, Shinji; Nakazawa, Takanobu; Kikuchi, Masataka; Nakaya, Akihiro; Hashimoto, Hitoshi; Imoto, Issei; Hashimoto, Ryota; Ohmori, Tetsuro

    2017-03-14

    Clozapine is an atypical antipsychotic, that is established as the treatment of choice for treatment-resistant schizophrenia (SCZ). To date, no study investigating comprehensive DNA methylation changes in SCZ patients treated with chronic clozapine has been reported. The purpose of the present study is to reveal the effects of clozapine on DNA methylation in treatment-resistant SCZ. We conducted a genome-wide DNA methylation profiling in peripheral leukocytes (485,764 CpG dinucleotides) from treatment-resistant SCZ patients treated with clozapine (n = 21) in a longitudinal study. Significant changes in DNA methylation were observed at 29,134 sites after one year of treatment with clozapine, and these genes were enriched for "cell substrate adhesion" and "cell matrix adhesion" gene ontology (GO) terms. Furthermore, DNA methylation changes in the CREBBP (CREB binding protein) gene were significantly correlated with the clinical improvements. Our findings provide insights into the action of clozapine in treatment-resistant SCZ.

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

    PubMed

    Moreno, José L; Holloway, Terrell; Umali, Adrienne; Rayannavar, Vinayak; Sealfon, Stuart C; González-Maeso, Javier

    2013-01-01

    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. This study evaluates the effects of chronic treatment with clozapine on the cellular and behavioral responses induced by the hallucinogenic serotonin 5-HT(2A) receptor agonist lysergic acid diethylamide (LSD) as a mouse model of psychosis. 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. [(3)H]Ketanserin binding and 5-HT ( 2A ) mRNA expression were determined in mouse somatosensory cortex. Head-twitch behavior, expression of c-fos, which is induced by all 5-HT(2A) agonists, and expression of egr-1 and egr-2, which are LSD-like specific, were assayed. Head-twitch response was decreased and [(3)H]ketanserin binding was downregulated in 1, 7, and 14 days after chronic clozapine. 5-HT ( 2A ) 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). Our findings provide a murine model of chronic atypical antipsychotic drug action and suggest downregulation of the 5-HT(2A) receptor as a potential mechanism involved in these persistent therapeutic-like effects.

  11. 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

  12. Adjunctive aripiprazole decreased metabolic side effects of clozapine treatment.

    PubMed

    Masopust, Jirí; Tůma, Ivan; Libiger, Jan

    2008-08-01

    Clozapine is an atypical antipsychotic indicated for the treatment of refractory schizophrenia. Clozapine treatment is associated with the metabolic side effects. Weight gain, hyperlipidemia and hyperglycemia are the risk factors for onset of diabetes and cardiovascular disorders. We report a case vignette of a patient in whom the decrease in negative and general psychopathology after adjunctive aripiprazole appeared simultaneously with a reduction of clozapine-induced increase in weight and metabolic measures. Combined application of clozapine and aripiprazole is in accordance with a neurobiological rationale and appears to be a safe and well tolerated.

  13. Treatment of Hypochondriasis in Two Schizophrenia Patients Using Clozapine.

    PubMed

    Tundo, Antonio; Proietti, Luca; de Filippis, Rocco

    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.

  14. 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

  15. Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia

    PubMed Central

    Kinoshita, Makoto; Numata, Shusuke; Tajima, Atsushi; Yamamori, Hidenaga; Yasuda, Yuka; Fujimoto, Michiko; Watanabe, Shinya; Umehara, Hidehiro; Shimodera, Shinji; Nakazawa, Takanobu; Kikuchi, Masataka; Nakaya, Akihiro; Hashimoto, Hitoshi; Imoto, Issei; Hashimoto, Ryota; Ohmori, Tetsuro

    2017-01-01

    Clozapine is an atypical antipsychotic, that is established as the treatment of choice for treatment-resistant schizophrenia (SCZ). To date, no study investigating comprehensive DNA methylation changes in SCZ patients treated with chronic clozapine has been reported. The purpose of the present study is to reveal the effects of clozapine on DNA methylation in treatment-resistant SCZ. We conducted a genome-wide DNA methylation profiling in peripheral leukocytes (485,764 CpG dinucleotides) from treatment-resistant SCZ patients treated with clozapine (n = 21) in a longitudinal study. Significant changes in DNA methylation were observed at 29,134 sites after one year of treatment with clozapine, and these genes were enriched for “cell substrate adhesion” and “cell matrix adhesion” gene ontology (GO) terms. Furthermore, DNA methylation changes in the CREBBP (CREB binding protein) gene were significantly correlated with the clinical improvements. Our findings provide insights into the action of clozapine in treatment-resistant SCZ. PMID:28335437

  16. 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.

  17. 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.

  18. Effects of acute and chronic clozapine on dopamine release and metabolism in the striatum and nucleus accumbens of conscious rats.

    PubMed

    Invernizzi, R; Morali, F; Pozzi, L; Samanin, R

    1990-08-01

    1. The effect of single and repeated (once daily for 23 days) oral doses of 20 and 60 mg kg-1 clozapine on dopamine release and metabolism were studied by intracerebral dialysis in the striatum and nucleus accumbens of conscious rats. 2. The basal output of dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum and nucleus accumbens of rats given clozapine 20 or 60 mg kg-1 chronically, measured one day after the last drug dose, was not significantly different from that of vehicle-treated animals. 3. Challenge doses of 20 or 60 mg kg-1 clozapine produced similar increases in dopamine levels in the striatum and nucleus accumbens of animals which had received vehicle or clozapine 20 or 60 mg kg-1 once daily for 23 days, except that 1 h after administration 60 mg kg-1 clozapine had a greater effect in the nucleus accumbens. 4. In animals treated chronically with clozapine 20 and 60 mg kg-1 or vehicle, DOPAC levels in the striatum and nucleus accumbens were increased to the same extent by challenge doses of clozapine (20 or 60 mg kg-1). In animals treated chronically with clozapine, a challenge dose of 60 mg kg-1 had significantly greater effect on HVA only in the nucleus accumbens. 5. When DOPAC and HVA were measured post mortem in the striatum and nucleus accumbens 2 h after various oral doses of clozapine, it was found that 10 mg kg-1 significantly increased dopamine metabolites only in the nucleus accumbens whereas 100 mg kg-1 had this effect in both regions. Clozapine, 30mgkg-' significantly raised DOPAC levels in both regions but HVA was elevated only in the nucleus accumbens. 6. There appeared to be no appreciable changes in dopamine release and metabolism nor any reduction in the effect of clozapine in the nucleus accumbens after chronic drug treatment. In fact the effect was greater in chronically treated rats, particularly in the nucleus accumbens of animals given 60mgkg' clozapine. 7. It was confirmed that measurement of

  19. 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.

  20. Pharmacoeconomic evaluation of clozapine in treatment-resistant schizophrenia: a cost-utility analysis.

    PubMed

    Oh, P I; Iskedjian, M; Addis, A; Lanctôt, K; Einarson, T R

    2001-01-01

    The high costs and efficacy of clozapine warrant a systematic pharmacoeconomic evaluation to assess its relative cost-utility compared with that of older antipsychotic therapies. An economic analysis of clozapine consisted of a meta-analysis and a cost-utility analysis. Clozapine was compared with haloperidol and chlorpromazine. An incidence-based deterministic decision analysis was used to model the management of chronic schizophrenia over one year. Probabilities of clinical outcomes were obtained from a random effects, single arm meta-analysis. Utility weights were evaluated in a cohort of patients by using a standard gamble methodology. A government payer perspective was adopted for this analysis. Clozapine was the dominant therapy in this analysis because it was associated with the lowest overall expected cost and highest expected number of quality-adjusted life years (QALYs). Compared with chlorpromazine, clozapine might save $38,879/year while producing 0.04 more QALYs. This analysis was limited in that studies were of short duration, the sample size for health utility analysis was small and the analysis was based on a model. Clozapine appears to be a very cost effective therapy in patients with treatment-resistant schizophrenia compared with haloperidol and chlorpromazine.

  1. Metabolic differences between Asian and Caucasian patients on clozapine treatment.

    PubMed

    Subramaniam, Mythily; Ng, Chee; Chong, Siow-Ann; Mahendran, Rathi; Lambert, Tim; Pek, Elaine; Huak, Chan Yiong

    2007-06-01

    To establish if there are ethnic differences in the various metabolic disturbances that are common with clozapine treatment. Forty subjects (20 Asians and 20 Caucasians) with a diagnosis of schizophrenia were recruited for the study. Clozapine blood levels as well as fasting blood glucose, lipid levels, and liver function tests were established. Other clinical parameters such as blood pressure and Body Mass Index (BMI) were recorded for each patient. The mean clozapine dose was significantly higher in the Caucasian subjects (432.5+/-194.7 mg) as compared to the Asian subjects (175.6+/-106.9 mg) (p<0.001) while the mean weight-corrected dose for Asian patients was lower (3.0+/-1.9 and 5.0+/-2.1 mg/kg, respectively, p=0.005). There were, however, no ethnic differences in the mean plasma clozapine concentration (415.3+/-185.8 ng/ml in Caucasians and 417.1+/-290.8 ng/ml in Asians). BMI were significantly higher in Caucasians, as were the number of subjects with hypertension; levels of hepatic enzymes were higher in the Asian group. Not only are there pharmacokinetic differences between Asian and Caucasian patients receiving clozapine, but there may also be differential emergence of certain metabolic abnormalities like hypertension and weight gain in these two ethnic groups. However, the effects of life style including diet and exercise cannot be excluded. Copyright (c) 2007 John Wiley & Sons, Ltd.

  2. Should obesity be a limiting factor for clozapine treatment?

    PubMed

    Pons i Villanueva, Alexandre; Romero, Anna; Goti, Javier; Fernandez-Egea, Emilio; Undurraga, Juan; Carne, Xavier; Bernardo, Miquel

    2013-01-01

    Clozapine is the first choice in drug-resistant schizophrenia but also causes important weight changes. This might discourage clinicians concerned about the risk of developing health problems. To assess this issue we measured change in body mass index (cBMI) induced by clozapine at 18 and 56 weeks. Baseline body weight and height were measured and weight weekly thereafter during the first 18 weeks of treatment. After that, measurements were made monthly. Steady clozapine dose, clozapine and norclozapine blood concentrations, concomitant medication, gender and age were recorded. At 18 weeks (n=76) mean cBMI was 1.83 kg/m(2). Baseline BMI was inversely correlated with cBMI. At 56 weeks (n=57) cBMI was 2.67 kg/m(2) and was inversely correlated with basal BMI. Multiple regression analysis replicated the results. When split with BMI categories, obese patients had lesser risk for further weight gain. Obesity should not discourage clinicians from starting clozapine in drug-resistant patients. Copyright © 2012 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

  3. Successful treatment of polydipsia, water intoxication, and delusional jealousy in an alcohol dependent patient with clozapine.

    PubMed

    Margetić, Branimir; Aukst-Margetić, Branka; Zarković-Palijan, Tija

    2006-09-30

    The beneficial effect of clozapine on polydipsia and water intoxication in patients with schizophrenia has been demonstrated many times. The authors report a successful clozapine treatment of polydipsia, intermittent water intoxication, and delusional jealousy of an alcoholic. This is a rare case of clozapine treatment of a non-schizophrenic patient affected by polydipsia.

  4. 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…

  5. 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…

  6. Time to Initiation of Clozapine Treatment in Children and Adolescents with Early-Onset Schizophrenia.

    PubMed

    Trinczek, E; Heinzel-Gutenbrunner, M; Haberhausen, M; Bachmann, C J

    2016-11-01

    Introduction: Early-onset schizophrenia (EOS) has a poor prognosis and is difficult to treat, which often leads to the initiation of clozapine treatment. Studies in adults have shown that the initiation of clozapine treatment is often delayed. There is a lack of studies concerning the initiation of clozapine in children and adolescents with EOS. The aim of this study was to investigate the time span from first EOS-related psychiatric hospitalization to clozapine initiation. Methods: We retrospectively studied a consecutive cohort of children and adolescents with EOS and first-time clozapine prescriptions from a tertiary care child and adolescent psychiatric center in Germany. Results: Clinical records with data on clozapine initiation were available for 112 patients (35.7% females, mean age: 15.2±1.6 years). The mean time from first EOS-related hospitalization to clozapine initiation was 1.1 (±1.0) years, with an average of 2.3 (±1.1) prior antipsychotic treatment episodes. Higher age and higher IQ predicted earlier clozapine initiation. At the time of clozapine initiation, 40.2% of patients received antipsychotic polypharmacy. Prior to clozapine, 33.9% of patients had received 3 or more antipsychotic treatment episodes. Discussion: In our study, clozapine treatment was initiated markedly earlier than in the few existing studies, which may partly be due to the expected poor prognosis of EOS. The significant portion of patients undergoing 3 or more antipsychotic trials or antipsychotic polypharmacy prior to clozapine may indicate a need for improved dissemination of knowledge on the effectiveness of clozapine in treatment-resistant schizophrenia in order to promote timely clozapine prescriptions in these cases. © Georg Thieme Verlag KG Stuttgart · New York.

  7. 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…

  8. 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…

  9. 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.

  10. Acute and long-term effectiveness of clozapine in treatment-resistant psychotic depression.

    PubMed

    Ranjan, R; Meltzer, H Y

    1996-08-15

    The treatment of refractory major depression, including the psychotic subtype, is a therapeutic challenge. Three cases of resistant psychotic depression were treated with clozapine monotherapy, an atypical antipsychotic drug effective in treatment-resistant schizophrenia and mania. Both psychotic and mood symptoms responded well to clozapine monotherapy, although response was delayed in one case. Tardive dyskinesia improved markedly, and tardive dystonia improved moderately in one patient. No patient relapsed during a follow-up period of 4-6 years of clozapine treatment. Clozapine was well-tolerated with few side effects. These observations suggest controlled trials of clozapine in the treatment of psychotic depression that fails to respond to electroconvulsive therapy or typical neuroleptics plus tricyclic antidepressants are indicated. The same is true for the use of clozapine in maintenance treatment for psychotic depression in those cases in which typical neuroleptic drugs are required, in order to reduce the risk of tardive dyskinesia and dystonia.

  11. Chronic Underactivity of Medial Frontal Cortical β2-Containing Nicotinic Receptors Increases Clozapine-Induced Working Memory Impairment in Female Rats

    PubMed Central

    Levin, Edward D.; Perkins, Abigail; Brotherton, Terrell; Qazi, Melissa; Berez, Chantal; Montalvo-Ortiz, Janitza; Davis, Kasey; Williams, Paul; Christopher, N. Channelle

    2009-01-01

    Nicotinic receptor decreases in the frontal cortex and hippocampus are important mediators of cognitive impairment in both schizophrenia and Alzheimer's disease. Drug treatments for these diseases should take into account the impacts of compromised brain function on drug response. This study investigated the impact of compromised nicotinic receptor activity in the frontal cortex in rats on memory function. Since both Alzheimer's disease and schizophrenia can involve psychosis, antipsychotic drugs are often given. The impacts of antipsychotic drugs on cognitive function have been found to be quite variable. It is the hypothesis of this and previous studies that the cognitive effects of antispychotic drugs on cognitive function depend on the integrity of brain systems involved in cognition. Previously in studies of the hippocampus, we found that chronic inhibition of β2-containing nicotinic receptors with dihydro-β-erythrodine (DHβE) impaired working memory and that this effect was attenuated by the antipsychotic drug clozapine. In contrast, chronic hippocampal α7 nicotinic receptor blockade with methyllycaconitine (MLA) potentiated the clozapine-induced memory impairment which is seen in rats without compromised nicotinic receptor activity. The current study determined medial frontal cortical α7 and β2-containing nicotinic receptor involvement in memory and the interactions with antipsychotic drug therapy with clozapine. Chronic DHβE and MLA infusion effects and interactions with systemic clozapine were assessed in female rats tested for memory on the radial-arm maze. Antipsychotic drug interactions with chronic systemic nicotine were investigated because nicotinic procognitive treatment has been proposed. The same local infusion DHβE dose that impaired memory with hippocampal infusion did not impair memory when infused in the medial frontal cortex. Frontal DHβE infusion potentiated clozapine-induced memory impairment, whereas previously the memory

  12. A successful treatment strategy for clozapine-induced parotid swelling: a clinical case and systematic review.

    PubMed

    Immadisetty, Vyasa; Agrawal, Pradeep

    2012-12-01

    Parotid gland swelling is a less frequently reported side effect of clozapine and has no licensed treatment. A 58-year-old man treated with clozapine for treatment-resistant schizophrenia developed bilateral painful parotid swellings and hypersalivation. Initial trials of dose alteration and antihypersalivatory medication had limited success. A combination of benzatropine and terazosin was successful in treating the parotid hyperplasia. Clozapine was the probable cause of parotid swelling in our case, as established using the Naranjo adverse drug reaction probability scale and World Health Organization causality categories. Literature for treatments of clozapine-induced parotid gland swellings was reviewed. None of the published articles suggested a treatment regimen for clozapine-induced parotid hyperplasia. Most reports only highlighted the occurrence of salivary gland swelling with clozapine. Others mentioned management strategies, which included spontaneous resolution, or resolution on discontinuing clozapine. One report, a trial with benzatropine and ipratropium, had variable success. In this case the re-emergence of parotid swelling when terazosin and benzatropine doses were missed followed by a quick resolution upon recompliance, goes some way in proving that this combination is indeed effective. The combination of terazosin and benzatropine appears to have a role in treating parotid gland swellings induced by clozapine.

  13. The influence of clozapine treatment and other antipsychotics on the 18 kDa translocator protein, formerly named the peripheral-type benzodiazepine receptor, and steroid production.

    PubMed

    Danovich, Lena; Veenman, Leo; Leschiner, Svetlana; Lahav, Michal; Shuster, Vered; Weizman, Abraham; Gavish, Moshe

    2008-01-01

    It has been shown that the atypical antipsychotic drug clozapine increases the levels of the neurosteroid allopregnanolone in the rat brain. The 18 kDa translocator protein (TSPO), formerly known as the peripheral-type benzodiazepine receptor, has been demonstrated to be involved in the process of steroid biosynthesis, in peripheral steroidogenic tissues as well as in glia cells in the brain. In the current study, we investigated the influence of chronic treatment with clozapine and other antipsychotics (thioridazine,sulpiride and risperidone) on TSPO binding in cell cultures and rat tissues. Clozapine significantly increased TSPO binding density in C6 rat glioma cells and in MA-10 mouse Leydig tumor cells, while the antipsychotic sulpiride had no effect on TSPO binding density in both cell lines. In addition, clozapine, but not sulpiride, significantly increased progesterone synthesis by MA-10 Leydig tumor cells. In an animal experiment, male Sprague-Dawley rats were treated with clozapine (20 mg/kg), risperidone (0.5 mg/kg), thioridazine (20 mg/kg), or sulpiride (20 mg/kg) for 21 days, followed by 7 days of withdrawal. Clozapine induced significant increases in TSPO binding in brain and peripheral steroidogenic tissues, whereas the other antipsychotics did not show such pronounced effects on TSPO binding. Our results suggest that TSPO may be involved in the modulation of steroidogenesis by clozapine.

  14. 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

  15. Ivabradine, a novel treatment for clozapine-induced sinus tachycardia: a case series

    PubMed Central

    Brook, Jennifer; Dixon, Thomas; Gaughran, Fiona; Shergill, Sukhi; Melikian, Narbeh; MacCabe, James H.

    2014-01-01

    Objectives: Clozapine is the most efficacious treatment for treatment-resistant schizophrenia; however its use can be limited by intolerability. Sinus tachycardia is a common adverse event associated with clozapine use, which may lead to the premature discontinuation of clozapine. Traditionally, β blockers are used to treat clozapine-associated tachycardia, though problems with intolerability and ineffectiveness can limit their utility. Methods: In this article, we present two cases of patients with treatment-resistant schizophrenia who developed symptomatic tachycardia associated with clozapine therapy. Results: We demonstrate that the novel heart rate controlling agent ivabradine can be effectively and safely used to control the heart rate and to allow for continued treatment with clozapine. Conclusion: This is the first report in the literature demonstrating that ivabradine appears to be a well tolerated agent, which should be considered as a symptomatic treatment of clozapine-induced tachycardia if the use of a β blocker fails due to a lack of response or intolerability. PMID:25057344

  16. Clozapine Treatment and Cannabis Use in Adolescents with Psychotic Disorders – A Retrospective Cohort Chart Review

    PubMed Central

    Tang, Sephora M.; Ansarian, Aylar; Courtney, Darren B.

    2017-01-01

    Objectives To examine the association between clozapine treatment and frequency of cannabis use in adolescents with co-occurring psychotic and cannabis use disorder in a retrospective cohort chart review. Method We conducted a retrospective cohort chart review of patients diagnosed with a psychotic disorder and concurrent cannabis use disorder admitted to a tertiary care youth inpatient unit from 2010–2012. Longitudinal exposure and outcome data was coded month-by-month. Frequency of cannabis use was measured using a 7-point ordinal scale. Severity of psychosis was measured on a 3-point ordinal scale. Mixed effects regression modeling was used to describe the relationship between exposure and outcome variables. Results Thirteen patients had exposure to clozapine and fourteen had no exposure to clozapine. Cannabis use decreased in patients treated with clozapine, compared to patients treated with other antipsychotics (OR 2.8; 95% CI 0.97–7.9). Compared to no medication, clozapine exposure was associated with significantly less cannabis use (OR 7.1; 95% CI 2.3–22.3). Relative to treatment with other antipsychotics, clozapine exposure was significantly associated with lower severity of psychotic symptoms (OR 3.7; 95% CI 1.2–11.8). Conclusions Clozapine may lead to decreased cannabis use and psychotic symptoms in adolescents with concurrent psychosis and substance use. Clinical trials are warranted. PMID:28331504

  17. Clozapine Treatment and Cannabis Use in Adolescents with Psychotic Disorders - A Retrospective Cohort Chart Review.

    PubMed

    Tang, Sephora M; Ansarian, Aylar; Courtney, Darren B

    2017-01-01

    To examine the association between clozapine treatment and frequency of cannabis use in adolescents with co-occurring psychotic and cannabis use disorder in a retrospective cohort chart review. We conducted a retrospective cohort chart review of patients diagnosed with a psychotic disorder and concurrent cannabis use disorder admitted to a tertiary care youth inpatient unit from 2010-2012. Longitudinal exposure and outcome data was coded month-by-month. Frequency of cannabis use was measured using a 7-point ordinal scale. Severity of psychosis was measured on a 3-point ordinal scale. Mixed effects regression modeling was used to describe the relationship between exposure and outcome variables. Thirteen patients had exposure to clozapine and fourteen had no exposure to clozapine. Cannabis use decreased in patients treated with clozapine, compared to patients treated with other antipsychotics (OR 2.8; 95% CI 0.97-7.9). Compared to no medication, clozapine exposure was associated with significantly less cannabis use (OR 7.1; 95% CI 2.3-22.3). Relative to treatment with other antipsychotics, clozapine exposure was significantly associated with lower severity of psychotic symptoms (OR 3.7; 95% CI 1.2-11.8). Clozapine may lead to decreased cannabis use and psychotic symptoms in adolescents with concurrent psychosis and substance use. Clinical trials are warranted.

  18. 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.

  19. Long-term impacts of adolescent risperidone treatment on behavioral responsiveness to olanzapine and clozapine in adulthood.

    PubMed

    Qiao, Jing; Zhang, Qinglin; Li, Ming

    2014-01-03

    This preclinical study investigated how a short-term risperidone treatment in adolescence impacts antipsychotic response to olanzapine and clozapine in adulthood. Antipsychotic effect was indexed by a drug's suppressive effect on avoidance responding in a rat conditioned avoidance response (CAR) model. Male adolescent Sprague-Dawley rats were first treated with risperidone (1.0mg/kg, sc) or sterile water and tested in the CAR model for 5 consecutive days from postnatal days P 40 to 44. After they became adults (~P 80-84), they were switched to olanzapine (0.5mg/kg, sc), clozapine (5.0mg/kg, sc) or vehicle treatment and tested for avoidance for 5days. During the adolescent period, repeated risperidone treatment produced a persistent inhibition of avoidance response. Throughout the 5days of adulthood drug testing, rats previously treated with risperidone in adolescence made significantly fewer avoidance responses than the vehicle ones when they all were switched to olanzapine, indicating a risperidone-induced enhancement of behavioral sensitivity to olanzapine. In contrast, when switched to clozapine, rats previously treated with risperidone made significantly more avoidance responses than the vehicle rats, indicating a risperidone-induced decrease of behavioral sensitivity to clozapine. Performance in the prepulse inhibition of acoustic startle response in adulthood was not altered by adolescent risperidone treatment. Collectively, adolescent risperidone exposure induced a long-term change in behavioral sensitivity to other atypical antipsychotic drugs, with the specific direction of change (i.e., increase or decrease) dependent on the drug to be switched to. These long-lasting changes are likely mediated by drug-induced neuroplastic changes and may also have significant clinical implications for antipsychotic treatment of chronic patients with an early onset of psychotic symptoms.

  20. Clozapine for treatment-resistant schizophrenia: National Institute of Clinical Excellence (NICE) guidance in the real world.

    PubMed

    Mortimer, Ann M; Singh, Praveen; Shepherd, Charles J; Puthiryackal, Junais

    2010-04-01

    Clozapine, a poorly tolerated antipsychotic drug, is widely recognized as the only efficacious option in treatment-resistant psychosis. The United Kingdom (U.K.) National Institute of Clinical Excellence (NICE) guidance for its consideration defined a threshold for treatment resistance substantially more liberal than that utilized in seminal studies of efficacy. This study documented adherence to NICE guidance in a patient group likely to be enriched for treatment resistance: 150 consecutive assertive outreach and former rehabilitation inpatients. Evidence of a NICE-compliant treatment trial was adduced from case notes: treatment resistance was determined through discussion with key workers about ongoing clinical problems, including treatment-resistant patients already on clozapine. Reasons for treatment-resistant patients not receiving clozapine were documented. Levels of ongoing clinical problems were compared between treatment-resistant patients on clozapine, treatment-resistant patients not on clozapine, and non-treatment-resistant patients. Patients' mean age was 41, with illness duration of 16 years. Twelve percent (18 patients) had not had a NICE-compliant trial of treatment, but all 3 treatment-resistant patients in this subgroup were on clozapine already. Forty-five percent of the whole group was treatment resistant: 54% of the treatment-resistant group was treated with clozapine. Of the remaining 46% (i.e., 31 treatment-resistant patients not taking clozapine), 16 refused and 15 could not be treated for medical reasons including the failure of previous trials and neutropenia. Levels of ongoing clinical problems were generally similar between clozapine-treated patients and nontreatment-resistant patients, with significantly greater problems in treatment-resistant patients not taking clozapine. However, positive symptoms remained relatively high in the clozapine group, while substance abuse was actually lower than in the other two groups, and there were no

  1. 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

  2. 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

  3. Plasma concentrations of amino acids in chronic schizophrenics treated with clozapine.

    PubMed

    Tortorella, A; Monteleone, P; Fabrazzo, M; Viggiano, A; De Luca, L; Maj, M

    2001-01-01

    Peripheral amino acid changes have been reported in schizophrenia, but results are not consistent. We measured serum levels of different amino acids in 11 neuroleptic-resistant schizophrenic patients before and after clozapine treatment and in 11 age- and sex-matched healthy subjects. The schizophrenic patients exhibited significantly higher levels of serum aspartate, glutamate, isoleucine, histidine and tyrosine and significantly lower concentrations of serum asparagine, tryptophan and serine. In patients, the ratio between tryptophan and large neutral amino acids (LNAA) was significantly lower than in matched controls, whereas the tyrosine/LNAA ratio did not differ significantly. Moreover, 12 weeks of clozapine administration significantly reduced serum levels of glutamate but did not restore the values observed in normal controls, nor did it affect other amino acid concentrations. These data show changes in serum amino acids that may influence central serotonergic, dopaminergic and glutamatergic transmission in neuroleptic-resistant schizophrenics. Copyright 2001 S. Karger AG, Basel

  4. Clozapine in schizophrenia and its association with treatment satisfaction and quality of life: Findings of the three national surveys on use of psychotropic medications in China (2002-2012).

    PubMed

    Li, Qian; Xiang, Yu-Tao; Su, Yun-Ai; Shu, Liang; Yu, Xin; Correll, Christoph U; Ungvari, Gabor S; Chiu, Helen F K; Ma, Cui; Wang, Gao-Hua; Bai, Pei-Shen; Li, Tao; Sun, Li-Zhong; Shi, Jian-Guo; Chen, Xian-Sheng; Mei, Qi-Yi; Li, Ke-Qing; Si, Tian-Mei; Kane, John M

    2015-10-01

    We examined the time trends and correlates of clozapine use in schizophrenia patients in China. A total of 14,013 patients with schizophrenia treated in 45 psychiatric hospitals/centers nationwide were interviewed in 2002, 2006 and 2012. Patients' socio-demographic and clinical characteristics including psychopathology, medication side effects, satisfaction with treatment and quality of life (QOL) were recorded in a standardized fashion. Clozapine was used in 32.9% of the whole sample; with corresponding figures of 39.7%, 32.5% and 26.4% in 2002, 2006 and 2012 (p<0.001). Families of clozapine users had lower satisfaction with treatment than those of the non-clozapine group, without significant differences with respect to patients' treatment satisfaction and mental or physical QOL. In multiple logistic regression analyses, compared to the non-clozapine group, patients on clozapine had an earlier age of onset, longer illness duration, more global illness severity and drug-induced central nervous system, gastrointestinal and other side effects, lower antipsychotic doses, less delusions and hallucinations, more negative symptoms, were more likely male, inpatients, to have a family history of psychiatric disorders, receive treatments in regional centers and receive antipsychotic polypharmacy, but less likely to have health insurance and receive first-generation antipsychotics and benzodiazepines (R(2)=0.498, p<0.001). Clozapine was used in one-third of schizophrenia patients in China, with decreasing frequency since 2002. Patients prescribed clozapine had multiple markers of greater global illness severity/chronicity and decreased satisfaction with treatment by the families, but similar QOL and less delusions and hallucinations than patients not prescribed clozapine. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. 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.

  6. Blood Pressure and Heart Rate Changes During Clozapine Treatment.

    PubMed

    Norman, Sarah M; Sullivan, Kelli M; Liu, Fang; DiPaula, Bethany A; Jose, Pedro A; Kitchen, Christopher A; Feldman, Stephanie M; Kelly, Deanna L

    2017-09-01

    People with schizophrenia are 3-4 times more likely to die from cardiovascular disease than the general population. Clozapine (CLZ) is the gold standard of treatment for refractory schizophrenia. It has been associated with tachycardia and recent evidence shows individuals prescribed CLZ may develop blood pressure (BP) elevation and hypertension. The purpose of this study was to examine the effects of CLZ on BP and heart rate (HR). This was a retrospective chart review of patients 18-75 years old with a DSM IV diagnosis of Schizophrenia or Schizoaffective disorder. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR measured 12 weeks before and 24 weeks during CLZ treatment. Eighteen patient records were included in this study. The mean stabilized CLZ dose was 441.7 ± 171.8 mg/day. DBP (t = 1.02, df = 79.5, = 2.00, 0.049) and HR (t = 1.32, df = 355  = -4.61, < 0.0001) were significantly higher after CLZ initiation. A trend was noted for increase in SBP (p = 0.071). 22 % of patients met criteria for hypertension before CLZ and 67 % during CLZ treatment (Chi Square = 6.25, df = 1, p = 0.0124). No significant changes in weight or renal function occured during CLZ treatment. No patients had evidence of cardiomyopathy. The data suggest CLZ may be associated with a rise in BP and HR. The results of this study support previous literature that found an increase in SBP/DBP regardless of CLZ dose, occurring early in treatment. Due to high risk of cardiovascular morbidity and mortality, more work is needed to determine risk factors and understand the mechanism of action that may cause this side effect.

  7. Neuropeptide Y mRNA expression levels following chronic olanzapine, clozapine and haloperidol administration in rats.

    PubMed

    Huang, X-F; Deng, Chao; Zavitsanou, Katerina

    2006-06-01

    Using quantitative in situ hybridization, this study examined regional changes in rat brain mRNA levels encoding neuropeptide Y (NPY) following olanzapine, clozapine and haloperidol administration (1.2, 1.5 and 2.0 mg/kg, oral) for 36 days. The NPY mRNA expression levels and patterns were examined after the last drug administration at both time points enabling the measurement of immediate effect at 2h and the effects after 48 h of drug administration. It was found that all these drugs had an immediate effect on NPY mRNA expression, while virtually all these changes normalized 48 h after the drug treatments. A similarity in altered NPY mRNA expression patterns was seen between the olanzapine and clozapine groups; however, haloperidol was very different. Olanzapine and clozapine administration decreased NPY mRNA levels in the nucleus accumbens, striatum and anterior cingulate cortex (from -60% to -77%, p<0.05). Haloperidol decreased NPY mRNA expression in the amygdala and hippocampus (-69%, -64%, p<0.05). In the lateral septal nucleus, NPY mRNA levels significantly decreased in the olanzapine group (-66%, p<0.05), a trend toward a decrease was observed in the clozapine group, and no change was found in the haloperidol treated group. These results suggest that the different effects of atypical and typical antipsychotics on NPY systems may reflect the neural chemical mechanisms responsible for the differences between these drugs in their effects in treating positive and negative symptoms of schizophrenia. The immediate decrease of NPY mRNA levels suggests an immediate reduction of NPY biosynthesis in response to these drugs.

  8. 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…

  9. 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…

  10. [Clozapine for the treatment of psychosis in 3 elderly patients with Parkinson's disease].

    PubMed

    Diraoui, S; van Melick, E J M; Jansen, P A F

    2004-11-27

    Three patients with Parkinson's disease developed psychosis. None of the three showed any other somatic cause for the psychosis except the Parkinson's disease. The first patient, a 73-year-old male, was initially treated with olanzapine and rivastigmine, without any effect. While treating the second patient, a 75-year-old male who had been suffering from Parkinson's disease for years, the Parkinson medication was first reduced and later on olanzapine and rivastigmine were prescribed, without a lasting effect on the psychotic symptoms. In the third patient, an 85-year-old male, medication reduction was unsuccessful. Finally, all three were treated effectively with clozapine. Psychosis in Parkinson's disease is a serious disorder that is often difficult to treat. In most cases, antipsychotic medication is needed. The atypical antipsychotic clozapine is effective without aggravation of the motor symptoms. Despite the side effects, such as the risk of agranulocytosis, drowsiness and weight gain, clozapine should be considered as a possible treatment.

  11. Clozapine users in Australia: their characteristics and experiences of care based on data from the 2010 National Survey of High Impact Psychosis.

    PubMed

    Siskind, D J; Harris, M; Phillipou, A; Morgan, V A; Waterreus, A; Galletly, C; Carr, V J; Harvey, C; Castle, D

    2017-06-01

    Clozapine is the most effective medication for treatment refractory schizophrenia. However, descriptions of the mental health and comorbidity profile and care experiences of people on clozapine in routine clinical settings are scarce. Using data from the 2010 Australian Survey of High Impact Psychosis, we aimed to examine the proportion of people using clozapine, and to compare clozapine users with other antipsychotic users on demographic, mental health, adverse drug reaction, polypharmacy and treatment satisfaction variables. Data describing 1049 people with a diagnosis of schizophrenia or schizoaffective disorder, who reported taking any antipsychotic medication in the previous 4 weeks, were drawn from a representative Australian survey of people with psychotic disorders in contact with mental health services in the previous 12 months. We compared participants taking clozapine (n = 257, 22.4%) with those taking other antipsychotic medications, on a range of demographic, clinical and treatment-related indicators. One quarter of participants were on clozapine. Of participants with a chronic course of illness, only one third were on clozapine. After adjusting for diagnosis and illness chronicity, participants taking clozapine had significantly lower odds of current alcohol, cannabis and other drug use despite similar lifetime odds. Metabolic syndrome and diabetes were more common among people taking clozapine; chronic pain was less common. Psychotropic polypharmacy did not differ between groups. Consistent with international evidence of clozapine underutilisation, a large number of participants with chronic illness and high symptom burden were not taking clozapine. The lower probabilities of current substance use and chronic pain among clozapine users warrant further study.

  12. Clozapine in a patient with treatment-resistant schizophrenia and hypertrophic cardiomyopathy: a case report

    PubMed Central

    Sanchez, Asiel Yair Adan; Foster, Jessica J.; Plymen, Carla M.; Shergill, Sukhi

    2016-01-01

    Background There is currently limited experience in the initiation and maintenance of clozapine for treatment-resistant psychosis in adults with established structural heart disease. These complex patients require close supervision and liaison between colleagues. Here we present the successful experience of treating one such patient within our service and describe a monitoring plan to ensure that these treatments can be provided both safely and effectively. Case presentation A 36-year-old man with treatment-resistant schizophrenia and known hypertrophic cardiomyopathy (HCM) was admitted to a specialist unit for a trial of clozapine. His psychiatric illness was characterised by multimodal hallucinations and delusions combined with low mood and poor motivation. The diagnosis of HCM was made 3 years previously following a routine electrocardiogram (ECG), and he had remained asymptomatic throughout this time; there were concerns about the risk of initiating clozapine given his pre-existing cardiac condition. Baseline investigations were performed as per local guidelines prior to commencing clozapine; these were within normal limits other than a mildly raised troponin level of 54 ng/L (normal <16 ng/L), which was attributed to the HCM. In addition, baseline transthoracic echocardiography (TTE) was performed which showed no change in the structural heart disease in comparison with previous TTEs. Clozapine was started at 12.5 mg daily and up-titrated to 150 mg twice daily over 14 days as per our institute’s guidelines. The patient was monitored with regular testing of troponins, inflammatory markers and ECG. On day 18, the troponin level increased to 1371 ng/L. Creatine kinase and inflammatory markers remained stable. No changes in ECG or TTE were noted and the patient remained clinically asymptomatic. Cardiology opinion was sought and reported that the finding of an isolated elevated troponin was likely to reflect a ‘troponin leak’ in the context of increased

  13. [Study on clozapine treatment at the Charles Perrens Hospital in Bordeaux, 15 years after its marketing].

    PubMed

    Mercier, C; Bret, P; Bret, M-C; Queuille, E

    2009-09-01

    The international consensus conferences concerning schizophrenia and the authorization to market (French AMM) reserve this molecule for the treatment of resistant schizophrenia. Resistant schizophrenia, as defined by the marketing authorisation, corresponds to the absence of improvement in a patient's state despite two successive treatments with antipsychotics, or at least an atypical drug at an adequate dose for a sufficient length of time. Our investigation compares hospital practices to the marketing authorisation and guidelines regarding resistant schizophrenia. All clozapine prescriptions delivered by the pharmacists at the Charles Perrens Hospital were recorded during the month of February 2007. General information concerning the patient and his or her treatment were collected, based on different support teams set up in the hospital. First, the hospital administrative program was used to manage the patients. Then, the treatment establishment form, filled out by psychiatrists before the beginning of the treatment, listed all previous treatments given to the patient and indicated any inefficacy or intolerances to prior treatments. Then, a program monitored the delivery of this molecule and finally, prescriptions were recorded to describe present treatment. Our study consisted of 61 patients, mostly male subjects averaging 40 years of age, single, who had been under psychiatric care for about 15 years, and were, for the most part, professionally inactive. Clozapine was prescribed for schizophrenic (90%) and for bipolar patients (10%). Clozapine was also often prescribed for patients whose illness had not improved with prior treatments. The average dose was of 489 mg/day for patients considered stable, i.e., those for whom clozapine was prescribed with efficacy observed for a sufficiently long time. It was associated in 88% of all cases with another psychotropic: anxiolytic (68% of cases), normothymic (26% of cases), antidepressant (16%) and antipsychotic (42

  14. Comparative study of clozapine versus risperidone in treatment-naive, first-episode schizophrenia: A pilot study.

    PubMed

    Sahni, Sukhtej; Chavan, B S; Sidana, Ajeet; Kalra, Priyanka; Kaur, Gurjit

    2016-11-01

    Clozapine may be more useful in treatment-naive patients with first-episode schizophrenia for better symptoms control and improving quality of life. The current study was carried out to compare the efficacy and tolerability of clozapine versus risperidone in treatment-naive, first-episode patients of schizophrenia. This was a comparative, open-label, six months prospective study of treatment-naive, first-episode patients with schizophrenia between the age group of 18 and 40 yr diagnosed as per the International Classification of Diseases-10 (ICD-10) criteria. A total of 63 patients were recruited and randomly assigned to clozapine group or risperidone group using computer-generated random number tables. Eight patients were lost to follow up. The dosages of the respective drugs were kept in therapeutic range of 200-600 mg/day and 4-8 mg/day orally for clozapine and risperidone, respectively. On general psychopathology score, after six months of intervention, clozapine led to 60.32 per cent mean reduction in Positive and Negative Syndrome Scale (PANSS) for Schizophrenia total score while risperidone led to 56.35 per cent mean reduction in PANSS total score, which meant more improvement with clozapine. Clozapine group was found to have significant improvement in quality of life (P = 0.04339). On Glasgow Antipsychotic Side-effect Scale, clozapine was superior to risperidone. The most common side effects observed in clozapine group were oversedation (78.96%) and dizziness (55.23%), and in risperidone group, common side effects were rigidity (62.36%), sedation (38.69%), tremors (65.69%) and menstrual irregularities in 80.25 per cent of female patients. The findings of this preliminary study showed clozapine as a better choice than risperidone in terms of efficacy, tolerability and better quality of life in treatment-naive, first-episode schizophrenia. However, further studies need to be done on a larger group of patients to confirm the findings.

  15. Blood Draw Barriers for Treatment with Clozapine and Development of Point-of-Care Monitoring Device.

    PubMed

    Kelly, Deanna L; Ben-Yoav, Hadar; Payne, Gregory F; Winkler, Thomas E; Chocron, Sheryl E; Kim, Eunkyoung; Stock, Veronika; Vyas, Gopal; Love, Raymond C; Wehring, Heidi J; Sullivan, Kelli M; Feldman, Stephanie; Liu, Fang; McMahon, Robert P; Ghodssi, Reza

    2015-07-28

    Clozapine is the most effective antipsychotic drug for schizophrenia treatment, however it is currently underused. In order to understand the barriers of frequent blood draws for white blood cell counts (WBCs) and clozapine levels, we developed a psychiatrist survey and began and integrative approach of designing a point-of-care device that could eventually have real-time monitoring with immediate results. We ascertained barriers related to clozapine management and the acceptance of possible solutions by sending an anonymous survey to physicians in psychiatric practice (N=860). In parallel we tested clozapine sensing using a prototype point-of-care monitoring device. 255 responses were included in the survey results. The two barriers receiving mean scores with the highest agreement as being a significant barrier were patient nonadherence to blood work and blood work's burden on the patient (out of 28). Among nine solutions, the ability to obtain lab results in the physician's office or pharmacy was top-ranked (mean±sd Likert scale (4.0±1.0)). Physicians responded that a point-of-care device to measure blood levels and WBCs would improve care and increase clozapine use. Residents ranked point-of-care devices higher than older physicians (4.07±0.87 vs. 3.47±1.08, p<0.0001). Also, the prototype device was able to detect CLZ reliably in 1.6, 8.2, and 16.3μg/mL buffered solutions. Survey results demonstrate the physician's desire for point-of-care monitoring technology, particularly among younger prescribers. Prototype sensor results identify that clozapine can be detected and integrated for future device development. Future development will also include integration of WBCs for a complete detection device.

  16. »Treatment Resistance« Enigma Resolved by Pharmacogenomics 3 A Case Study of Clozapine Therapy in Schizophrenia

    PubMed Central

    Marić, Nadja P.; Nikolić, Slobodanka Pejović; Buzadžić, Ivana; Jovičić, Milica; Andrić, Sanja; Mihaljević, Marina; Pavlović, Zorana

    2015-01-01

    Summary The introduction of antipsychotic medication in the 1950s forever changed the outlook on the treatment of schizophrenia, although there is still a large proportion of patients who do not reach functional recovery. At least 30% of patients do not respond to clozapine, the tricyclic dibenzodiazepine with complex pharmacological actions, which was proven to be more effective than any other antipsychotic in the treatment of schizophrenia. According to most of the therapeutic guidelines for schizophrenia, clozapine is the third line therapy for patients who did not respond to other antipsychotics. Large inter-individual variability exists for clozapine bioavailability and plasma steady-state concentrations and clearance. Clozapine is metabolized by the cytochrome P450 oxidase enzyme family (CYP450). Cytochrome P450 1A2 (CYP1A2), which is polymorphically expressed in humans, is the main enzyme of clozapine metabolism. This case report addresses the influence of CYP1A2*1F genetic polymorphism on clozapine metabolism, explains the primary non-response of a young patient with schizophrenia due to increased gene expression in homozygous genotype *1F/*1F (increased metabolism of clozapine) and underlies the importance of personalizing schizophrenia treatment by means of genetic and other molecular tools, at least in the cases of »treatment resistance«. PMID:28356835

  17. Lamotrigine augmentation in patients with schizophrenia who show partial response to clozapine treatment.

    PubMed

    Vayısoğlu, Sefa; Anıl Yağcıoğlu, A Elif; Yağcıoğlu, Süha; Karahan, Sevilay; Karcı, Oğuzhan; Gürel, S Can; Yazıcı, M Kâzım

    2013-01-01

    Several placebo controlled studies investigating lamotrigine augmentation of clozapine in schizophrenia patients with partial response have shown varying results. The aim of this study was to further investigate the efficacy and safety of this augmentation strategy, and its effect on the glutamatergic system through utilizing mismatch negativity (MMN) component of auditory event related potentials. The study was designed to evaluate the efficacy and safety of lamotrigine augmentation of clozapine in a 12-week, double-blind, placebo-controlled, prospective, randomized design. Thirty-four patients diagnosed according to DSM-IV schizophrenia criteria and with partial response to clozapine were included. Patients were randomized to 25mg/day of lamotrigine or placebo, gradually increasing up to 200mg/day on the 6th week. The change in psychopathology was assessed with Positive and Negative Syndrome (PANSS), Calgary Depression (CDS) and Clinical Global Impression-Severity (CGI-S) scales. A neuropsychological test battery was administered and MMN measurements were also obtained at baseline and endpoint. Safety evaluation included physical examination, UKU Side Effect Rating Scale (UKU) assessment and serum drug level measurements. No significant differences were found between the two treatment groups in PANSS Positive and General Psychopathology, CDS, neurocognitive test and UKU scores, as well as MMN measurements. PANSS Total, Negative and CGI-S scores showed significant improvement compared to lamotrigine in the placebo group. This study did not show any benefit of augmentation of clozapine with lamotrigine in schizophrenia patients with partial response. The need for further investigation of other augmentation strategies of clozapine in partially responsive schizophrenia patients is evident. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Efficacy and safety of combining clozapine with electrical or magnetic brain stimulation in treatment-refractory schizophrenia.

    PubMed

    Arumugham, Shyam Sundar; Thirthalli, Jagadisha; Andrade, Chittaranjan

    2016-09-01

    A substantial proportion (40-70%) of patients with treatment-resistant schizophrenia experience persistent symptoms despite an adequate clozapine trial. Brain stimulation techniques (BST) such as electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS) have shown promise in medication-refractory schizophrenia. However, their co-administration with clozapine raises some safety concerns. We conducted a systematic literature search through Pubmed and cross-references for relevant publications evaluating the safety and efficacy of combining BST with clozapine. Expert commentary: Evidence from a randomized controlled trial and open-label trials suggest that ECT is an effective intervention in clozapine-refractory schizophrenia. There is limited evidence that the combination is safe. However, until sufficient data accumulate, it would be prudent to be vigilant against adverse effects related to lowered seizure threshold, cognitive impairment, and cardiovascular events. Both high frequency rTMS over the dorsolateral prefrontal cortex and low frequency rTMS over the temporoparietal cortex have been safely administered in patients receiving clozapine. However, rTMS efficacy in clozapine-refractory patients remains uncertain. The evidence for tDCS-clozapine combination is in the form of case reports and needs to be evaluated in controlled trials. Newer methods of brain stimulation and refinement of existing BSTs hold promise for the future.

  19. Randomized trial of clozapine vs. risperidone in treatment-naïve first-episode schizophrenia: results after one year.

    PubMed

    Sanz-Fuentenebro, Javier; Taboada, Diana; Palomo, Tomás; Aragües, María; Ovejero, Santiago; Del Alamo, Cristina; Molina, Vicente

    2013-09-01

    In first-episode patients with psychosis, clozapine may be potentially valuable as an initial treatment seeking to limit early on clinical and cognitive deterioration. Nevertheless, until recently its restricted use has limited the study of this possibility. Our research group is developing a non-commercial, multicentric and open label study on the differential efficacy between clozapine and risperidone in first-episode schizophrenia. In this paper, we present the results related to clinical variables after a one-year follow-up. So far, we have recruited 30 patients diagnosed with schizophrenia or schizophreniform disorder with illness duration of less than two years. The patients had not received any previous treatment and they were randomized to treatment with clozapine or risperidone. Our results indicate that on average, patients on clozapine adhered to their original treatment for a longer time period than patients on risperidone. By last observation carried forward (LOCF) analysis, patients on clozapine and risperidone displayed similar clinical improvements, although marginally greater improvements in positive and total symptoms scores were found in the clozapine group. At the 12-month point we observed a marginal improvement in negative symptom scores in patients on clozapine. Subjective secondary effects, as measured with the Udvalg for KliniskeUndersøgelser (UKU) scale, correlated negatively with negative symptoms at follow-up. Our data, although preliminary, suggest that clozapine may have a slightly superior efficacy in the initial year of treatment of first-episode treatment-naïve patients with schizophrenia, and this can be explained for the most part by greater adherence to this treatment. © 2013.

  20. Augmentation strategies in partial responder and/or treatment-resistant schizophrenia patients treated with clozapine.

    PubMed

    Muscatello, Maria Rosaria A; Bruno, Antonio; De Fazio, Pasquale; Segura-Garcia, Cristina; Pandolfo, Gianluca; Zoccali, Rocco

    2014-11-01

    Although clozapine (CLZ) is considered the best evidence-based therapeutic option for treatment of resistant schizophrenia patients, a significant proportion of CLZ-treated patients show a partial or inadequate response to treatment, leading to increased healthcare cost and poor quality of life for affected individuals. This paper comprises a review of main research in CLZ augmentation strategies for treatment-refractory schizophrenia, with a focus on research conducted between 1990 and 2014. Databases that were searched include: PubMed, CINAHL, EMBASE PsychINFO, AgeLine and Cochrane Database of Systematic Reviews. Primary search terms were 'clozapine augmentation', 'clozapine and add-on' and 'treatment-resistant schizophrenia', with cross reference to specific agents covered in this article. We reviewed the available evidence on CLZ augmentation with antipsychotics, antidepressants, mood stabilizers and other agents. Many drugs have been evaluated as CLZ add-on therapies without demonstrating convincing efficacy in treating refractory schizophrenia symptoms. More research is needed to better define outcomes in schizophrenia, the topic of treatment-resistance and more well-designed trials are required to establish true efficacy and safety of CLZ augmentation strategies.

  1. Ziprasidone vs clozapine in schizophrenia patients refractory to multiple antipsychotic treatments: the MOZART study.

    PubMed

    Sacchetti, Emilio; Galluzzo, Alessandro; Valsecchi, Paolo; Romeo, Fabio; Gorini, Barbara; Warrington, Lewis

    2009-05-01

    This 18-week, randomized, flexible-dose, double-blind, double-dummy trial evaluated ziprasidone as an alternative to clozapine in treatment-refractory schizophrenia patients. Patients had a DSM-IV diagnosis of schizophrenia, a history of resistance and/or intolerance to at least three acute cycles with different antipsychotics given at therapeutic doses, PANSS score >or=80, and CGI-S score >or=4. Patients were randomized to ziprasidone (80-160 mg/day, n=73) or clozapine (250-600 mg/day, n=74). On the primary ITT-LOCF analysis, baseline-to-endpoint decreases in PANSS total scores were similar in the ziprasidone (-25.0+/-22.0, 95% CI -30.2 to -19.8) and clozapine (-24.5+/-22.5, 95% CI -29.7 to -19.2) groups. A progressive and significant reduction from baseline in PANSS total score was observed from day 11 in both study arms. There were also significant improvements on PANSS subscales, CGI-S, CG-I, CDSS, and GAF, without between-drug differences. The two treatment groups had similar rates of early discontinuations due to AEs. AEs were mostly of similar mild-moderate severity in the two groups. There were also no detrimental effects on prolactin, renal and liver function, hematology, and cardiovascular parameters. However, ziprasidone but not clozapine showed a significant reduction of SAS and AIMS scores. Moreover, when compared with clozapine, ziprasidone also had a more favorable metabolic profile, with significant endpoint differences in weight, fasting glucose, total cholesterol, LDL cholesterol, and triglycerides. In conclusion, this trial indicates that both ziprasidone and clozapine, having comparable efficacy coupled with satisfactory general safety and tolerability, may be regarded as valuable options for the short-term treatment of difficult-to-treat schizophrenia patients with a history of multiple resistance and/or intolerance to antipsychotics. The more favorable metabolic profile of ziprasidone may represent an added value that could guide clinicians

  2. Ziprasidone vs clozapine in schizophrenia patients refractory to multiple antipsychotic treatments: the MOZART study.

    PubMed

    Sacchetti, Emilio; Galluzzo, Alessandro; Valsecchi, Paolo; Romeo, Fabio; Gorini, Barbara; Warrington, Lewis

    2009-08-01

    This 18-week, randomized, flexible-dose, double-blind, double-dummy trial evaluated ziprasidone as an alternative to clozapine in treatment-refractory schizophrenia patients. Patients had a DSM-IV diagnosis of schizophrenia, a history of resistance and/or intolerance to at least three acute cycles with different antipsychotics given at therapeutic doses, PANSS score >or= 80, and CGI-S score >or= 4. Patients were randomized to ziprasidone (80-160 mg/day, n = 73) or clozapine (250-600 mg/day, n = 74). On the primary ITT-LOCF analysis, baseline-to-endpoint decreases in PANSS total scores were similar in the ziprasidone (- 25.0 +/- 22.0, 95% CI - 30.2 to - 19.8) and clozapine (- 24.5 +/- 22.5, 95% CI - 29.7 to - 19.2) groups. A progressive and significant reduction from baseline in PANSS total score was observed from day 11 in both study arms. There were also significant improvements on PANSS subscales, CGI-S, CG-I, CDSS, and GAF, without between-drug differences. The two treatment groups had similar rates of early discontinuations due to AEs. AEs were mostly of similar mild-moderate severity in the two groups. There were also no detrimental effects on prolactin, renal and liver function, hematology, and cardiovascular parameters. However, ziprasidone but not clozapine showed a significant reduction of SAS and AIMS scores. Moreover, when compared with clozapine, ziprasidone also had a more favorable metabolic profile, with significant endpoint differences in weight, fasting glucose, total cholesterol, LDL cholesterol, and triglycerides. In conclusion, this trial indicates that both ziprasidone and clozapine, having comparable efficacy coupled with satisfactory general safety and tolerability, may be regarded as valuable options for the short-term treatment of difficult-to-treat schizophrenia patients with a history of multiple resistance and/or intolerance to antipsychotics. The more favorable metabolic profile of ziprasidone may represent an added value that could

  3. [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

  4. Use of clozapine alongside chemotherapy in a treatment-resistant bipolar disorder patient with ovarian carcinoma: A case report and brief review

    PubMed Central

    Pakhre, Ashish; Krishnan, Aarya; Pattanayak, Raman Deep; Khandelwal, Sudhir K.

    2016-01-01

    Regular monitoring of blood counts ensures the safety of clozapine use; however, certain clinical situations may pose a dilemma for management such as use of clozapine in the presence of myelosuppressive chemotherapy. Further, there is very limited literature to guide such decisions. We report a case of a clozapine-stabilized, treatment-resistant bipolar disorder patient with ovarian carcinoma requiring chemotherapy. The clinical challenges are discussed in light of a brief review of the available reports. PMID:28197007

  5. Retrospective review of clozapine in the treatment of patients with autism spectrum disorder and severe disruptive behaviors.

    PubMed

    Beherec, Laurène; Lambrey, Simon; Quilici, Gwendoline; Rosier, Antoine; Falissard, Bruno; Guillin, Olivier

    2011-06-01

    Autism spectrum disorder (ASD) is a serious childhood-onset disorder in which social and language development are primarily affected, with associated repetitive behavior and, in some patients, behavioral symptoms including aggression and self-injury. In ASD, risperidone and aripiprazole are the only second-generation antipsychotic drugs that have shown to decrease disruptive behaviors in large-scale, controlled, double-blind studies. However, in some patients, these medications are not effective. Clozapine, a second-generation antipsychotic drug known to be effective in the treatment of aggression associated with schizophrenia, has received little attention in ASD.We conducted a retrospective analysis of the changes in disruptive behaviors for all patients with ASD treated with clozapine from 2002 to 2010. Disruptive behaviors were monitored during the 4 to 6 months before and after the initiation of clozapine. Long-term tolerance (10 months to 7 years) was also assessed. The relationship between disruptive behaviors and period of treatment (before and after clozapine) was studied with a generalized linear marginal model. Clozapine resulted in a significant 2-fold decrease in the number of the days with aggression, a decrease in the number of psychotropic drugs, and a decrease in the dose of the antipsychotic drugs. The long-term tolerance of clozapine (white blood cell count and extrapyramidal effects) was good, with the exception of significant weight gain (14.3 ± 10.9 kg), the occurrence of metabolic syndrome in 1 patient, and tachycardia in another patient.These results suggest that clozapine should be considered for the management of disruptive behaviors in patients with ASD not improved by first-line antipsychotic drugs.

  6. Comparison of sole nurse and team-delivered community clozapine services for people with treatment-resistant schizophrenia.

    PubMed

    Gage, Heather; Family, Hannah; Murphy, Fenella; Williams, Peter; Sutton, Jane; Taylor, Denise

    2015-03-01

    To compare sole nurse and doctor-led multidisciplinary team delivery of community clozapine services for people with treatment-resistant schizophrenia. Around 20% of people with schizophrenia are treatment resistant and fail to respond to front line medications. Clozapine, a second-line treatment, has potentially serious side effects requiring regular monitoring. Different models of community clozapine services are emerging in the British National Health Service, but there is little evidence about which is best. Questionnaire survey of service users. All patients on the lists of seven clozapine clinics (four sole nurse, three multidisciplinary team) in one trust were invited to participate, 2009-2010. Forward stepwise regression was used to investigate associations between patient well-being, functioning, self-efficacy and satisfaction, and clinic model attended, controlling for socio-demographic and health characteristics and processes of care. Use (and costs) of other health and social services accessed was compared between models. Sixty-six service users (35% participation rate) responded. Well-being and functioning were associated with patient characteristics and processes of care, not clinic model. Patients managed by sole nurses reported, over 3 months: more community psychiatric nurse visits and hospital psychiatrist appointments. Clinic list size affects costs per patient. Multidisciplinary team delivery may reduce use of other services. Although multidisciplinary team delivery is regarded as best practice, sole nurses can effectively provide clozapine services and may be warranted in areas of low population density. © 2014 John Wiley & Sons Ltd.

  7. Clozapine safety, 35 years later.

    PubMed

    Raja, Michele

    2011-07-01

    Clozapine is the best treatment option in several clinical circumstances, including treatment-resistant schizophrenia, non treatment-resistant schizophrenia, suicide risk in schizophrenia spectrum disorders, aggressiveness or violence in psychiatric patients, psychosis in Parkinson's disease, prevention and treatment of tardive dyskinesia. However, clozapine is associated with many serious side effects. Furthermore, monitoring requirements, i.e., frequent blood draws and frequent visits, discourage clozapine use. Therefore, the drug is underused. The only way to avoid the underuse of clozapine is full awareness of its side effects and competence to minimize them. The aim of the paper is reviewing the safety profile of clozapine and the suggested strategies in the management of its side effects, including neutropenia, eosinophilia, seizures, myocarditis, weight gain, diabetes, metabolic syndrome, hypersalivation, fever, constipation, ileus, urinary incontinence, sweating. The neuropsychiatric side effects of clozapine are not discussed in this review.

  8. The Porirua Protocol in the Treatment of Clozapine-Induced Gastrointestinal Hypomotility and Constipation: A Pre- and Post-Treatment Study.

    PubMed

    Every-Palmer, Susanna; Ellis, Pete M; Nowitz, Mike; Stanley, James; Grant, Eve; Huthwaite, Mark; Dunn, Helen

    2017-01-01

    Clozapine, an antipsychotic used in treatment-resistant schizophrenia, causes slow gastrointestinal transit in 50-80% of patients. Clozapine-induced gastrointestinal hypomotility is both common and serious, and potential complications include severe constipation, ileus, bowel obstruction and related complications, with a higher mortality rate than clozapine-related agranulocytosis. Little evidence exists on its prevention and management. Using a well-validated radiopaque marker ('Metcalf') method, we compared colonic transit times (CTTs) of clozapine-treated inpatients not receiving laxatives with their transit times when receiving laxatives, with treatment prescribed according to the Porirua Protocol for clozapine-related constipation (docusate and senna augmented by macrogol 3350 in treatment-resistant cases). The median age of participants was 35 years, and median clozapine dose, plasma level and duration of treatment were 575 mg/day, 506 ng/mL and 2.5 years, respectively. Overall, 14 participants (10 male) were enrolled and all completed the study. Transit times improved markedly with laxative treatment. Median colonic transit without laxatives was 110 h (95% confidence interval [CI] 76-144 h), over four times longer than normative values (p < 0.0001). Median CTT with laxatives was 62 h (95% CI 27-96 h), a 2-day reduction in average transit time (p = 0.009). The prevalence of gastrointestinal hypomotility decreased from 86% pre-treatment to 50% post-treatment (p = 0.061). Severe gastrointestinal hypomotility decreased from 64 to 21% (p = 0.031). Subjective reporting of constipation did not correlate well with objective hypomotility, and did not change significantly with treatment. Treating clozapine-treated patients with docusate and senna augmented by macrogol appears effective in reducing CTTs in clozapine-induced constipation. Randomised controlled trials are the next step. Australian New Zealand Clinical Trial Registry ACTRN12616001405404

  9. Changes in serum lipids, independent of weight, are associated with changes in symptoms during long-term clozapine treatment

    PubMed Central

    Procyshyn, Ric M.; Wasan, Kishor M.; Thornton, Allen E.; Barr, Alasdair M.; Chen, Eric Y.H.; Pomarol-Clotet, Edith; Stip, Emmanuel; Williams, Richard; MacEwan, G. William; Birmingham, C. Laird; Honer, William G.

    2007-01-01

    Objective Investigators have reported that weight gain attributed to clozapine is associated with its clinical response. However, weight gain is a nonspecific physiological variable that, in itself, does not explain the mechanism underlying this relation. Alternatively, other biological variables that are often associated with weight gain, such as serum lipids, may assist in explaining this observation. The primary objective of this study was to determine whether an increase in serum lipids is associated with improvement in schizophrenia symptoms during steady state treatment with clozapine. Methods The data for this study represent a subset of data from a randomized, double-blinded trial that evaluated subjects with schizophrenia who demonstrated a poor treatment response to clozapine. While continuing their clozapine therapy, subjects were randomly assigned to receive either risperidone 3 mg daily or placebo for 8 weeks. This course of treatment was followed by an optional (open-label) 18 weeks of augmentation with risperidone. In the present study, we included all subjects from the previously reported trial who had fasting lipid analyses and Positive and Negative Syndrome Scale (PANSS) scores from days 7 and 63 (n = 55). For the primary analyses, we used multiple regression to examine the association between serum lipid concentrations and PANSS scores, after controlling for weight. Results The analyses showed that the change in serum lipid concentration predicted change in symptoms over that of change in weight. Specifically, an increase in serum triglyceride concentration was associated with a decrease in the total PANSS score (p = 0.037). In addition, an increase in either serum total cholesterol concentration (p = 0.007), serum triglyceride concentration (p = 0.017) or their combined effect (p = 0.010) was associated with a decrease in PANSS negative subscale scores. Conclusion Elevation of serum lipids is associated with an improvement in schizophrenia

  10. Hematological and cardiometabolic safety of clozapine in the treatment of very early onset schizophrenia: a retrospective chart review.

    PubMed

    Midbari, Yael; Ebert, Tanya; Kosov, Ira; Kotler, Moshe; Weizman, Abraham; Ram, Anca

    2013-10-01

    There are very few studies in the literature regarding clozapine use in children <13 years of age. In this retrospective chart review, we compared the safety of clozapine--as determined by hematological and cardiometabolic changes - to that of non-clozapine antipsychotics used in the treatment of childhood-onset schizophrenia (COS). The clozapine treatment group (CTG) consisted of 17 COS patients (mean age 10.4 ± 2 years) who were hospitalized in a psychiatric ward between the years 2005 and 2012. The control group consisted of 19 COS patients (mean age 10.1 ± 1.4 years) who were hospitalized in the same ward during the same time period, and were treated with non-clozapine antipsychotics. A retrospective chart review was conducted. Hematological (white blood cells, absolute neutrophil count [ANC], red blood cells, platelets), metabolic (aspartate transaminase, alanine transaminase, triglycerides, total cholesterol, bilirubin) and cardiac (heart rate) values were extracted from the medical charts. The average follow-up periods for the CTG and the control group were 332.9 ± 200.5 days and 291.7 ± 157 days, respectively. In the CTG, moderate neutropenia (ANC<1500/mm(3)) and mild neutropenia (1500/mm(3)Treatment with clozapine was permanently discontinued only in one child (6%). There were no cases of agranulocytosis or severe infection in the CTG. In the control group, two children (11%) showed hematological abnormalities. Hyperlipidemia was observed in one child (6%) in the CTG at release from the hospital. Significantly more children (47%) in the CTG had tachycardia (heart rate>100 beats per minute) at release from the hospital, compared with only one child (5%) in the control group (p=0.006). It appears that clozapine use in very early onset schizophrenia is safe. Although hematological adverse effects did occur in our study, the

  11. 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.

  12. Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia in routine clinical care: a randomized, controlled trial.

    PubMed

    Barbui, Corrado; Accordini, Simone; Nosè, Michela; Stroup, Scott; Purgato, Marianna; Girlanda, Francesca; Esposito, Eleonora; Veronese, Antonio; Tansella, Michele; Cipriani, Andrea

    2011-06-01

    This multisite study was conducted to compare the efficacy and tolerability of combination treatment with clozapine plus aripiprazole versus combination treatment with clozapine plus haloperidol in patients with schizophrenia who do not have an optimal response to clozapine. Patients continued to take clozapine and were randomly assigned to receive daily augmentation with aripiprazole or haloperidol. Physicians prescribed the allocated treatments according to usual clinical care. Withdrawal from allocated treatment within 3 months was the primary outcome. Secondary outcomes included severity of symptoms on the Brief Psychiatric Rating Scale and antipsychotic subjective tolerability on the Liverpool University Neuroleptic Side Effect Rating Scale. A total of 106 patients with schizophrenia were randomly assigned to treatment. After 3 months, we found no difference in the proportion of patients who discontinued treatment between the aripiprazole and haloperidol groups (13.2% vs 15.1%, P = 0.780). The 3-month change of the Brief Psychiatric Rating Scale total score was similar in the aripiprazole and haloperidol groups (-5.9 vs -4.4 points, P = 0.523), whereas the 3-month decrease of the Liverpool University Neuroleptic Side Effect Rating Scale total score was significantly higher in the aripiprazole group than in the haloperidol group (-7.4 vs -2.0 points, P = 0.006). These results suggest that augmentation of clozapine with aripiprazole offers no benefit with regard to treatment withdrawal and overall symptoms in schizophrenia compared with augmentation with haloperidol. However, an advantage in the perception of adverse effects with aripiprazole treatment may be meaningful for patients.

  13. Loxapine and Cyproheptadine Combined Limit Clozapine Rebound Psychosis and May Also Predict Clozapine Response.

    PubMed

    Aboueid, Lila; McCarthy, Richard H

    2016-01-01

    Clozapine has been consistently shown to be superior to other antipsychotics in the treatment of psychosis. However, clozapine usage has been limited due to required routine blood monitoring and the potential for life threatening side effects. We report a case of a 66-year-old female patient, who developed clozapine-induced agranulocytosis after 10 weeks of clozapine treatment and was subsequently successfully treated with a combination of loxapine and cyproheptadine. The combination is thought to mimic the pharmacological profile of clozapine, rendering it as a possible alternative to traditional clozapine treatment.

  14. Loxapine and Cyproheptadine Combined Limit Clozapine Rebound Psychosis and May Also Predict Clozapine Response

    PubMed Central

    McCarthy, Richard H.

    2016-01-01

    Clozapine has been consistently shown to be superior to other antipsychotics in the treatment of psychosis. However, clozapine usage has been limited due to required routine blood monitoring and the potential for life threatening side effects. We report a case of a 66-year-old female patient, who developed clozapine-induced agranulocytosis after 10 weeks of clozapine treatment and was subsequently successfully treated with a combination of loxapine and cyproheptadine. The combination is thought to mimic the pharmacological profile of clozapine, rendering it as a possible alternative to traditional clozapine treatment. PMID:27433365

  15. Clozapine v. chlorpromazine in treatment-naive, first-episode schizophrenia: 9-year outcomes of a randomised clinical trial.

    PubMed

    Girgis, Ragy R; Phillips, Michael R; Li, Xiaodong; Li, Kejin; Jiang, Huiping; Wu, Chengjing; Duan, Naihua; Niu, Yajuan; Lieberman, Jeffrey A

    2011-10-01

    The differential effects of so-called 'first- and second generation' antipsychotic medications, when given in the first episode, on the long-term outcome of schizophrenia remain to be elucidated. We compared the 9-year outcomes of individuals initially randomised to clozapine or chlorpromazine. One-hundred and sixty individuals with treatment-naive, first episode schizophrenia or schizophreniform disorder in a mental health centre in Beijing, China were randomised to clozapine or chlorpromazine treatment for up to 2 years,followed by up to an additional 7 years of naturalistic treatment. The primary outcome was remission status for individuals in each group. Individuals in both groups spent essentially equal amounts of time in each clinical state over the follow-up time period(remission, 78%; intermediate, 8%; relapse, 14%). There were no significant differences on other measures of illness severity. The clozapine group was more likely than the chlorpromazine group to remain on the medication to which they were originally assigned (26% v. 10%, P = 0.01). There were no significant differences between the two groups on other secondary efficacy outcomes. These findings support the comparability in effectiveness between antipsychotic medications but with slightly greater tolerability of clozapine in the treatment of first-episode psychosis.

  16. Chronic Myeloproliferative Neoplasms Treatment

    MedlinePlus

    ... Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Chronic Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Chronic ...

  17. 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.

  18. Reason for clozapine cessation.

    PubMed

    Pai, N B; Vella, S C

    2012-01-01

    Approximately 30% of individuals diagnosed with schizophrenia suffer from treatment-resistant or refractory schizophrenia. The gold standard for treatment of refractory schizophrenia is clozapine. However, a significant number of patients cease clozapine therapy; therefore this study explores patient's motives for cessation. The motives for cessation and duration of clozapine treatment from a retrospective database of 151 patients with schizophrenia or schizo-affective disorder who had ceased clozapine once or more were reviewed, with the motives for cessation coded. The general motives for cessation were non-compliance, own decision, medical, poor response and other. In addition, the medical reasons for cessation were further codified: cardiac complications, neutropenia, fevers, other side effects and pregnancy. The majority of patients ceased clozapine owing to non-compliance with medical protocols or citing their own decision. Approximately half ceased after a period of 6 months or less. Seventeen per cent of patients ceased owing to medical reasons, with the largest proportions discontinuing treatment because of other side effects or neutropenia. Future research should seek to further investigate why patients decide to be non-compliant and formulate their own decision to cease treatment, as this will facilitate strategies to promote adherence amongst these two groups that are potentially the most amenable to change. © 2011 John Wiley & Sons A/S.

  19. Changes in plasma D-serine, L-serine, and glycine levels in treatment-resistant schizophrenia before and after clozapine treatment.

    PubMed

    Yamamori, Hidenaga; Hashimoto, Ryota; Fujita, Yuko; Numata, Shusuke; Yasuda, Yuka; Fujimoto, Michiko; Ohi, Kazutaka; Umeda-Yano, Satomi; Ito, Akira; Ohmori, Tetsuro; Hashimoto, Kenji; Takeda, Masatoshi

    2014-10-17

    Hypofunction of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors may be involved in the pathophysiology of schizophrenia. Many studies have investigated peripheral NMDA receptor-related glutamatergic amino acid levels because of their potential as biological markers. Peripheral d-serine levels and the ratio of d-serine to total serine have been reported to be significantly lower in patients with schizophrenia than in controls. Peripheral d-serine levels and the d-/l-serine ratio have also been reported to significantly increase in patients with schizophrenia as their clinical symptoms improve from the time of admission to the time of discharge. In this study, we examined whether peripheral NMDA receptor-related glutamatergic amino acids levels were altered in patients with treatment-resistant schizophrenia compared to controls and whether these peripheral amino acids levels were altered by clozapine treatment. Twenty-two patients with treatment-resistant schizophrenia and 22 age- and gender-matched healthy controls were enrolled. The plasma levels of d-serine, l-serine, glycine, glutamate, and glutamine were measured before and after clozapine treatment. We found that the plasma levels of d-serine and the d-/l-serine ratio were significantly lower in the patients before clozapine treatment than in the controls. The d-/l-serine ratio was significantly increased by clozapine treatment in patients, and no significant difference was observed in the plasma levels of d-serine and the d-/l-serine ratio between the patients after clozapine treatment and the controls. We also found that plasma glycine levels and the glycine/l-serine ratio were significantly increased following clozapine treatment in the patients, and the glycine/l-serine ratio was significantly higher in the patients after clozapine treatment than in the controls. There was no significant difference in the plasma levels of glutamate and glutamine both between the controls and patients and

  20. 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…

  1. Risk of New-Onset Diabetes After Long-Term Treatment With Clozapine in Comparison to Other Antipsychotics in Patients With Schizophrenia.

    PubMed

    Schulte, Peter F J; Bocxe, Johanna T H; Doodeman, Hieronymus J; van Haelst, Ingrid M M; Cohen, Dan

    2016-04-01

    It has been suggested that clozapine has one of the largest diabetic effects of all atypical antipsychotics. To confirm these findings, we examined retrospectively the risk of new-onset diabetes in long-term clozapine treatment compared to treatment with other antipsychotics in a matched control population with schizophrenia or schizoaffective disorder. Ninety-four adult patients with schizophrenia or schizoaffective disorder who had been treated with clozapine for 5 years or longer were matched on age, diagnosis, and sex to 94 patients without any use of clozapine. The groups were followed up for as long as 20 years. The cumulative incidence of new detection of diabetes in the clozapine group was 22.3% (mean follow-up, 12.3 years; absolute risk difference, 6.3%; 95% confidence interval, -4.9% to 17.5%). An additional rigorous analysis of the 83 matched pairs with normal glucose measurement before end point showed a significant risk difference between the 2 groups (21.7% compared with 8.4%) but may have been biased against clozapine. We conclude that definitive evidence showing a clinically significant larger risk for new-onset diabetes after long-term treatment with clozapine in comparison to other antipsychotics is lacking.

  2. Gabapentin treatment in clozapine-induced restless legs syndrome: two cases and a review of the literature

    PubMed Central

    Kumar, Vijaya; Venkatasubramanian, Ganesan

    2016-01-01

    Restless legs syndrome (RLS) is a neuro-sensorimotor disorder affecting 2–4% of adults. It is characterized by intense urges to move the legs, associated with unpleasant sensory disturbances in the legs occurring at rest and manifests mostly in the evening and night, relieved by movement. Diagnosis is primarily based on clinical presentation and the consensus criteria for the diagnosis have been established. Antipsychotics, the dopamine antagonists, have been reported to induce RLS. Dopamine agonists, the effective first-line treatment of RLS, carry the risk of inducing or worsening psychosis. Many nondopaminergic agents including antiepileptic medications have also been used in the treatment of primary RLS. In this report we describe clozapine-induced RLS in two patients with schizophrenia and its successful treatment with gabapentin, a nondopaminergic agent. In addition, we have reviewed the available literature on clozapine-induced RLS and its management. PMID:28101323

  3. Gabapentin treatment in clozapine-induced restless legs syndrome: two cases and a review of the literature.

    PubMed

    Kumar, Vijaya; Venkatasubramanian, Ganesan

    2017-01-01

    Restless legs syndrome (RLS) is a neuro-sensorimotor disorder affecting 2-4% of adults. It is characterized by intense urges to move the legs, associated with unpleasant sensory disturbances in the legs occurring at rest and manifests mostly in the evening and night, relieved by movement. Diagnosis is primarily based on clinical presentation and the consensus criteria for the diagnosis have been established. Antipsychotics, the dopamine antagonists, have been reported to induce RLS. Dopamine agonists, the effective first-line treatment of RLS, carry the risk of inducing or worsening psychosis. Many nondopaminergic agents including antiepileptic medications have also been used in the treatment of primary RLS. In this report we describe clozapine-induced RLS in two patients with schizophrenia and its successful treatment with gabapentin, a nondopaminergic agent. In addition, we have reviewed the available literature on clozapine-induced RLS and its management.

  4. 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.

  5. Clozapine-induced interstitial nephritis - a rare but important complication: a case report

    PubMed Central

    2009-01-01

    Introduction Given the limited range of effective drug treatments for patients with schizophrenia, increasing numbers of patients, often termed 'treatment-resistant' are prescribed clozapine. While the induction of neutropenia or agranulocytosis by clozapine is well appreciated, other rare potentially fatal adverse reactions may also occur including acute interstitial nephritis as reported in this case. Case presentation A 57-year-old Caucasian woman with treatment-resistant chronic schizophrenia developed acute renal failure following initiation of treatment with clozapine. The adverse reaction occurred after only four doses of the drug had been administered (titrated from 12.5 to 25 mg per day). After clozapine had been withdrawn, the patient's renal function returned to normal with no other changes to medication. The patient had been exposed to clozapine about 4 years previously when she had developed a similar reaction. Conclusion Renal reactions to clozapine are extremely rare but, if not recognized promptly, may prove fatal. Psychiatrists need to be aware of this possible complication when clozapine is initiated. PMID:20126316

  6. Prescribing and monitoring clozapine in Christchurch.

    PubMed

    McKean, Andrew; Vella-Brincat, Jane; Begg, Evan

    2008-08-01

    The aim of the study was to identify the pattern of usage of clozapine in Christchurch, New Zealand, including daily dose, indication and use of drug concentration monitoring. Patients (n=353) were identified retrospectively from the pharmacy computer system. Data gathered included patient demographics, the daily clozapine dose and the number of occasions that clozapine drug concentration monitoring occurred. In addition, each psychiatrist who had prescribed clozapine was surveyed, regarding their indications for the use of clozapine and their use of clozapine drug concentration monitoring. The majority (63%) of patients on clozapine were male. The mean age of the patients was 43 years (range 15-88 years). The mean daily dose of clozapine was 325 mg (range 12.5-900 mg). Patients over the age of 65 years were on a significantly lower dose (mean=143 mg, 95% CI=103-183 mg) compared with those under 65 years of age (mean=350 mg, 95% CI=330-370 mg). The median duration of treatment on clozapine was 4 years. Fifty-one percent of patients had undergone drug concentration monitoring, the majority on multiple occasions. In females, increasing age correlated with an increase in dose-corrected plasma clozapine concentrations (r(2)=0.29, p<0.001). This was not demonstrated in the male population. Of the psychiatrists surveyed, 44% prescribed clozapine for unlicensed indications and 79% used clozapine drug concentration monitoring in their patients. This was most commonly performed to assess compliance or confirm toxicity. The mean daily dose of clozapine of 325 mg was similar to that found in other studies. An age-related decline in dose was observed, probably due to different indications, with many of the elderly patients receiving clozapine for Parkinsonian related symptoms. There was also an age-related decline apparent in clearance in females. Clozapine was often used for unlicensed indications, and a clear majority of psychiatrists use drug concentration monitoring.

  7. A systematic review and meta-analysis of randomised controlled trials of treatments for clozapine-induced obesity and metabolic syndrome.

    PubMed

    Zimbron, Jorge; Khandaker, Golam M; Toschi, Chiara; Jones, Peter B; Fernandez-Egea, Emilio

    2016-09-01

    Metabolic complications are commonly found in people treated with clozapine. Reviews on the management of this problem have generally drawn conclusions by grouping different types of studies involving patients treated with various different antipsychotics. We carried out a systematic review and meta-analysis of pharmacological and non-pharmacological treatments for clozapine-induced obesity or metabolic syndrome. Two researchers independently searched PubMed and Embase for randomised controlled trials (RCTs) of treatments for clozapine-induced obesity or metabolic syndrome. All other types of studies were excluded. We only included RCTs where more than 50% of participants were taking clozapine. We identified 15 RCTs. Effective pharmacological treatments for clozapine-induced obesity and metabolic syndrome include metformin, aripiprazole, and Orlistat (in men only). Meta-analysis of three studies showed a robust effect of metformin in reducing body mass index and waist circumference but no effects on blood glucose, triglyceride levels, or HDL levels. In addition, there is limited evidence for combined calorie restriction and exercise as a non-pharmacological alternative for the treatment of clozapine-induced obesity, but only in an in-patient setting. Rosiglitazone, topiramate, sibutramine, phenylpropanolamine, modafinil, and atomoxetine have not shown to be beneficial, despite reports of efficacy in other populations treated with different antipsychotics. We conclude that randomised-controlled trial data support the use of metformin, aripiprazole, and Orlistat (in men only) for treating clozapine-induced obesity. Calorie restriction in combination with an exercise programme may be effective as a non-pharmacological alternative. Findings from trials in different populations should not be extrapolated to people being treated with clozapine.

  8. Clozapine-Induced Microseizures, Orofacial Dyskinesia, and Speech Dysfluency in an Adolescent with Treatment Resistant Early Onset Schizophrenia on Concurrent Lithium Therapy

    PubMed Central

    Haq, Ayman; Song, Michael M.; Aligeti, Manish

    2017-01-01

    Clozapine is an atypical antipsychotic used in the treatment of refractory schizophrenia. It has a well-known side effect profile, including agranulocytosis, decreased seizure threshold, and tardive dyskinesia. In addition, numerous case reports have described clozapine-induced stuttering in adults. However, there has been only one previous case report describing it in the adolescent population. In addition, concurrent lithium therapy has been shown to enhance the neurotoxic effects of antipsychotics and lower the seizure threshold. Here, we report on the development of clozapine-induced microseizures, orofacial dyskinesia, and stuttering in a 17-year-old adolescent male with treatment of refractory early onset schizophrenia on clozapine and concurrent lithium therapy. The patient's symptoms of schizophrenia responded well to the clozapine regimen. However, with the escalating dose of clozapine, the patient developed speech dysfluency in the form of stuttering and perioral twitching. An electroencephalogram confirmed seizure activity. Due to similarities with tardive dyskinesia, symptoms of microseizures induced by atypical antipsychotics may not be accurately diagnosed. A multidisciplinary treatment of speech dysfluency is of particular importance in the adolescent schizophrenic patients, who are expected to have longer duration of lifetime exposure to antipsychotics and in whom peer group interaction is crucial for normal personal and social development. PMID:28835863

  9. Circadian rhythm of neutrophil counts and granulocyte macrophage-colony stimulating factor (GM-CSF) under clozapine treatment: a case report.

    PubMed

    Ferrea, Stefano; Fehsel, Karin; Cordes, Joachim; Luckhaus, Christian

    2010-03-01

    Agranulocytosis is a severe side effect of clozapine which requires stopping this medication immediately in the case of progressive neutropenia. There are, however, cases of benign neutropenia under clozapine that do not progress. The ability to predict progression vs. non-progression in neutropenia cases under clozapine would be highly valuable for avoiding unnecessary treatment withdrawals. In this context, we closely monitored circadian neutrophil counts and granulocyte macrophage-colony stimulating factor (GM-CSF) levels in a patient who had low normal neutrophil counts at baseline and developed neutropenia under clozapine treatment. Venous blood samples were drawn in close intervals for 4 weeks. At several time points blood was sampled in the morning between 08:30 and 9:30 h and a second time in the afternoon between 14:00 and 15:00 h. The circadian rhythm of neutrophil counts and GM-CSF levels was unchanged. There was no progression to agranulocytosis, and clozapine could be continued. In view of the available literature and the presented case it is suggested that further studying of circadian profiles of neutrophil counts, neutrophil regulatory factors, such as GM-CSF, and their intercorrelation may help to find a biomarker of benign vs. malign neutropenia under clozapine.

  10. Presynaptic Dopamine Capacity in Patients with Treatment-Resistant Schizophrenia Taking Clozapine: An [(18)F]DOPA PET Study.

    PubMed

    Kim, Euitae; Howes, Oliver D; Veronese, Mattia; Beck, Katherine; Seo, Seongho; Park, Jin Woo; Lee, Jae Sung; Lee, Yun-Sang; Kwon, Jun Soo

    2017-03-01

    Some patients with schizophrenia show poor response to first-line antipsychotic treatments and this is termed treatment-resistant schizophrenia. The differential response to first-line antipsychotic drugs may reflect a different underlying neurobiology. Indeed, a previous study found dopamine synthesis capacity was significantly lower in patients with treatment-resistant schizophrenia. However, in this study, the treatment-resistant patients were highly symptomatic, whereas the responsive patients showed no or minimal symptoms. The study could not distinguish whether this was a trait effect or reflected the difference in symptom levels. Thus, we aimed to test whether dopaminergic function is altered in patients with a history of treatment resistance to first-line drugs relative to treatment responders when both groups are matched for symptom severity levels by recruiting treatment-resistant patients currently showed low symptom severity with the clozapine treatment. Healthy controls (n=12), patients treated with clozapine (n=12) who had not responded to first-line antipsychotics, and patients who had responded to first-line antipsychotics (n=12) were recruited. Participants were matched for age and sex and symptomatic severity level in patient groups. Participants' dopamine synthesis capacity was measured by using [(18)F]DOPA PET. We found that patients treated with clozapine show lower dopamine synthesis capacity than patients who have responded to first-line treatment (Cohen's d=0.9191 (whole striatum), 0.7781 (associative striatum), 1.0344 (limbic striatum), and 1.0189 (sensorimotor striatum) in line with the hypothesis that the dopaminergic function is linked to treatment response. This suggests that a different neurobiology may underlie treatment-resistant schizophrenia and that dopamine synthesis capacity may be a useful biomarker to predict treatment responsiveness.

  11. 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.

  12. Risks and Benefits of Rapid Clozapine Titration

    PubMed Central

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

    2016-01-01

    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. PMID:27403276

  13. 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…

  14. Augmentation of clozapine with electroconvulsive therapy in treatment resistant schizophrenia: A systematic review and meta-analysis.

    PubMed

    Lally, John; Tully, John; Robertson, Dene; Stubbs, Brendon; Gaughran, Fiona; MacCabe, James H

    2016-03-01

    The primary aim of this systematic review and meta-analysis was to assess the proportion of patients with Treatment Resistant Schizophrenia (TRS) that respond to ECT augmentation of clozapine (C+ECT). We searched major electronic databases from 1980 to July 2015. We conducted a random effects meta-analysis reporting the proportion of responders to C+ECT in RCTs and open-label trials. Five clinical trials met our eligibility criteria, allowing us to pool data from 71 people with TRS who underwent C+ ECT across 4 open label trials (n=32) and 1 RCT (n=39). The overall pooled proportion of response to C+ECT was 54%, (95% CI: 21.8-83.6%) with some heterogeneity evident (I(2)=69%). With data from retrospective chart reviews, case series and case reports, 192 people treated with C+ECT were included. All studies together demonstrated an overall response to C+ECT of 66% (95% CI: 57.5-74.3%) (83 out of 126 patients responded to C+ECT). The mean number of ECT treatments used to augment clozapine was 11.3. 32% of cases (20 out of 62 patients) with follow up data (range of follow up: 3-468weeks) relapsed following cessation of ECT. Adverse events were reported in 14% of identified cases (24 out of 166 patients). There is a paucity of controlled studies in the literature, with only one single blinded randomised controlled study located, and the predominance of open label trials used in the meta-analysis is a limitation. The data suggests that ECT may be an effective and safe clozapine augmentation strategy in TRS. A higher number of ECT treatments may be required than is standard for other clinical indications. Further research is needed before ECT can be included in standard TRS treatment algorithms.

  15. The Business Case for Expanded Clozapine Utilization.

    PubMed

    Gören, Jessica L; Rose, Adam J; Smith, Eric G; Ney, John P

    2016-11-01

    In most settings, less than 25% of patients with treatment-resistant schizophrenia receive clozapine, the only medication proven effective for treatment-resistant schizophrenia. Therefore, a business case analysis was conducted to assess whether increasing clozapine utilization for treatment-resistant schizophrenia in a health care system would result in direct health care cost savings. Veterans with treatment-resistant schizophrenia who were treated in the Veterans Health Administration (VHA) were studied. Treatment response, suicides, adverse drug reactions (and associated mortality), and effects on inpatient hospitalization related to clozapine were derived from a systematic review of published studies. A one-factor sensitivity analysis and a probabilistic sensitivity analysis (PSA) with Monte Carlo simulation were conducted to calculate the cost-benefits of increased clozapine utilization. Despite monitoring costs, in the base case analysis, the VHA would save $22,444 per veteran with treatment-resistant schizophrenia over the first year of clozapine therapy, primarily from 18.6 fewer inpatient days per patient. If current utilization was doubled, and 50% of those veterans continued clozapine treatment for one year, VHA would save an estimated $80 million. Cost savings were most sensitive to the proportion of treatment-resistant patients who received clozapine, decrease in inpatient days, cost of inpatient stays, clozapine response rate, and number of patients with treatment-resistant schizophrenia. In the PSA, initiation of clozapine for all VHA patients with treatment-resistant schizophrenia who were not currently treated with clozapine would save at least $290 million in 95% of simulations. Increased clozapine utilization would result in net cost savings for the VHA.

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

    PubMed Central

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

    2015-01-01

    Background 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. Method 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. Aims 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. Conclusions 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. Declaration of interest 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. Copyright and usage © 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. PMID:27703725

  17. 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.

  18. Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

    PubMed Central

    Nosè, Michela; Accordini, Simone; Artioli, Paola; Barale, Francesco; Barbui, Corrado; Beneduce, Rossella; Berardi, Domenico; Bertolazzi, Gerardo; Biancosino, Bruno; Bisogno, Alfredo; Bivi, Raffaella; Bogetto, Filippo; Boso, Marianna; Bozzani, Alberto; Bucolo, Piera; Casale, Marcello; Cascone, Liliana; Ciammella, Luisa; Cicolini, Alessia; Cipresso, Gabriele; Cipriani, Andrea; Colombo, Paola; Dal Santo, Barbara; De Francesco, Michele; Di Lorenzo, Giorgio; Di Munzio, Walter; Ducci, Giuseppe; Erlicher, Arcadio; Esposito, Eleonora; Ferrannini, Luigi; Ferrato, Farida; Ferro, Antonio; Fragomeno, Nicoletta; Parise, Vincenzo Fricchione; Frova, Maria; Gardellin, Francesco; Garzotto, Nicola; Giambartolomei, Andrea; Giupponi, Giancarlo; Grassi, Luigi; Grazian, Natalia; Grecu, Lorella; Guerrini, Gualtiero; Laddomada, Francesco; Lazzarin, Ermanna; Lintas, Camilla; Malchiodi, Francesca; Malvini, Lara; Marchiaro, Livio; Marsilio, Alessandra; Mauri, Massimo Carlo; Mautone, Antonio; Menchetti, Marco; Migliorini, Giuseppe; Mollica, Marco; Moretti, Daniele; Mulè, Serena; Nicholau, Stylianos; Nosè, Flavio; Occhionero, Guglielmo; Pacilli, Anna Maria; Pecchioli, Stefania; Percudani, Mauro; Piantato, Ennio; Piazza, Carlo; Pontarollo, Francesco; Pycha, Roger; Quartesan, Roberto; Rillosi, Luciana; Risso, Francesco; Rizzo, Raffella; Rocca, Paola; Roma, Stefania; Rossattini, Matteo; Rossi, Giuseppe; Rossi, Giovanni; Sala, Alessandra; Santilli, Claudio; Saraò, Giuseppe; Sarnicola, Antonio; Sartore, Francesca; Scarone, Silvio; Sciarma, Tiziana; Siracusano, Alberto; Strizzolo, Stefania; Tansella, Michele; Targa, Gino; Tasser, Annamarie; Tomasi, Rodolfo; Travaglini, Rossana; Veronese, Antonio; Ziero, Simona

    2009-01-01

    Background One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study. Methods/Design The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome. Discussion The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol

  19. Clozapine and risperidone: combination/augmentation treatment of refractory schizophrenia: a preliminary observation.

    PubMed

    Raskin, S; Katz, G; Zislin, Z; Knobler, H Y; Durst, R

    2000-04-01

    Clozapine and risperidone were the first two antipsychotic drugs of a new class of agents for the pharmacotherapy of schizophrenia. It has been suggested that refractory schizophrenic patients who fail to respond to neither clozapine nor risperidone may respond to a combination/augmentation strategy of both medicaments. Three cases of individuals with unremittent schizophrenia treated via this combination are presented. Response was evaluated by clinical follow-up and PANSS rating scale. Good clinical results with no noticeable adverse side effects, ascertained by a reduction from baseline scores of the Positive and Negative Syndrome Scale (PANSS) were obtained in all three patients. The findings from this pilot study suggest this combination as a possible therapeutic approach for treating resistant schizophrenic patients.

  20. Capillary compared to venous blood sampling in clozapine treatment: patients׳ and healthcare practitioners׳ experiences with a point-of-care device.

    PubMed

    Bogers, Jan P A M; Bui, Hong; Herruer, Martien; Cohen, Dan

    2015-03-01

    Underuse of the antipsychotic clozapine for schizophrenia is an impediment to improving outcomes for patients. Because of its possible severe side effects, including granulocytopenia or even agranulocytosis, clozapine treatment entails regular WBC monitoring, which can be a major drawback for patients and practitioners. The HemoCue WBC DIFF system is a point-of-care device using capillary blood sampling which provides WBC counts with differentials, including granulocytes. We investigated if capillary sampling instead of conventional venous sampling might diminish the burden for patients and practitioners and motivate them to continue clozapine treatment. A randomized cross-over trial design was used to compare the two sampling methods. Patients׳ subjective experiences of various aspects of blood sampling were rated on a 10-cm visual analogue scale (VAS). Patients and practitioners were also asked if they had any preference for venous or capillary sampling and patients were asked if the sampling method influenced their motivation to continue clozapine treatment. Seventy-three patients were included in this study. Three dropped out before completion. The VAS ratings on all five aspects and the total burden experienced showed a consistent pattern favouring capillary blood sampling (p<0.001). This pattern was more pronounced for inpatients than for outpatients. Patients strongly preferred capillary testing (p<0.001). The method used moderately influenced their motivation for clozapine therapy. In this study patients tolerated capillary blood testing with a point-of-care device better than traditional venous sampling at a laboratory and practitioners also preferred it. Using this method might therefore boost clozapine prescription rates.

  1. Effectiveness of ultra-rapid dose titration of clozapine for treatment-resistant bipolar mania: case series

    PubMed Central

    Turan, Şenol; Demirel, Ömer Faruk; Usta Sağlam, Nazife Gamze; Yıldız, Nazım; Duran, Alaattin

    2015-01-01

    Treatment of severe and refractory manic episodes in hospital settings can occasionally be very difficult. In particular, severely excited patients showing aggressive, hostile, impulsive behaviours frequently require physical restraint and seclusion, high doses of antipsychotics and benzodiazepines, and sometimes, electroconvulsive therapy. Hospital stay is generally prolonged and such patients cause great emotional distress for other patients in the ward and clinical staff involved in their care. Here we report on three patients with a diagnosis of bipolar disorder and one patient with a diagnosis of schizoaffective disorder bipolar subtype, all of whom were hospitalized for severe manic episodes with psychotic features. These patients were extremely difficult to manage in the ward as no response could be obtained in the first week of treatment despite high doses of antipsychotics and benzodiazepine administration. The introduction and rapid titration of clozapine proved remarkably effective and was well tolerated in the acute management of these patients. We observed that clozapine had a superior and fast mood stabilization effect with rapid titration and could be extremely helpful in the management of such patients. PMID:26301080

  2. Effectiveness of ultra-rapid dose titration of clozapine for treatment-resistant bipolar mania: case series.

    PubMed

    Aksoy Poyraz, Cana; Turan, Şenol; Demirel, Ömer Faruk; Usta Sağlam, Nazife Gamze; Yıldız, Nazım; Duran, Alaattin

    2015-08-01

    Treatment of severe and refractory manic episodes in hospital settings can occasionally be very difficult. In particular, severely excited patients showing aggressive, hostile, impulsive behaviours frequently require physical restraint and seclusion, high doses of antipsychotics and benzodiazepines, and sometimes, electroconvulsive therapy. Hospital stay is generally prolonged and such patients cause great emotional distress for other patients in the ward and clinical staff involved in their care. Here we report on three patients with a diagnosis of bipolar disorder and one patient with a diagnosis of schizoaffective disorder bipolar subtype, all of whom were hospitalized for severe manic episodes with psychotic features. These patients were extremely difficult to manage in the ward as no response could be obtained in the first week of treatment despite high doses of antipsychotics and benzodiazepine administration. The introduction and rapid titration of clozapine proved remarkably effective and was well tolerated in the acute management of these patients. We observed that clozapine had a superior and fast mood stabilization effect with rapid titration and could be extremely helpful in the management of such patients.

  3. Clozapine and Fever: A Case of Continued Therapy With Clozapine.

    PubMed

    Bruno, Valentina; Valiente-Gómez, Alicia; Alcoverro, Oscar

    2015-01-01

    Clozapine is a major atypical antipsychotic drug used in treatment-resistant schizophrenia (Patel and Allin. Ther Adv Psychopharmacol 2011;1:25-29). It interferes with dopamine binding to D1, D2, D3, and D5 receptors but has high affinity to D4. It also has an anticholinergic effect and antagonizes α-adrenergic, histaminergic, and serotoninergic receptors (Oerther and Ahlenius. J Pharmacol Exp Ther 2000;292:731-736). Clozapine has proved effective in treating positive and negative symptoms in patients with refractory schizophrenia, thus accounting for its frequent use. Despite its effectiveness, this drug is not without its adverse effects. The most well known is agranulocytosis. There are, however, many others, such as myocarditis, aspiration pneumonia, ileus, fever, hyperglycemia, hyperlipidemia, hypertriglycemia, tachycardia, and weight gain, among others (Bruijnzeel et al. Asian J Psychiatr 2014;11:3-7). Fever induced by clozapine is a common phenomenon (Lowe et al. Ann Pharmacother 2007;41:1700-1704), which usually occurs in the first 4 weeks of treatment, and its prevalence oscillates from 0.5% and 55%, depending on the study (Jeong et al. Schizophr Res 2002;56:191-193; Young et al. Schizophr Bull 1998;24:381-390). The fever lasts for 2.5 days on average, and unless the treatment is discontinued, it generally abates between day 8 and 16 of treatment (Kohen et al. Ann Pharmacother 2009;43:143-146). There are several different theories about the physiopathological mechanism; it could be a variation of malignant neuroleptic syndrome, an infection secondary to neutropenia, and allergic reaction or the emergence of the immunomodulating effect of clozapine. Some case reports in the bibliography have shown that patients in treatment with clozapine can develop a mild leukocytosis, but the presence of other concurrent symptoms, which indicate infection, is not common (Tham and Dickson. J Clin Psychiatry 2002;63:880-884). The theory of an allergic reaction is

  4. Combined Clozapine and Electroconvulsive Therapy in a Japanese Schizophrenia Patient: A Case Report

    PubMed Central

    Ozaki, Yuki; Kawasoe, Koichiro; Ochi, Shinichiro; Niiya, Takanori; Sonobe, Naomi; Matsumoto, Teruhisa; Ueno, Shu-ichi

    2014-01-01

    Clozapine is well-known for successful use in schizophrenic patients treatment resistant to other antipsychotics. However, even with clozapine, 25% of schizophrenic patients are not in remission. Recently, as adjunctive treatment with clozapine, electroconvulsive therapy has been reported to be an effective and safe adjunctive treatment. We report a Japanese schizophrenic woman who was not in remission with clozapine alone but with both clozapine and electroconvulsive therapy. PMID:25191508

  5. Restarting clozapine after neutropenia: evaluating the possibilities and practicalities.

    PubMed

    Whiskey, Eromona; Taylor, David

    2007-01-01

    Clozapine remains the antipsychotic of choice for refractory schizophrenia despite its propensity for serious blood disorders. When neutropenia or agranulocytosis occur in people taking clozapine, cessation of treatment is mandated and relapse often results. Because such patients are usually unresponsive to other antipsychotics, many clinicians consider restarting clozapine, despite the risks involved. However, the risks of clozapine rechallenge vary according to the cause and nature of the blood dyscrasia. Neutropenia can arise because of factors unrelated or indirectly related to clozapine treatment. These include benign ethnic neutropenia, concomitant drug therapy, co-existing medical conditions and drug interactions. In such cases, clozapine may be restarted if non-clozapine causes of neutropenia are identified and eliminated, although concurrent treatment with lithium (to induce leukocytosis) is sometimes necessary. Close monitoring of the patient is essential because it is rarely possible to completely rule out the contribution of clozapine to the blood dyscrasia and because lithium does not protect against clozapine-related agranulocytosis. In cases of clozapine-induced neutropenia (as distinct from agranulocytosis, which may have a different pathology) rechallenge may also be considered and, again, lithium co-therapy may be required. Where clozapine is clearly the cause of agranulocytosis, rechallenge should not be considered or undertaken unless there are very exceptional circumstances (severe and prolonged relapse following clozapine discontinuation). In these cases, re-exposure to clozapine may rarely be attempted where there are facilities for very close and frequent monitoring. Granulocyte colony-stimulating factor is likely to be required as co-therapy, given the very high likelihood of recurrence. Uncertainty over the likely cause of blood dyscrasia in people taking clozapine, coupled with uncertainty over the mechanism by which clozapine causes both

  6. The importance of the recognition of benign ethnic neutropenia in black patients during treatment with clozapine: case reports and database study.

    PubMed

    Whiskey, Eromona; Olofinjana, Olubanke; Taylor, David

    2011-06-01

    Clozapine is the treatment of choice in refractory schizophrenia. Its more extensive use is limited by adverse effects and the need for regular blood monitoring. However, black patients are disadvantaged with respect to clozapine usage. Lower baseline Absolute Neutrophil Count compared with Whites leads to a greater frequency of blood testing, treatment interruptions and discontinuation. This may in part be explained by Benign Ethnic Neutropenia, but too few black patients are thus registered. The four cases described in this report underline some of the difficulties if this problem is under-recognized. Moreover, in our sample of 191 clozapine recipients in an inner London hospital, black patients account for approximately half, but only a small proportion, 8/95 (8.4%) are registered as having Benign Ethnic Neutropenia. None of the Benign Ethnic Neutropenia-registered patients discontinued treatment for haematological reasons. To optimize clozapine treatment and improve long-term outcomes, a significantly greater proportion of Black patients should be registered as having Benign Ethnic Neutropenia.

  7. Ciprofloxacin strongly inhibits clozapine metabolism: two case reports.

    PubMed

    Brouwers, E E M; Söhne, M; Kuipers, S; van Gorp, E C M; Schellens, J H M; Koks, C H W; Beijnen, J H; Huitema, A D R

    2009-01-01

    We report on two cases of drug-drug interactions between ciprofloxacin and clozapine. The first case was a 46-year-old male patient receiving a daily dose of clozapine 900 mg. He was admitted to hospital with urosepsis and was treated with a 5-day course of ciprofloxacin and amoxicillin. Two days after completion of antibacterial therapy, the patient developed symptoms of rhabdomyolysis. Clozapine therapy was discontinued and measurement of the patient's clozapine plasma concentration 1 day after cessation of clozapine therapy and 3 days after cessation of ciprofloxacin treatment showed that it was in excess of recommended therapeutic levels. The second patient was a 58-year-old male patient treated with a daily dose of clozapine 300 mg. He was admitted to hospital because of delirium and suspected urinary tract infection or pneumonia. Treatment with ciprofloxacin was initiated. Measurement of clozapine plasma concentrations prior to and 3 days after commencement of ciprofloxacin showed that clozapine concentrations doubled over that time period. We suggest that inhibition of cytochrome P450 (CYP) enzymes 1A2 and 3A4 by ciprofloxacin resulted in delayed clozapine metabolism and elevated clozapine plasma concentrations. This might cause severe adverse effects. We advise using another antibacterial agent or reducing the clozapine dose and monitoring clozapine levels when this antipsychotic agent is used in combination with ciprofloxacin.

  8. [Relationship between clozapine plasma levels and withdrawal symptoms].

    PubMed

    Berecz, R; de la Rubia Martínez, A; Norberto Gamero, M J; Gutiérrez Casares, J R; Glaub, T; Degrell, I; Llerena, A

    2002-01-01

    Discontinuation of clozapine and an attempt to change his medication to sertindol has led to serious psychotic and somatic symptoms in an schizophrenic patient treated with clozapine for five years, however after readministration of clozapine these symptoms rapidly disappeared. To further analyse the case we have developed an HPLC method for the measurement of plasma levels of clozapine and its main metabolite N-desmethyl clozapine in order to monitor the plasma levels of clozapine and to correlate with the clinical symptoms. The present results confirmed that after discontinuation of clozapine no measurable amount of drug or its main metabolite were present in the plasma of the patient. The correlation between the plasma levels of clozapine and the changes in the clinical state of the patient confirmed that the patient's severe psychotic and somatic symptoms were the result of discontinuation of clozapine treatment. The clozapine plasma concentration of the patient reported here was low (100 ng/ml) compared to the generally accepted plasma levels for antipsychotic action of clozapine (350 ng/ml), however the somatic and psychotic clozapine withdrawal symptoms rapidly and completely disappeared.

  9. Clozapine safety, 40 years later.

    PubMed

    Raja, Michele; Raja, Silvia

    2014-01-01

    Clozapine is, and will remain in the coming years, an irreplaceable drug in psychiatry which has elective indication in treatment-resistant schizophrenia, suicide risk in schizophrenia spectrum disorders, aggressiveness or violence in psychiatric patients, psychosis in Parkinson's disease, prevention and treatment of tardive dyskinesia. Unfortunately, the drug is largely underused for many and serious side effects. Only a good knowledge of these side effects and of the main strategies to prevent their occurrence or minimize their impact can allow overcoming the underutilization of this valuable therapy. The article describes the clinical and epidemiological features of the non-motor side effects of clozapine including blood dyscrasias, constipation, diabetes, enuresis, fever, hepatitis, hypersalivation, ileus, myocarditis, nephritis, priapism, seizures, serositis, weight gain and metabolic syndrome. The paper suggests several strategies, supported by scientific evidence, in the management of these side effects. The neuropsychiatric side effects of clozapine are not discussed in this review.

  10. 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; I(2) = 62%), separating the two groups as early as weeks 1-2 with an SMD of -0.58 (p<0.00001; I(2) = 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.

  11. [Therapeutic drug monitoring of clozapine].

    PubMed

    Djerada, Zoubir; Daviet, Françoise; Llorca, Pierre-Michel; Eschalier, Alain; Saint-Marcoux, Franck; Bentué-Ferrer, Danièle; Libert, Fréderic

    2016-08-24

    Clozapine is a prototypical atypical antipsychotic used to treat severe schizophrenia and for which a therapeutic drug monitoring (TDM) is quite commonly proposed. Clozapine is rapidly absorbed (maximum concentration reached within 1 to 4hours), and is extensively metabolized in the liver by CYP1A2 to an active metabolite (and to a lesser extent, to inactive metabolites via other enzymes). Its half-life is 8 to 16h. A therapeutic range has been proposed for clozapine as some studies have reported both a relationship between low plasmatic concentrations and resistance to treatment (threshold level is likely between 250 and 400μg/L), and a relationship between high plasmatic concentrations and an increase in the occurrence of toxicity (alert level=1000μg/L). Given the data obtained in different studies, the TDM was evaluated for this molecule, to recommended.

  12. Severe Relapsing Clozapine-Withdrawal Catatonia

    PubMed Central

    Shahrour, Tarek; Siddiq, Muez; Ghalib, Saad

    2015-01-01

    Catatonia as a clozapine-withdrawal syndrome has only been documented in the medical literature as case reports. We are reporting a case in which a 32-year-old man develops a catatonic state upon withdrawal of clozapine. The state was quite severe and needed ICU admission. The course was chronic and intermittent which we think was caused by the poor adherence to antipsychotics. The importance of identifying such cases early is underlined. PMID:26788394

  13. Generic clozapine: a cost-saving alternative to brand name clozapine?

    PubMed

    Tse, Gordon; Thompson, Deborah; Procyshyn, Ric M

    2003-01-01

    As a consequence of its prevalence, early onset and chronicity, schizophrenia imposes clinical and economic impediments to healthcare practitioners and society alike. Among the many antipsychotics available to treat the symptoms of this devastating illness, clozapine has emerged and differentiated itself from the others as the agent most efficacious for the treatment of refractory patients. Since the patent for Clozaril (Novartis) expired in 1998, three manufacturers of generic clozapine have submitted abbreviated new drug applications to the US FDA for review and approval to market a generic clozapine product. In each case, the US FDA deemed the generic formulations to be bioequivalent to the brand name Clozaril. Apart from case reports, industry-sponsored studies have been conducted comparing Clozaril with two generic formulations. In one case, a generic formulation of clozapine manufactured by Creighton Products Corporation (formerly a subsidiary [generic house] of Sandoz Pharmaceuticals) was found to be bioequivalent to Clozaril. On the other hand, studies (sponsored by Novartis) have challenged the bioequivalence, therapeutic equivalence and interchangeability between Clozaril and a generic formulation manufactured by Zenith Goldline Pharmaceuticals (now IVAX Corporation). The IVAX Corporation-sponsored studies refuted these claims citing data from two patient registry database studies and one small clinical trial. Apart from a single in-house bioequivalence study, no further investigations have been conducted with a third generic formulation manufactured by Mylan Pharmaceutical. Although the clinical significance of the above discrepancy is obvious, what is less than obvious is the pharmacoeconomic implications that arises from this debate. Clearly, if the brand name and generic formulations are 'truly' bioequivalent, then the cost savings realised would be the difference in acquisition cost. On the other hand, if the various formulations are not

  14. Neuroleptic-resistant schizophrenic patients treated by clozapine: clinical evolution, plasma and red blood cell clozapine and desmethylclozapine levels.

    PubMed

    Aymard, N; Baldacci, C; Leyris, A; Smagghe, P O; Tribolet, S; Vacheron, M N; Viala, A; Caroli, F

    1997-01-01

    The aim of this open study was to determine a more rational therapeutic approach for psychotic patients treated with clozapine for several months, using measurement of plasma and red blood cell levels (P, RBC) of clozapine (cloza) and N-desmethylclozapine (descloza), the major metabolite of clozapine, which has been reported to be less active but more toxic (agranulocytosis) than clozapine itself. The RBC concentration may be considered as more representative of the free fraction drug. The study concerned 7 patients suffering from chronic paranoid schizophrenia according to the DSM-IV criteria. All of them were treatment-refractory schizophrenic inpatients (4 men, 3 women, mean age +/- SD: 38.2 +/- 8.4 years; mean duration of illness +/- SD: 14.4 +/- 5.1 years). They had received at least two different neuroleptics, for 6 weeks, before entering the study. Treatment started in our hospitalization unit with clozapine 25 mg up to a maximum of 900 mg/d (mean stabilized daily dose +/- SD: 507 +/- 211 mg and mean daily dose per kg: 6.91 +/- 3.08 mg). Clinical evaluations (Quality of Life Scale: QLS), regular blood monitoring and biological samples were conducted at the same time, weekly for 18 weeks and then monthly (duration of the study: 4 to 38 months; mean +/- SD: 12.9 +/- 11.5 months). Plasma and RBC (after lysis) levels were determined by reversed phase HPLC and UV detection after extraction with hexane. All the patients improved very quickly after the first week of treatment and six were able to leave the hospitalization unit and start outpatient care such as daily hospitalization, returning home or in sheltered accommodation. With the following plasma (P) and RBC levels: mean cloza +/- SD: (P = 294 +/- 146 ng/ml; RBC = 110 +/- 82 ng/ml) and mean descloza +/- SD: (P = 173 +/- 106 ng/ml; RBC = 76 +/- 54 ng/ml); none of the seven patients developed agranulocytosis. The blood levels, ensuring better surveillance, have a predictive value for clinical improvement. A

  15. [Chronic migraine: treatment].

    PubMed

    Pascual, Julio

    2012-04-10

    We define chronic migraine as that clinical situation in which migraine attacks appear 15 or more days per month. Until recently, and in spite of its negative impact, patients with chronic migraine were excluded of the clinical trials. This manuscript revises the current treatment of chronic migraine. The first step should include the avoidance of potential precipitating/aggravating factors for chronic migraine, mainly analgesic overuse and the treatment of comorbid disorders, such as anxiety and depression. The symptomatic treatment should be based on the use of nonsteroidal anti-inflammatory agents and triptans (in this case < 10 days per month). It is necessary to avoid the use of combined analgesics, opioids and ergotamine-containing medications. Preventive treatment includes a 'transitional' treatment with nonsteroidal anti-inflammatory agents or steroids, while preventive treatment exerts its actions. Even though those medications efficacious in episodic migraine prevention are used, the only drugs with demonstrated efficacy in the preventive treatment of chronic migraine are topiramate and pericranial infiltrations of Onabotulinumtoxin A.

  16. Association studies of genomic variants with treatment response to risperidone, clozapine, quetiapine and chlorpromazine in the Chinese Han population.

    PubMed

    Xu, Q; Wu, X; Li, M; Huang, H; Minica, C; Yi, Z; Wang, G; Shen, L; Xing, Q; Shi, Y; He, L; Qin, S

    2016-08-01

    Schizophrenia is a widespread mental disease with a prevalence of about 1% in the world population. Continuous long-term treatment is required to maintain social functioning and prevent symptom relapse of schizophrenia patients. However, there are considerable individual differences in response to the antipsychotic drugs. There is a pressing need to identify more drug-response-related markers. But most pharmacogenomics of schizophrenia have typically focused on a few candidate genes in small sample size. In this study, 995 subjects were selected for discovering the drug-response-related markers. A total of 77 single-nucleotide polymorphisms of 25 genes have been investigated for four commonly used antipsychotic drugs in China: risperidone, clozapine, quetiapine, and chlorpromazine. Significant associations with treatment response for several genes, such as CYP2D6, CYP2C19, COMT, ABCB1, DRD3 and HTR2C have been verified in our study. Also, we found several new candidate genes (TNIK, RELN, NOTCH4 and SLC6A2) and combinations (haplotype rs1544325-rs5993883-rs6269-rs4818 in COMT) that are associated with treatment response to the four drugs. Also, multivariate interactions analysis demonstrated the combination of rs6269 in COMT and rs3813929 in HTR2C may work as a predictor to improve the clinical antipsychotic response. So our study is of great significance to improve current knowledge on the pharmacogenomics of schizophrenia, thus promoting the implementation of personalized medicine in schizophrenia.The Pharmacogenomics Journal advance online publication, 18 August 2015; doi:10.1038/tpj.2015.61.

  17. Helping clozapine help: a role for support groups.

    PubMed

    Zita, David F; Goethe, John

    2002-01-01

    A successful clozapine support group operates from the principle that the drug is most successful when the person takes it as prescribed. The likelihood of initial and ongoing collaboration with treatment is increased when the tangible gains of the treatment can be experienced in the self and demonstrated in others. Clozapine support groups can advance the goals of collaboration and recovery.

  18. Acute clozapine overdose: plasma concentration and outcome.

    PubMed

    Broich, K; Heinrich, S; Marneros, A

    1998-07-01

    Clozapine is a tricyclic dibenzodiazepine derivative that is classified as an "atypical neuroleptic" drug for treatment of psychotic diseases. A 19-year-old schizophrenic female, treated with 400 mg clozapine per day, was admitted to the emergency department after ingestion of 5000 mg (50 x 100 mg tablets) of clozapine. Clozapine plasma level 2.5 hours after ingestion was 3.8 microg/ml (normal range 0.2-0.7 microg/ml) and very high in gastric lavage. Contrary to reported cases with such high plasma concentrations the patient suffered only from somnolence with intermittent periods of agitation and a mild anticholinergic syndrome with sinus tachycardia and slight hypotension. After detoxication with gastric lavage and short-term administration of pyridostigmine she remained stable, and 24 hours after ingestion she was transferred to the psychiatric unit without further sequelae. To prevent late-onset complications she was carefully monitored for five days. The clozapine plasma level 24 hours after the first measurement was normal. This case and others reported in the literature confirm that signs and symptoms after clozapine intoxication are variable and that high plasma levels are not lethal in every case.

  19. Resistin as an inflammatory marker in patients with schizophrenia treated with clozapine.

    PubMed

    Klemettilä, Jari-Pekka; Kampman, Olli; Seppälä, Niko; Viikki, Merja; Hämäläinen, Mari; Moilanen, Eeva; Leinonen, Esa

    2017-02-01

    Schizophrenia is associated with excess cardiovascular comorbidity and mortality related to lifestyle factors, such as lack of physical activity, poor diet, and smoking. The prevalence of metabolic syndrome is increased among patients with schizophrenia, with the highest rates among patients on clozapine treatment. Smoking, obesity, physical inactivity, airway inflammation and obstruction, and adipose tissue and inflammatory marker activation are related in systemic inflammation. Low-grade inflammation is also associated with schizophrenia. Adipokine resistin is a biomarker involving several acute and chronic inflammatory states. However, the inflammatory role of resistin is so far inconclusive and studies in schizophrenia are scanty. The aim of the present study was to explore the role of serum resistin as an inflammatory marker in patients with schizophrenia on clozapine treatment. Associations between serum levels of resistin and some other selected cytokines/adipokines (adiponectin, leptin, adipsin, IL-6, IL-1Ra, TNF-α, hs-CRP) and metabolic markers in 190 patients with schizophrenia on clozapine treatment were studied using a cross-sectional study design. Among male patients especially, smokers had higher levels of resistin than non-smokers, and among smokers resistin levels were associated with IL-1Ra and hs-CRP levels. In the whole patient group levels of resistin associated with levels of IL-1Ra, and among male patients with low HDL-cholesterol. Resistin is a biomarker of systemic inflammation associated with smoking among patients with schizophrenia on clozapine treatment. Resistin might have a role as a marker of cardiovascular comorbidity.

  20. 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.

  1. 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…

  2. 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…

  3. 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…

  4. Clozapine versus other atypical antipsychotics for schizophrenia.

    PubMed

    Asenjo Lobos, Claudia; Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Leucht, Stefan

    2010-11-10

    Clozapine is an atypical antipsychotic demonstrated to be superior in the treatment of refractory schizophrenia which causes fewer movement disorders. Clozapine, however, entails a significant risk of serious blood disorders such as agranulocytosis which could be potentially fatal. Currently there are a number of newer antipsychotics which have been developed with the purpose to find both a better tolerability profile and a superior effectiveness. To compare the clinical effects of clozapine with other atypical antipsychotics (such as amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, sertindole, ziprasidone and zotepine) in the treatment of schizophrenia and schizophrenia-like psychoses. We searched the Cochrane Schizophrenia Groups Register (June 2007) and reference lists of all included randomised controlled trials. We also manually searched appropriate journals and conference proceedings relating to clozapine combination strategies and contacted relevant pharmaceutical companies. All relevant randomised, at least single-blind trials, comparing clozapine with other atypical antipsychotics, any dose and oral formulations, for people with schizophrenia or related disorders. We selected trials and extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD) again based on a random-effects model. The review currently includes 27 blinded randomised controlled trials, which involved 3099 participants. Twelve randomised control trials compared clozapine with olanzapine, five with quetiapine, nine with risperidone, one with ziprasidone and two with zotepine. Attrition from these studies was high (overall 30.1%), leaving the interpretation of results problematic. Clozapine had a higher attrition rate due to adverse effects than

  5. Clozapine versus other atypical antipsychotics for schizophrenia

    PubMed Central

    Asenjo Lobos, Claudia; Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Leucht, Stefan

    2014-01-01

    Background Clozapine is an atypical antipsychotic demonstrated to be superior in the treatment of refractory schizophrenia which causes fewer movement disorders. Clozapine, however, entails a significant risk of serious blood disorders such as agranulocytosis which could be potentially fatal. Currently there are a number of newer antipsychotics which have been developed with the purpose to find both a better tolerability profile and a superior effectiveness. Objectives To compare the clinical effects of clozapine with other atypical antipsychotics (such as amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, sertindole, ziprasidone and zotepine) in the treatment of schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Groups Register (June 2007) and reference lists of all included randomised controlled trials. We also manually searched appropriate journals and conference proceedings relating to clozapine combination strategies and contacted relevant pharmaceutical companies. Selection criteria All relevant randomised, at least single-blind trials, comparing clozapine with other atypical antipsychotics, any dose and oral formulations, for people with schizophrenia or related disorders. Data collection and analysis We selected trials and extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD) again based on a random-effects model. Main results The review currently includes 27 blinded randomised controlled trials, which involved 3099 participants. Twelve randomised control trials compared clozapine with olanzapine, five with quetiapine, nine with risperidone, one with ziprasidone and two with zotepine. Attrition from these studies was high (overall 30.1%), leaving the interpretation

  6. Successful clozapine re-challenge in a patient with three previous episodes of clozapine-associated blood dyscrasia.

    PubMed

    Foster, Jessica; Lally, John; Bell, Victoria; Shergill, Sukhi

    2017-01-01

    A case is presented of a 30-year-old female with treatment-resistant schizoaffective disorder who was referred to a tertiary-level specialist psychosis service. We describe the history of clozapine trials and associated episodes of agranulocytosis and neutropenia, followed by the successfully tolerated third clozapine re-challenge within our service.

  7. Electroconvulsive therapy augmentation in clozapine-resistant schizophrenia: a prospective, randomized study.

    PubMed

    Petrides, Georgios; Malur, Chitra; Braga, Raphael J; Bailine, Samuel H; Schooler, Nina R; Malhotra, Anil K; Kane, John M; Sanghani, Sohag; Goldberg, Terry E; John, Majnu; Mendelowitz, Alan

    2015-01-01

    Up to 70% of patients with treatment-resistant schizophrenia do not respond to clozapine. Pharmacological augmentation to clozapine has been studied with unimpressive results. The authors examined the use of ECT as an augmentation to clozapine for treatment-refractory schizophrenia. In a randomized single-blind 8-week study, patients with clozapine-resistant schizophrenia were assigned to treatment as usual (clozapine group) or a course of bilateral ECT plus clozapine (ECT plus clozapine group). Nonresponders from the clozapine group received an 8-week open trial of ECT (crossover phase). ECT was performed three times per week for the first 4 weeks and twice weekly for the last 4 weeks. Clozapine dosages remained constant. Response was defined as ≥40% reduction in symptoms based on the psychotic symptom subscale of the Brief Psychiatric Rating Scale, a Clinical Global Impressions (CGI)-severity rating <3, and a CGI-improvement rating ≤2. The intent-to-treat sample included 39 participants (ECT plus clozapine group, N=20; clozapine group, N=19). All 19 patients from the clozapine group received ECT in the crossover phase. Fifty percent of the ECT plus clozapine patients met the response criterion. None of the patients in the clozapine group met the criterion. In the crossover phase, response was 47%. There were no discernible differences between groups on global cognition. Two patients required the postponement of an ECT session because of mild confusion. The augmentation of clozapine with ECT is a safe and effective treatment option. Further research is required to determine the persistence of the improvement and the potential need for maintenance treatments.

  8. Haloperidol and Clozapine Differentially Affect the Expression of Arrestins, Receptor Kinases, and Extracellular Signal-Regulated Kinase Activation

    PubMed Central

    Ahmed, Mohamed Rafiuddin; Gurevich, Vsevolod V.; Dalby, Kevin N.; Benovic, Jeffrey L.; Gurevich, Eugenia V.

    2009-01-01

    Dopamine and other G protein-coupled receptors (GPCRs) represent the major target of antipsychotic drugs. GPCRs undergo desensitization via activation-dependent phosphorylation by G protein-coupled receptor kinases (GRKs) followed by arrestin binding. Arrestins and GRKs are major regulators of GPCR signaling. We elucidated changes in expression of two arrestins and four GRKs following chronic (21 days) treatment with haloperidol (1 mg/kg i.p.) or clozapine (20 mg/kg i.p.) 2 or 24 h after the last injection in 11 brain regions. Haloperidol decreased GRK3 in ventrolateral caudate-putamen and transiently down-regulated GRK5 in globus pallidus and caudal caudate-putamen. Clozapine also caused a short-term suppression of the GRK5 expression in the caudal caudate-putamen and globus pallidus, but, unlike haloperidol, elevated GRK5 in the caudal caudate-putamen after 24 h. Unlike haloperidol, clozapine decreased arrestin2 and GRK3 in hippocampus and GRK3 in globus pallidus but increased arrestin2 in the core of nucleus accumbens and ventrolateral caudate-putamen and GRK2 in prefrontal cortex. Clozapine, but not haloperidol, induced long-term activation of extracellular signal-regulated kinase (ERK) 2 in ventrolateral caudate-putamen and transient in prefrontal cortex. The data demonstrate that haloperidol and clozapine differentially affect the expression of arrestins and GRKs and ERK activity, which may play a role in determining their clinical profile. PMID:18178904

  9. Treatment Options for Chronic Myeloproliferative Neoplasms

    MedlinePlus

    ... Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Chronic Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Chronic ...

  10. Treatment Option Overview (Chronic Myeloproliferative Neoplasms)

    MedlinePlus

    ... Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Chronic Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Chronic ...

  11. Clozapine augments delta, theta, and right frontal EEG alpha power in schizophrenic patients.

    PubMed

    Maccrimmon, D; Brunet, D; Criollo, M; Galin, H; Lawson, J S

    2012-01-01

    Objective. To explore the Quantitative EEG (QEEG) effects of established clozapine therapy regimes compared to those of previous ineffective antipsychotic regimes among 64 chronic (DSM-IV) schizophrenic patients. Methods. Data from 20 EEG channels referenced to linked ears were collected before and during maintenance clozapine therapy (mean duration 1.4 years). Absolute power was calculated in six frequency bands: delta (0.4-3.6 Hz), theta (4.2-7.8 Hz), alpha (8.2-11.8 Hz), beta1 (12.2-15.8 Hz), beta2 (16.2-19.8 Hz), and beta3 (20.2-23.8 Hz). Results. Clozapine augments power globally in the delta and theta bands, but this effect is more pronounced over frontal areas. Beta3 power was reduced. Alpha showed a frontal increase, more pronounced in the right, coupled with a posterior decrease with no net change in overall power. Conclusion. The demonstration of a significant clozapine-induced alpha topographic shift frontally and to the right is a novel discovery that may serve to encourage further investigations of subcortical structures in attempts to better understand the diverse aetiologies and optimal treatments of the schizophrenias.

  12. Clozapine Augments Delta, Theta, and Right Frontal EEG Alpha Power in Schizophrenic Patients

    PubMed Central

    MacCrimmon, D.; Brunet, D.; Criollo, M.; Galin, H.; Lawson, J. S.

    2012-01-01

    Objective. To explore the Quantitative EEG (QEEG) effects of established clozapine therapy regimes compared to those of previous ineffective antipsychotic regimes among 64 chronic (DSM-IV) schizophrenic patients. Methods. Data from 20 EEG channels referenced to linked ears were collected before and during maintenance clozapine therapy (mean duration 1.4 years). Absolute power was calculated in six frequency bands: delta (0.4–3.6 Hz), theta (4.2–7.8 Hz), alpha (8.2–11.8 Hz), beta1 (12.2–15.8 Hz), beta2 (16.2–19.8 Hz), and beta3 (20.2–23.8 Hz). Results. Clozapine augments power globally in the delta and theta bands, but this effect is more pronounced over frontal areas. Beta3 power was reduced. Alpha showed a frontal increase, more pronounced in the right, coupled with a posterior decrease with no net change in overall power. Conclusion. The demonstration of a significant clozapine-induced alpha topographic shift frontally and to the right is a novel discovery that may serve to encourage further investigations of subcortical structures in attempts to better understand the diverse aetiologies and optimal treatments of the schizophrenias. PMID:23738206

  13. 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.

  14. A review of the safety of clozapine during pregnancy and lactation.

    PubMed

    Mehta, Taylor M; Van Lieshout, Ryan J

    2017-02-01

    Clozapine is an antipsychotic used in the management of treatment-resistant schizophrenia. However, little is known about clozapine use during pregnancy and lactation, or its impact on the mother, foetus, and infant. This review aims to summarize the available literature on the safety of clozapine use during the perinatal period. EMBASE, PsycINFO, and MEDLINE were searched from their inceptions through June 2016. The review encompasses 21 studies that have examined clozapine use during pregnancy and lactation. The limited available data do not support an increased risk of congenital malformations in foetuses exposed to clozapine during pregnancy, though rates of gestational diabetes are twice as high in pregnant women using clozapine. Clozapine accumulation in foetal serum possibly contributes to increased rates of floppy infant syndrome at delivery, decreased foetal heart rate variability, and seizures in infancy. Clozapine crosses the placenta and also accumulates in breast milk, which may increase the risk of agranulocytosis in infants and may necessitate infant testing. The majority of these data come from case reports and case series, making it unclear if the published risks associated with clozapine are due to mental illness, lifestyle factors, or co-treatment with other psychotropic medications. While the available literature on clozapine use during the perinatal period is very limited, the risks of clozapine use during pregnancy and the postpartum period should be discussed with women and weighed against those associated with other treatments and partially or untreated schizophrenia.

  15. [Blood clozapine level and therapeutic adjustment].

    PubMed

    Préterre, P

    1995-06-01

    We specify first the pharmacokinetic parameters of clozapine and the utilized dosage technique. In forty-four patients, aged 40 (25-66), suffering from schizophrenia developing for 20 years, with 11 years of hospitalisation. Clozapine has been prescribed for at least three months (until 44 months). We base ourselves on the opinion of the clinicians to show that the measurement of the plasma level can improve therapeutic-results. We analyse different situations where the adaptation of the posology is usefully conditioned by clozapinemia, particularly in case of important side effects, of high posology (over 600 mg) and of non response or inadequate response to the treatment.

  16. Sudden cardiac death with clozapine and sertraline combination.

    PubMed

    Hoehns, J D; Fouts, M M; Kelly, M W; Tu, K B

    2001-01-01

    To report a case of sudden cardiac death in a patient receiving combination therapy with clozapine and sertraline. A 26-year-old white man was discovered dead at his residence. His medical history included chronic paranoid schizophrenia, obsessive-compulsive disorder, major depressive disorder, obstructive sleep apnea, and akathisia. He had no prior history of cardiovascular disease. His medication regimen included clozapine 100 mg twice daily (started 4 y prior to his death), risperidone 3 mg twice daily, sertraline 200 mg once daily, atenolol 50 mg twice daily, and lorazepam 0.5 mg four times daily. Autopsy and toxicology studies revealed cardiomegaly suggestive of idiopathic cardiomyopathy, single-vessel coronary artery disease, sertraline and clozapine blood concentrations in the expected range, undetectable lorazepam and risperidone blood concentrations, obesity, and moderate fatty changes to the liver. The most likely cause of death was sudden cardiac death due to acute cardiac arrhythmia. Clozapine is structurally similar to the tricyclic antidepressants, which have type 1 A antiarrhythmic properties. Case reports have described electrocardiographic abnomalities, cardiomyopathy, and fatal myocarditis associated with its use. Unexplained death in patients on clozapine therapy has also been reported. Sertraline appears to have less cardiac effect; however, one report has observed clinically significant QT prolongation during sertraline therapy. Clozapine-induced cardiomyopathy and cardiac arrhythmia from clozapine and/or sertraline use may have contributed to this man's death.

  17. Cytochrome P450 and therapeutic drug monitoring with respect to clozapine.

    PubMed

    Buur-Rasmussen, B; Brøsen, K

    1999-12-01

    Clozapine is an atypical antipsychotic drug that is mainly used for the treatment of refractory schizophrenia. Clozapine is eliminated by oxidation in the liver, predominantly by cytochrome P4501A2 (CYP1A2). Due to the influence of inhibitors, inducers and genetic factors on CYP1A2-activity, several studies have reported a very large interindividual variability in clozapine plasma concentrations at a fixed dose. A number of methods have been published for the measurement of clozapine and metabolites in plasma. Plasma concentrations are most frequently measured by high-performance liquid chromatography. Most methods measure clozapine and the main metabolite, norclozapine, whereas two methods measure clozapine and two metabolites. Several studies suggest that a minimum effective clozapine plasma concentration of >350 microg/l must be achieved in order to ensure acceptable clinical response, whereas the upper limit of the therapeutic interval not yet has been clearly defined. The occurrence of agranulocytosis, the most serious side-effect of clozapine treatment does not seem to be dose-related and it is not possible to predict which patients are at risk of developing agranulocytosis. The risk of central nervous system side-effects seems to increase with concentrations above 1300 microg/l. Monitoring of clozapine plasma concentrations is recommended during concomitant use of other drugs that are known to interact with the oxidation of clozapine, such as carbamazepine (inducer) or fluvoxamine (inhibitor). Overall, it is concluded that therapeutic drug monitoring may be of value in the clinical management of clozapine.

  18. Impact of clozapine prescription on inpatient resource utilization.

    PubMed

    Sernyak, M J; Rosenheck, R; Desai, R; Stolar, M; Ripper, G

    2001-11-01

    Although clozapine has been demonstrated to be clinically superior to typical neuroleptics in refractory schizophrenia, it is also more expensive. It had been hoped that the increased costs associated with its use would be offset by decreases in the utilization of other expensive resources, especially inpatient care. All patients who had clozapine initiated during an inpatient hospitalization within the VA for schizophrenia over a 4-year period (N = 1415) were matched with a comparison group (N = 2,830) on key service utilization variables and other possible confounding demographic and clinical variables using propensity scoring-an accepted statistical method, although still relatively little used in psychiatry. By using centralized VA databases, subsequent inpatient resource utilization for the 3 years after index discharge was examined. Veterans exposed to clozapine while inpatients recorded 33 (36%) more inpatient days in the subsequent 3 years after discharge than the comparison group (124 +/- 190 days vs. 91 +/- 181 days, p = .0002). When all patients exposed to clozapine were divided according to whether they had received 1 year of clozapine treatment after discharge, those that received less than 1 year's treatment recorded significantly more inpatient days than either those maintained on clozapine or controls. These results suggest that in actual practice clozapine treatment may cost substantially more than treatment with conventional neuroleptics.

  19. Impact of Pharmacist Counselling on Clozapine Knowledge

    PubMed Central

    Young, Ailish

    2017-01-01

    Clozapine is the only antipsychotic with evidence for efficacy in treatment of resistant schizophrenia but it carries a high side effect burden. Patient information is provided but may be poorly retained. This study aims to examine the impact of pharmacist counselling upon patient knowledge of clozapine. Outpatients, aged 18 years and over, attending St. Patrick's University Hospital, Dublin, participated in this study between June and August 2015. The intervention consisted of pharmacist counselling on two occasions one month apart. Knowledge was assessed using a 28-point checklist devised from the currently available clozapine patient information sources, at baseline and after each counselling session. Ethics approval was obtained. Twenty-five participants (40% female; mean age 45.1 years, SD 9.82; 64% unemployed, 28% smokers) showed an improvement in knowledge scores of clozapine from baseline to postcounselling on each occasion with an overall improvement in knowledge score, from baseline to postcounselling at one month, of 39.43%; p < 0.001. This study adds to the evidence that interventions involving pharmacist counselling can improve patient knowledge, whilst the specific knowledge gained relating to recognition of side effects may help patients towards more empowerment regarding their treatment. PMID:28695011

  20. 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.

  1. Amisulpride Augmentation for Clozapine-Refractory Positive Symptoms: Additional Benefit in Reducing Hypersialorrhea

    PubMed Central

    Bogorni, Fabiani; Moreira, Frederico Fernandes; Pimentel, Eduardo Mylius; Grohs, Géder Evandro Motta; Diaz, Alexandre Paim

    2015-01-01

    One-third to half of patients taking clozapine suffer from refractory symptoms despite adequate treatment. Among other adverse effects, clozapine-induced hypersalivation (CIH) occurs in approximately half of all patients. This is a case of a 30-year-old male with refractory schizophrenia; in this patient, the remission of residual positive symptoms, as well as the reduction of CIH, was achieved by treatment with clozapine augmented with amisulpride. PMID:25838958

  2. Inflammatory response to clozapine in the absence of myocarditis: case report

    PubMed Central

    Gee, Siobhan; Shergill, Sukhi S.

    2016-01-01

    Summary A case is presented of a 25-year-old man with treatment-resistant paranoid schizophrenia whose only previous trial of clozapine had been stopped following a suspected clozapine-induced myocarditis. Due to the failure of his psychosis to respond to a number of antipsychotic treatments and augmentation strategies, clozapine was restarted on admission. His rechallenge was marked by intermittent pyrexia, tachycardia and elevated C-reactive protein (CRP), but eosinophilia was absent. Clozapine was started and then stopped twice following extensive investigation and with specialist cardiology consultation. Physical symptoms and CRP elevation resolved shortly after clozapine cessation. We believe this constituted an idiosyncratic systemic inflammatory response to clozapine treatment. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. PMID:27703781

  3. Clozapine-induced myoclonus: a case report and review of the literature

    PubMed Central

    Osborne, Ian J.; McIvor, Ronan J.

    2015-01-01

    We describe the case of a young man with treatment-resistant schizophrenia, who developed myoclonus during clozapine titration. This subsequently led to a full tonic–clonic seizure. Clozapine treatment can result in a range of seizure-like activity, the most well-known being tonic–clonic seizures. This case highlights the importance of recognizing and treating clozapine-induced myoclonus, as it can herald the onset of a full seizure, even at low serum clozapine levels. We highlight the variety of ways myoclonus can present clinically and suggest treatment options. PMID:26834968

  4. Multimodal Treatment of Chronic Pain.

    PubMed

    Dale, Rebecca; Stacey, Brett

    2016-01-01

    Most patients with chronic pain receive multimodal treatment. There is scant literature to guide us, but when approaching combination pharmacotherapy, the practitioner and patient must weigh the benefits with the side effects; many medications have modest effect yet carry significant side effects that can be additive. Chronic pain often leads to depression, anxiety, and deconditioning, which are targets for treatment. Structured interdisciplinary programs are beneficial but costly. Interventions have their place in the treatment of chronic pain and should be a part of a multidisciplinary treatment plan. Further research is needed to validate many common combination treatments. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Use of Clozapine for Borderline Personality Disorder: A Case Report

    PubMed Central

    Amamou, Badii; Salah, Walid Bel Hadj; Mhalla, Ahmed; Benzarti, Nejla; Elloumi, Hend; Zaafrane, Ferid; Gaha, Lotfi

    2016-01-01

    Patients with borderline personality disorder (BPD) show significant impairment in functioning, particularly in the interpersonal and social domains. Prior reports suggest that clozapine may be effective in the management of BPD. We present the case of a patient with BPD who experienced persistent suicidal ideation and was treated with clozapine at a state psychiatric hospital. After treatment failure with other psychotropic medications, clozapine medication was initiated; not only did suicidal ideation cease, but social and professional functioning also greatly improved to the point of no longer requiring intensive levels of observation or restrictive procedures. Clozapine appears to be efficacious in the management of suicide attempts and self-injurious behavior. Moreover, it appears to be promising as a therapeutic measure for ameliorating the global functioning of patients with severe BPD. Larger, randomized, blinded, and controlled prospective studies are needed to confirm these findings and to determine optimal dosage. PMID:27121437

  6. Clozapine Monitoring in Clinical Practice: Beyond the Mandatory Requirement

    PubMed Central

    Kar, Nilamadhab; Barreto, Socorro; Chandavarkar, Rahul

    2016-01-01

    Clozapine is effective in treatment resistant schizophrenia; however, it is underutilised probably because of its side effects. The side effects are also the potential reasons for clozapine discontinuation. A mandatory requirement for its use is regular monitoring of white blood cell count and absolute neutrophil count. However there are many side effects that need monitoring in clinical practice considering their seriousness. This article tries to summarise the clinical concerns surrounding the serious side effects of clozapine some of which are associated with fatalities and presents a comprehensive way to monitor patients on clozapine in clinical practice. It emphasizes the need to broaden the monitoring beyond the mandatory investigations. This may help in improving the safety in clinical practice and increasing clinician confidence for greater and appropriate use of this effective intervention. PMID:27776383

  7. Atypical Antipsychotics in the Treatment of Depressive and Psychotic Symptoms in Patients with Chronic Schizophrenia: A Naturalistic Study

    PubMed Central

    Baratta, Stefano; Di Vittorio, Cristina; Lester, David; Girardi, Paolo; Pompili, Maurizio

    2013-01-01

    Objectives. The aim of this naturalistic study was to investigate whether treatment with clozapine and other atypical antipsychotics for at least 2 years was associated with a reduction in psychotic and depressive symptoms and an improvement in chronic schizophrenia patients' awareness of their illness. Methods. Twenty-three adult outpatients (15 men and 8 women) treated with clozapine and 23 patients (16 men and 7 women) treated with other atypical antipsychotics were included in the study. Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS), depressive symptoms were assessed with the Calgary Depression Scale for Schizophrenia (CDSS), and insight was assessed with the Scale to Assess Unawareness of Mental Disorder (SUMD). Results. The sample as a whole had a significant reduction in positive, negative, and general symptoms, whereas the reduction in depression was significant only for patients with CDSS scores of 5 and higher at the baseline. At the follow-up, patients treated with other atypical antipsychotics reported a greater reduction in depression than patients treated with clozapine, but not when limiting the analyses to those with clinically relevant depression. Conclusions. Atypical antipsychotics may be effective in reducing psychotic and depressive symptoms and in improving insight in patients with chronic schizophrenia, with no differences in the profiles of efficacy between compounds. PMID:23401771

  8. Atypical antipsychotics in the treatment of depressive and psychotic symptoms in patients with chronic schizophrenia: a naturalistic study.

    PubMed

    Innamorati, Marco; Baratta, Stefano; Di Vittorio, Cristina; Lester, David; Girardi, Paolo; Pompili, Maurizio; Amore, Mario

    2013-01-01

    Objectives. The aim of this naturalistic study was to investigate whether treatment with clozapine and other atypical antipsychotics for at least 2 years was associated with a reduction in psychotic and depressive symptoms and an improvement in chronic schizophrenia patients' awareness of their illness. Methods. Twenty-three adult outpatients (15 men and 8 women) treated with clozapine and 23 patients (16 men and 7 women) treated with other atypical antipsychotics were included in the study. Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS), depressive symptoms were assessed with the Calgary Depression Scale for Schizophrenia (CDSS), and insight was assessed with the Scale to Assess Unawareness of Mental Disorder (SUMD). Results. The sample as a whole had a significant reduction in positive, negative, and general symptoms, whereas the reduction in depression was significant only for patients with CDSS scores of 5 and higher at the baseline. At the follow-up, patients treated with other atypical antipsychotics reported a greater reduction in depression than patients treated with clozapine, but not when limiting the analyses to those with clinically relevant depression. Conclusions. Atypical antipsychotics may be effective in reducing psychotic and depressive symptoms and in improving insight in patients with chronic schizophrenia, with no differences in the profiles of efficacy between compounds.

  9. Clozapine: Its Impact on Aggressive Behavior among Children and Adolescents with Schizophrenia.

    ERIC Educational Resources Information Center

    Kranzler, Harvey; Roofeh, David; Gerbino-Rosen, Ginny; Dombrowski, Carolyn; McMeniman, Marjorie; DeThomas, Courtney; Frederickson, Anne; Nusser, Laurie; Bienstock, Mark D.; Fisch, Gene S.; Kumra, Sanjiv

    2005-01-01

    Objective: To evaluate the effectiveness of clozapine on aggressive behavior for treatment-refractory adolescents (age range 8.5-18) with schizophrenia (295.X) at Bronx Children's Psychiatric Center. Method: Clozapine treatment was administered in an open-label fashion using a flexible titration schedule. The frequency of administration of…

  10. Clozapine: Its Impact on Aggressive Behavior among Children and Adolescents with Schizophrenia.

    ERIC Educational Resources Information Center

    Kranzler, Harvey; Roofeh, David; Gerbino-Rosen, Ginny; Dombrowski, Carolyn; McMeniman, Marjorie; DeThomas, Courtney; Frederickson, Anne; Nusser, Laurie; Bienstock, Mark D.; Fisch, Gene S.; Kumra, Sanjiv

    2005-01-01

    Objective: To evaluate the effectiveness of clozapine on aggressive behavior for treatment-refractory adolescents (age range 8.5-18) with schizophrenia (295.X) at Bronx Children's Psychiatric Center. Method: Clozapine treatment was administered in an open-label fashion using a flexible titration schedule. The frequency of administration of…

  11. Reduction of clozapine-induced hypersalivation by pirenzepine is safe.

    PubMed

    Schneider, B; Weigmann, H; Hiemke, C; Weber, B; Fritze, J

    2004-03-01

    Hypersalivation is known as a frequent, disturbing, and socially stigmatizing side effect of therapy with the atypical antipsychotic clozapine. It has been shown that the addition of the anticholinergic pirenzepine is able to reduce clozapine-induced hypersalivation, probably by blocking M4-receptors. Nevertheless, a pharmacokinetic interaction between both compounds cannot be excluded. In this pilot study, 29 schizophrenic patients (ICD-10; 51.7 % female; age: 36.7 +/- 8.7 years [mean +/- SD]) were included. Serum concentrations of clozapine and its pharmacologically active metabolite N-desmethylclozapine were determined under steady-state conditions by automated HPLC with UV detection before and after addition of pirenzepine for 3 days. Significantly fewer patients reported hypersalivation after addition of pirenzepine (69 % vs. 34.5 %, P = 0.002). No significant differences of clozapine and N-desmethylclozapine serum levels before (329 +/- 181 ng/ml and 218.0 +/- 123.4 ng/ml, respectively) and 3 days after (336 +/- 215 ng/ml and 235.9 +/- 164.4 ng/ml, respectively) addition of pirenzepine were found. In three patients, however, clozapine serum levels increased; this was probably unrelated to pirenzepine. In conclusion, treatment of clozapine-induced hypersalivation with pirenzepine is a recommendable combination with low risk of additional side effects.

  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.

  13. Adult response to olanzapine or clozapine treatment is altered by adolescent antipsychotic exposure: A preclinical test in the phencyclidine hyperlocomotion model

    PubMed Central

    Shu, Qing; Hu, Gang; Li, Ming

    2016-01-01

    This study examined how repeated olanzapine (OLZ) or clozapine (CLZ) treatment in adolescence alters sensitivity to the same drug in adulthood in the phencyclidine (PCP) hyperlocomotion model. Male adolescent Sprague-Dawley rats (postnatal day (P) 44–48) were first treated with OLZ (1.0 or 2.0 mg/kg, subcutaneously (sc)) or CLZ (10.0 or 20.0 mg/kg, sc) and tested in the PCP (3.2 mg/kg, sc)-induced hyperlocomotion model for five consecutive days. Then a challenge test with OLZ (0.5 mg/kg) or CLZ (5.0 mg/kg) was administered either during adolescence (~P 51) or after the rats matured into adults (~P 76 and 91). During adolescence, repeated OLZ or CLZ treatment produced a persistent inhibition of PCP-induced hyperlocomotion across the five test days. In the challenge test during adolescence, rats previously treated with OLZ did not show a significantly stronger inhibition of PCP-induced hyperlocomotion than those previously treated with vehicle (VEH). In contrast, those previously treated with CLZ showed a weaker inhibition than the VEH controls. When assessed in adulthood, the enhanced sensitivity to OLZ and the decreased sensitivity to CLZ were detected on ~P 76, even on ~P 91 in the case of OLZ. These findings suggest that adolescent OLZ or CLZ exposure can induce long-term alterations in antipsychotic response that persist into adulthood. PMID:24257809

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

    SciTech Connect

    Husain, Zaheed; Almeciga, Ingrid; Delgado, Julio C.; Clavijo, Olga P.; Castro, Januario E.; Belalcazar, Viviana; Pinto, Clara; Zuniga, Joaquin; Romero, Viviana; Yunis, Edmond J. . E-mail: edmond_yunis@dfci.harvard.edu

    2006-08-01

    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-60 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.

  15. Randomized controlled augmentation trials in clozapine-resistant schizophrenic patients: a critical review.

    PubMed

    Kontaxakis, Vassilis P; Ferentinos, Panayotis P; Havaki-Kontaxaki, Beata J; Roukas, Dimitris K

    2005-08-01

    Approximately 40-70% of treatment-resistant schizophrenic patients fail to benefit from clozapine monotherapy or are partial responders. During the last years several clozapine adjunctive agents have come into clinical practice. This study aims to critically review all published randomized, double-blind, placebo-controlled clinical trials (RCTs) regarding the efficacy and safety of adjunctive agents in clozapine-resistant schizophrenic or schizoaffective patients. A MEDLINE search for RCTs on clozapine adjunctive agents published from January 1980 to February 2004 was conducted. All identified papers were critically reviewed and examined against several methodological features as well as clinical and pharmacological parameters. Eleven trials including 270 patients, partial or non-responders to clozapine, assessed the efficacy of sulpiride, lithium, lamotrigine, fluoxetine, glycine, d-serine, d-cycloserine and ethyl-eicosapentanoate (E-EPA) as clozapine adjuncts. There were eight parallel-group and three crossover trials. The inclusion criteria varied widely. The duration as well as the dosage of clozapine monotherapy were reported adequate in only one trial. Plasma clozapine levels were assessed in only three trials. Main side-effects reported were hypersalivation, sedation, diarrhea, nausea, hyperprolactinaemia. The outcome favored clozapine augmentation with sulpiride, lamotrigine and E-EPA. Lithium was shown to benefit only schizoaffective patients. However, the methodological shortcomings of trials analyzed limit the impact of evidence provided.

  16. Chronic Pruritus: Clinics and Treatment

    PubMed Central

    Grundmann, Sonja

    2011-01-01

    Chronic pruritus, one of the main symptoms in dermatology, is often intractable and has a high impact on patient's quality of life. Beyond dermatologic disorders, chronic pruritus is associated with systemic, neurologic as well as psychologic diseases. The pathogenesis of acute and chronic (>6 weeks duration) pruritus is complex and involves in the skin a network of resident (e.g., sensory neurons) and transient inflammatory cells (e.g., lymphocytes). In the skin, several classes of histamine-sensitive or histamine-insensitve C-fibers are involved in itch transmission. Specific receptors have been discovered on cutaneous and spinal neurons to be exclusively involved in the processing of pruritic signals. Chronic pruritus is notoriously difficult to treat. Newer insights into the underlying pathogenesis of pruritus have enabled novel treatment approaches that target the pruritus-specific pathophysiological mechanism. For example, neurokinin-1 antagonists have been found to relieve chronic pruritus. PMID:21738356

  17. Treatment of chronic lymphocytic leukemia.

    PubMed

    Ferrajoli, Alessandra; O'Brien, Susan M

    2004-04-01

    Treatment options for patients with chronic lymphocytic leukemia have changed over the past two decades. This article reviews the experience accumulated with the use of alkylating agents alone and in combination; purine analogues alone and in combination and monoclonal antibodies such as rituximab, and alemtuzumab alone and in combination. The results obtained with different treatment strategies are summarized, compared, and reviewed.

  18. 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…

  19. 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…

  20. 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…

  1. 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…

  2. Negative Correlation between Serum S100B and Leptin Levels in Schizophrenic Patients During Treatment with Clozapine and Risperidone: Preliminary Evidence.

    PubMed

    Hendouei, Narjes; Hosseini, Seyed Hamzeh; Panahi, Amin; Khazaeipour, Zahra; Barari, Fatemeh; Sahebnasagh, Adeleh; Ala, Shahram

    2016-01-01

    Recently, extensive efforts have been made to understand the rate of energy expenditure and the weight gain associated with atypical antipsychotic treatment, including identification of markers of obesity risk. In recent years, leptin, an adipocyte hormone, has gained significant interest in psychiatric disorders. S100B has been considered as a surrogate marker for astrocyte-specific damage in neurologic disorders. Also, S100B has been detected in adipose with concentration as high as nervous tissue as a second release source. In this study we evaluated the relationship between S100B and leptin in schizophrenic patients under treatment with clozapine and risperidone.This study included 19 patients meeting the DSM-IV-TR criteria for schizophrenia, having body mass index (BMI) of 16- 25 kg/m(2) and suffering schizophrenia for more than 3 years and from this study. Twenty five healthy controls were group matched for age and gender whose BMI was 16-25 kg/m(2). Serum S100B and leptin levels and positive and negative symptom scale (PANSS) were assessed at admission and after six weeks. During the study, S100B showed a strong and negative correlation with leptin (r = -0.5, P = 0.01). Also, there were negative correlation between serum S100B level and PANSS negative subscale after 6 weeks of treatment (r = -0.048, P = 0.8). Positive correlation between leptin level and PANSS suggested a potential role for leptin which can mediate the link between antipsychotic induced weight gain and therapeutic response in schizophrenia.

  3. Chronic pancreatitis: diagnosis and treatment.

    PubMed

    Sidhu, S; Tandon, R K

    1996-06-01

    Three-dimensional magnetic resonance cholangiopancreatography is currently the most exciting new imaging technique for chronic pancreatitis. Endoscopy-assisted duodenal intubation during the secretin-cholecystokinin test reduces intubation time in difficult cases. The NBT-para-amino benzoic acid test has been refined to enhance its discriminant power. The cholesteryl-[C13]octanoate breath test and the faecal elastase test are newer highly sensitive and specific tubeless tests. Pain in chronic pancreatitis continues to be a vexing therapeutic issue. Enzyme treatment continues despite criticism. Neurotensin is the new suspected mediator of the feedback mechanism, which is downregulated by enzyme therapy. Steroid ganglion block is an exciting therapeutic tool for pain relief. Endoscopic pancreatic sphincterotomy, Dormia basketing and pancreatic stenting in conjunction with extracorporeal shock wave lithotripsy should be performed early in chronic pancreatitis to prevent parenchymal atrophy with ensuing exocrine and endocrine pancreatic dysfunction. The modified Puestow's procedure preserves endocrine and exocrine pancreatic functions besides relieving pain. Closed loop insulin infusion allows superior management of pancreatic diabetes following near total pancreatectomy. The standardised incidence rate of pancreatic cancer is 16.5 in patients with alcoholic chronic pancreatitis and 100 for tropical chronic pancreatitis. Aggressive treatment protocols combining neo-adjuvant chemoradiation and intra-operative radiation with surgery are being used to improve the prognosis in this dismal complication of chronic pancreatitis.

  4. Increased Impulsivity and Disrupted Attention Induced by Repeated Phencyclidine are not Attenuated by Chronic Quetiapine Treatment

    PubMed Central

    Amitai, Nurith; Markou, Athina

    2009-01-01

    Atypical antipsychotic medications differ in how effectively they attenuate cognitive and other deficits in schizophrenia. The present study aimed to explore whether quetiapine, an atypical antipsychotic medication, would reverse disruptions of performance in the 5-choice serial reaction time task (5-CSRTT), a test of attention and impulsivity, induced by repeated administration of the psychotomimetic phencyclidine (PCP). In confirmation of previous findings, repeated PCP administration (2 mg/kg, s.c., 30 min before behavioral testing, for two consecutive days, followed by a 2-week PCP-free period and then five consecutive days of PCP treatment) increased premature responding (impulsivity), decreased accuracy (attention), and increased response latencies (processing speed) and timeout responding (impulsivity/cognitive inflexibility). Chronic quetiapine (5 or 10 mg/kg/day, s.c.) did not attenuate these PCP-induced disruptions in performance, while at the highest dose used, quetiapine disrupted 5-CSRTT performance in the absence of PCP treatment and tended to exacerbate the PCP-induced increase in premature responding. Considering that clozapine, another atypical antipsychotic, was shown previously to reverse PCP-induced deficits in the same task (Amitai et al. 2007), the present findings demonstrate differences between clozapine and quetiapine in their effectiveness on schizophrenia-like cognitive deficits and impulsivity that may be attributable to their different receptor affinity profiles. PMID:18809428

  5. [Neurosurgical treatment of chronic pain].

    PubMed

    Fontaine, D; Blond, S; Mertens, P; Lanteri-Minet, M

    2015-02-01

    Neurosurgical treatment of pain used two kind of techniques: 1) Lesional techniques interrupt the transmission of nociceptive neural input by lesionning the nociceptive pathways (drezotomy, cordotomy, tractotomy…). They are indicated to treat morphine-resistant cancer pain and few cases of selected neuropathic pain. 2) Neuromodulation techniques try to decrease pain by reinforcing inhibitory and/or to limit activatory mechanisms. Chronic electrical stimulation of the nervous system (peripheral nerve stimulation, spinal cord stimulation, motor cortex stimulation…) is used to treat chronic neuropathic pain. Intrathecal infusion of analgesics (morphine, ziconotide…), using implantable pumps, allows to increase their efficacy and to reduce their side effects. These techniques can improve, sometimes dramatically, selected patients with severe and chronic pain, refractory to all other treatments. The quality of the analgesic outcome depends on the relevance of the indications.

  6. CHRONIC URTICARIA AND TREATMENT OPTIONS

    PubMed Central

    Godse, Kiran Vasant

    2009-01-01

    Chronic urticaria has a wide spectrum of clinical presentations and causes. Still, despite our best efforts no cause may be found in the majority of cases. The treatment options are: Primary prevention in the form of avoidance of aggravating factors; counseling; antihistamines; leukotriene receptor antagonists; prednisolone; sulfasalazine and a host of immunosuppressives like methotrexate, cyclosporine, omalizumab etc. PMID:20101328

  7. 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

  8. 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.

  9. Atypical Neuroleptic Malignant Syndrome Associated with Use of Clozapine.

    PubMed

    Leonardo, Quevedo-Florez; Juliana, Granada-Romero; Fernando, Camargo-Arenas Juan

    2017-01-01

    The Neuroleptic Malignant Syndrome (NMS) is a medical emergency of infrequent presentation in the emergency department, which is associated with the use of psychiatric drugs, such as typical and atypical antipsychotics. Our case addresses a 55-year-old patient diagnosed with undifferentiated schizophrenia for 10 years, who had been receiving clozapine and clonazepam as part of their treatment. This patient presents the symptoms of Neuroleptic Malignant Syndrome without fever, which improves with treatment especially with the withdrawal of clozapine. In the absence of fever and clinical improvement, the patient is considered to have an atypical presentation of this disease.

  10. Atypical Neuroleptic Malignant Syndrome Associated with Use of Clozapine

    PubMed Central

    Juliana, Granada-Romero; Fernando, Camargo-Arenas Juan

    2017-01-01

    The Neuroleptic Malignant Syndrome (NMS) is a medical emergency of infrequent presentation in the emergency department, which is associated with the use of psychiatric drugs, such as typical and atypical antipsychotics. Our case addresses a 55-year-old patient diagnosed with undifferentiated schizophrenia for 10 years, who had been receiving clozapine and clonazepam as part of their treatment. This patient presents the symptoms of Neuroleptic Malignant Syndrome without fever, which improves with treatment especially with the withdrawal of clozapine. In the absence of fever and clinical improvement, the patient is considered to have an atypical presentation of this disease. PMID:28303200

  11. Clozapine's Effect on Recidivism Among Offenders with Mental Disorders.

    PubMed

    Mela, Mansfield; Depiang, Gu

    2016-03-01

    Mental disorder is associated with criminal reoffending, especially violent acts of offending. Features of mental disorder, psychosocial stresses, substance use disorder, and personality disorder combine to increase the risk of criminal recidivism. Clozapine, an atypical antipsychotic, is indicated in the treatment of patients with psychotic disorders. This article is the report of a community follow-up study of a matched control of those treated with clozapine (n = 41) and those treated with other antipsychotics (n = 21). Rates of reoffending behavior in the general, nonviolent, violent, and sexual categories were calculated after two years of follow-up. Although not statistically significant, the two-year criminal conviction rates of those treated with other antipsychotics in all offense categories except sexual reoffending were two-fold higher than in those treated with clozapine. The time from release to the first offense and crime-free time in the community were significantly longer in the clozapine group. By prolonging the time it takes from release to first offense, clozapine confers additional crime-reduction advantages.

  12. Switching bipolar disorder patients treated with clozapine to another antipsychotic medication: a mirror image study

    PubMed Central

    Ifteni, Petru; Teodorescu, Andreea; Moga, Marius Alexandru; Pascu, Alina Mihaela; Miclaus, Roxana Steliana

    2017-01-01

    Bipolar disorder (BD) is associated with periodic symptom exacerbations, leading to functional impairment, and increased risk of suicide. Although clozapine has never been approved for the treatment of BD, it is occasionally used in severe mania. The aim of the study is to evaluate the risks and benefits of switching clozapine in remitted BD patients. This is an observational, mirror image study of 62 consecutive remitted BD outpatients treated with clozapine. Twenty-five patients were switched to another antipsychotic following a change in a drug reimbursement rule, while 37 continued on clozapine. The mean time in remission was shorter for the switched group (9.2±4 months vs 13±6 months, P=0.018), and the number of patients who relapsed was larger (n=21 vs n=8, P<0.0001). The results suggest that switching from clozapine to another antipsychotic may increase the risk of relapses in remitted patients with BD. PMID:28182153

  13. Impramine, fluoxetine and clozapine differently affected reactivity to positive and negative stimuli in a model of motivational anhedonia in rats.

    PubMed

    Scheggi, S; Pelliccia, T; Ferrari, A; De Montis, M G; Gambarana, C

    2015-04-16

    Anhedonia is a relevant symptom in depression and schizophrenia. Chronic stress exposure induces in rats escape deficit, disrupts the dopaminergic response to palatable food and the competence to acquire sucrose self-administration (SA), thus configuring a possible model of motivational anhedonia. Repeated lithium administration reverts stress effects and brings back to control values the breaking point (BP) score, a measure of reward motivation. In this study, we tested on this model two antidepressants, imipramine and fluoxetine, and two antipsychotics, haloperidol and clozapine. The dopaminergic response to sucrose consumption was studied in non food-deprived rats in terms of dopamine D1 receptor signaling in the nucleus accumbens shell (NAcS). More specifically, we studied the modifications in dopamine and cAMP-regulated phosphoprotein of Mr 32,000 (DARPP-32) phosphorylation pattern following sucrose consumption. Fluoxetine reverted the escape deficit and showed no effects on dopaminergic response and sucrose SA. Imipramine reverted sucrose SA and dopamine response deficit in half of the rats and the escape deficit in all animals. Haloperidol did not affect stress-induced deficits. Clozapine-treated rats recovered the dopaminergic response to sucrose consumption and the competence to acquire sucrose SA, although they still showed the escape deficit, thus confirming that motivation toward reward may be dissociated from that to punishment escape. These results indicate that imipramine or fluoxetine are not endowed with a rapid onset antianhedonic effect. On the other hand, clozapine treatment showed a motivational antianhedonic activity similar to that observed after lithium treatment.

  14. Effect of Scopolamine Butylbromide on Clozapine-induced Hypersalivation in Schizophrenic Patients: A Case Series.

    PubMed

    Takeuchi, Ippei; Suzuki, Tatsuyo; Kishi, Taro; Kanamori, Daisuke; Hanya, Manako; Uno, Junji; Fujita, Kiyoshi; Kamei, Hiroyuki

    2015-04-30

    Clozapine has been demonstrated to be useful for treating refractory schizophrenia. However, hypersalivation occurs in 31.0- 97.4% of the patients treated with clozapine. Accordingly, some patients who are disturbed by their hypersalivation refuse to continue with clozapine treatment. This study investigated the efficacy of the anticholinergic agent scopolamine butylbromide against clozapine-induced hypersalivation. Five schizophrenia patients were coadministered scopolamine butylbromide (30-60 mg/ day) for 4 weeks. At the baseline and after 4 weeks' treatment, we subjectively evaluated hypersalivation using a visual analog scale and objectively assessed it using the Drooling Severity Scale and Drooling Frequency Scale. As a result, improvements in the patients' Drooling Severity Scale and Drooling Frequency Scale scores, but no improvements in their visual analog scale scores, were observed after scopolamine butylbromide treatment. These results indicate that at least some schizophrenic patients with clozapine-induced hypersalivation would benefit from scopolamine butylbromide treatment. We conclude that clozapine-induced hypersalivation is one factor of stress to patients. Subjective hypersalivation was not improved, but objective hypersalivation was, by scopolamine butylbromide treatment. However, scopolamine butylbromide and clozapine possess anticholinergic effects so clinicians should closely monitor patients who take scopolamine butylbromide.

  15. 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.

  16. Effect of clozapine on neutrophil kinetics in rabbits.

    PubMed

    Iverson, Suzanne; Kautiainen, Antti; Ip, Julia; Uetrecht, Jack P

    2010-07-19

    Clozapine is an atypical antipsychotic drug effective in the treatment of refractory schizophrenia; however, its use is limited due to its propensity to cause agranulocytosis in some patients. Little is known about the mechanism of idiosyncratic drug-induced agranulocytosis, in part because of the lack of a valid animal model. Clozapine is oxidized by activated human neutrophils and bone marrow cells to a reactive nitrenium ion by the myeloperoxidase-hydrogen peroxide system of neutrophils. This reactive metabolite has been shown in vitro to induce the apoptosis of neutrophils and bone marrow cells. While in vitro studies demonstrated the toxic potential of clozapine upon oxidation, it is not clear if similar conditions occur in vivo. In response to the difficulties encountered with detecting apoptotic neutrophils in vivo, we conducted a series of studies in rabbits using two fluorescent cell-labeling techniques to study the effect of clozapine treatment on neutrophil kinetics, that is, their rates of production and removal from circulation. The fluorescein dye, 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE), was used as a general cell label to measure the half-life of neutrophils in blood. In addition, the thymidine analogue, 5-bromo-2-deoxyuridine (BrdU), was used to label dividing cells, thus enabling the measurement of the efflux of neutrophils from the bone marrow. Clozapine, indeed, increased the rate of both the release of neutrophils from the bone marrow and their subsequent disappearance from circulation. Failure of the bone marrow to compensate for a shorter neutrophil half-life could lead to agranulocytosis. Alternatively, the damage to neutrophils caused by clozapine could, in some patients, lead to an immune-mediated response against neutrophils resulting in agranulocytosis.

  17. [Criminal clozapine intoxications].

    PubMed

    Sliundin, D G; Livanov, A S; Anuchin, V V; Bobrinskaia, I G; Gutova, E V

    2007-01-01

    The paper deals with the topical problem--study criminal clozapine intoxications that have recently ranked first in the total structure of criminal intoxications, by ousting poisoning by clofelin. Thus, in 2004 to 2006, the number of victims taken to the Prof. A. A. Ostroumov Moscow City Hospital No. 33 increased by 1.9 times, by amounting to 1120 cases in 2006. At the same time, its correct prehospital diagnosis was made only in 1.76% of the victims. Abundant clinical material (2720 cases) has been analyzed, by using the currently performed studies. The specific features of the development and clinical manifestations of these intoxications, including those concurrent with alcoholic intoxication, are described in detail. The characteristic manifestations of impaired consciousness, hypersalivation, and myosis in the absence of generally, respiratory failure and hemodynamic disorders, as well as altered clinical and biochemical blood parameters are shown. At the same time there were elevated ammonia levels within the first hours after intoxication, which, in the authors' opinion, may suggest the development of hepatic dysfunction. Emphasis is laid on the fact that the leading component in the complex of medical measures is the administration of central anticholinesterase agents (aminostigmine and galantamine hydrobromide) that may be used as an antidote and for the differential diagnosis of these intoxications.

  18. Successful clozapine re-challenge in a patient with three previous episodes of clozapine-associated blood dyscrasia

    PubMed Central

    Foster, Jessica; Bell, Victoria; Shergill, Sukhi

    2017-01-01

    A case is presented of a 30-year-old female with treatment-resistant schizoaffective disorder who was referred to a tertiary-level specialist psychosis service. We describe the history of clozapine trials and associated episodes of agranulocytosis and neutropenia, followed by the successfully tolerated third clozapine re-challenge within our service. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:28243462

  19. NeuN+ neuronal nuclei in non-human primate prefrontal cortex and subcortical white matter after clozapine exposure.

    PubMed

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

    2016-02-01

    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.

  20. 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

  1. Structural and functional neuroimaging findings associated with the use of clozapine in schizophrenia: a systematic review.

    PubMed

    Garcia, Giovana J; Chagas, Marcos H; Silva, Carlos H; Machado-de-Sousa, João P; Crippa, José A; Hallak, Jaime E

    2015-01-01

    Schizophrenia is one of the most severe psychiatric disorders, and its current treatment relies on antipsychotic medications with only partial effectiveness. Clozapine is an atypical antipsychotic with a specific profile of action indicated for treatment-resistant schizophrenia. Neuroimaging studies assessing the effects of clozapine could help shed light on the neural underpinnings of the effects of this drug in the brain. The objective of this study was to review the available literature on the structural and functional neuroimaging findings associated with use of clozapine. We conducted a systematic review of the indexed literature using the PubMed, BIREME, and ISI Web of Knowledge search engines and the following keywords: clozapine, neuroimaging, computed tomography, MRI, functional magnetic resonance, PET, SPECT, and DTI. A total of 23 articles were included in the review. In structural studies, the use of clozapine was associated with volume reductions in the basal ganglia, especially the caudate nucleus, where functional neuroimaging studies also found decreased perfusion. In the frontal lobe, clozapine treatment was associated with increased gray matter volume and reduced perfusion. The results of the studies reviewed suggest that the use of clozapine is associated with distinctive structural and functional neuroimaging findings that are not shared with other antipsychotics.

  2. Clozapine prescription and quality of life in Chinese patients with schizophrenia treated in primary care.

    PubMed

    Hou, C-L; Cai, M-Y; Ma, X-R; Zang, Y; Jia, F-J; Lin, Y-Q; Chiu, H F K; Ungvari, G S; Ng, C H; Zhong, B-L; Cao, X-L; Li, Y; Shinfuku, N; Xiang, Y-T

    2015-09-01

    Clozapine is frequently used to treat schizophrenia in China. Maintenance treatment for clinically stable patients with schizophrenia is usually provided by Chinese primary care physicians, but no study has investigated the frequency of its use prescribed by primary care physicians. This study described the frequency, demographic and clinical characteristics of clozapine treatment and its impact on insight and quality of life (QOL) of patients with schizophrenia treated in primary care in China. A total of 623 patients with schizophrenia treated in 22 primary care services in Guangzhou, China in 2013 formed the study sample. Patients' socio-demographic and clinical characteristics including psychopathology, medication side effects and QOL were recorded using a standardized protocol and data collection. The frequency of clozapine prescription was 35.6% with a mean daily dose of 127.7±88.2 mg. There were no significant differences between the patients with and without clozapine in either of the QOL domains after controlling the confounding factors. Multiple logistic regression analyses revealed that patients on clozapine had younger age of onset, more hospitalizations, more severe extrapyramidal side effects, but better insight and fewer prescriptions of first generation antipsychotics. Clozapine use was found to be common and associated with better insight in patients with schizophrenia treated in primary care in China. Further examination of the rationale and appropriateness of clozapine in primary care in China is warranted. © Georg Thieme Verlag KG Stuttgart · New York.

  3. Trends in the prescription of clozapine in a psychiatric hospital: a 5-year observational study.

    PubMed

    Niehues, Gabriela Danielski; Balan, Alexandre Balestieri; Prá, Vinicius Brum; Pellizzaro, Raphaela Santos; da Silva, Paulo Roberto Antunes; Niehues, Manuela Danielski; Costa, Ana Paula; Schwarzbold, Marcelo Liborio; Diaz, Alexandre Paim

    2017-01-01

    Clozapine is a well-recognized effective treatment for some patients with treatment-resistant schizophrenia (TRS). Although it has potential benefits and approximately 30% of patients have a clinical indication for clozapine use, prescription rates are low. To evaluate clozapine prescription trends over a 5-year period in a tertiary psychiatric hospital. In this observational study, data prospectively collected by the Medical and Statistical File Service (Serviço de Arquivo Médico e Estatístico) and the Pharmacy Division of Instituto de Psiquiatria de Santa Catarina between January 2010 and December 2014 were summarized and analyzed by investigators blinded to data collection. The number of 100 mg clozapine pills dispensed by the Pharmacy Division to the inpatient units was the outcome and considered a proxy measure of clozapine prescriptions. The number of occupied inpatient unit beds and the number of patients admitted with F20-F29 (ICD-10) diagnoses during the study period were considered to be possible confounders. A multiple linear regression model showed that time in months was independently associated with an increase in the number of clozapine pills dispensed by the Pharmacy Division (β coefficient = 15.82; 95% confidence interval 10.88-20.75). Clozapine prescriptions were found to have increased during the 5-year period studied, a trend that is opposite to reports from several other countries.

  4. Converting patients from brand-name clozapine to generic clozapine.

    PubMed

    Sajbel, T A; Carter, G W; Wiley, R B

    2001-03-01

    To evaluate safety and dosage requirements when patients taking brand-name clozapine (Clozaril, Novartis Pharmaceuticals) are converted to generic clozapine (Zenith Goldline). In November 1999, patients at Colorado Mental Health Institute at Pueblo taking Clozaril were changed to generic clozapine. Seventeen patients had been prescribed Clozaril for three years and were included in the study. Drug dosage, white blood cell (WBC) count values, and adverse drug reaction reports were compared. Data regarding patients on the brand-name product were evaluated retrospectively for the months of November, December, January, and February during the years 1996/1997, 1997/1998, and 1998/1999. These data were compared with those from the same patients after switching to generic clozapine for the same months in 1999/2000. A one-year comparison of brand-name (1998/1999) with generic drug (1999/2000) was also performed. Statistical analysis included a standard test comparing WBC values and a Brown-Forsythe test for comparing dosages. There were no differences between the values obtained for the brand-name and generic products. WBC counts for the three-year data resulted in a p value of 0.9992. There was no difference when comparing the samples one year prior to switching and after the switch (p = 0.9991). There was no difference in dosages at three years or one year (p = 0.9999 and p = 0.9993, respectively). No adverse events were noted with the generic product. No differences were found between the brand-name and generic clozapine groups with regard to WBC count, dosage, and adverse events. The conversion to the generic product is projected to save the pharmacy $90,000 annually.

  5. [Risk minimization evolution of agranulocytosis caused by the administration of pharmaceutical products containing Clozapine in Argentina].

    PubMed

    Bergman, Maximiliano; Bignone, Inés; Bisio, Agustina; Bologna, Viviana; Sabatini, Analía

    2011-01-01

    Clozapine is an antipsychotic medication used in the treatment of schizophrenia. Compared to other drugs, Clozapine has shown remarkable advantages. However, its use entails a serious risk of causing hematologic alterations (including granulocytopenia/agranulocytosis). Such alterations may result in death if they are not detected early. Clozapine was recalled from the worldwide market and it was reintroduced some years later, but a mandatory hematologic monitoring program was implemented. The program was established in Argentina by ANMAT's regulation 935/00. It helped to monitor of the use of the drug. Currently, the incidence of agranulocytosis in our country is lower than the international incidence rates.

  6. The Effect of Clozapine on Hematological Indices: A 1-Year Follow-Up Study.

    PubMed

    Lee, Jimmy; Takeuchi, Hiroyoshi; Fervaha, Gagan; Powell, Valerie; Bhaloo, Amaal; Bies, Robert; Remington, Gary

    2015-10-01

    Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and is linked to a need for mandatory hematological monitoring. Besides agranulocytosis, other hematological aberrations have resulted in premature termination in some cases. Considering clozapine's role in immunomodulation, we proceeded to investigate the impact of clozapine on the following 3 main hematological cell lines: red blood cells, platelets, white blood cells (WBCs), and its differential counts. Data were extracted from patients initiated on clozapine between January 2009 and December 2010 at a single hospital. Patients with a preclozapine complete blood count, who were receiving clozapine during the 1-year follow-up period, were included in the present investigation. Counts of red blood cells, platelets, WBC, and its differential including neutrophils, lymphocytes, monocytes, eosinophils, and basophils were extracted and trajectories plotted. One hundred one patients were included in this study and 66 remained on clozapine at the end of 1 year. There was a synchronized but transient increase in WBC, neutrophils, monocytes, eosinophils, basophils, and platelets beginning as early as the first week of clozapine treatment. There were no cases of agranulocytosis reported in this sample, and five developed neutropenia. A spike in neutrophils immediately preceded the onset of neutropenia in three of the five. The cumulative incidence rates were 48.9% for neutrophilia, 5.9% for eosinophilia, and 3% each for thrombocytosis and thrombocytopenia. Early hematological aberrations are visible across a range of cell lines, primarily of the myeloid lineage. These disturbances are transient and are probably related to clozapine's immunomodulatory properties. We do not suggest discontinuing clozapine as a consequence of the observed aberrations.

  7. 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

  8. 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.

  9. Treatment of Chronic Lymphocytic Leukemia by Risk Group

    MedlinePlus

    ... Chronic Lymphocytic Leukemia Typical Treatment of Chronic Lymphocytic Leukemia Treatment options for chronic lymphocytic leukemia (CLL) vary ... Treating Hairy Cell Leukemia More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  10. Treatment of Chronic Spontaneous Urticaria

    PubMed Central

    2012-01-01

    Chronic spontaneous urticaria is defined as persistent symptoms of urticaria for 6 weeks or more. It is associated with autoimmunity in approximately 45 percent of patients. Therapy is often difficult however the initial approach should employ high-dose non-sedating antihistamines; 4-6 tablets/day may be necessary. It has been shown that the response to 4 tablets/day exceeds 3, and exceeds 2, which exceeds 1. However the dose that corresponds to the maximal dose of first generation antihistamines (hydroxyzine, diphenhydramine) used previously, is 6/day. Yet over half the patients are refractory to antihistamines and other agents should be tried next. Whereas current guidelines (published) often add leukotriene antagonists and/or H2 receptor antogonists next, these are of little utility. Likewise drugs effective for urticarial vasculitis (colchicine, dapsone, sulfasalazine, hydroxychloroquine) are effective in a small percentage of patients and no study suggests that the response rate of any of them exceeds the 30% placebo responses seen in most double-blind, placebo controlled studies. The drugs that are effective for antihistamine-resistant chronic spontaneous urticaria are corticosteroids, cyclosporine, and Omalizumab. Use of steroids is limited by toxicity. If used at all, a dose of no more than 10 mg/day should be employed with a weekly reduction of 1 mg. The response rates to cyclosporine and Omalizumab are each close to 75%. Cyclosporine can be used effectively if care is taken to monitor blood pressure, urine protein, blood urea nitrogen, and creatinine, every 6 weeks. Omalizumab has the best profile in terms of efficacy/toxicity and, once approved by federal agencies for use in chronic spontaneous urticaria, a dramatic change in the treatment paradigm, whether associated with autoimmunity or not, is predicted. A phase 3 trial is currently in place. Refractoriness to both Omalizumab and cyclosporine is expected to be less than 5 percent of patients. Other

  11. Knowledge of Psychiatric Nurses About the Potentially Lethal Side-Effects of Clozapine.

    PubMed

    De Hert, Marc; De Beugher, Annelien; Sweers, Kim; Wampers, Martien; Correll, Christoph U; Cohen, Dan

    2016-02-01

    Clozapine is an antipsychotic with superior efficacy in treatment refractory patients, and has unique anti-suicidal properties and a low propensity to cause extrapyramidal side-effects. Despite these advantages, clozapine utilization is low. This can in part be explained by a number of potentially lethal side effects of clozapine. Next to psychiatrists nurses play a crucial role in the long-term management of patients with schizophrenia. It is therefore important that nurses know, inform and monitor patients about the specific side-effects of clozapine. A recent study of psychiatrists published in 2011 has shown that there was a gap in the knowledge about side-effects of clozapine. The knowledge about side-effects of clozapine in nurses has never been studied. This cross-sectional study evaluated the knowledge base regarding the safety of clozapine, and its potential mediators, of psychiatric nurses in 3 psychiatric hospitals in Belgium with a specifically developed questionnaire based on the literature and expert opinion (3 clozapine experts). A total of 85 nurses completed the questionnaire. The mean total score was 6.1 of a potential maximum score of 18. Only 3 of the 18 multiple choice knowledge questions were answered correctly by more than 50% of nurses. Only 24.9% of participants passed the test (>50% correct answers). Nurses working on psychosis units were more likely to pass the test (xx.y% vs yy.z%, p=0.0124). There was a trend that nurses with a lower nursing diploma were more likely to fail the test (p=0.0561). Our study clearly identifies a large gap in the basic knowledge of psychiatric nurses about clozapine and its side-effects. Knowledge could be increased by more emphasis on the topic in nurse's training curricula as well as targeted onsite training. Only 23.5% of participants indicate that there was sufficient information in their basic nursing training.

  12. Satisfaction With Chronic Pain Treatment

    PubMed Central

    Islami Parkoohi, Parisa; Amirzadeh, Kimia; Mohabbati, Vahid; Abdollahifard, Gholamreza

    2015-01-01

    Background: The effects of chronic pain (CP) on physical function and emotional and mental health of individuals, families, and community are well established. No adequate research is conducted in this field in Iran. Objectives: The current study aimed to assess the prevalence of CP, types of treatments used for CP and patients’ satisfaction with the CP treatments in an Iranian urban population. Patients and Methods: In the current study, CP was investigated using the international CP questionnaire administered to 1,050 adults living in Shiraz, Iran. The questionnaire consisted of 28 questions used to evaluate the effects of CP on the studied population including the prevalence of CP, pharmacological and non-pharmacological treatments for CP, and participants’ satisfaction with CP treatments. All the statistical analyses were performed using SPSS software, version 18. Results: In the current study, 6.95% of the 1,050 subjects willing to participate in the study had CP for more than six months. According to the results, 54% of the subjects with CP used analgesics, mostly non-steroidal anti-inflammatory drugs (NSAIDs) and narcotic analgesics. Besides, 37% of the subjects used other pain relief methods such as traditional medicine and acupuncture. The results also showed an acceptable rate of satisfaction with treatments. Conclusions: The number of subjects with CP proved it as a prevalent problem in the study population. Furthermore, characteristics and associations of those experiencing CP demonstrated that it might have significant negative health and psychosocial outcomes in this group. The problem was found significant enough to consider special health programs to prevent and manage CP in urban population of Shiraz. PMID:26473099

  13. Satisfaction With Chronic Pain Treatment.

    PubMed

    Islami Parkoohi, Parisa; Amirzadeh, Kimia; Mohabbati, Vahid; Abdollahifard, Gholamreza

    2015-08-01

    The effects of chronic pain (CP) on physical function and emotional and mental health of individuals, families, and community are well established. No adequate research is conducted in this field in Iran. The current study aimed to assess the prevalence of CP, types of treatments used for CP and patients' satisfaction with the CP treatments in an Iranian urban population. In the current study, CP was investigated using the international CP questionnaire administered to 1,050 adults living in Shiraz, Iran. The questionnaire consisted of 28 questions used to evaluate the effects of CP on the studied population including the prevalence of CP, pharmacological and non-pharmacological treatments for CP, and participants' satisfaction with CP treatments. All the statistical analyses were performed using SPSS software, version 18. In the current study, 6.95% of the 1,050 subjects willing to participate in the study had CP for more than six months. According to the results, 54% of the subjects with CP used analgesics, mostly non-steroidal anti-inflammatory drugs (NSAIDs) and narcotic analgesics. Besides, 37% of the subjects used other pain relief methods such as traditional medicine and acupuncture. The results also showed an acceptable rate of satisfaction with treatments. The number of subjects with CP proved it as a prevalent problem in the study population. Furthermore, characteristics and associations of those experiencing CP demonstrated that it might have significant negative health and psychosocial outcomes in this group. The problem was found significant enough to consider special health programs to prevent and manage CP in urban population of Shiraz.

  14. Clinical management of clozapine patients in relation to efficacy and side-effects.

    PubMed

    Naber, D; Holzbach, R; Perro, C; Hippius, H

    1992-05-01

    Medical charts of 480 schizophrenic in-patients (581 treatments) were analysed to evaluate the efficacy and side-effects of clozapine. Clozapine treatment lasted for mean 49 (s.d. 38) days. Of the sample, 11.0% showed worsening or no change, 31.5% slight improvement, 53.0% marked improvement and 4.5% almost total reduction of symptoms. At least one major side-effect occurred in 68.0% of patients. A combination of clozapine with classical neuroleptics, antidepressants, benzodiazepines or lithium is tolerated by most patients, but increases the incidence of some side-effects. Clozapine treatment had to be discontinued because of severe side-effects in 8.6% of patients. In 81 schizophrenic out-patients, clozapine significantly reduced the days of in-patient treatment and number of hospital readmissions. Two patients developed leucopenia but had no complications after clozapine withdrawal. This study indicates a satisfactory benefit/risk ratio and compliance in most of the patients.

  15. Use of aripiprazole in clozapine induced enuresis: report of two cases.

    PubMed

    Lee, Myung-Ji; Kim, Chul-Eung

    2010-02-01

    This report describes the efficacy of combined use of aripiprazole in the treatment of a patient with clozapine induced enuresis. Aripiprazole acts as a potential dopamine partial agonist and the dopamine blockade in the basal ganglia might be one of the causes of urinary incontinence and enuresis. We speculate that aripiprazole functioned as a D2 agonist in hypodopaminergic state of basal ganglia caused by clozapine and maintained dopamine level that would improve enuresis ultimately.

  16. Clozapine influences cytoskeleton structure and calcium homeostasis in rat cerebral cortex and has a different proteomic profile than risperidone.

    PubMed

    Kedracka-Krok, Sylwia; Swiderska, Bianka; Jankowska, Urszula; Skupien-Rabian, Bozena; Solich, Joanna; Buczak, Katarzyna; Dziedzicka-Wasylewska, Marta

    2015-03-01

    For over the last 50 years, the molecular mechanism of anti-psychotic drugs' action has been far from clear. While risperidone is very often used in clinical practice, the most efficient known anti-psychotic drug is clozapine (CLO). However, the biochemical background of CLO's action still remains elusive. In this study, we performed comparative proteomic analysis of rat cerebral cortex following chronic administration of these two drugs. We observed significant changes in the expression of cytoskeletal, synaptic, and regulatory proteins caused by both antipsychotics. Among other proteins, alterations in collapsin response mediator proteins, CRMP2 and CRMP4, were the most spectacular consequences of treatment with both drugs. Moreover, risperidone increased the level of proteins involved in cell proliferation such as fatty acid-binding protein-7 and translin-associated factor X. CLO significantly up-regulated the expression of visinin-like protein 1, neurocalcin δ and mitochondrial, stomatin-like protein 2, the calcium-binding proteins regulating calcium homeostasis, and the functioning of ion channels and receptors. Using two-dimensional differential electrophoresis, we demonstrate that chronic treatment the healthy rats with anti-psychotics, clozapine and risperidone, induce changes in expression of cytoskeletal, synaptic, and regulatory proteins in the cerebral cortex. While risperidone increases the level of proteins regulating cell proliferation, namely, fatty acid-binding protein-7 and translin-associated factor X, the clozapine significantly up-regulates calcium sensors, i.e., visinin-like protein 1 and neurocalcin δ. 2D DIGE, Differential in Gel Electrophoresis; Cy2, Cy3, and Cy5 are cyanine dyes. © 2014 International Society for Neurochemistry.

  17. Augmentation of Clozapine with Aripiprazole in Severe Psychotic Bipolar and Schizoaffective Disorders: A Pilot Study

    PubMed Central

    Benedetti, Alessandra; Di Paolo, Antonello; Lastella, Marianna; Casamassima, Francesco; Candiracci, Chiara; Litta, Antonella; Ciofi, Laura; Danesi, Romano; Lattanzi, Lorenzo; Del Tacca, Mario; Cassano, Giovanni Battista

    2010-01-01

    Aim: To evaluate the efficacy and safety of the augmentation of clozapine with aripiprazole in patients with treatment-resistant schizoaffective and psychotic bipolar disorders in a retrospective manner. Pharmacodynamic and pharmacokinetic interactions between the two drugs were also investigated. Patients: Three men and 4 women (median age 36 and 40 years, respectively) who had mean scores at BPRS and CGI-Severity of 59.1±12.0 and 5.4±0.5, respectively, were treated with clozapine (mean dose 292.9±220.7 mg/day). Patients received an adjunctive treatment with aripiprazole (mean dose 6.8 ± 3.7 mg/day). Clozapine, norclozapine and aripiprazole plasma levels were measured by means of a high performance liquid chromatograpy with UV detection. Results: Total scores at BPRS decreased significantly (from 59.1±12.0 to 51.1±15.6, p=0.007) after aripirazole augmentation. In particular, the factors “thought disorder” (from 10.4±4.4 to 9.0±4.5, p=.047) and “anergia” (from 10.0±2.7 to 8.0±2.4, p=.018) significantly improved. Concomitant administration of aripiprazole and clozapine did not result in an increase in side effects over the period of treatment. Dose-normalized plasma levels of both clozapine and norclozapine and the clozapine/norclozapine metabolic ratio in all patients did not vary as well. Conclusion: The augmentation of clozapine with aripirazole was safe and effective in severe psychotic schizoaffective and bipolar disorders which failed to respond to atypical antipsychotics. A possible pharmacokinetic interaction between clozapine and aripiprazole does not account for the improved clinical benefit obtained after aripiprazole augmentation. PMID:20648219

  18. 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

  19. Chronic metformin treatment facilitates seizure termination.

    PubMed

    Yang, Yong; Zhu, Binglin; Zheng, Fangshuo; Li, Yun; Zhang, Yanke; Hu, Yida; Wang, Xuefeng

    2017-03-04

    The AMP-activated protein kinase (AMPK) is a key energy sensor. Its activator metformin could suppress epileptogenesis in the pentylenetetrazol (PTZ) kindling model. However, the effect of metformin on the acute and chronic seizures has not been studied. We first detected the expression of AMPK in the brain tissue of human and mice with chronic seizures, as well as in mice with acute seizures. Second, using behavioral assay and local filed potentials (LFPs) recording, we investigated the effect of chronic metformin treatment on seizures in a acute seizure model and a chronic seizure model. Our results showed that AMPK was expressed in neurons in the epileptic brain. The expression level was decreased in the brain tissue that experienced chronic and acute seizures. In PTZ-induced acute seizures model, behavioral assay showed that chronic metformin treatment decreased the mortality, and LFPs recording showed that chronic metformin treatment shortened the duration of generalized tonic-clonic seizures and prolonged the duration of postictal depression. Moreover, in kainic acid-induced chronic seizures model, LFPs recording showed that chronic metformin treatment shortened the duration of epileptic activity. Our study suggests that chronic metformin treatment could facilitate seizure termination. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Comparative analysis of the treatment of chronic antipsychotic drugs on epileptic susceptibility in genetically epilepsy-prone rats.

    PubMed

    Citraro, Rita; Leo, Antonio; Aiello, Rossana; Pugliese, Michela; Russo, Emilio; De Sarro, Giovambattista

    2015-01-01

    Antipsychotic drugs (APs) are of great benefit in several psychiatric disorders, but they can be associated with various adverse effects, including seizures. To investigate the effects of chronic antipsychotic treatment on seizure susceptibility in genetically epilepsy-prone rats, some APs were administered for 7 weeks, and seizure susceptibility (audiogenic seizures) was evaluated once a week during treatment and for 5 weeks after drug withdrawal. Furthermore, acute and subchronic (5-day treatment) effects were also measured. Rats received haloperidol (0.2-1.0 mg/kg), clozapine (1-5 mg/kg), risperidone (0.03-0.50 mg/kg), quetiapine (2-10 mg/kg), aripriprazole (0.2-1.0 mg/kg), and olanzapine (0.13-0.66 mg/kg), and tested according to treatment duration. Acute administration of APs had no effect on seizures, whereas, after regular treatment, aripiprazole reduced seizure severity; haloperidol had no effects and all other APs increased seizure severity. In chronically treated rats, clozapine showed the most marked proconvulsant effects, followed by risperidone and olanzapine. Quetiapine and haloperidol had only modest effects, and aripiprazole was anticonvulsant. Finally, the proconvulsant effects lasted at least 2-3 weeks after treatment suspension; for aripiprazole, a proconvulsant rebound effect was observed. Taken together, these results indicate and confirm that APs might have the potential to increase the severity of audiogenic seizures but that aripiprazole may exert anticonvulsant effects. The use of APs in patients, particularly in patients with epilepsy, should be monitored for seizure occurrence, including during the time after cessation of therapy. Further studies will determine whether aripiprazole really has a potential as an anticonvulsant drug and might also be clinically relevant for epileptic patients with psychiatric comorbidities.

  1. Surgical Treatment of Chronic Orofacial Pain

    PubMed Central

    Sisk, Allen L.

    1983-01-01

    There are many conditions in which chronic orofacial pain is a major diagnostic and therapeutic problem. It is generally accepted that surgical treatment for these chronic pain problems should be resorted to only when more conservative treatments have been ineffective. Literature concerning selected orofacial pain problems is reviewed and the indications for surgical management are discussed. PMID:6370045

  2. Chronic diarrhoea: investigation, treatment and nursing care.

    PubMed

    Metcalf, Chris

    Chronic diarrhoea is a distressing symptom of a number of conditions. This article explains the assessment of patients at the initial outpatient visit through the various investigations and finally medical and surgical treatment. Emphasis is placed on the nursing management of chronic diarrhoea, particularly the treatment of physical effects such as dehydration and perianal skin soreness, and the psychological aspects of care.

  3. Chronic depression: update on classification and treatment.

    PubMed

    Torpey, Dana C; Klein, Daniel N

    2008-12-01

    A significant proportion of patients with depressive disorders suffer from chronic conditions. The DSM-IV recognizes several forms of chronic depression. Chronic depressions differ from nonchronic major depressive disorder (MDD) on many clinical, psychosocial, and familial variables. However, less support exists for current distinctions between the various forms of chronic depression. Antidepressant medications and at least some forms of psychotherapy are efficacious in treating chronic depression, and the combination of pharmacotherapy and psychotherapy appears to be superior to either monotherapy alone. Still, chronic depression is often inadequately treated, and many patients fail to respond or continue to experience residual symptoms after treatment. An important direction for future research is to elucidate the multiple pathways to chronic depression and to tailor treatments to specific etiopathogenetic subgroups.

  4. The novel use of clozapine in an adolescent with borderline personality disorder

    PubMed Central

    Hill, Simon Alastair

    2014-01-01

    Background: Clozapine has been used to good effect in the treatment of adults with borderline personality disorder, but there is scant evidence of it being used in an adolescent population with these difficulties. Methods: Clozapine was trialled in an adolescent with a clinical presentation consistent with an emerging borderline personality disorder. Results: There was a large reduction in the number of incidents involving abuse to staff, or harm to self, in the 8 weeks after commencing clozapine therapy, compared with the 8 weeks prior, and also a large reduction in the number of episodes of the use of seclusion in the 13 weeks after commencing clozapine therapy, compared with the 13 weeks prior. The young person was also able to be reintegrated in to the ward environment once established on clozapine therapy, which had not been possible full-time, for a whole year prior. Conclusions: Although limited by involving just one adolescent, this very preliminary data does nonetheless suggest that clozapine may have a role in treating adolescents with emerging borderline personality disorder when other treatment options have been exhausted. PMID:25083274

  5. 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

  6. Remission of irreversible aripiprazole-induced tardive dystonia with clozapine: a case report.

    PubMed

    Joe, Soohyun; Park, Jangho; Lim, Jongseok; Park, Choongman; Ahn, Joonho

    2015-10-19

    Aripiprazole can cause irreversible tardive dystonia in some individuals, and additional intervention is sometimes needed. Here, we report the first case of aripiprazole-induced irreversible tardive dystonia in which complete recovery of motor function was achieved using the antipsychotic drug clozapine. A 24-year-old man with bipolar disorder was treated with aripiprazole and gradually developed tardive dystonia. Thorough medical and neurological examinations were performed to rule out other possible causes of tardive dystonia. Clozapine was administered when the patient did not improve following long-term withdrawal of aripiprazole or adjuvant medications. Before administration of clozapine, the patient was experiencing severe dystonia as assessed by the Extrapyramidal Symptom Rating Scale. Dystonic symptoms began to improve about 1 month after starting administration of clozapine and were completely resolved 3 months after clozapine administration. Clinicians should note the risk of aripiprazole-induced tardive dystonia and consider clozapine as an alternative and effective treatment modality in cases of irreversible tardive dystonia, particularly when concomitant treatment of psychotic symptoms is required.

  7. 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.

  8. Genetic association between the DRD4 promoter polymorphism and clozapine-induced sialorrhea.

    PubMed

    Rajagopal, Veeramanikandan; Sundaresan, Lakshmikirupa; Rajkumar, Anto P; Chittybabu, Chithra; Kuruvilla, Anju; Srivastava, Alok; Balasubramanian, Poonkuzhali; Jacob, Kuruthukulangara S; Jacob, Molly

    2014-12-01

    The use of clozapine, an effective antipsychotic drug used in treatment-resistant schizophrenia, is associated with adverse effects. Sialorrhea is one such effect, which can be distressing for many patients. Studies on the pharmacogenetics of the adverse effects of clozapine are limited. The aim of the present study was to determine whether clozapine-induced sialorrhea is associated with a 120 base-pairs (bp) tandem duplication polymorphism in the dopamine receptor subtype D4 (DRD4) gene. Ninety-five patients, mean age 35.43±9.43 years, with treatment-resistant schizophrenia and on clozapine were included in the study. Development of sialorrhea in response to the drug, as manifested by drooling of saliva, was documented in 45 (47.4%) patients. Genotyping of the patients was carried out to detect the presence of the polymorphism of interest. Clozapine-induced sialorrhea was found to be associated significantly with the 120-bp duplication in DRD4. The association was found to fit a log-additive model with an odds ratio of 2.95 (95% confidence interval 1.51-5.75; P=0.0006). Thus, the presence of the 120-bp duplication in DRD4 appears to confer a risk for sialorrhea in response to clozapine therapy. The underlying pathophysiology and clinical significance of this phenomenon warrant further investigation.

  9. Fasting serum levels of neuropeptide y in patients with schizophrenia on clozapine monotherapy.

    PubMed

    Wysokiński, Adam

    2015-01-01

    Neuropeptide Y (NPY) is one of the hypothalamic hormones that works by increasing appetite and decreasing metabolism, leading to weight gain. We checked whether NPY level in subjects with schizophrenia on clozapine is higher compared with healthy controls. We determined the fasting NPY levels of 24 subjects with schizophrenia on clozapine monotherapy and 24 age- and sex-matched healthy controls. There was no difference for NPY between the clozapine group and the control group (mean [SD], 323.33 [138.50] vs 295.83 [25.28] pg/mL, P = 0.25). Neuropeptide Y was higher in women in the clozapine group (376.00 [162.15] vs 275.45 [96.99] pg/mL, P = 0.048) but not in the control group (P = 0.31) or in the whole study group (P = 0.20). We found no correlations between NPY and age, weight, body mass index, fat mass index, body circumferences, blood pressure, waist-to-hip ratio, levels of cholesterol, high-density lipoproteins, low-density lipoproteins, triglycerides, uric acid, calcium, homocysteine, glucose, insulin, insulin resistance, treatment duration, dose of clozapine, body composition, or basal metabolic rate. We cannot conclude that treatment with clozapine is associated with increased level of NPY. We did not find previously described differences in NPY for obesity or associations between NPY and metabolic parameters.

  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. Evaluation of a general practitioner-led cardiometabolic clinic: Physical health profile and treatment outcomes for clients on clozapine.

    PubMed

    Coates, Dominiek; Woodford, Patricia; Higgins, Oliver; Grover, Deborah

    2017-02-24

    The present study is a review of a cardiometabolic clinic for consumers taking clozapine. This clinic was recently established and co-located with the clozapine clinic at a regional hospital in New South Wales, Australia, to enhance engagement and improve the physical health outcomes of consumers taking antipsychotic medication. A descriptive analysis of clients' (n = 73) information collected during routine care for the first 6 months of the clinic's operation, from January 2016 to July 2016, was conducted. First-visit data were analysed to establish a client profile, consisting of weight, height, blood pressure, pulse, a range of blood measurements, smoking status, alcohol consumption, and eating and exercise habits. Data collected for clients who had three or more visits with the general practitioner (n = 40) were analysed separately for outcomes. Two case studies are used to depict the service received and client profile. At the first appointment, the majority of clients had metabolic syndrome that was mostly left untreated; many of these clients were commenced on metformin. The outcomes are positive, and show that the majority of clients lost weight (82.5%) and had a reduction in body mass index (84.6%); nearly half (44.4%) had a reduction in waist circumference. The majority of clients self-reported increased physical activity (72.5%, n = 29) and positive dietary changes (77.5%, n = 31) since their first appointment. The model trialled by the cardiometabolic clinic integrated a specialist mental health and primary care service, and demonstrates success in engaging clients with severe mental illness in physical health care. Co-location is conceptualized as critical for positive patient outcomes and high levels of engagement.

  12. [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.

  13. 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.

  14. The comparative effects of clozapine versus haloperidol on initiation and maintenance of alcohol drinking in male alcohol-preferring P rat.

    PubMed

    Chau, David T; Khokhar, Jibran Y; Dawson, Ree; Ahmed, Jayme; Xie, Haiyi; Green, Alan I

    2013-12-01

    Alcohol use disorder, characterized by modest levels of alcohol use, commonly occurs in patients with schizophrenia and dramatically worsens their course. Recent data indicate that the atypical antipsychotic clozapine, but not the typical antipsychotic haloperidol, decreases alcohol drinking both in patients with schizophrenia and also in the Syrian golden hamster, an animal model of moderate alcohol drinking. The present study was designed to assess the comparative effects of clozapine and haloperidol in the alcohol-preferring (P) rat, an animal model of alcoholism. First, the study investigated the comparative effects of clozapine and haloperidol on initiation of alcohol consumption in P rats, which models the early stage of alcoholism. Second, the study assessed the comparative effects of clozapine and haloperidol on maintenance of chronic alcohol consumption in P rats to provide a clue as to whether either drug may also limit alcohol consumption in alcohol-dependent patients. Clozapine attenuated the initiation of alcohol drinking and development of alcohol preference while haloperidol did not. However, neither clozapine nor haloperidol attenuated maintenance of chronic alcohol drinking. Taken together, the current data suggest that clozapine, but not haloperidol, may be effective at reducing alcohol abuse or non-dependent drinking and the P rat, used within an alcohol initiation paradigm, and may differentiate the effects of clozapine and haloperidol on alcohol drinking.

  15. Relationship between clozapine dose, serum concentration, and clinical outcome in children and adolescents in clinical practice.

    PubMed

    Wohkittel, Christopher; Gerlach, Manfred; Taurines, Regina; Wewetzer, Christoph; Unterecker, Stefan; Burger, Rainer; Schreck, Diana; Mehler-Wex, Claudia; Romanos, Marcel; Egberts, Karin

    2016-08-01

    Information on dose- and concentration-related clinical effects of clozapine treatment in children and adolescents is scarce. This study aimed to examine the relationship between dose, serum concentration, and clinical outcome as well as the influencing factors thereof in paediatric patients treated with clozapine. Data from a routine Therapeutic Drug Monitoring (TDM) service between 2004 and 2014 were studied in 68 patients, aged 11-18 years. Severity of illness, therapeutic effectiveness and adverse drug reactions (ADRs) were assessed by standardized means. A relationship between the daily dose (mean 319 mg, 4.9 mg/kg) and serum concentration (mean 387 ng/ml) of clozapine was found with the variation in dose explaining 30 % of the variability in clozapine serum concentrations. Also gender contributed to the variability, however, no influence of age or concomitant medications was detected. Furthermore, a significant association was found between clozapine serum concentration and the occurrence of ADRs. Patients without ADRs had a lower mean serum concentration than those with mild (261.4 vs 407.3 ng/ml, P = 0.018) and moderate ADRs (261.4 vs 416.3 ng/ml, P = 0.028). As clozapine was estimated to be effective in lower blood concentrations, guidance on a possibly lower therapeutic range of clozapine serum levels in paediatric patients is provided. With ADRs increasing under higher concentrations, TDM is strongly recommended in paediatric clozapine therapy for individualized dosing. Dose adjustment in females also might be reasonable according to gender-related differences in serum concentrations. However, regarding the limitations of this study results should be validated in larger studies with more standardized designs.

  16. 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…

  17. 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

  18. Psychosis or Obsessions? Clozapine Associated with Worsening Obsessive-Compulsive Symptoms

    PubMed Central

    2016-01-01

    One underrecognized adverse event of clozapine is the emergence or worsening of obsessive-compulsive symptoms (OCS). OCS, particularly violent thoughts, can be inaccurately described as psychosis and result in a misdiagnosis. We report a case of a 42-year-old man, initially diagnosed with schizoaffective, who was placed on clozapine for the management of “violent delusions.” However, clozapine led to a worsening of these violent thoughts resulting in suicidal ideation and hospitalization. After exploration of the intrusive thoughts and noting these to be egodystonic, clearly disturbing, and time consuming, an alternative diagnosis of obsessive-compulsive disorder (OCD) was made. Clozapine was inevitably discontinued resulting in a significant reduction of the intrusive thoughts without emergence of psychosis or adverse events. While an overlapping phenomenology between OCD and psychotic disorders has been described, clozapine and other antiserotonergic antipsychotics have been implicated with the emergence or worsening of OCS. Unique to our case is that the patient's obsessions had been treated as psychosis leading to the inadequate treatment of his primary illness, OCD. This case highlights the potential for OCD to masquerade as a psychotic disorder and reminds clinicians that clozapine may worsen OCS. PMID:27313938

  19. Clozapine--a dangerous drug in a clozapine-naïve subject.

    PubMed

    Stanworth, D; Hunt, N C A; Flanagan, R J

    2012-01-10

    Clozapine is a uniquely effective antipsychotic, but is very toxic in clozapine-naïve subjects. A 34-year-old male patient in a mental health facility, who was not prescribed clozapine, took 350 mg clozapine obtained from another patient at night. He was found dead the next morning. The presence of cardiomegaly related to obesity may have increased the risk of suffering an acute cardiac event after ingestion of clozapine. The medication prescribed to the patient was not thought to have contributed to the fatal outcome. Post mortem femoral blood clozapine and norclozapine concentrations were 0.48 and 0.20mg/L, respectively. By way of comparison, audit of 104,127 plasma samples (26,796 patients) assayed for therapeutic drug monitoring purposes 1993-2007, showed plasma clozapine 0.35 mg/L or more in 57.5% samples (8.4% 1mg/L or more). Those involved in the investigation of clozapine-associated deaths need to be aware that that death in an adult may occur after a single 'therapeutic' dose. A diagnosis of fatal clozapine poisoning cannot be made solely on the basis of a post mortem blood clozapine measurement.

  20. Clozapine may partially compensate for task-related brain perfusion abnormalities in risperidone-resistant schizophrenia patients.

    PubMed

    Molina, V; Tamayo, P; Montes, C; De Luxán, A; Martin, C; Rivas, N; Sancho, C; Domínguez-Gil, A

    2008-05-15

    Previous reports show different cerebral activity patterns during treatment with clozapine and typical neuroleptics. However, to date no study has directly compared the brain activity patterns while subjects are undergoing treatment with clozapine and other atypical antipsychotics. This comparison is of interest, given the probably different mechanism of action of clozapine in comparison with other atypicals. To assess the effect of clozapine on perfusion deviations still evident during treatment with risperidone. Here we used hexamethylene-propylenaminoxime single photon emission computed tomography to compare the perfusion patterns observed during the performance of a Stroop test in 10 patients sequentially treated with risperidone and clozapine, owing to a lack of response to the former, and in 10 healthy controls. Patients on risperidone showed decreased perfusion as compared to controls in the medial prefrontal, middle cingulate and insular regions, as well as increased activities in brain stem and the posterior hippocampus. After receiving clozapine, the same patients showed an even wider prefrontal perfusion deficit and the brain stem was still hyperactive, but the abnormalities in the cingulate cortex, insula and hippocampus had disappeared. Clinical improvement was directly related to an increase in thalamic perfusion. Clozapine may alleviate hyperactivity in the limbic system in schizophrenia and may facilitate activation of the regions involved in cognitive tasks to a greater degree than risperidone, as well as eliciting greater inhibition of the PF region.

  1. Management and treatment of chronic urticaria (CU).

    PubMed

    Maurer, M; Church, M K; Gonçalo, M; Sussman, G; Sánchez-Borges, M

    2015-06-01

    Developments increasing our understanding of chronic urticaria have resulted in the simplification and improvement of available treatments. Currently, many treatments target mast cell mediators, but we can now disrupt mast cell activation with the anti-IgE antibody omalizumab, which has markedly advanced the treatment landscape for patients with difficult-to-treat urticaria. Current guidelines provide a framework for the management and treatment of patients with CU but, as each patient is different, knowledge and experience of specialist dermatologists and allergists are key to effective pharmacotherapy. This article reviews the different therapeutic options for patients with chronic spontaneous urticaria (also called chronic idiopathic urticaria) or chronic inducible urticaria and discusses management of special populations or special circumstances related to CU.

  2. In a randomized placebo-controlled add-on study orlistat significantly reduced clozapine-induced constipation.

    PubMed

    Chukhin, Evgeny; Takala, Pirjo; Hakko, Helinä; Raidma, Mirjam; Putkonen, Hanna; Räsänen, Pirkko; Terevnikov, Viacheslav; Stenberg, Jan-Henry; Eronen, Markku; Joffe, Grigori

    2013-03-01

    Constipation is a common and potentially fatal side effect of clozapine treatment. Another important side effect of clozapine may also be significant weight gain. Orlistat is a weight-control medication that is known to induce loose stools as a common side effect. This study aimed to explore whether orlistat used to control clozapine-induced weight gain can simultaneously tackle clozapine-related constipation. In this 16-week randomized-controlled study, clozapine-treated patients received add-on orlistat (n=30) or add-on placebo (n=24). Colonic function was measured using the Bristol Stool Form Scale. There was a significant (P=0.039) difference in the prevalence of constipation in favor of orlistat over placebo in completers (n=40) at the endpoint. A decrease in the prevalence of constipation within the orlistat group (P=0.035) was observed (vs. no statistically significant changes in the placebo group). In clozapine-treated patients, orlistat may be beneficial not only for weight control but also as a laxative. As no established treatments for clozapine-induced constipation exist, orlistat can be considered for this population, although more studies are required.

  3. Chronic laminitis: current treatment strategies.

    PubMed

    Parks, Andrew; O'Grady, Stephen E

    2003-08-01

    Laminitis is divided into four different phases: developmental, acute, subacute, and chronic. The focus of this article is on treating the laminitic horse after the cessation of therapy for the acute phase, that is, usually 2 to 4 weeks after the onset of clinical signs.

  4. [Operative treatment of chronic pleuritis].

    PubMed

    Duzhyĭ, I D; Hres'ko, I Ia; Chumak, S O; Elastal, R Z

    2008-09-01

    Basing on the literature data and own experience, grounded on results of follow-up on 2000 patients, suffering an acute pleuritis and performance of more than 200 operative interventions--pleurectomy, the clinic-radiological classification of chronic pleuritis, mostly answering the practical health care necessities, was proposed by the authors.

  5. 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.

  6. 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

  7. Life-threatening clozapine-induced gastrointestinal hypomotility: an analysis of 102 cases.

    PubMed

    Palmer, Susanna E; McLean, Rachael M; Ellis, Peter M; Harrison-Woolrych, Mira

    2008-05-01

    To raise awareness of potentially lethal clozapine-induced gastrointestinal hypomotility (CIGH) by reviewing cases from the literature and unpublished pharmacovigilance data and to offer strategies aimed at prevention and early treatment. Databases (PsycINFO, 1967-2007; MEDLINE, 1950-2007; and EMBASE, 1988-2007) were searched using the term clozapine together with each of the following: gastrointestinal, dysmotility, constipation, obstipation, fecal impaction, fecaloma, paralytic ileus, adynamic ileus, subileus, ischemic colitis, colon ischemia, bowel ischemia, gastrointestinal ischemia, gut ischemia, obstruction, necrosis, gangrene, bowel perforation, micro-perforation, megacolon, toxic megacolon, acquired megacolon, pseudo-obstruction, Ogilvie, and Ogilvie's syndrome. We analyzed the electronic database entries held by the Adverse Drug Reactions Advisory Committee and the New Zealand Intensive Medicines Monitoring Program, which cited suspected clozapine-related gastrointestinal side effects, as well as all relevant published case reports. We reviewed the literature on the treatment of gastrointestinal hypomotility and constipation. We compiled a database of 102 cases of suspected life-threatening CIGH. There was a mortality rate of 27.5% and considerable morbidity, largely due to bowel resection. Within Australasia, at least 15 patients have died of CIGH. Probable risk factors are identified as recent instigation of clozapine, high clozapine dose or serum level, concomitant anticholinergic use, or intercurrent illness. The paucity of literature on CIGH suggests that the significance of this uncommon but important and frequently fatal side effect has not been recognized. Clozapine can affect the entire gastrointestinal system, from esophagus to rectum, and may cause bowel obstruction, ischemia, perforation, and aspiration. The mechanism is likely to be anticholinergic and antiserotonergic. Clozapine prescribing should be accompanied by regular physical monitoring

  8. 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.

  9. Effects of clozapine on memory function in the rat neonatal hippocampal lesion model of schizophrenia.

    PubMed

    Levin, Edward D; Christopher, N Channelle

    2006-03-01

    Clozapine is an effective atypical antipsychotic drug used to treat schizophrenia. It has the advantage of producing fewer extrapyramidal motor side effects than typical antipsychotic drugs such as haloperidol. Schizophrenia involves more than the hallmark symptom of psychosis. Substantial cognitive impairment is also seen. Effective drug treatments against the cognitive impairment of schizophrenia need to be developed. The current study was conducted to determine the effects of clozapine on working memory in the rat neonatal hippocampal lesion model of schizophrenia, which includes symptoms of cognitive impairment. Infant Sprague-Dawley rats were given ibotenic acid lesions of the hippocampus on day 7 of age (using the day of birth as day 0). Controls were given vehicle infusions. In adulthood, the rats were trained on the 8-arm radial maze using the win-shift procedure. After 6 sessions of training, the lesioned rats and their controls were administered repeated injections of saline or clozapine (2.5 mg/kg) for the next 12 sessions of training. The females had significant radial-arm maze choice accuracy impairments caused by either clozapine or the hippocampal lesion, but the combination of the two treatments had no additive effect. The males showed a different pattern of effects. Intact males did not show a significant clozapine-induced impairment, whereas males with hippocampal lesions did show significant clozapine-induced impairment although hippocampal lesions by themselves did not significantly impair male choice accuracy. These data show that clozapine can cause memory impairment and it potentiates rather than reverses hippocampal lesion-induced deficits. There are critical sex-related differences in these effects.

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

    PubMed Central

    Mcmillan, Sara S.

    2016-01-01

    Background: 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. Objective: 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. Method: 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. Results: 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. Conclusion: 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

  11. Clozapine-Induced Gastrointestinal Hypomotility: A 22-Year Bi-National Pharmacovigilance Study of Serious or Fatal 'Slow Gut' Reactions, and Comparison with International Drug Safety Advice.

    PubMed

    Every-Palmer, Susanna; Ellis, Pete M

    2017-08-01

    Clozapine is the preferred antipsychotic for treatment-resistant schizophrenia, but has significant adverse effects, including gastrointestinal hypomotility or 'slow gut', which may result in severe constipation, ileus, bowel obstruction, and even death. These gastrointestinal effects remain inadequately recognized. We reviewed all reports of serious clozapine-induced gastrointestinal hypomotility (CIGH) submitted to the Australian Therapeutic Goods Administration and New Zealand Pharmacovigilance Centre between 1992 and 2013. We extracted relevant demographic, clinical, and outcome data and derived a numerator from clozapine registries. We examined whether clozapine drug safety information in Australia, New Zealand, the US, and the UK was adequate and consistent with pharmacoepidemiologic evidence. A total of 43,132 people commenced clozapine over the study period. 160 were reported as having serious gastrointestinal hypomotility with clozapine the suspected cause (37/10,000 clozapine users). Of these, 66.3% were male, age range was 17-76 years, clozapine dose range 25-1000 mg/day (mean 439 mg/day) and median duration of clozapine treatment 2.5 years. Few had received laxatives. At least 29 patients died (7/10,000 clozapine users), a reported case fatality rate of 18%. The CIGH prevalence, while similar to other smaller studies, differs significantly from clozapine prescribing information issued by regulators and pharmaceutical companies, none of which mention CIGH, and which report serious gastrointestinal complications at rates of <1/10,000, almost a 40-fold difference. This is the largest study to date of serious CIGH. The reported prevalence of serious CIGH was 37/10,000, a likely underestimation of true prevalence. Current prescribing guidelines provide inadequate information on CIGH. This may be contributing to poor awareness and high associated morbidity and mortality. It is time regulators and manufacturers update their guidance.

  12. 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

  13. 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.

  14. Treatment of Refractory Chronic Urticaria

    PubMed Central

    Mehta, Aayushi; Godse, Kiran; Patil, Sharmila; Nadkarni, Nitin; Gautam, Manjyot

    2015-01-01

    Chronic spontaneous urticaria is a distressing disease encountered frequently in clinical practice. The current mainstay of therapy is the use of second-generation, non-sedating antihistamines. However, in patients who do not respond satisfactorily to these agents, a variety of other drugs are used. This article examines the available literature for frequently used agents including systemic corticosteroids, leukotriene receptor antagonists, dapsone, sulfasalazine, hydroxychloroquine, H2 antagonists, methotrexate, cyclosporine A, omalizumab, autologous serum therapy, and mycophenolate mofetil, with an additional focus on publications in Indian literature. PMID:26120147

  15. 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? Many ... person's outlook and whether they will need treatment. New drugs for chronic lymphocytic leukemia Dozens of new ...

  16. Low-dose Amisulpride for Debilitating Clozapine-induced Sialorrhea: Case Series and Review of Literature

    PubMed Central

    Kulkarni, Ranganath R.

    2015-01-01

    Clozapine-induced sialorrhea (CIS) affects about one-third of patients treated with clozapine, at times can be stigmatizing, socially embarrassing, disabling, affect quality-of-life, cause poor compliance and can be potentially life-threatening adverse effect. Prompt and effective treatment of CIS may assist treatment tolerability, adherence, and better outcomes in patients with treatment nonresponsive schizophrenia. The beneficial effect of amisulpride augmentation of clozapine therapy for such patients may be enhanced by its anti-salivatory effect on CIS. Current series of five subjects who developed CIS that responded poorly to anticholinergic drugs found drastic improvement in daytime and nocturnal CIS with very low-dose (50-100 mg/day) of amisulpride. Low-dose amisulpride augmentation may also provide strong ameliorating effect on CIS. Nevertheless, a long-term, large-scale study with a broader dose range is warranted to evaluate the stability of this effect across time. PMID:26702180

  17. Clozapine induces oxidative stress and proapoptotic gene expression in neutrophils of schizophrenic patients.

    PubMed

    Fehsel, Karin; Loeffler, Stefan; Krieger, Klaus; Henning, Uwe; Agelink, Markus; Kolb-Bachofen, Victoria; Klimke, Ansgar

    2005-10-01

    The present study examined cellular effects of the atypical antipsychotic drug clozapine on blood cells of treated patients with and without clozapine-induced agranulocytosis (CA). Blood from one patient who commenced clozapine treatment was examined at weekly intervals for 128 days. Olanzapine-treated (n = 5) and polymedicated (n = 14) schizophrenic patients, as well as healthy subjects (n = 19) and septic shock patients (n = 8), were studied for comparison. We observed dramatically increased numbers of native neutrophils stained for superoxide anion production (P < or = 0.005, n = 10) and significantly elevated expression levels of the proapoptotic genes p53 (P < or = 0.020), bax alpha (P < or = 0.001), and bik (P < or = 0.002) in all tested non-CA patients (n = 19) and CA patients (n = 4). In non-CA patients, the expression of these genes did not correlate to the percentage of apoptotic neutrophils (2.0% +/- 1.3%), but in CA patients about 37% of the neutrophils show morphologic signs of apoptosis (P < or = 0.001). Under G-CSF therapy of CA, the number of apoptotic neutrophils and the expression of the proapoptotic genes decreased significantly. In conclusion, high production of reactive oxygen species in neutrophils of clozapine-treated patients, together with increased expression of proapoptotic genes, suggests that neutrophils are predisposed to apoptosis in schizophrenic patients under clozapine therapy. The correlation between drug and proapoptotic markers was highest for clozapine and bax alpha as well as superoxide anion radicals. This indicates oxidative mitochondrial stress in neutrophils of clozapine-treated patients which probably contributes to the induction of apoptosis and sudden loss of neutrophils and their precursors in CA patients.

  18. The Drug-Drug Effects of Rhein on the Pharmacokinetics and Pharmacodynamics of Clozapine in Rat Brain Extracellular Fluid by In Vivo Microdialysis.

    PubMed

    Hou, Mei-Ling; Lin, Chi-Hung; Lin, Lie-Chwen; Tsai, Tung-Hu

    2015-10-01

    Clozapine, an atypical antipsychotic agent, is highly effective in treatment-resistant schizophrenia; however, its major side effect is constipation. Instead of laxatives, rhein is a pharmacologically active component found in Rheum palmatum L., a medicinal herbal remedy for constipation. The purpose of this study is to determine whether rhein impacts the pharmacokinetics (PK) and pharmacodynamics (PD) of clozapine in brain when used to relieve clozapine-induced constipation. Here, we have investigated not only the PK of clozapine in blood but also the effects of rhein on the PK of clozapine in blood and in brain extracellular fluid together with the PD effects on neurotransmitters in extracellular fluid. The concentrations of clozapine and norclozapine in biologic samples were measured by ultra-performance liquid chromatography-tandem mass spectrometry. The drug-drug effects of rhein on extracellular neurotransmitter efflux in the rat medial prefrontal cortex (mPFC) produced by clozapine were assayed by high-performance liquid chromatography-electrochemical detection. The results demonstrate that the clozapine PK was nonlinear. Pretreatment with rhein for 7 days increased the total blood concentration of clozapine, but significantly reduced the unbound clozapine concentrations in the mPFC by approximately 3-fold. Furthermore, 7 days of rhein pretreatment thoroughly abolished the efflux of dopamine and its metabolite (3,4-dihydroxyphenylacetic acid) and altered the profile of homovanillic acid, another metabolite of dopamine, in the mPFC. In conclusion, rhein was found to substantially decrease clozapine and norclozapine concentrations in the mPFC dialysate, and this is accompanied by lower concentrations in the neurotransmitters in the same biophase. These findings suggest that a detailed clinical study for drug-drug interactions is recommended.

  19. A case study evaluating the use of clozapine in depression with psychotic features

    PubMed Central

    Jeyapaul, Premkumar; Vieweg, Ray

    2006-01-01

    The purpose of this case study was to use an evidence based medicine approach to work through an unusual way of treating a common problem. We looked at an example of an in-patient with severe refractory psychotic depression who had been resistant to treatment with a combination of antidepressant, antipsychotics, mood stabiliser, and concomitant ECT therapy. We then undertook a literature search for the use of clozapine in a patient with severe refractory depression. Although the resulting evidence was low level and thin, we felt on balance that a trial of clozapine was justified. We used a BPRS inventory to monitor her mood prior to commencing clozapine. Her mood and functional abilities were monitored as her clozapine was titrated upwards. Our patient showed a significant improvement in mood and functional abilities and a reduction in her BPRS score during this period. Her symptoms improved to the point where she was successfully discharged home on a combination of clozapine and an antidepressant. The improvement was sustained for a further two years. We thought this was an important case to highlight the limited evidence in using this successful form of treatment for a common clinical problem and that further research in this area was needed. PMID:17134508

  20. 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

  1. 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

  2. Chronic psychotropic drug treatment causes differential expression of Reelin signaling system in frontal cortex of rats.

    PubMed

    Fatemi, S Hossein; Reutiman, Teri J; Folsom, Timothy D

    2009-06-01

    Disruption of the Reelin and GABAergic signaling systems have been observed in psychiatric disorders including autism, schizophrenia, bipolar disorder, and major depression. Less is known of therapeutic interventions that may help ameliorate the effects of these disruptions. The current study investigated whether chronic administration of psychotropic medications (clozapine, fluoxetine, haloperidol, lithium, olanzapine, and valproic acid) used in the treatment of psychiatric disorders alters levels of Reelin, its receptor Vldlr, downstream molecules Gsk3 beta, Dab-1, and Gad65/67 in rat prefrontal cortex as measured by qRT-PCR and SDS-PAGE and western blotting. qRT-PCR revealed that mRNAs for Reelin, Vldlr, Dab-1, Gsk3 beta, and Gad65 were each significantly altered by at least one of the drugs tested, and in the case of Reelin, Dab-1, and Gsk3 beta, by multiple drugs. To verify our results, we also performed SDS-PAGE and western blotting experiments. Again, several of the protein products for Reelin, Vldlr, Dab-1, Gsk3 beta, Gad65, and Gad67 were also significantly altered by multiple drugs. The present results suggest that the Reelin signaling and GABAergic systems are affected by commonly used psychotropic medications. These changes may help explain the efficacy of these drugs and provide further support for the investigation of the Reelin and GABAergic signaling systems as therapeutic targets for the treatment of neuropsychiatric diseases.

  3. Midodrine treatment for chronic fatigue syndrome

    PubMed Central

    Naschitz, J; Dreyfuss, D; Yeshurun, D; Rosner, I

    2004-01-01

    The long term results of midodrine treatment in a patient having debilitating chronic fatigue syndrome (CFS) are reported. Midodrine treatment, directed at the autonomic nervous system, resulted in correction of the dysautonomia followed by improvement of fatigue. This finding is consistent with the hypothesis that dysautonomia plays a major part in the pathophysiology of CFS and that therapies directed at the autonomic nervous system may be effective in the treatment of CFS. PMID:15082846

  4. [Local invasive treatment of chronic pain].

    PubMed

    Medvedeva, L A; Zagorul'ko, O I; Gnezdilov, A V

    2014-01-01

    The literature on methods of invasive local treatment of chronic pain was analyzed. We reviewed 14 publications including meta-analyses and systematic reviews. The use of regional anesthesia conducted by anesthesiologists in pain clinics demonstrated the evidence based efficacy of different types of peridural injections of local anesthetics with steroids in patients with root pain syndromes at cervical and lumbar levels. Therapeutic blockades of the occipital nerve is effective method of treatment of cervicogenic and cluster headache as well as occipital nerve neuralgia. There are clear indications of the efficacy of local injections in primary chronic cephalgia (migraine and headache of tension). The possibility of the abortion of the pain information flow in peripheral nociceptive pathways and, as a consequence, breaking the vicious circle is emphasized. Issues on the efficacy of local injections at trigger points in the treatment of chronic pain are highlighted.

  5. Treatment of chronic prostatitis/chronic pelvic pain syndrome

    PubMed Central

    Nickel, J. Curtis

    2008-01-01

    Acceptance of the National Institutes of Health definition of Category III Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) and the development and validation of the Chronic Prostatitis Symptom Index has stimulated significant research into treatment of this condition. Evidence-based suggestions for treatment include the following. (i) Antimicrobials cannot be recommended for men with longstanding, previously treated CP/CPPS. (ii) Alpha-blockers can be recommended as first-line medical therapy, particularly in alpha-blocker-naïve men with moderately severe symptoms who have relatively recent onset of symptoms. (iii) Alpha-blockers cannot be recommended in men with longstanding CP/CPPS who have tried and failed alpha-blockers in the past. And (iv) anti-inflammatory therapy, finasteride and pentosan polysulfate are not recommended as primary treatment; however, they may have a useful adjunctive role in a multimodal therapeutic regimen. Early data on herbal therapies, particularly quercetin and cernilton, are intriguing, but larger multicentre, randomised, placebo-controlled trials are required before a high level of evidence recommendation can be made on its use. At this time, surgery (including minimally invasive) is recommended only for definitive indications and not generally for CP/CPPS. PMID:17954024

  6. Clozapine

    MedlinePlus

    ... used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of ... Contrave); escitalopram (Lexapro); medications for high blood pressure, mental illness, or nausea; medications for irregular heartbeat such as ...

  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. Diagnosis and treatment of chronic ankle pain.

    PubMed

    Wukich, Dane K; Tuason, Dominick A

    2011-01-01

    The differential diagnosis for chronic ankle pain is quite broad. Ankle pain can be caused by intra-articular or extra-articular pathology and may be a result of a traumatic or nontraumatic event. A detailed patient history and physical examination, coupled with judicious selection of the appropriate imaging modalities, are vital in making an accurate diagnosis and providing effective treatment. Chronic ankle pain can affect all age groups, ranging from young athletes to elderly patients with degenerative joint and soft-tissue disorders. It has been estimated that 23,000 ankle sprains occur each day in the United States, representing approximately 1 sprain per 10,000 people per day. Because nearly one in five ankle injuries result in chronic symptoms, orthopaedic surgeons are likely to see patients with chronic ankle pain. Many patients with chronic ankle pain do not recall any history of trauma. Reviewing the management of the various disorders that can cause chronic ankle pain will help orthopaedic surgeons provide the best treatment for their patients.

  9. Update on the treatment of chronic urticaria.

    PubMed

    Curto-Barredo, L; Silvestre, J F; Giménez-Arnau, A M

    2014-06-01

    Chronic spontaneous urticaria, also known as chronic idiopathic urticaria or simply chronic urticaria, is a common disorder that has a prevalence in the general population that ranges between 0.5% and 1%. This condition negatively affects the patient's quality of life and has considerable impact on direct and indirect health-related costs. Chronic urticaria is difficult to manage. Nonsedating H1 antihistamines are the first line of therapy, but fewer than 50% of patients experience relief at recommended dosages. Although guidelines call for increasing the dosage when response is inadequate, some patients still do not achieve adequate control of symptoms. New treatment alternatives, with proven efficacy under the standards of evidence-based medical practice, must therefore be developed.

  10. 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.

  11. Clozapine use by state programs: public mental health systems respond to a new medication.

    PubMed

    Reid, W H; Pham, V A; Rago, W

    1993-08-01

    The authors present data from a national survey of state departments of mental health showing that two years after reaching the U.S. market, clozapine is available to only a small fraction of the patients whom it might benefit. The primary continuing hurdle for the public sector, where most schizophrenic patients get their care, is funding. Several arguments support the use of clozapine in state mental health systems: it is the most effective or only effective medication for many patients, it can decrease the enormous costs of schizophrenia and related disorders, and access to the medication has become an important issue for advocacy groups and other mental health activists. Two years of experience with clozapine in the Texas mental health system have shown that availability of clozapine in the community is a vital factor for successful use of the drug in hospitals. The authors discuss ways to encourage outpatient clozapine programs that are critical to successful treatment in both the hospital and the community.

  12. Probiotics in the Treatment of Chronic Rhinoconjunctivitis and Chronic Rhinosinusitis

    PubMed Central

    Kramer, Matthias F.; Heath, Matthew D.

    2014-01-01

    Chronic rhinitis and rhinosinusitis (CRS) are relevant health conditions affecting significant percentages of the western population. They are frequently coexisting and aggravating diseases. Both are chronic, noninfectious, and inflammatory conditions sharing to a certain extent important pathophysiologic similarities. Beneficial effects of probiotics are long known to mankind. Research is beginning to unravel the true nature of the human microbiome and its interaction with the immune system. The growing prevalence of atopic diseases in the developed world led to the proposition of the “hygiene hypothesis.” Dysbiosis is linked to atopic diseases; probiotic supplementation is able to alter the microbiome and certain probiotic strains have immunomodulatory effects in favour of a suppression of Th-2 and stimulation of a Th1 profile. This review focuses on randomized, double-blind, placebo-controlled trials investigating clinical parameters in the treatment of chronic rhinitis and CRS. An emerging number of publications demonstrate beneficial effects using probiotics in clinical double-blind placebo-controlled (dbpc) trials in allergic rhinitis (AR). Using probiotics as complementary treatment options in AR seems to be a promising concept although the evidence is of a preliminary nature to date and more convincing trials are needed. There are no current data to support the use of probiotics in non-AR or CRS. PMID:24872820

  13. [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.

  14. 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.

  15. Treatment of chronic myelogenous leukemia.

    PubMed

    Giralt, S; Kantarjian, H; Talpaz, M

    1995-08-01

    Allogeneic BMT and IFN-A-based therapy have undoubtedly changed the natural history of CML. Despite these advances, many patients still die from their disease. Most patients do not qualify for an allogeneic BMT either because of age or lack of an appropriate donor, and only a fraction of patients achieve a complete cytogenetic remission with IFN-A-based therapy. The timing of BMT and treatment sequences of IFN-A and BMT have been discussed. Prior treatment with IFN-A does not seem to affect transplant outcome; however, delaying transplantation has been reported to impact adversely on transplant results. Until controlled trials are performed, the issue of optimal timing of allogeneic BMT will remain controversial. The use of alternative donors may extend the option of allogeneic BMT to younger patients; however, for older patients this therapeutic modality still has an unacceptably high incidence of morbidity and mortality with current BMT regimens and other alternative treatments are needed. Investigational strategies searching for ways of improving the proportion of patients achieving complete cytogenetic remissions with IFN-A therapy need to be actively explored. These include new agents (eg, HHT) or new modalities such as intensive chemotherapy with autologous stem cell transplantation with in vitro purging. Investigators in the field must decide whether to continue randomized trials of IFN-A versus conventional chemotherapy, or to explore strategies that may enhance the effect of IFN-A-based therapy. Only when the durable cytogenetic response rates with IFN-A combinations increase to 40% or 50% will it be of value to proceed to phase III trials. Further understanding in the basic biology of CML and the effect of IFN-A in this disease will also provide clues to improving therapy with the goal of obtaining long-term disease control and cures in the majority of patients with the least burden of therapy.

  16. New treatments for chronic prostatitis/chronic pelvic pain syndrome

    PubMed Central

    Strauss, Adam C.; Dimitrakov, Jordan D.

    2010-01-01

    Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition among men of a wide age range, with detrimental effects on quality of life. The etiology, pathogenesis, and optimal treatment of CP/CPPS remain unknown, although progress has been made in these domains in recent years. A wide variety of pharmacologic and nonpharmacologic therapies have been studied in clinical trials, but most have shown limited efficacy in symptom alleviation. CP/CPPS is increasingly viewed as a condition that involves variable degrees of neuropathic pain. Medications such as gabapentin, pregabalin, memantine, and tricyclic antidepressants are often used in other neuropathic pain conditions and, therefore, are considered potential treatments for CP/CPPS. Few studies of these agents in patients with CP/CPPS have been reported, but future clinical trials should help to determine their utility and to characterize the pathogenetic mechanisms of pain in CP/CPPS. Combining treatment trials with biomarker, genomic, and imaging studies, in addition to epidemiologic and symptom-based assessments, will maximize the ability to probe disease etiology and pathogenesis, as well as identify effective treatment. PMID:20142810

  17. Diagnosis and treatment for chronic migraine

    PubMed Central

    Moriarty, Maureen; Mallick-Searle, Theresa

    2016-01-01

    Abstract: Migraine is a debilitating headache disorder that is underdiagnosed and undertreated worldwide, partially attributable to misdiagnosis and expectations of poor treatment outcomes. This article provides a review of chronic migraine, including pathophysiology, burden, diagnosis, and management, with special emphasis on the role of NPs. PMID:27203455

  18. Treatment of chronic airways obstruction with indomethacin.

    PubMed

    Hume, M; Eddey, V

    1977-10-01

    The effect of indomethacin is reported in five patients with chronic asthma. There was both subjective and objective improvment and, in three of the patients, a reduction in steroid dosage. The results suggest that the drug may be of value in the treatment of this condition.

  19. 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.

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

    PubMed Central

    Leung, Janni; Russell, Anthony W.; Wysoczanski, Daniel; Kisely, Steve

    2016-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. Trial Registration PROSPERO registration number: CRD42015029723 PMID:27304831

  1. 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 Central

    Tungaraza, Tongeji E.

    2016-01-01

    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. PMID:27721972

  2. Aripirazole augmentation in clozapine-associated obsessive-compulsive symptoms in schizophrenia

    PubMed Central

    2013-01-01

    Objective Patients with schizophrenia often experience comorbid obsessive-compulsive symptoms. Within these patients, a significant subgroup developed secondary obsessive-compulsive symptoms during treatment with clozapine. Method In this paper, we report on four cases in which adjunctive therapy with aripiprazole was tested to alleviate obsessive-compulsive symptoms in schizophrenia. Results All four patients had a significant improvement in obsessive-compulsive symptoms. The combination of clozapine and aripiprazole was well tolerated. Conclusion This case series demonstrates the clinical efficacy of aripiprazole adjunctive therapy with clozapine in schizophrenic patients with comorbid obsessive-compulsive symptoms. Larger-sampled and controlled studies are required in order to test and confirm these observations. PMID:24330737

  3. Pharmacogenetics of Chronic Pain and Its Treatment

    PubMed Central

    Světlík, Svatopluk; Hronová, Karolína; Bakhouche, Hana; Matoušková, Olga; Slanař, Ondřej

    2013-01-01

    This paper reviews the impact of genetic variability of drug metabolizing enzymes, transporters, receptors, and pathways involved in chronic pain perception on the efficacy and safety of analgesics and other drugs used for chronic pain treatment. Several candidate genes have been identified in the literature, while there is usually only limited clinical evidence substantiating for the penetration of the testing for these candidate biomarkers into the clinical practice. Further, the pain-perception regulation and modulation are still not fully understood, and thus more complex knowledge of genetic and epigenetic background for analgesia will be needed prior to the clinical use of the candidate genetic biomarkers. PMID:23766564

  4. Augmentative Asenapine in a Recurrent Manic Catatonic Patient with Partial Response to Clozapine

    PubMed Central

    Buoli, Massimiliano; Dobrea, Cristina; Caldiroli, Alice; Cremaschi, Laura; Altamura, A. Carlo

    2013-01-01

    Catatonia is a severe but treatable neuropsychiatric syndrome known since the middle of the nineteenth century. It has been considered for a long time as a subtype of schizophrenia, even though this association occurs only in 10% of cases. In contrast, it is frequently observed in bipolar patients. First-line treatment consists of benzodiazepines, while in case of resistance electroconvulsive therapy (ECT) and clozapine have shown positive results. In addition, recent studies reported the efficacy of some atypical antipsychotics. The present case shows the clinical response to augmentative asenapine in a catatonic manic patient with a partial response to clozapine. PMID:24171130

  5. Pipamperone augmentation of clozapine and sodium valproate in refractory schizophrenia: a case report.

    PubMed

    Paraschakis, Antonios

    2014-01-01

    Refractory schizophrenia poses many therapeutic dilemmas. Clozapine is currently considered as the most effective medication for the treatment of refractory schizophrenia. Unfortunately, it carries serious and often life-threatening adverse effects such as agranulocitosis, hypersalivation, somnolence, weight gain, diabetes, and epileptic seizures. Various combinations of clozapine with typical and other atypical antipsychotics have been suggested to improve its efficacy and reduce its often dose-related adverse effects. We present a case of a 37-year-old patient with refractory schizophrenia who has responded well to the combination of clozapine, sodium valproate, and pipamperone. The improvement was more evident in the following symptoms: auditory hallucinations, delusions, formal thought disorder, anhedonia, and social withdrawal. The combination was well tolerated: No extrapyramidal adverse effects were noted and the patient's full blood count was within normal limits. Pipamperone, a butyrophenone derivative, is a more selective antagonist of dopaminergic D4 receptors compared with D2 receptors and a serotoninergic 5HT-2A receptors antagonist. Thus, it shows "atypicality" and shares common characteristics with clozapine: 5HT-2A antagonism and D4 > D2 blockade selectivity. Therefore, augmentation of clozapine with pipamperone theoretically should have a synergistic effect that may provide several benefits to the patient: better antipsychotic efficacy with low risk for extrapyramidal adverse effects. This combination may also allow a decrease in clozapine dose, limiting its challenging adverse effects. To the author's knowledge, successful treatment of refractory schizophrenia with this drug combination is reported for the first time in the literature and probably merits further research.

  6. Evaluation and treatment of chronic meningitis.

    PubMed

    Baldwin, Kelly J; Zunt, Joseph R

    2014-10-01

    Chronic meningitis is defined as an inflammatory cerebrospinal fluid (CSF) profile that persists for at least 1 month. The presentation often includes headache, nausea, vomiting, cranial neuropathies, symptoms of elevated intracranial pressure, or focal neurologic deficits. The most common etiologies of chronic meningitis fall into 3 broad categories: infectious, autoimmune, and neoplastic. Evaluation of the patient with suspected chronic meningitis should include a detailed history and physical examination as well as repeated CSF diagnostics, serologic studies, and biopsy of the brain or other abnormal tissue (eg, lymph node or lung), when indicated. Early identification of the etiology and rapid treatment are crucial for improving morbidity and mortality, but potential infectious and neoplastic conditions should be excluded prior to empirically starting steroids or immunosuppressive medications.

  7. Evaluation and Treatment of Chronic Meningitis

    PubMed Central

    Zunt, Joseph R.

    2014-01-01

    Chronic meningitis is defined as an inflammatory cerebrospinal fluid (CSF) profile that persists for at least 1 month. The presentation often includes headache, nausea, vomiting, cranial neuropathies, symptoms of elevated intracranial pressure, or focal neurologic deficits. The most common etiologies of chronic meningitis fall into 3 broad categories: infectious, autoimmune, and neoplastic. Evaluation of the patient with suspected chronic meningitis should include a detailed history and physical examination as well as repeated CSF diagnostics, serologic studies, and biopsy of the brain or other abnormal tissue (eg, lymph node or lung), when indicated. Early identification of the etiology and rapid treatment are crucial for improving morbidity and mortality, but potential infectious and neoplastic conditions should be excluded prior to empirically starting steroids or immunosuppressive medications. PMID:25360204

  8. Adaptive Treatment Strategies in Chronic Disease

    PubMed Central

    Lavori, Philip W.; Dawson, Ree

    2009-01-01

    An adaptive treatment strategy (ATS) is a rule for adapting a treatment plan to a patient’s history of previous treatments and the response to those treatments. The ongoing management of chronic disease defines an ATS, which may be implicit and hidden, or explicit and well-specified. The ATS is characterized by the use of intermediate, early markers of response to dynamically alter treatment decisions, in order to achieve a favorable ultimate outcome. We illustrate the concept of ATS with some examples and describe the way that the effect of initial treatment decisions depends on the performance of subsequent decisions at later stages. We show how to compare two or more ATS, or to determine an optimal ATS, using a sequential multiple assignment randomized (SMAR) trial. We observe that clinical trials designers might find the ATS concept useful in improving the efficiency and ecological relevance of clinical trials. PMID:17914924

  9. Impact of complete blood count sampling time change on white blood cell and absolute neutrophil count values in clozapine recipients.

    PubMed

    McKee, Jerry R; Wall, Trossie; Owensby, Jessica

    2011-04-01

    Despite its superior efficacy, clozapine is typically reserved for treatment-refractory schizophrenia due to the risk of agranulocytosis with an occurrence of up to 1% in recipients. The FDA has rigid treatment guidelines for hematologic monitoring for clozapine patients. If the white blood cell (WBC) count or absolute neutrophil count (ANC) falls below predetermined values, clozapine treatment must be held or discontinued. Diurnal and ethnic variations in complete blood count (CBC) values, somewhat dependent upon blood sampling time have been reported, and called pseudoneutropenia, which appears independent of clozapine therapy. Unnecessary treatment interruption or discontinuation is costly and may lead to disease relapse. The purpose of this study was to evaluate the effect of a time change in CBC sampling on WBC and ANC values in a group of clozapine patients in a regional public inpatient psychiatric facility. Facility CBC sampling for clozapine patients was switched from 0630 to on or after 0830. A retrospective record review was conducted for all patients who were receiving clozapine before and after the time switch, with a minimum of six values pre- and post-change. CBC values sampled on or after 0830 were accepted as applicable post data, as patients are awakened daily at 0630, and a minimum of two hours of wakefulness/mobility had occurred. Patient medical records, automated lab information system, and the Clozapine National Registry were data sources. Data extracted included WBC/ANC values (with date/time of sampling) and demographic information (DOB, sex, weight, height, BMI, and ethnicity). The data were analyzed using repeated measures ANOVA. Ten patients (80% male, 90% Caucasian, mean age=55.7 years) met study criteria. The difference in the pre/post time change WBC values was marginally significant (mean increase=667/mm3, p=.07), with a significant difference (mean increase=1,130/mm3, p=.003) between the pre/post time change ANC values. ANC values

  10. Effects of clozapine on perceptual abnormalities and sensory gating: a preliminary cross-sectional study in schizophrenia.

    PubMed

    Micoulaud-Franchi, Jean-Arthur; Aramaki, Mitsuko; Geoffroy, Pierre Alexis; Richieri, Raphaëlle; Cermolacce, Michel; Faget, Catherine; Ystad, Sølvi; Kronland-Martinet, Richard; Lancon, Christophe; Vion-Dury, Jean

    2015-04-01

    The aim of the present study was to investigate the effect of second-generation antipsychotics (clozapine or another second-generation antipsychotic) on perceptual abnormalities related to sensory gating deficit. Although clozapine is known to improve sensory gating assessed neurophysiologically, we hypothesized that patients with schizophrenia treated with clozapine would report less perceptual abnormalities related to sensory gating deficit than patients treated with other second-generation antipsychotics do. Forty patients with a diagnosis of schizophrenia were investigated (10 patients treated with clozapine and 30 patients treated with another second-generation antipsychotic drug). Perceptual abnormalities were assessed with the Sensory Gating Inventory. Sensory gating was assessed through electroencephalogram with the auditory event-related potential method by measuring P50 amplitude changes in a dual click conditioning-testing procedure. Patients treated with clozapine present normal sensory gating and report less perceptual abnormalities related to sensory gating than patients treated with other second-generation antipsychotics do. Although the cross-sectional design of this study is limited because causal inferences cannot be clearly concluded, the present study suggests clinical and neurophysiological advantages of clozapine compared with other second-generation antipsychotics and provides a basis for future investigations on the effect of this treatment on perceptual abnormalities related to sensory gating deficit in patients with schizophrenia.

  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.

  12. [Carboxytherapy - supportive therapy in chronic wound treatment].

    PubMed

    Sinozić, Tamara; Kovacević, Jadranka

    2013-10-01

    Carboxytherapy is a supportive method in chronic wound treatment conducted by cutaneous and subcutaneous injection of medical carbon dioxide (CO2). The primary effect of the injected CO2 is the correction of tissue hypoxia due to the Bohr effect. With its effects on endothelial growth factors, it stimulates neoangiogenesis and fibroblast collagen synthesis consequently leading to better wound healing. Carboxytherapy is used in many areas from chronic wound treatment, peripheral venous and arterial diseases, dermatological diseases, to cosmetic medicine. It is minimally invasive, patients take it well, it is economically acceptable, and it can be conducted in outpatient conditions by properly trained doctors. The application of new technologic innovations in the healing processes, education and teamwork combined with developed holistic individual approach ensure good cooperation and mutual doctor-patient communication, enhance patient care and improve their quality of life.

  13. Clozaphobia: Is avoidance of clozapine in diabetes warranted?

    PubMed

    Sreeraj, Vanteemar S; Dinakaran, Damodaran; Nagendrappa, Sachin; Rao, Naren P; Kesavan, Muralidaran; Varambally, Shivarama; Venkatasubramanian, Ganesan

    2017-08-01

    Despite its superior efficacy, clozapine is an underutilized agent, primarily owing to the "Clozaphobia"-fear of clozapine's adverse effects. Emergent cautions on metabolic side-effects have contributed to avoidance of clozapine prescription. Here, we describe our clinical experience with nine patients having schizophrenia/schizoaffective disorders with comorbid diabetes mellitus and treated with clozapine. Interestingly, all patients could be maintained on optimal glycemic control even after clozapine. In conclusion, a critique on the potential risks versus benefits of clozapine amidst our observations from this case series adds further supporting evidence to the emerging literature on the clinical utility of clozapine in treating schizophrenia patients with diabetes mellitus. Copyright © 2017. Published by Elsevier B.V.

  14. Treatment of chronic prostatitis in Chinese men

    PubMed Central

    Liang, Chao-Zhao; Li, Hong-Jun; Wang, Zhi-Ping; Xing, Jun-Ping; Hu, Wei-Lie; Zhang, Tao-Fu; Ge, Wei-Wei; Hao, Zong-Yao; Zhang, Xian-Sheng; Zhou, Jun; Li, Yu; Zhou, Zheng-Xing; Tang, Zhi-Guo

    2009-01-01

    The aim of this study is to assess the status of treatment of chronic prostatitis (CP) in Chinese men. A population-based cross-sectional survey was performed, in which 15 000 men aged between 15 and 60 years were randomly selected to receive a questionnaire designed to assess National Institutes of Health Chronic Prostatitis Symptoms Index (NIH-CPSI) status, therapeutic efficacy and 28 other items. A total of 12 743 men (84.95%) completed the questionnaire, of whom 1 071 (8.4%) were identified as having prostatitis-like symptoms and 517 (4.5%) were diagnosed with CP according to NIH-CPSI criteria and prostatitis-like symptomatology. Of the CP patients, 372 (65%) underwent long-term routine treatment 12 times per year. Additionally, 217 (72.8%) patients received antibiotic therapy and 215 (79.3%) men showed therapeutic effects. The treatment cost USD 1 151 (8 059 yuan) per person per year on average. Most CP patients received routine treatment, in most cases with antibiotics. Treatment was costly and most CP patients were not satisfied with its effectiveness. Antibacterial treatment might have been effective primarily in patients with bacterial disease. PMID:19151735

  15. 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…

  16. 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…

  17. Increased CSF levels of endorphines in chronic psychosis.

    PubMed

    Terenius, L; Wahlström, A; Lindström, L; Widerlöv, E

    1976-10-01

    The levels of two endorphines, endogenously occurring morphinomimetic peptides, were measured in serial samples of CSF from seven psychiatric patients. Four cases with chronic schizophrenia were studied before and after treatment with the antipsychotic agent clozapine (Leponex). Supernormal fraction II levels were found on at least one sampling occasion in each patient. Two patients, who responded well to clozapine treatment, showed a clear-cut drop in fraction II levels, whereas two patients showed increased levels which paralleled a deterioration of the schizophrenic symptoms. Three manic-depressive cases showed abnormally high levels of endorphine fraction I in the manic phase which declined during normal or depressed phases. Levels of fraction II varied in a less consistent manner and appeared to be at maximum during the apparently normal phases. Although preliminary, the data indicate that endorphines may reach supernormal levels in patients with chronic psychoses.

  18. Clozapine-treated Patients Have Marked Gastrointestinal Hypomotility, the Probable Basis of Life-threatening Gastrointestinal Complications: A Cross Sectional Study.

    PubMed

    Every-Palmer, Susanna; Nowitz, Mike; Stanley, James; Grant, Eve; Huthwaite, Mark; Dunn, Helen; Ellis, Pete M

    2016-03-01

    Gastrointestinal side effects are particularly common with clozapine and occur with other antipsychotics, ranging from mild constipation to fatal bowel obstruction and/or ischemia. While this adverse-effect spectrum has been attributed to 'gastrointestinal hypomotility', gastrointestinal transit times in antipsychotic-treated patients have not previously been measured, making this mechanism speculative. Using standardized radiopaque marker ('Metcalf') methods we established colonic transit times of antipsychotic-treated psychiatric inpatients and compared them with population normative values. We analyzed results by antipsychotic type, antipsychotic dose equivalent, anticholinergic load, duration of treatment, gender, ethnicity, and age. For patients not prescribed clozapine, median colonic transit time was 23 h. For patients prescribed clozapine, median transit time was 104.5 h, over four times longer than those on other antipsychotics or normative values (p < 0.0001). Eighty percent of clozapine-treated patients had colonic hypomotility, compared with none of those prescribed other antipsychotics (olanzapine, risperidone, paliperidone aripiprazole, zuclopenthixol or haloperidol). In the clozapine group, right colon, left colon and rectosigmoid transit times were all markedly abnormal suggesting pan-colonic pathology. Hypomotility occurred irrespective of gender, age, ethnicity, or length of clozapine treatment. Transit times were positively correlated with clozapine plasma level (rho = 0.451, p = 0.045), but not with duration of treatment, total antipsychotic load or demographic factors. Clozapine, unlike the other antipsychotics examined, causes marked gastrointestinal hypomotility, as previously hypothesized. Pre-emptive laxative treatment is recommended when starting clozapine.

  19. Acute and Chronic Urticaria: Evaluation and Treatment.

    PubMed

    Schaefer, Paul

    2017-06-01

    Urticaria commonly presents with intensely pruritic wheals, sometimes with edema of the subcutaneous or interstitial tissue. It has a lifetime prevalence of about 20%. Although often self-limited and benign, it can cause significant discomfort, continue for months to years, and uncommonly represent a serious systemic disease or life-threatening allergic reaction. Urticaria is caused by immunoglobulin E- and non-immunoglobulin E-mediated release of histamine and other inflammatory mediators from mast cells and basophils. Diagnosis is made clinically; anaphylaxis must be ruled out. Chronic urticaria is idiopathic in 80% to 90% of cases. Only a limited nonspecific laboratory workup should be considered unless elements of the history or physical examination suggest specific underlying conditions. The mainstay of treatment is avoidance of triggers, if identified. The first-line pharmacotherapy is second-generation H1 antihistamines, which can be titrated to greater than standard doses. First-generation H1 antihistamines, H2 antihistamines, leukotriene receptor antagonists, high-potency antihistamines, and brief corticosteroid bursts may be used as adjunctive treatment. In refractory chronic urticaria, patients can be referred to subspecialists for additional treatments, such as omalizumab or cyclosporine. More than one-half of patients with chronic urticaria will have resolution or improvement of symptoms within a year.

  20. 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

  1. Clozapine promotes the proliferation of granulocyte progenitors in the bone marrow leading to increased granulopoiesis and neutrophilia in rats.

    PubMed

    Lobach, Alexandra R; Uetrecht, Jack

    2014-07-21

    Clozapine is an atypical antipsychotic that is limited in its use due to the risk of idiosyncratic agranulocytosis. The bone marrow is suspected to be the site of the reaction, and indirect measurements in patients suggest that neutrophil production and maturation are altered in the marrow by clozapine. Specifically, the majority of patients have elevated neutrophil counts at the start of treatment, often paired with increased serum granulocyte-colony stimulating factor (G-CSF). Employing a rat model of clozapine treatment, we set out to determine if the neutrophilia observed at the start of treatment is characteristic of G-CSF-associated bone marrow stimulation. Female Sprague-Dawley rats were treated with 30 mg/kg/day of clozapine for 10 days, and sustained neutrophilia was evident after 1 week of treatment paired with spikes in G-CSF. Within the bone marrow, clozapine was found to induce proliferation of the granulocyte progenitor colonies as measured by a methylcellulose assay. This led to elevated granulopoiesis observed by H&E and myeloperoxidase staining of bone marrow slices. Increased release of neutrophils from the marrow to the circulation was measured through 5-bromo-2'-deoxyuridine labeling in vivo, and these neutrophils appeared to be less mature based on (a) a decrease in the nuclear lobe count and (b) increased expression of surface CD62L. Furthermore, faster transit of the neutrophils through the marrow was suggested by a shift toward elevated numbers of neutrophils in the bone marrow maturation pool and increased CD11b and CD18 staining on the less mature neutrophils residing in the marrow. Taken together, these data indicate that clozapine stimulates the bone marrow to produce more neutrophils in a manner that is characteristic of endogenous G-CSF stimulation, and it is consistent with the inflammatory response observed in patients treated with clozapine.

  2. Chronic rhinosinusitis and emerging treatment options

    PubMed Central

    Piromchai, Patorn; Kasemsiri, Pornthep; Laohasiriwong, Supawan; Thanaviratananich, Sanguansak

    2013-01-01

    This review describes the epidemiology and various treatments in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Evidence for short-term use of systemic corticosteroids has been shown to be favorable in CRSwNP, but still limited in CRSsNP. Topical corticosteroids improve symptom scores in both CRS subgroups. The role of microbes in CRS is still controversial. Culture-directed antibiotics are recommended for CRSsNP with exacerbation. Long-term use of low dosage antibiotics is recommended for CRSsNP for their anti-inflammatory effects. Other emerging treatment options are also discussed. PMID:23785241

  3. Indications for treatment in chronic HCV infection.

    PubMed

    Dávalos Moscol, Milagros

    2010-01-01

    HCV Infection is a global burden disease and it is related to the development of progressive liver fibrosis, cirrhosis and hepatocellular carcinoma. At least 80% of the persons that have an acute infection evolve to chronicity. This event affects the patient and their contacts for the risk of acquiring the infection. Once chronic HCV is present some factors accelerate progression: older age, obesity, alcohol consumption, etc. Severity of fibrosis is one of the most important factors to be analyzed before deciding to treat a patient. Pegylated interferon and ribavirin is the .standard of care. for this disease, however, it has many side effects, some of them life threatening. That is the reason why this treatment must be indicated in the right moment in the right patient. A complete medical evaluation must be done previously to initiate treatment. Other concurrent problems must be ruled out or treated. Decompensated cirrhosis, autoimmune diseases or other uncontrolled disease are contraindication to HCV treatment. Previous failure to treatment for HCV must be analyzed to identify the reasons for that event and consider retreatment. Cryoglobulinemia and membranoproliferative glomerulonephritis are indications for treatment independent from the severity of liver disease.

  4. [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.

  5. [New treatments for chronic obstructive pulmonary disease].

    PubMed

    Miravitlles, Marc

    2005-06-11

    Treatment of chronic obstructive pulmonary disease (COPD) has underwent a very important advance in the last five years. It has been developed a new long-lasting anticholynergic drug, tiotrope bromure, which has been found to improve lung function and exercise capacity and to decrease relapses. Also the combined treatment of long lasting beta 2 adrenergics with inhaled steroids (salmeterol/fluticasone and formoterol/budesonide) has proven similar results. However, the response to these new drugs is not the same in all patients. Individual characteristics such as gravity, degree of bronchial hyperresponsiveness, frequency of relapses, comorbidity, etc will determine the response to several agents. Thus, it is necessary to perform a detailed diagnostic study in COPD patients in order to select the best treatment in an individualized form. In the future, new specific antiinflammatories such as phosphodiesterase 4 inhibitors or agents with a potential action in tissue regeneration could lead to new perspectives, as well as to new questions, in COPD treatment.

  6. Successful switch to olanzapine after rhabdomyolysis caused by water intoxication and clozapine use.

    PubMed

    Tényi, T; Vörös, V

    2006-07-01

    We report on a case of rhabdomyolysis induced by the correction of hyponatremia after psychogenic polydipsia and clozapine use, where the switch to a high dose of olanzapine resulted in the non-recurrence of rhabdomyolysis. The 46-year-old patient with the diagnosis of schizophrenia paranoid type, who had been on clozapine treatment for the previous 4 years, was admitted with the symptoms of generalized seizure and vomiting, and as severe hyponatremia was proved, its correction with the parallel use of clozapine treatment was done. CK concentrations increased to 48 120 U/L without any symptom of neuroleptic malignant syndrome. To prevent acute renal insufficiency, high-volume alkaline diuresis was initiated and clozapine was tapered and stopped. On the day 12 of treatment, olanzapine was started and was elevated to 30 mg/day. CK concentration began to fall returning to the normal concentration on day 20. Six months after the switch to olanzapine no recurrence of rhabdomyolysis was detected; clinical and laboratory findings were normal. We suggest that after a benzodiazepine-type antipychotic-induced rhabdomyolysis, a switch to another atypical antipsychotic can be a cautious clinical strategy.

  7. 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

  8. A Questionnaire-based Study of the Views of Schizophrenia Patients and Psychiatric Healthcare Professionals in Japan about the Side Effects of Clozapine

    PubMed Central

    Takeuchi, Ippei; Hanya, Manako; Uno, Junji; Amano, Yuhei; Fukai, Keiko; Fujita, Kiyoshi; Kamei, Hiroyuki

    2016-01-01

    Objective It is well documented that clozapine treatment causes agranulocytosis, but it can also induce drowsiness, constipation, and hypersalivation; however, these symptoms are usually less severe. It has been reported that clozapine-treated patients with schizophrenia and psychiatric healthcare professionals consider different side effects to be important. The aim of this study was to assess current practice related to the side effects of clozapine in clozapine-treated patients with schizophrenia and psychiatric healthcare professionals in Japan. Methods Data were collected from January 2014 to August 2015 in Okehazama Hospital, Kakamigahara Hospital, and Numazu Chuo Hospital. Clozapine-treated patients with schizophrenia and psychiatric healthcare professionals (psychiatrists and pharmacists) were enrolled in this study. Results Of the 106 patients and 120 psychiatric healthcare professionals screened, 100 patients and 104 healthcare professionals were included in this study. We asked the patients what side effects caused them trouble and we asked psychiatric healthcare professionals what side effects caused them concern. The patients and psychiatrists held similarly positive views regarding the efficacy of clozapine. The healthcare professionals were concerned about agranulocytosis (92.4%), blood routines (61.3%). On the other hand, the patients experienced hypersalivation (76.0%), sleepiness (51.0%). A positive correlation (R=0.696) was found between patient satisfaction and DAI-10 score. Conclusion Patients experienced more problems than healthcare professionals expected. However, usage experience of clozapine healthcare professionals tended to have similar results to patients. It is necessary that all healthcare professionals fully understand the efficacy and potential side effects of clozapine. This is very important for promoting clozapine treatment in Japan. PMID:27489383

  9. Targeted treatment for chronic lymphocytic leukemia

    PubMed Central

    Masood, Aisha; Sher, Taimur; Paulus, Aneel; Miller, Kena C; Chitta, Kasyapa S; Chanan-Khan, Asher

    2011-01-01

    The treatment of chronic lymphocytic leukemia (CLL) has evolved over the last few decades. Recognition has increased of several key components of CLL biology currently manipulated for therapeutics. A milestone in the treatment of CLL was reached with the incorporation of immunotherapy with conventional chemotherapy. The fludarabine/cyclophosphamide/rituximab combination has demonstrated survival advantage for the first time in the treatment of CLL. Several other biological compounds are being explored with the hope of improving responses, impacting survival, and ultimately curing CLL. Important agents being tested are targeted on CLL surface molecules and their ligands, signal transduction protein and oncogenes. This review provides a brief summary of the recent advances made in preclinical and clinical investigation of selected promising therapeutic agents, which lead the target-directed therapeutic approach. PMID:22162923

  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. Omalizumab for the treatment of chronic urticaria.

    PubMed

    Zuberbier, Torsten; Maurer, Marcus

    2015-02-01

    Urticaria is a common and often debilitating dermatological condition defined by the sudden appearance of wheals, angioedema or both. It is further classified into specific subtypes based on duration and specific triggers. Awareness and understanding of urticaria are important to ensure a correct initial diagnosis and initiate appropriate guideline-based treatment outlining a stepwise approach. However, in chronic urticaria, approximately 50% of patients are refractory to the first step, the use of licensed doses of second-generation H1-antihistamines. If the second step, an increase in the dose of the second-generation H1-antihistamines, is also not successful, in the third step omalizumab (Xolair™, Novartis Pharma AG(©)/Genentech, Inc.(©)), an anti-IgE therapy, is recommended as an add-on. Of all alternative treatments mentioned in the guidelines, omalizumab is currently the only licensed treatment for H1-antihistamine-refractory chronic spontaneous urticaria, has a favorable risk/benefit ratio and was well tolerated in clinical studies.

  12. Valacyclovir treatment of chronic fatigue in adolescents.

    PubMed

    Henderson, Theodore A

    2014-01-01

    Chronic fatigue syndrome (CFS) presents with fatigue, low motivation, diminished mood, and reduced activity, all symptoms having extensive diagnostic overlaps with depression. Studies have linked chronic viral infections with CFS, and antiviral therapy has effectively treated CFS in adult patients. In a retrospective case series, 15 adolescents and preteens referred to the author for treatment-resistant depression or mood disorder were evaluated and found to have met the Fukuda diagnostic criteria for CFS. While a subset (4/15) had been diagnosed in the past with CFS, the majority had a current diagnosis of depression or a mood disorder. The Diagnostic and Statistical Manual-IV Text Revision (DSM-IV TR) criteria for depression were not met in all patients, although 3 cases of mood disorder not otherwise specified (MD-NOS) and 1 case of Tourette syndrome (TS) plus MD-NOS were diagnosed. Baseline scores on the Children's Depression Inventory (CDI) were below the cutoff for depression in all but 1 patient. Baseline self-assessment scales for CFS or fatigue were obtained and sleep was evaluated with sleep logs. All patients were treated subsequently with valacyclovir, with 93% having a positive response. At the end of treatment, scores on fatigue self-assessment scales improved significantly (P < .001). Vigor subscale scores also improved significantly (P < .001). Some patients experienced complete resolution of symptoms. Although not every patient was tested, available laboratory testing revealed increased counts of natural killer (NK) cells and decreased human herpesvirus 6 (HHV-6) antibody titers in all patients who responded to valacyclovir. This article discusses the significance of infectious agents in the pathogenesis of psychiatric symptoms. The study's data support an intriguing hypothesis that a portion of treatment-resistant depression in fact may be undiagnosed CFS or other chronic viral infection.

  13. Case report: treatment of chronic osteomyelitis.

    PubMed

    Wolfe, Cameron R

    2011-06-01

    Presented is a case of chronic methicillin-resistant Staphylococcus aureus osteomyelitis, which was unsuccessfully treated with multiple courses of debridement and potent antibiotic therapies. Amputation of the patient's lower limb was believed to be the only option remaining. A compassionate access program, with approval from the US Food and Drug Administration and the institutional review board, enabled the patient to undergo a course of treatment with oral fusidic acid (CEM-102). The patient tolerated the drug well, with no significant toxicities noted to date. His infection improved rapidly, his flap healed, he has returned to work part-time, and he continues to take daily suppressive doses of oral CEM-102.

  14. [Prozac treatment of chronic tension headache].

    PubMed

    Voznesenskaia, T G

    1999-01-01

    The paper summarizes the experience of therapy of chronic tension type headache (TTH) with prozac (fluoxetine)--a selective serotonine reuptake inhibitor. The data are presented concerning clinical psychologic examination of 20 outpatients with chronic TTH both before and after therapy with prozac in daily dose of 20 mg during 6 weeks. Background study of the patients revealed severe depression (according to Beck's and SCL-90 scales), anxiety (Spilberger scale) and alexitimia (Toronto scale). Before the treatment, a frequency of TTH attacks was at least four times a week, the intensivity was equal to 8.9 scores according to visual analogous scale. Together with a headache there were psychopathologic and psychoautonomic manifestations. After the course of therapy the headaches disappeared completely in 25%, while considerable improvement was observed in 75% of the patients. The levels of depression, anxiety, somatization have decreased significantly too. Side effects as well as withdrawal syndrome weren't found. The role of depression in formation of chronic TTH, as well as the role of alixetimia in formation of somatizated variation of the depression were considered.

  15. Expectations predict chronic pain treatment outcomes.

    PubMed

    Cormier, Stéphanie; Lavigne, Geneviève L; Choinière, Manon; Rainville, Pierre

    2016-02-01

    Accumulating evidence suggests an association between patient pretreatment expectations and numerous health outcomes. However, it remains unclear if and how expectations relate to outcomes after treatments in multidisciplinary pain programs. The present study aims at investigating the predictive association between expectations and clinical outcomes in a large database of chronic pain patients. In this observational cohort study, participants were 2272 patients treated in one of 3 university-affiliated multidisciplinary pain treatment centers. All patients received personalized care, including medical, psychological, and/or physical interventions. Patient expectations regarding pain relief and improvements in quality of life and functioning were measured before the first visit to the pain centers and served as predictor variables. Changes in pain intensity, depressive symptoms, pain interference, and tendency to catastrophize, as well as satisfaction with pain treatment and global impressions of change at 6-month follow-up, were considered as treatment outcomes. Structural equation modeling analyses showed significant positive relationships between expectations and most clinical outcomes, and this association was largely mediated by patients' global impressions of change. Similar patterns of relationships between variables were also observed in various subgroups of patients based on sex, age, pain duration, and pain classification. Such results emphasize the relevance of patient expectations as a determinant of outcomes in multimodal pain treatment programs. Furthermore, the results suggest that superior clinical outcomes are observed in individuals who expect high positive outcomes as a result of treatment.

  16. Optimized Treatment Schedules for Chronic Myeloid Leukemia

    PubMed Central

    He, Qie; Dingli, David; Foo, Jasmine; Leder, Kevin Zox

    2016-01-01

    Over the past decade, several targeted therapies (e.g. imatinib, dasatinib, nilotinib) have been developed to treat Chronic Myeloid Leukemia (CML). Despite an initial response to therapy, drug resistance remains a problem for some CML patients. Recent studies have shown that resistance mutations that preexist treatment can be detected in a substantial number of patients, and that this may be associated with eventual treatment failure. One proposed method to extend treatment efficacy is to use a combination of multiple targeted therapies. However, the design of such combination therapies (timing, sequence, etc.) remains an open challenge. In this work we mathematically model the dynamics of CML response to combination therapy and analyze the impact of combination treatment schedules on treatment efficacy in patients with preexisting resistance. We then propose an optimization problem to find the best schedule of multiple therapies based on the evolution of CML according to our ordinary differential equation model. This resulting optimization problem is nontrivial due to the presence of ordinary different equation constraints and integer variables. Our model also incorporates drug toxicity constraints by tracking the dynamics of patient neutrophil counts in response to therapy. We determine optimal combination strategies that maximize time until treatment failure on hypothetical patients, using parameters estimated from clinical data in the literature. PMID:27764087

  17. Switching from clozapine to zotepine in patients with schizophrenia: a 12-week prospective, randomized, rater blind, and parallel study.

    PubMed

    Lin, Chao-Cheng; Chiu, Hsien-Jane; Chen, Jen-Yeu; Liou, Ying-Jay; Wang, Ying-Chieh; Chen, Tzu-Ting; Bai, Ya-Mei

    2013-04-01

    Clozapine is the most effective antipsychotic for patients with treatment-refractory schizophrenia, but many adverse effects are noted. Clinicians usually hesitate to switch from clozapine to other antipsychotics because of the risk of a re-emergence or worsening of the psychosis, although empirical studies are very limited. Zotepine, an atypical antipsychotic with a pharmacologic profile similar to clozapine, was found to be an effective treatment for patients with treatment-resistant schizophrenia in Japan. This 12-week study is the first prospective, randomized, and rater-blind study to investigate the efficacy and tolerability of switching from clozapine to zotepine. Fifty-nine patients with schizophrenia, who had taken clozapine for at least 6 months with a Clinical Global Impression-Severity score of at least 3, were randomly allocated to the zotepine and the clozapine groups. At the end of the study, 52 patients (88%) had completed the trial. The 7 withdrawal cases were all in the zotepine group. The final mean (SD) dose of zotepine and clozapine was 397.1 (75.7) versus 377.1 (62.5) mg/d, respectively. Patients in the zotepine group showed a significant increase in the Brief Psychiatric Rating Scale [mean (SD), 4.7 (8.7) vs -1.3 (6.3); P = 0.005], more general adverse effects as revealed by the Udvalg for Kliniske Undersogelser Rating Scale [mean (SD), 1.74 (3.9) vs -0.2 (2.8); P = 0.039], more extrapyramidal adverse effects as demonstrated by the Simpson and Angus Scale [mean (SD), 1.29 (3.5) vs 0.17 (2.1); P = 0.022], an increased use of propranolol (37.1% vs 0%, P < 0.0001) and anticholinergics (25.7% vs 0%, P = 0.008), and an increased level of prolactin (29.6 vs -3.8 ng/ mL, P < 0.0005), compared with the clozapine group. The results suggested that switching from clozapine to zotepine treatment should be done with caution.

  18. Olanzapine and clozapine differently affect sleep in patients with schizophrenia: results from a double-blind, polysomnographic study and review of the literature.

    PubMed

    Kluge, Michael; Schacht, Alexander; Himmerich, Hubertus; Rummel-Kluge, Christine; Wehmeier, Peter M; Dalal, Mira; Hinze-Selch, Dunja; Kraus, Thomas; Dittmann, Ralf W; Pollmächer, Thomas; Schuld, Andreas

    2014-01-01

    Schizophrenia is associated with impaired sleep continuity. The second generation antipsychotics clozapine and olanzapine have been reported to improve sleep continuity but also to rarely induce restless legs syndrome (RLS). The aims of this randomized double-blind study were to compare the effects of clozapine and olanzapine on sleep and the occurrence of RLS. Therefore, polysomnographies were recorded and RLS symptoms were assessed in 30 patients with schizophrenia before and after 2, 4 and 6 weeks of treatment with either clozapine or olanzapine. Treatment with both antipsychotics increased total sleep time, sleep period time and sleep efficiency and decreased sleep onset latency. These changes were similar in both groups, occurred during the first 2 treatment weeks and were sustained. For example, sleep efficiency increased from 83% (olanzapine) and 82% (clozapine) at baseline to 95% at week 2 and 97% at week 6 in both treatment groups. Sleep architecture was differently affected: clozapine caused a significantly stronger increase of stage 2 sleep (44%) than olanzapine (11%) but olanzapine a significantly stronger increase of REM-sleep. Olanzapine caused an 80% increase of slow wave sleep whereas clozapine caused a 6% decrease. No patient reported any of 4 RLS defining symptoms at baseline. During treatment, 1 patient of each group reported at one visit all 4 symptoms, i.e. met the diagnosis of an RLS. In conclusion, sleep continuity similarly improved and sleep architecture changed more physiologically with olanzapine. Neither of the antipsychotics induced RLS symptoms that were clinically relevant.

  19. Clozapine linked to nanocapsules minimizes tissue and oxidative damage to biomolecules lipids, proteins and DNA in brain of rats Wistar.

    PubMed

    da Costa Güllich, Angélica Aparecida; Coelho, Ritiéle Pinto; Pilar, Bruna Cocco; Ströher, Deise Jaqueline; Galarça, Leandro Alex Sander Leal; Vieira, Simone Machado; da Costa Escobar Piccoli, Jacqueline; Haas, Sandra Elisa; Manfredini, Vanusa

    2015-06-01

    Clozapine, atypical antipsychotic, can change oxidative stress parameters. It is known that reactive species, in excess, can have a crucial role in the etiology of diseases, as well as, can potentiating adverse effects induce by drugs. The nanocapsules have attracted attention as carriers of several drugs, with consequent reduction of adverse effects. This study aimed to evaluate histopathology and oxidative damage of biomolecules lipids, proteins and DNA in the brain of Wistar rats after treatment with nanocapsules containing clozapine. The study consisted of eight groups of male Wistar rats (n = 6): saline (SAL), free clozapine (CZP) (25 mg/Kg i.p.), blank uncoated nanocapsules (BNC), clozapine-loaded uncoated nanocapsules (CNC) (25 mg/Kg i.p.), blank chitosan-coated nanocapsules (BCSN), clozapine-loaded chitosan-coated nanocapsules (CCSN) (25 mg/Kg i.p.), blank polyethyleneglycol-coated nanocapsules (BPEGN), clozapine-loaded polyethyleneglycol-coated nanocapsules (CPEGN) (25 mg/Kg i.p.). The animals received the formulation once a day for seven consecutive days and euthanized in the eighth day. After euthanasia, the brain was collected and homogenate was processed for further analysis. The histopathology showed less brain tissue damage in nanocapsules-treated groups. The lipid peroxidation and carbonylation of proteins showed a significant increase (p < 0.05) induced by CZP. CNC and CPEGN groups obtained a reduction membrane of lipids damage and nanocapsules-treated groups showed significant improvement protein damage. CZP was able to induce genetic oxidative damage, while the nanocapsules causing less damage to DNA. The findings show that different coatings can act protecting target tissues decreasing oxidative damage, suggesting that the drug when linked to different nanocapsules is able to mitigate the harmful effects of clozapine.

  20. Pharmacological treatment of chronic obstructive pulmonary disease

    PubMed Central

    Montuschi, Paolo

    2006-01-01

    None of the drugs currently available for chronic obstructive pulmonary disease (COPD) are able to reduce the progressive decline in lung function which is the hallmark of this disease. Smoking cessation is the only intervention that has proved effective. The current pharmacological treatment of COPD is symptomatic and is mainly based on bronchodilators, such as selective β2-adrenergic agonists (short- and long-acting), anticholinergics, theophylline, or a combination of these drugs. Glucocorticoids are not generally recommended for patients with stable mild to moderate COPD due to their lack of efficacy, side effects, and high costs. However, glucocorticoids are recommended for severe COPD and frequent exacerbations of COPD. New pharmacological strategies for COPD need to be developed because the current treatment is inadequate. PMID:18044097

  1. [Conservative medical treatment of chronic pancreatitis].

    PubMed

    Binek, J

    1998-05-13

    The conservative medical treatment of chronic pancreatitis entails dealing prevalently with exocrine and endocrine insufficiency, diet and pain. As steatorrhoea can cause malabsorption, it is advisable to reduce first the fat content of the diet and secondly to prescribe, where necessary, pancreatic enzymes. Several factors can lead to a poor therapeutic enzyme effect. Attention should be given to the pharmacological properties of the enzyme-preparation and to the secretion of acid in the stomach. An endocrine insufficiency is more difficult to treat compared to a classical diabetes mellitus, for lack of endocrine regulatory mechanisms. Pain is the consequence of several pathophysiological processes. Before initiating analgetic treatment, a minimal diagnostic program should be completed allowing the exclusion of those primary causes of pain which require an alternative approach such as interventional endoscopy or surgery.

  2. Pharmacological Augmentation Strategies for Schizophrenia Patients With Insufficient Response to Clozapine: A Quantitative Literature Review

    PubMed Central

    Sommer, Iris E.; Begemann, Marieke J. H.; Temmerman, Anke; Leucht, Stefan

    2012-01-01

    Background. When schizophrenia patients have insufficient response to clozapine, pharmacological augmentation is often applied. This meta-analysis summarizes available evidence on efficacy of pharmacological augmentation of clozapine treatment in schizophrenia spectrum disorder. Methods. Only double-blind randomized controlled studies were included. Primary outcome measure was total symptom severity, and secondary outcome measures were subscores for positive and negative symptoms. Effect sizes were calculated from individual studies and combined to standardized mean differences (Hedges's g). Results. Twenty-nine studies reporting on 15 different augmentations were included. Significant better efficacy than placebo on total symptom severity was observed for lamotrigine, citalopram, sulpiride, and CX516 (a glutamatergic agonist). The positive effect of lamotrigine disappeared after outlier removal. The other positive findings were based on single studies. Significantly better efficacy on positive symptom severity was observed for topiramate and sulpiride. The effect of topiramate disappeared after outlier removal. Results for sulpiride were based on a single randomized controlled trial. Citalopram, sulpiride, and CX516 showed better efficacy for negative symptoms than placebo, all based on single studies. Conclusions. Evidence for efficacy of clozapine augmentation is currently scarce. Efficacy of lamotrigine and topiramate were both dependent on single studies with deviating findings. The effect of citalopram, sulpiride, and CX516 were based on single studies. Thus, despite their popularity, pharmacological augmentations of clozapine are not (yet) demonstrated to be superior to placebo. PMID:21422107

  3. What's New in Chronic Myeloid Leukemia Research and Treatment?

    MedlinePlus

    ... Myeloid Leukemia (CML) About Chronic Myeloid Leukemia What's New in Chronic Myeloid Leukemia Research and Treatment? Studies ... such as cyclosporine or hydroxychloroquine, with a TKI. New drugs for CML Because researchers now know the ...

  4. Effects of central activation of serotonin 5-HT2A/2C or dopamine D2/3 receptors on the acute and repeated effects of clozapine in the conditioned avoidance response test

    PubMed Central

    Feng, Min; Gao, Jun; Sui, Nan; Li, Ming

    2014-01-01

    Rationale: Acute administration of clozapine (a gold standard of atypical antipsychotics) disrupts avoidance response in rodents, while repeated administration often causes a tolerance effect. Objective: The present study investigated the neuroanatomical basis and receptor mechanisms of acute and repeated effects of clozapine treatment in the conditioned avoidance response test in male Sprague-Dawley rats. Methods: DOI (2,5-dimethoxy-4-iodo-amphetamine, a preferential 5-HT2A/2C agonist) or quinpirole (a preferential dopamine D2/3 agonist) was microinjected into the medial prefrontal cortex (mPFC) or nucleus accumbens shell (NAs), and their effects on the acute and long-term avoidance-disruptive effect of clozapine were tested. Results: Intra-mPFC microinjection of quinpirole enhanced the acute avoidance disruptive effect of clozapine (10 mg/kg, sc), while DOI microinjections reduced it marginally. Repeated administration of clozapine (10 mg/kg, sc) daily for 5 days caused a progressive decrease in its inhibition of avoidance responding, indicating tolerance development. Intra-mPFC microinjection of DOI at 25.0 (but not 5.0) μg/side during this period completely abolished the expression of clozapine tolerance. This was indicated by the finding that clozapine-treated rats centrally infused with 25.0 μg/side DOI did not show higher levels of avoidance responses than the vehicle-treated rats in the clozapine challenge test. Microinjection of DOI into the mPFC immediately before the challenge test also decreased the expression of clozapine tolerance. Conclusions: Acute behavioral effect of clozapine can be enhanced by activation of the D2/3 receptors in the mPFC. Clozapine tolerance expression relies on the neuroplasticity initiated by its antagonist action against 5-HT2A/2C receptors in the mPFC. PMID:25288514

  5. A systematic review of the evidence of clozapine's anti-aggressive effects.

    PubMed

    Frogley, Catherine; Taylor, David; Dickens, Geoff; Picchioni, Marco

    2012-10-01

    Reducing the risk of violent and aggressive behaviour in patients with schizophrenia remains a clinical priority. There is emerging evidence to suggest that the second-generation antipsychotic, clozapine, is effective at reducing this risk in patients with schizophrenia and some evidence to suggest that it may be best in selected patients. We conducted a systematic literature search in March 2011 of all prospective and retrospective studies, which investigated clozapine's anti-aggressive effects in a variety of mental disorders. The review identified six animal studies, four randomized controlled trials, 12 prospective non-controlled studies and 22 retrospective studies, with four case studies. We found considerable evidence in support of clozapine's ability to reduce violent and aggressive behaviour. Clozapine's anti-aggressive effect was most commonly explored in patients with schizophrenia, with less evidence available for other psychiatric disorders, including borderline personality disorder, autistic spectrum disorders, post-traumatic stress disorder, bipolar disorder and learning disability. There was mixed evidence to address the question of whether or not clozapine was any more effective than other antipsychotics. In the case of schizophrenia, there was evidence to suggest that clozapine's anti-aggressive effect was more marked particularly in those with treatment-resistant illness. Its anti-aggressive effects appeared to be 'specific', being to some extent greater than both its more general antipsychotic and sedative effects. There were significant methodological inconsistencies in the studies we identified, particularly surrounding patient recruitment criteria, the definition and measurement of violence and the lack of randomized, controlled trials. Data on therapeutic monitoring were also limited. Clozapine can reduce violence and persistent aggression in patients with schizophrenia and other psychiatric disorders. It may offer an advantage over other

  6. Blood serum levels of CART peptide in patients with schizophrenia on clozapine monotherapy.

    PubMed

    Wysokiński, Adam; Kłoszewska, Iwona

    2014-12-15

    CART (cocaine- and amphetamine-regulated transcript) is an endogenous inhibitor of food intake. We compared fasting serum CART levels in subjects with schizophrenia on clozapine monotherapy (n=24) with sex- and age-matched healthy controls (n=24). CART levels were higher in the clozapine group (262.76±359.91 vs. 90.40±169.90 pg/mL). CART levels were higher in subjects with metabolic syndrome compared to subjects without metabolic syndrome in the clozapine group (415.63±416.93 vs. 122.62±237.17 pg/mL, n=12 and 12, respectively) and in the whole study group (377.73±401.09 vs. 88.58±172.35 pg/mL, n=16 and 32, respectively). In the control group CART levels were higher in subjects with total body fat lower than the target maximum compared to subjects with total body fat below the target maximum (121.71±154.91 vs. 66.32±182.96 pg/mL, n=14 and 10, respectively). CART levels did not correlate with age, weight, BMI, abdominal, waist and hip circumferences, WHR, blood pressure, laboratory tests, clozapine dose, antipsychotic or clozapine treatment duration, body composition, and markers of insulin resistance in the study group. Further studies are required to confirm whether increased levels of circulating CART are compensatory in response to treatment-induced weight gain and abdominal obesity or a primary feature of schizophrenia. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Ciprofloxacin and Clozapine: A Potentially Fatal but Underappreciated Interaction

    PubMed Central

    Proctor, George; Cummings, Michael A.; Dardashti, Laura J.; Stahl, Stephen M.

    2016-01-01

    Objective. Clozapine provides a 50%–60% response rate in refractory schizophrenia but has a narrow therapeutic index and is susceptible to pharmacokinetic interactions, particularly with strong inhibitors or inducers of cytochrome P450 (CYP) 1A2. Case Report. We report the case of a 28-year-old nonsmoking female with intellectual disability who was maintained for 3 years on clozapine 100 mg orally twice daily. The patient was treated for presumptive urinary tract infection with ciprofloxacin 500 mg orally twice daily and two days later collapsed and died despite resuscitation efforts. The postmortem femoral clozapine plasma level was dramatically elevated at 2900 ng/mL, and the cause of death was listed as acute clozapine toxicity. Conclusion. Given the potentially fatal pharmacokinetic interaction between clozapine and ciprofloxacin, clinicians are advised to monitor baseline clozapine levels prior to adding strong CYP450 1A2 inhibitors, reduce the clozapine dose by at least two-thirds if adding a 1A2 inhibitor such as ciprofloxacin, check subsequent steady state clozapine levels, and adjust the clozapine dose to maintain levels close to those obtained at baseline. PMID:27872784

  8. Spatiotemporal Mapping Techniques Show Clozapine Impairs Neurogenic and Myogenic Patterns of Activity in the Colon of the Rabbit in a Dose-Dependent Manner

    PubMed Central

    Every-Palmer, Susanna; Lentle, Roger G.; Reynolds, Gordon; Hulls, Corrin; Chambers, Paul; Dunn, Helen; Ellis, Pete M.

    2017-01-01

    Background: Clozapine, an antipsychotic used in treatment-resistant schizophrenia, has adverse gastrointestinal effects with significant associated morbidity and mortality. However, its effects on defined patterns of colonic contractile activity have not been assessed. Method: We used novel radial and longitudinal spatiotemporal mapping techniques, combined with and monitoring of ambient lumen pressure, in ex vivo preparations of triply and of singly haustrated portions of rabbit colon. We identified the contractile patterns of mass peristalses, fast phasic, and ripple contractions and directly qualified the effects of clozapine, at concentrations of 10 μmol/L, 20 μmol/L, and 30 μmol/L, and of norclozapine, the main metabolite of clozapine, on contractile patterns. The effects of carbachol, serotonin and naloxone on clozapine-exposed preparations were also determined. Tetradotoxin was used to distinguish neurogenic from myogenic contractions. Results: At 10 μmol/L, clozapine temporarily abolished the longitudinal contractile components of mass peristalsis, which on return were significantly reduced in number and amplitude, as was maximal mass peristaltic pressure. These effects were reversed by carbachol (1 μmol/L) and to some extent by serotonin (15 μmol/L). At 10 μmol/L, myogenic ripple contractions were not affected. At 20 μmol/L, clozapine had a similar but more marked effect on mass peristalses with both longitudinal and radial components and corresponding maximal pressure greatly reduced. At 30 μmol/L, clozapine suppressed the radial and longitudinal components of mass peristalses for over 30 min, as well as ripple contractions. Similar dose-related effects were observed on addition of clozapine to the mid colon. At 20 μmol/L, norclozapine had opposite effects to those of clozapine, causing an increase in the frequency of mass peristalsis with slight increases in basal tone. These slightly augmented contractions were abolished on addition of

  9. Spatiotemporal Mapping Techniques Show Clozapine Impairs Neurogenic and Myogenic Patterns of Activity in the Colon of the Rabbit in a Dose-Dependent Manner.

    PubMed

    Every-Palmer, Susanna; Lentle, Roger G; Reynolds, Gordon; Hulls, Corrin; Chambers, Paul; Dunn, Helen; Ellis, Pete M

    2017-01-01

    Background: Clozapine, an antipsychotic used in treatment-resistant schizophrenia, has adverse gastrointestinal effects with significant associated morbidity and mortality. However, its effects on defined patterns of colonic contractile activity have not been assessed. Method: We used novel radial and longitudinal spatiotemporal mapping techniques, combined with and monitoring of ambient lumen pressure, in ex vivo preparations of triply and of singly haustrated portions of rabbit colon. We identified the contractile patterns of mass peristalses, fast phasic, and ripple contractions and directly qualified the effects of clozapine, at concentrations of 10 μmol/L, 20 μmol/L, and 30 μmol/L, and of norclozapine, the main metabolite of clozapine, on contractile patterns. The effects of carbachol, serotonin and naloxone on clozapine-exposed preparations were also determined. Tetradotoxin was used to distinguish neurogenic from myogenic contractions. Results: At 10 μmol/L, clozapine temporarily abolished the longitudinal contractile components of mass peristalsis, which on return were significantly reduced in number and amplitude, as was maximal mass peristaltic pressure. These effects were reversed by carbachol (1 μmol/L) and to some extent by serotonin (15 μmol/L). At 10 μmol/L, myogenic ripple contractions were not affected. At 20 μmol/L, clozapine had a similar but more marked effect on mass peristalses with both longitudinal and radial components and corresponding maximal pressure greatly reduced. At 30 μmol/L, clozapine suppressed the radial and longitudinal components of mass peristalses for over 30 min, as well as ripple contractions. Similar dose-related effects were observed on addition of clozapine to the mid colon. At 20 μmol/L, norclozapine had opposite effects to those of clozapine, causing an increase in the frequency of mass peristalsis with slight increases in basal tone. These slightly augmented contractions were abolished on addition of

  10. Treatment of chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Kleyman, Inna; Brannagan, Thomas H

    2015-07-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is one of the acquired demyelinating neuropathies and is considered to be immune mediated. Diagnosis is typically based on clinical history, neurologic examination, electrophysiologic studies, CSF studies, and pathologic examination. Early diagnosis and treatment is important to prevent irreversible axonal loss and optimize improvement in function. The first-line agents for treatment are intravenous immunoglobulin (IVIg), corticosteroids, and plasmapheresis, which have all been demonstrated to be effective in controlled studies. Studies have not shown a significant difference between these three treatments, and the initial choice of therapy is often based on availability, cost, ease of administration, and side effect profile. If patients do not respond to one of these agents, they may respond to one of the others and sometimes in combination. If the first-line agents are not effective, chemotherapeutic or immunosuppressive agents may be considered. There are limited controlled studies of these modalities, and they are often used in conjunction with a first-line treatment. The majority of patients require long-term therapy to maintain a response and to prevent relapse.

  11. 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.

  12. Chronic Spontaneous Urticaria: Pathogenesis and Treatment Considerations.

    PubMed

    Kaplan, Allen P

    2017-11-01

    The treatment of chronic spontaneous urticaria begins with antihistamines; however, the dose required typically exceeds that recommended for allergic rhinitis. Second-generation, relatively non-sedating H₁-receptor blockers are typically employed up to 4 times a day. First-generation antihistamines, such as hydroxyzine or diphenhydramine (Atarax or Benadryl), were employed similarly in the past. Should high-dose antihistamines fail to control symptoms (at least 50%), omalizumab at 300 mg/month is the next step. This is effective in 70% of antihistamine-refractory patients. H₂-receptor blockers and leukotriene antagonists are no longer recommended; they add little and the literature does not support significant efficacy. For those patients who are unresponsive to both antihistamines and omalizumab, cyclosporine is recommended next. This is similarly effective in 65%-70% of patients; however, care is needed regarding possible side-effects on blood pressure and renal function. Corticosteroids should not be employed chronically due to cumulative toxicity that is dose and time dependent. Brief courses of steroid e.g., 3-10 days can be employed for severe exacerbations, but should be an infrequent occurrence. Finally, other agents, such as dapsone or sulfasalazine, can be tried for those patients unresponsive to antihistamines, omalizumab, and cyclosporine. Copyright © 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.

  13. Biology and treatment of chronic myeloid leukemia.

    PubMed

    Jones, R J

    1997-01-01

    The BCR-ABL gene rearrangement, the initial event in the development of chronic myeloid leukemia, primarily produces clonal expansion in CML by blocking apoptosis, a genetically programmed process of autonomous cell death. The mechanism by which BCR-ABL blocks apoptosis remains unclear, although recent data are beginning to shed light on the signaling pathway. As with other antiapoptotic signals, BCR-ABL induces cellular resistance to a wide spectrum of cytotoxic antitumor agents. However, apoptosis induced by both cytotoxic T lymphocytes and natural killer or lymphokine-activated killer cells is not blocked by BCR-ABL. A substantial number of patients with chronic myeloid leukemia can now be cured, and the prognosis has improved even for those patients who are not cured. Interferon-alpha has emerged as the treatment of choice for patients who do not undergo an allogeneic bone marrow transplantation. The availability of allogeneic bone marrow transplantation has been increased by the ability to find unrelated donors, although graft-versus-host disease remains a major problem. Adoptive immunotherapy with donor lymphocyte transfusions will induce durable remissions and possibly cures in many patients who relapse after allogeneic BMT. Moreover, a number of investigational approaches, especially autologous BMT, appear promising.

  14. Diagnosis and treatment of chronic insomnia

    PubMed Central

    Saddichha, Sahoo

    2010-01-01

    Insomnia is a disorder characterized by inability to sleep or a total lack of sleep, prevalence of which ranges from 10 to 15% among the general population with increased rates seen among older ages, female gender, White population and presence of medical or psychiatric illness. Yet this condition is still under-recognized, under-diagnosed, and under-treated. This article aims to review the operational definitions and management of chronic insomnia. A computerized search on PubMed carried from 1980 to January 2009 led to the summarization of the results. There are several strategies to manage chronic insomnia. To initiate treatment, it is necessary to define it and differentiate it from other co-morbid psychiatric disorders. Non-pharmacologic strategies such as stimulus control therapy and relaxation and cognitive therapies have the best effect sizes followed by sleep restriction, paradoxical intention and sleep hygiene education which have modest to less than modest effect sizes. Among pharmacotherapeutic agents, non-benzodiazepine hypnotics are the first line of management followed by benzodiazepines, amitryptiline and antihistaminics. However, adequate trials of combined behavior therapy and pharmacotherapy are the best course of management. PMID:20814491

  15. [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

  16. Analysis of clozapine response and polymorphisms of the dopamine D4 receptor gene (DRD4) in schizophrenic patients

    SciTech Connect

    Shaikh, S.; Collier, D.A.; Sham, P.

    1995-12-18

    We have examined the hypothesis that a variable number of tandem repeats in the third cytoplasmic loop of the dopamine D4 receptor influences clinical response to clozapine using a sample of 189 schizophrenic patients. Alleles of the 48-bp repeat, which range from two to ten copies in the normal human population, were analysed by the polymerase chain reaction using genomic DNA as template. Association between these alleles and response to clozapine was tested using the difference in pre- and post-treatment GAS scores as a measure of response. We found no statistically significant variation between genotypic groups and response by analysis of variance. We conclude that the variation of the number of 48-bp repeats alone does not determine response to clozapine. Larger studies are underway to determine if there is a more subtle relationship with sequence variation within the repeats or at other polymorphic sites within the gene that may provide evidence for a component of clozapine`s action being at D4 receptors. 28 refs., 1 fig., 3 tabs.

  17. Therapeutic effect of pirenzepine for clozapine-induced hypersalivation: a randomized, double-blind, placebo-controlled, cross-over study.

    PubMed

    Bai, Y M; Lin, C C; Chen, J Y; Liu, W C

    2001-12-01

    The objective of this study was to investigate the efficacy of pirenzepine in the treatment of clozapine-induced hypersalivation. Pirenzepine is reported to counteract hypersalivation by its selective antagonistic activity on the M4-muscarinic receptor, which is stimulated by clozapine. Twenty patients with clozapine-induced hypersalivation underwent a random-order, double-blind, placebo-controlled, cross-over trial which lasted 8 weeks each for the pirenzepine and placebo investigations, with a 4-week washout period in between. The severity of hypersalivation was assessed using an objective measure: saliva production monitored through the diameter of wetted surface on tissue paper placed over the patient's pillow. Our study showed that pirenzepine had no significant therapeutic effect on hypersalivation compared with placebo, suggesting that hypersalivation induced by clozapine might have a neurobiological basis other than the M4-muscarinic receptor.

  18. Behavioural and biochemical effects in the adult rat after prolonged postnatal administration of clozapine.

    PubMed

    Cuomo, V; Cagiano, R; Mocchetti, I; Coen, E; Cattabeni, F; Racagni, G

    1983-01-01

    Rats were administered 10 mg/kg SC of clozapine (C) or vehicle solution (S) daily from day 1 after birth until 20 days of age. At 60 days of age (40 days after the postnatal treatment with C or S was interrupted) the stereotyped behaviour and the effects on locomotor activity elicited by apomorphine in S- and C-pretreated rats were investigated. The intensity of stereotyped behaviour as well as the decrement in locomotion induced by apomorphine (0.5--1 mg/kg SC) were not influenced by chronic C administration during development. Finally, at 80 days of age (60 days after the postnatal treatment with C or S was interrupted) rats were subjected to a differential reinforcement of low rates schedule (DRL15s). The results indicate that the acquisition of the DRL task performance criterion (Rs/Rf less than or equal to 2.5) was significantly more rapid in S-pretreated rats than in C-pretreated ones. In parallel biochemical experiments, homovanillic acid (HVA) content was measured in striatum in rats at 60 days of age (40 days after the postnatal treatment with C or S was interrupted). The results indicate that even if an acute challenge dose of 10 mg/kg C shows a certain degree of tolerance a single dose of 20 mg/kg C is still able to increase striatal HVA concentration in chronic C-pretreated animals. These data indicate that early postnatal administration of a non-cataleptogenic neuroleptic, like C, induces, in the adult rat, behavioural and biochemical changes which significantly differ from those elicited by a cataleptogenic neuroleptic, like haloperidol.

  19. [Treatment of hypertension in chronic kidney disease].

    PubMed

    Palomo-Piñón, Silvia; Rosas-Peralta, Martín; Paniagua-Sierra, José Ramón

    2016-01-01

    Systemic arterial hypertension (SAH) is a progressive cardiovascular syndrome caused by complex and interrelated causes. The early markers of this syndrome are often present even before the blood pressure (BP) elevation; therefore, SAH cannot only be classified by the BP elevation threshold, which sometimes is discreet. Its progression is strongly associated with structural and functional cardiovascular abnormalities, which lead to end-organ damage (heart, kidney, brain, blood vessels and other organs), and cause premature morbidity and death. In this sense, the BP is only a biomarker of this cardiovascular syndrome, which is why it is more useful to consider individual BP patterns of the ill patient rather than a single BP threshold. The study and treatment of hypertension in chronic kidney disease (CKD) has made some progresses, especially in patients requiring dialysis. The use of non-invasive technology to register the BP has reconfigured health care of patients in regards to the diagnosis, circadian pattern, clinical surveillance, pharmacological prescription, prognosis, and risk of cardiovascular events (as well as mortality). The opportunity in the diagnosis and treatment means a delay in the onset of complications and, also, of dialysis. The blockade of the renin-aldotensin-aldosterone system (RAAS), a regular monitoring of the dry weight of the population in dialysis, and non-pharmacological interventions to modify lifestyle are the maneuvers with greater impact on the morbidity and mortality of patients.

  20. Pegloticase: in treatment-refractory chronic gout.

    PubMed

    Lyseng-Williamson, Katherine A

    2011-11-12

    Intravenous pegloticase offers a novel approach to treating chronic gout refractory to conventional therapy. Pegloticase is a recombinant polyethylene glycol-conjugated form of uricase (a uric acid-specific enzyme lacking in humans) that catalyses the oxidation of uric acid to allantoin. In randomized, placebo-controlled, double-blind, 6-month, phase III trials, intravenous pegloticase 8 mg every 2 or 4 weeks provided sustained reductions in plasma uric acid levels to less than the therapeutic target of 6 mg/dL in a substantial proportion of patients with chronic gout who were refractory to, or intolerant of, conventional urate-lowering therapy. Pegloticase 8 mg every 2 weeks was associated with disease-modifying benefits relative to placebo, as shown by significant improvements from baseline in tophi resolution, frequency of gout flares and tender joint count, and clinically relevant and statistically significant improvements from baseline in health-related quality-of-life parameters related to disability, pain and physical function. Pegloticase 8 mg every 4 weeks was also significantly more effective than placebo with regard to most, but not all, of these endpoints. Preliminary data from an open-label extension of the phase III trials indicate that long-term treatment with pegloticase 8 mg every 2 or 4 weeks may maintain plasma uric acid normalization in patients who experienced a sustained uric acid response during the phase III trials. The most common serious adverse events associated with pegloticase are gout flares, infusion reactions and anaphylaxis. In addition, exacerbation of pre-existing congestive heart failure was reported in 2% of patients receiving pegloticase 8 mg every 2 weeks in the phase III trials.

  1. Diurnal neurobiological alterations after exposure to clozapine in first-episode schizophrenia patients.

    PubMed

    Sun, Hong-Qiang; Li, Su-Xia; Chen, Fang-Bin; Zhang, Yan; Li, Peng; Jin, Mei; Sun, Yan; Wang, Fan; Mi, Wei-Feng; Shi, Le; Yue, Jing-Li; Yang, Fu-De; Lu, Lin

    2016-02-01

    Irregular circadian rhythm and some of its most characteristic symptoms are frequently observed in patients with schizophrenia. However, changes in the expression of clock genes or neuropeptides that are related to the regulation of circadian rhythm may influence the susceptibility to recurrence after antipsychotic treatment in schizophrenia, but this possibility has not been investigated. Blood samples were collected from 15 healthy male controls and 13 male schizophrenia patients at 4h intervals for 24h before and after treatment with clozapine for 8 weeks. The outcome measures included the relative expression of clock gene mRNA PERIOD1 (PER1), PERIOD2 (PER2), PERIOD3 (PER3) and the levels of plasma cortisol, orexin, and insulin. Compared with healthy controls, schizophrenia patients presented disruptions in diurnal rhythms of the expression of PER1, PER3, and NPAS2 and the release of orexin, accompanied by a delayed phase in the expression of PER2, decreases in PER3 and NPAS2 expression, and an increase in cortisol levels at baseline. Several of these disruptions (i.e., in PER1 and PER3 expression) persisted after 8 weeks of clozapine treatment, similar to the decreases in the 24-h expression of PER3 and NPAS2. Clozapine treatment for 8 weeks significantly decreased the 24-h levels of PER2 and increased the 24-h levels of insulin. These persistent neurobiological changes that occur after 8 weeks of clozapine treatment may contribute to the vulnerability to recurrence and efficacy of long-term maintenance treatment in schizophrenia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Involvement of the histamine H4 receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells.

    PubMed

    Goto, Aya; Mouri, Akihiro; Nagai, Tomoko; Yoshimi, Akira; Ukigai, Mako; Tsubai, Tomomi; Hida, Hirotake; Ozaki, Norio; Noda, Yukihiro

    2016-09-01

    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 100μM) and doxorubicin (0.2µM) decreased the cell survival rate, but olanzapine (1-100µM) did not. Under granulocytic differentiation for 5days, clozapine, even at a concentration of 25μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H4 receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H4 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 H4 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 H4 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 differentiation.

  3. The effect of galantamine added to clozapine on cognition of five patients with schizophrenia.

    PubMed

    Bora, Emre; Veznedaroğlu, Baybars; Kayahan, Bülent

    2005-01-01

    Although clozapine may be beneficial for the treatment of cognitive dysfunction in schizophrenia, it may also impair some cognitive skills as a result of its anticholinergic activity. In this case series, the impact of galantamine administration on 5 patients with schizophrenia who had been treated with clozapine are reported. Neuropsychological assessment was administered before and after 8 weeks of 16 mg/d galantamine treatment. In this case series, galantamine was well tolerated by all of the patients. Three of the patients were much improved in sustained attention tasks. Most of the patients were also improved in psychomotor speed and selective attention tasks. Two patients with low pretreatment memory scores seemed to also be improved. Our results suggest that the possible role of galantamine as a cognitive enhancer in schizophrenia should be investigated in controlled trials.

  4. Chronic heart failure part 2: treatment and management.

    PubMed

    Brake, Rebecca; Jones, Ian David

    2017-01-11

    Chronic heart failure is a common and complex clinical syndrome that results from impaired cardiac relaxation or contraction. There have been considerable advances in the management of chronic heart failure; however, the mortality rate remains high. Patients with chronic heart failure may experience multiple debilitating symptoms, such as fatigue, pain, and peripheral oedema. However, breathlessness may be considered the most debilitating symptom. The management of chronic heart failure aims to improve the patient's quality of life by reducing symptoms and supporting the patient to manage their condition. Treatment of patients with chronic heart failure may involve a combination of pharmacological therapy, device implantation and cardiac rehabilitation. This is the second of two articles on chronic heart failure. Part 1 discussed the pathophysiology of chronic heart failure, its causes, assessment, signs and symptoms. Part 2 outlines the treatment and management of patients with the condition, including pharmacological strategies, device implantation, lifestyle modification, cardiac rehabilitation and palliative care.

  5. Treatment of chronic periodontitis decreases serum prohepcidin levels in patients with chronic kidney disease.

    PubMed

    Vilela, Eduardo Machado; Bastos, Jessica Amaral; Fernandes, Natalia; Ferreira, Ana Paula; Chaoubah, Alfredo; Bastos, Marcus Gomes

    2011-01-01

    To determine the impact of periodontal treatment on serum levels of prohepcidin (the prohormone of hepcidin) and systemic inflammation markers, as well as correlations among these markers, in patients with chronic periodontitis and chronic kidney disease who were not undergoing dialysis. We included 56 chronic periodontitis patients, 36 with chronic kidney disease and 20 without systemic diseases and with normal renal function (control group). Chronic kidney disease was defined as suggested by the clinical practice guidelines in the National Kidney Foundation. Chronic periodontitis was defined through clinical attachment level and by probing pocket depth, according to the American Association of Periodontology. The inflammatory markers ultrasensitive C-reactive protein, interleukin-6, and prohepcidin were evaluated before and 3 months after periodontal treatment. The efficacy of periodontal treatment was confirmed by the improvement in clinical parameters of chronic periodontitis in the control and chronic kidney disease groups. Periodontal treatment resulted in significant reductions in ultrasensitive C-reactive protein, interleukin-6 and serum prohepcidin levels in both groups. Moreover, in multivariate linear regression, the reduction in prohepcidin after periodontal treatment was significantly and independently associated with interleukin-6 levels in the control group. By inducing a decline in the systemic inflammatory response and a decrease in serum prohepcidin, successful periodontal treatment may represent an important means of ameliorating the inflammatory burden seen in patients with chronic kidney disease. ISRCTN59866656.

  6. Treatment of chronic periodontitis decreases serum prohepcidin levels in patients with chronic kidney disease

    PubMed Central

    Vilela, Eduardo Machado; Bastos, Jessica Amaral; Fernandes, Natalia; Ferreira, Ana Paula; Chaoubah, Alfredo; Bastos, Marcus Gomes

    2011-01-01

    OBJECTIVE: To determine the impact of periodontal treatment on serum levels of prohepcidin (the prohormone of hepcidin) and systemic inflammation markers, as well as correlations among these markers, in patients with chronic periodontitis and chronic kidney disease who were not undergoing dialysis. METHODS: We included 56 chronic periodontitis patients, 36 with chronic kidney disease and 20 without systemic diseases and with normal renal function (control group). Chronic kidney disease was defined as suggested by the clinical practice guidelines in the National Kidney Foundation. Chronic periodontitis was defined through clinical attachment level and by probing pocket depth, according to the American Association of Periodontology. The inflammatory markers ultrasensitive C-reactive protein, interleukin-6, and prohepcidin were evaluated before and 3 months after periodontal treatment. RESULTS: The efficacy of periodontal treatment was confirmed by the improvement in clinical parameters of chronic periodontitis in the control and chronic kidney disease groups. Periodontal treatment resulted in significant reductions in ultrasensitive C-reactive protein, interleukin-6 and serum prohepcidin levels in both groups. Moreover, in multivariate linear regression, the reduction in prohepcidin after periodontal treatment was significantly and independently associated with interleukin-6 levels in the control group. CONCLUSIONS: By inducing a decline in the systemic inflammatory response and a decrease in serum prohepcidin, successful periodontal treatment may represent an important means of ameliorating the inflammatory burden seen in patients with chronic kidney disease. Trial registration: ISRCTN59866656. PMID:21655762

  7. Determination of clozapine in serum of patients with schizophrenia as a measurement of medication compliance.

    PubMed

    Mennickent, S; Sobarzo, A; Vega, M; de Diego, M; Godoy, G; Rioseco, P; Saavedra, L

    2010-03-01

    Abstract Although antipsychotic drugs have been effective in reducing symptoms of schizophrenia, issues with adherence to these agents continue to be a barrier to the implementation and delivery of a successful treatment plan. An estimated 25% of patients with schizophrenia are partially adherent or non-adherent within 7-10 days of beginning therapy. There are some ways to evaluate the pharmacotherapy adherence of the patients: evaluation of the disease symptoms and/or the side effects of the drugs, questionnaires to evaluate quality of life, patient attitude toward his (her) drugs and pill counts. Although these methods represent a good option, they are subjective; for example, if the patients lie this leads to false results. Drug monitoring of patients' biological fluids can be a useful tool to evaluate adherence by relating the serum or plasma levels of drugs with pharmacotherapy compliance. The aim of this study was to determine if serum clozapine levels are a suitable method for evaluating patient adherence to clozapine therapy. Clozapine concentration was determined in serum of 26 volunteer patients who were using this drug as pharmacotheraphy for 6 months to 5 years (steady state conditions at 7-10 days of treatment with the drug). The analysis was done for 6 months, with three samples taken for each patient during this time, relating clozapine serum concentration of lower than therapeutic range with pharmacotherapy non-adherence of patients. Moreover, we compared the evaluation of the pharmacotherapy adherence from serum levels of the drug, with the evaluation of the pharmacotherapy adherence from an indirect tool to evaluate symptoms of disease. Twelve patients were found non-adherent by clozapine serum concentration (46.15%), whereas eight patients were found non-adherent using clinician questionnaire (30.76%). After to evaluate some factors (cigarettes, co-medication, inter-individual variability) that could give different results of adherence from

  8. The effects of clozapine on levels of total cholesterol and related lipids in serum of patients with schizophrenia: a prospective study.

    PubMed Central

    Dursun, S M; Szemis, A; Andrews, H; Reveley, M A

    1999-01-01

    OBJECTIVE: To investigate the effects of 12 weeks of clozapine treatment on levels of cholesterol and related lipids in patients with schizophrenia. DESIGN: Prospective study. SETTING: University department associated with a teaching hospital. PARTICIPANTS: Eight patients (6 women and 2 men) with a clinical diagnosis of schizophrenia consistent with DSM-IV criteria. The patients were classified as treatment-resistant and had not responded to treatment with at least 2 conventional antipsychotics. INTERVENTIONS: Current antipsychotic medications were tapered and treatment with clozapine was initiated. OUTCOME MEASURES: Cholesterol and serum lipid levels, as well as Brief Psychiatric Rating Scale (BPRS) scores were measured before and after 12 weeks of treatment with clozapine. RESULTS: Clozapine treatment significantly improved the BPRS scores but did not significantly alter serum lipid levels, except triglyceride levels, which increased. CONCLUSION: The previously reported lower levels of cholesterol in treatment-resistant patients with schizophrenia cannot be attributed to the effects of clozapine administration. Further research is required to support and clarify the effects of antipsychotic drugs on lipid levels. Images Fig. 1 PMID:10586536

  9. 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.

  10. Potential Mechanisms of Hematological Adverse Drug Reactions in Patients Receiving Clozapine in Combination With Proton Pump Inhibitors.

    PubMed

    Wiciński, Michał; Węclewicz, Mateusz M; Miętkiewicz, Mateusz; Malinowski, Bartosz; Grześk, Elżbieta; Klonowska, Joanna

    2017-03-01

    Clozapine is a second-generation antipsychotic which has proven efficacy in treating the symptoms of schizophrenia. Although clozapine therapy is associated with a number of adverse drug reactions, it is frequently used. One of the most common adverse drug reactions is gastroesophageal reflux disease which is an indication for treatment with proton pump inhibitors (PPIs). Coadministration of clozapine and PPIs increases the risk of hematological adverse drug reactions, including neutropenia and agranulocytosis. The mechanism in idiosyncratic agranulocytosis is not dose related and involves either a direct toxic or an immune-allergic effect. It is suspected that the clozapine metabolites nitrenium ion and N-desmethylclozapine may cause apoptosis or impair growth of granulocytes. Formation of N-desmethylclozapine is correlated with activity of the cytochrome P450 enzymes 1A2 and 3A4 (CYP1A2 and CYP3A4). Nitrenium ion is produced by the flavin-containing monooxygenase system of leukocytes. A drug interaction between clozapine and a PPI is a consequence of the induction of common metabolic pathways either by the PPI or clozapine. Findings to date suggest that indirect induction of flavin-containing monooxygenase by omeprazole through the aryl hydrocarbon receptor increases the expression of the enzyme mRNA and in the long term may cause the increase in activity. Moreover, induction of CYP1A2, especially by omeprazole and lansoprazole, may increase the serum concentration of N-desmethylclozapine, which can accumulate in lymphocytes and may achieve toxic levels. Another hypothesis that may explain hematological adverse drug reactions is competitive inhibition of CYP2C19, which may contribute to increased serum concentrations of toxic metabolites.

  11. Electroconvulsive therapy and clozapine in adolescents with schizophrenia spectrum disorders: is it a safe and effective combination?

    PubMed

    Flamarique, Itziar; Castro-Fornieles, Josefina; Garrido, Juan Miguel; de la Serna, Elena; Pons, Alexandre; Bernardo, Miguel; Baeza, Inmaculada

    2012-12-01

    To evaluate the safety and effectiveness of the combination of electroconvulsive therapy (ECT) and clozapine compared to ECT with other antipsychotics or benzodiazepines in a sample of adolescents diagnosed with schizophrenia spectrum disorders. Data regarding 28 adolescent subjects aged 13 to 18 with diagnoses of schizophrenia spectrum disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision and treated with ECT were retrospectively collected. Twelve subjects were also treated with clozapine and 16 with other antipsychotics or benzodiazepines during ECT course and follow-up. Electroconvulsive therapy parameters and adverse effects were assessed using a systematic protocol. Positive and Negative Syndrome Scale and Clinical Global Impression scores before ECT and after acute ECT, and rate of rehospitalization during 1-year follow-up were used to assess effectiveness. Response was defined as a 20% decrease in Positive and Negative Syndrome Scale scores. No differences were observed in the mean charge needed to induce seizure and electroencephalographic duration, but there was a slight difference in the current used. The nonclozapine group showed greater restlessness and agitation, although no differences were found in other adverse effects. The percentage of responders was similar: 66.7% in the clozapine group and 68.8% in the nonclozapine group. However, the rate of rehospitalization was lower in the patients treated with clozapine during 1-year follow-up (7.1%) compared to that of the nonclozapine group (58.3%) (P = 0.009). The main findings of this study were that combining ECT with clozapine, compared to ECT with other antipsychotics or benzodiazepines, was safe and that both treatments were equally effective. Charges needed to induce seizure were similar in both groups. Patients treated with clozapine during 1-year follow-up had a lower rate of rehospitalization.

  12. 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

  13. Effects of risperidone, clozapine and the 5-HT6 antagonist GSK-742457 on PCP-induced deficits in reversal learning in the two-lever operant task in male Sprague Dawley rats.

    PubMed

    de Bruin, N M W J; van Drimmelen, M; Kops, M; van Elk, J; Wetering, M Middelveld-van de; Schwienbacher, I

    2013-05-01

    Reasoning and problem solving deficits have been reported in schizophrenic patients. In the present study, we have tested rats in a two-lever reversal learning task in a Skinner box to model these deficits. In other studies using the Skinner box, atypical antipsychotics fully reversed phencyclidine (PCP)-induced impairments in reversal learning which is in contrast to clinical observations where antipsychotics lack the ability to fully reverse cognitive deficits in schizophrenia. Therefore, it can be argued that the outcome of these tests may lack predictive value. In the present study, after training on a spatial discrimination between two levers, rats were exposed to a reversal of the previously learned stimulus-response contingency during 5 days. We first investigated the effects of sub-chronic treatment with the non-competitive N-methyl-d-aspartate (NMDA) antagonists dizocilpine (MK-801) and PCP on reversal learning and extinction in male Sprague Dawley rats. Subsequently, we studied the effects of different PCP treatment regimes. Then, we investigated whether the atypical antipsychotics risperidone and clozapine and the 5-hydroxytryptamine6 (5-HT6) antagonist GSK-742457 could reverse the PCP-induced deficits. All drugs were administered subcutaneously (s.c.). MK-801 did not impair reversal learning, while PCP (1.0 and 2.0 mg/kg) induced a clear deficit in reversal learning. Both compounds, however, disrupted extinction at all tested doses. Risperidone and clozapine were both ineffective in significantly ameliorating the PCP-induced deficit in reversal learning which fits well with the clinical observations. The lowest dose of clozapine (1.25 mg/kg) had an intermediate effect in ameliorating the deficit in reversal learning induced by PCP (not different from control or PCP-treated rats). The lowest dose of GSK-742457 (0.63 mg/kg) fully reversed the PCP-induced deficits while the higher dose (5.0 mg/kg) had an intermediate effect.

  14. Effectiveness of Electroconvulsive Therapy Augmentation on Clozapine-Resistant Schizophrenia

    PubMed Central

    Kim, Hye Sung; Kim, Se Hyun; Lee, Nam Young; Youn, Tak; Lee, Jeoung Hyuk; Chung, Seunghyun; Kim, Yong Sik

    2017-01-01

    Objective This retrospective case series study of the effectiveness of electroconvulsive therapy (ECT) augmentation on clozapine-resistant schizophrenia was conducted by EMR review. Methods Clozapine-resistance was defined as persistent psychotic symptoms despite at least 12 weeks of clozapine administration with blood levels over 350 ng/mL in order to rule out pseudo-resistance. Seven in-patients who were taking clozapine and treated with ECT were selected. We analyzed the psychopathology and subscales changed by ECT. Results The average number of ECT sessions was 13.4 (±4.6). Total Positive and Negative Syndrome Scale (PANSS) score was significantly reduced by 17.9 (±12.8) points (p=0.0384) on average, which represented a reduction of 25.5% (±14.3). 71.4% (5/7) of patients were identified as clinical remission, with at least a 20% reduction in PANSS score. PANSS reduction was associated with number of ECT sessions, stimulus level in the final session, and blood clozapine levels before ECT. However, the negative subscale on the PANSS were not reduced by ECT in any patient. We did not observe any persistent adverse cognitive effects. Conclusion This study supports that ECT augmentation on clozapine-resistant schizophrenia reveals clinically effective and safe. Further research should be done involving a larger number of patients to investigate the effectiveness of clozapine/ECT combination therapy. PMID:28096876

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

    PubMed

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

    2017-08-22

    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.

  16. 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

  17. 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.

  18. 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

  19. Psychological Neuromodulatory Treatments for Young People with Chronic Pain.

    PubMed

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

    2016-12-06

    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.

  20. [Treatment options for chronic blepharitis considering current evidence].

    PubMed

    Auw-Hädrich, C; Reinhard, T

    2016-12-01

    The goal of the treatment of chronic blepharitis lies in the reduction of inflammation, which can be achieved by warming, mechanical, and immunomodulatory measures as well as acaricide medication in cases with pathogenetically relevant demodicosis.

  1. A clozapine-like effect of cyproheptadine on progressive ratio schedule performance.

    PubMed

    Olarte-Sánchez, C M; Valencia Torres, L; Body, S; Cassaday, H J; Bradshaw, C M; Szabadi, E; Goudie, A J

    2012-06-01

    The atypical antipsychotic drug clozapine has multiple pharmacological actions, some of which, including 5-hydroxytryptamine (5-HT₂) and histamine (H₁) receptor antagonist effects, are shared by the non-selective 5-HT receptor antagonist cyproheptadine. Atypical antipsychotics have a characteristic profile of action on operant behaviour maintained by progressive ratio schedules, as revealed by Killeen's (1994) mathematical model of schedule controlled behaviour. These drugs increase the values of a parameter that expresses the 'incentive value' of the reinforcer (a) and a parameter that is inversely related to the 'motor capacity' of the organism (δ). This experiment examined the effects of acute treatment with cyproheptadine and clozapine on performance on a progressive ratio schedule of food reinforcement in rats; the effects of a conventional antipsychotic, haloperidol, and two drugs with food intake-enhancing effects, chlordiazepoxide and Δ⁹-tetrahydrocannabinol (THC), were also examined. Cyproheptadine (1, 5 mg kg⁻¹) and clozapine (3.75, 7.5 mg kg⁻¹) increased a and δ. Haloperidol (0.05, 0.1 mg kg⁻¹) reduced a and increased δ. Chlordiazepoxide (3, 10 mg kg⁻¹) increased a but reduced δ. THC (1, 3 mg kg⁻¹) had no effect. Interpretation based on Killeen's (1994) model suggests that cyproheptadine and clozapine enhanced the incentive value of the reinforcer and impaired motor performance. Motor impairment may be due to sedation (possibly reflecting H₁ receptor blockade). Enhancement of incentive value may reflect simultaneous blockade of H₁ and 5-HT₂ receptors, which has been proposed as the mechanism underlying the food intake-enhancing effect of cyproheptadine. In agreement with previous findings, haloperidol impaired motor performance and reduced the incentive value of the reinforcer. Chlordiazepoxide's effect on a is consistent with its food intake-enhancing effect.

  2. 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

  3. 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.

  4. [Chronic venous insufficiency: Update on pathophysiology, diagnosis and treatment].

    PubMed

    Gkogkolou, P; Meyer, V; Goerge, T

    2015-05-01

    Chronic venous insufficiency is very common and has an important socioeconomic impact. It is associated with a high morbidity for the patients and causes high costs for the healthcare systems. In recent years novel treatment modalities have evolved and their efficacy has been evaluated in many studies. Knowledge of pathophysiology, the diagnostic procedures and therapeutic options for chronic venous insufficiency is important for effective treatment of affected patients.

  5. Clozapine-induced hypersensitivity myocarditis presenting as sudden cardiac death

    PubMed Central

    Balla, Sudarshan; Aggarwal, Kul

    2016-01-01

    Hypersensitivity myocarditis is a rare but serious adverse effect of clozapine, a commonly used psychiatric drug. We report the case of sudden cardiac death from clozapine-induced hypersensitivity myocarditis diagnosed at autopsy. A 54-year-old Caucasian male on clozapine therapy for bipolar disorder presented with a sudden onset of shortness of breath. Laboratory studies were significant for elevated N-terminal prohormone of brain natriuretic peptide. During his hospital stay, the patient died of sudden cardiac arrest from ventricular tachycardia. The autopsy revealed hypersensitivity myocarditis, which usually occurs in the first 4 weeks after the initiation of clozapine. A 4-week monitoring protocol, including laboratory assessment of troponin and C-reactive protein, may assist in the early diagnosis of this potentially fatal condition. PMID:28210568

  6. Interaction of St John's wort (Hypericum perforatum) with clozapine.

    PubMed

    Van Strater, Annelies C P; Bogers, Jan P A M

    2012-03-01

    St John's wort (Hypericum perforatum) is notorious for its ability to induce the enzymes of the P450 system. Especially, it induces CYP1A2 and CYP3A4, enzymes that are closely involved in the metabolism of clozapine. We present a patient with schizophrenia, who was stable on a fixed dose with stable plasma level of clozapine, and who deteriorated after she started self-medicating with St John's wort. The reduced plasma clozapine level and the psychiatric condition normalized after the withdrawal of St John's wort. It is possible that, beside the induction of P450-enzymes, the induction of P-glycoprotein by St John's wort aggravated psychiatric deterioration of the patient. Physicians should be alert to patients self-medicating with over-the-counter medicines, especially when these medicines can lower clozapine concentrations below the therapeutic range.

  7. Prevalence and treatment of giardiasis in chronic diarrhoea and malnutrition.

    PubMed Central

    Sullivan, P B; Marsh, M N; Phillips, M B; Dewit, O; Neale, G; Cevallos, A M; Yamson, P; Farthing, M J

    1991-01-01

    To determine the prevalence of giardiasis in Gambian children with chronic diarrhoea and to assess their response to treatment, 31 children with chronic diarrhoea and malnutrition were investigated for giardiasis using a combination of serology (specific antigiardia IgM antibody) and microscopy of faeces and jejunal biopsy specimens. Fourteen of 31 children with chronic diarrhoea had giardiasis compared with only four of 33 healthy age and sex matched control children. Four of 15 malnourished children without diarrhoea were giardia positive. Twenty-three children with chronic diarrhoea were reinvestigated after treatment with metronidazole; giardia was found in 11 of them. These results show that giardia is highly prevalent in children with chronic diarrhoea and malnutrition and that the infection does not respond to standard therapeutic measures. PMID:2025005

  8. Treatment of chronic pulmonary blastomycosis with caspofungin.

    PubMed

    Mardini, Joëlle; Nguyen, Bich; Ghannoum, Marc; Couture, Christian; Lavergne, Valéry

    2011-12-01

    Current practice guidelines recommend that pulmonary blastomycosis be treated with antifungal agents such as amphotericin B and itraconazole. Echinocandins are not recommended because of poor in vitro activity against Blastomyces dermatitidis and lack of supporting clinical data. We report a case of chronic pulmonary blastomycosis treated successfully with caspofungin. © 2011 SGM

  9. Evaluation and treatment of chronic hand conditions.

    PubMed

    Darowish, Michael; Sharma, Jyoti

    2014-07-01

    Hand and wrist problems are frequently the cause of patients' complaints in the primary care setting. Common problems include hand numbness, pain, loss of motion, or unexplained masses in the hand. Many problems can be successfully managed or treated with nonoperative measures. This article focuses on commonly encountered causes of chronic hand pain.

  10. Chronic Antidepressant Treatment Impairs the Acquisition of Fear Extinction

    PubMed Central

    Burghardt, Nesha S.; Sigurdsson, Torfi; Gorman, Jack M.; McEwen, Bruce S.; LeDoux, Joseph E.

    2012-01-01

    Background Like fear conditioning, the acquisition phase of extinction involves new learning that is mediated by the amygdala. During extinction training, the conditioned stimulus is repeatedly presented in the absence of the unconditioned stimulus and the expression of previously learned fear gradually becomes suppressed. Our previous study revealed that chronic treatment with a selective serotonin reuptake inhibitor (SSRI) impairs the acquisition of auditory fear conditioning. To gain further insight into how SSRIs affect fear learning, we tested the effects of chronic SSRI treatment on the acquisition of extinction. Methods Rats were treated chronically (22 days) or subchronically (9 days) with the SSRI citalopram (10 mg/kg/day) before extinction training. The results were compared to those following chronic and subchronic treatment with tianeptine (10 mg/kg/day), an antidepressant with a different method of action. The expression of the NR2B subunit of the NMDA receptor in the amygdala was examined after behavioral testing. Results Chronic but not subchronic administration of citalopram impaired the acquisition of extinction and downregulated the NR2B subunit of the NMDA receptor in the lateral and basal nuclei of the amygdala. Similar behavioral and molecular changes were found with tianeptine treatment. Conclusions These results provide further evidence that chronic antidepressant treatment can impair amygdala-dependent learning. Our findings are consistent with a role for glutamatergic neurotransmission in the final common pathway of antidepressant treatment. PMID:23260230

  11. Omalizumab in the Treatment of Chronic Inducible Urticaria.

    PubMed

    Chicharro, P; Rodríguez, P; de Argila, D

    2017-06-01

    Omalizumab is a recombinant humanized monoclonal antibody that inhibits immunoglobulin E. It has been approved for the treatment of severe asthma and chronic spontaneous urticaria refractory to other treatments. Its use in the management of chronic inducible urticaria (a type triggered by certain stimuli) is still considered off-label, although this use has been discussed in some consensus papers. This review brings together case reports and case series describing the use of omalizumab to treat chronic inducible urticaria. We analyze the most important aspects of the cases and the outcomes reported. The results seem to position omalizumab as a potentially effective, safe treatment alternative in some cases of chronic inducible urticaria. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. 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

  13. 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

  14. Chronic Cholangitides: Aetiology, Diagnosis, and Treatment*

    PubMed Central

    Sherlock, Sheila

    1968-01-01

    A number of different chronic diseases affect the intrahepatic bile radicles or cholangioles. They include primary and secondary sclerosing cholangitis, primary biliary cirrhosis, chronic cholestatic drug jaundice, atresia, and carcinoma. Aetiological factors include infection, immunological changes, hormones, and congenital defects. Patients with chronic cholestasis have decreased bile salts in the intestinal contents and suffer from a bile salt deficiency syndrome. Failure to absorb dietary fat is managed by a low-fat diet and by medium-chain trigly-cerides which are absorbed in the absence of intestinal bile salts. Fat-soluble vitamin deficiencies are prevented by parenteral vitamins A, D, and K1. Calcium absorption is defective, and improvement may follow intramuscular vitamin D, medium-chain triglycerides, a low-fat diet, and oral calcium supplements. In partial intestinal bile salt deficiency the anionic bile-salt-chelating resin cholestyramine controls pruritus though steatorrhoea increases. Pruritus associated with total lack of intestinal bile salts is managed by methyl-testosterone or norethandrolone, though the jaundice increases. PMID:4971054

  15. [Treatment of chronic back pain: current standards].

    PubMed

    Märker-Hermann, E; Kiltz, U; Braun, J

    2014-12-01

    Back pain is a significant medical problem and one of the most common causes of medical consultations and missed work. In acute low back pain, patients with "red flags" indicating a serious underlying spinal or extraspinal disease must be identified by medical evaluation. Most cases of acute back pain are non-specific, and education, physical activity and pain medication is recommended. In addition, yellow flags (risks of developing chronic pain) should be recognized. The management of low back pain has been addressed by the German National Disease Management Guideline (NVL) low back pain published in 2010. This guideline evaluates the evidence and effectiveness of diagnostic and therapeutic interventions with a focus on nonspecific back pain. For chronic nonspecific low back pain intervention based on nondrug and drug therapy and a multiprofessional assessment is recommended. In patients with chronic inflammatory low back pain with onset before the age of 45, rheumatic spondyloarthritis should be considered. Recently, a guideline (S3-Leitlinie) for the management of axial spondyloarthritis including ankylosing spondylitis has become available. It provides evidence of physical and drug therapy including nonsteroidal antirheumatic and Tumor necrosis factor (TNF) inhibitor therapy.

  16. Evidence-based Management Strategies for Treatment of Chronic Wounds

    PubMed Central

    Werdin, Frank; Tennenhaus, Mayer; Schaller, Hans-Eberhardt; Rennekampff, Hans-Oliver

    2009-01-01

    The care and management of patients with chronic wounds and their far-reaching effects challenge both the patient and the practitioner. Further complicating this situation is the paucity of evidence-based treatment strategies for chronic wound care. After searching both MEDLINE and Cochrane databases, we reviewed currently available articles concerning chronic wound care. Utilizing this information, we have outlined a review of current, evidence-based concepts as they pertain to the treatment of chronic wounds, focusing on fundamental treatment principles for the management of venous, arterial, diabetic, and pressure ulcers. Individualized treatment options as well as general wound management principles applicable to all varieties of chronic wounds are described. Classification and treatment guidelines as well as the adoption of the TIME acronym facilitate an organized conceptional approach to wound care. In so doing, individual aspects of generalized wound care such as debridement, infection, and moisture control as well as attention to the qualities of the wound edge are comprehensively evaluated, communicated, and addressed. Effective adjuvant agents for the therapy of chronic wounds including nutritional and social support measures are listed, as is a brief review of strategies helpful for preventing recurrence. An appreciation of evidence-based treatment pathways and an understanding of the pathophysiology of chronic wounds are important elements in the management of patients with chronic wounds. To achieve effective and long-lasting results, a multidisciplinary approach to patient care, focused on the education and coordination of patient, family as well as medical and support staff can prove invaluable. PMID:19578487

  17. [Clozapine and agranulocitosis in Spain: do we have a safer population? A 5-year hematologic follow-up].

    PubMed

    Pons, Alexander; Undurraga, Juan; Batalla, Albert; Bernardo, Miquel

    2012-01-01

    Clozapine is an efective antipsychotic. However, its use has been associated with agranulocitosis. For this reason, it has been restricted for the treatment of resistant schizophrenia under a strict hematologic control. The objective of this work was to assess the risk of hematologic dyscrasias in a sample of clozapine-treated patients in a 5-year period. This is a follow-up study in a cohort of clozapine-treated patients in which the risk of haematological dyscrasias was assessed. Complete blood cell count was made for each patient in a weekly basis for the first 18 weeks and thereafter monthly. 271 patients in treatment with clozapine were followed up. The mean age was 32.3 years, with 36.5% women. The mean dose was 227,6 mg, ranging from 25 to 600 mg/day. During the first 18 weeks of follow-up, we observed a 3% incidence of neutropenia and 1.3% of leucopenia. During the next two years, only one new case of neutropenia and leucopenia was observed (n=120). No new cases were observed during the rest of follow up (n=69). No cases of agranulocytosis were observed. A 3% incidence of neutropenia concentrated in the first months of follow up and no cases of agranulocitosis were observed in our sample. Actual evidence on clozapine effectiveness and safety and the results of this study suggests that a critical revision of follow-up protocols is suitable. Copyright © 2011 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

  18. Chronic Urticaria in Returning Travellers: The Role of Anthelmintic Treatment.

    PubMed

    Nahshoni, Avishai; Baum, Sharon; Barzilai, Aviv; Schwartz, Eli

    2016-01-01

    Chronic urticaria often poses a therapeutic challenge. The human immune response to helminths has a high degree of similarity to an allergic response in terms of skin manifestations, eosinophilia, and IgE elevation. Unfortunately, it is often complicated to diagnose such infections. We sought to assess the effect of empirical anthelmintic treatment among returning travellers diagnosed with chronic urticaria, without clear proof of helminthic infection. This is a retrospective case series of 19 returning travellers with chronic urticaria. All patients were treated with anthelmintic treatment given based on clinical suspicion only. A randomly selected control group of 20 patients with chronic urticaria, with no history of travel, was also enrolled. A positive clinical response was reported in 68.4% (13 patients) of the travellers' group within 3 months after treatment with anthelmintic therapy compared with 10% (2 patients) of chronic urticaria patients in the control group. No adverse effects from treatment were recorded. In patients with chronic urticaria, travel history to developing countries must be obtained. Empiric anthelmintic therapy might be beneficial, even in the absence of findings suggestive of helminthic infection. © 2016 S. Karger AG, Basel.

  19. [Acceptance and commitment therapy in the treatment of chronic pain].

    PubMed

    Dionne, Frédérick; Blais, Marie-Claude; Monestès, Jean-Louis

    2013-01-01

    The purpose of this article is to present the characteristics of the Acceptance and Commitment Therapy (ACT) for the treatment of chronic pain. The historical context of the development of cognitive and behavioural therapy (CBT) for chronic pain will be described and the theoretical aspects of ACT will be introduced. The components of an acceptance and mindfulness based treatment will also be presented by exploring various processes of the psychological flexibility model. Finally, the article will summarize the scientific evidence supporting ACT based on experimental, correlational and clinical studies in the field of chronic pain. The theoretical aspects underlying ACT, as well as its clinical components in the specific domain of chronic pain were described based on major books in this area, such as McCracken (2005) and Dahl et al. (2005). A descriptive literature review was undertaken to explore the data on the efficacy of ACT for the treatment of chronic pain. Psycinfo and Medline, as well as the Association for Contextual Science website were analyzed for relevant articles. The key search terms were: "Acceptance and Commitment Therapy" or "ACT" or "acceptance" or "mindfulness" or "defusion" and "chronic pain" or "pain." The reference lists of the articles retrieved were also analyzed. The articles that were not in English or French were excluded as well as those that were not specific to ACT and chronic pain. Results show that ACT is a relevant and empirically supported approach that may be used as a complement to CBT strategies in the treatment of chronic pain. There is growing evidence stemming from experimental and correlational studies that support the majority of the ACT processes. Clinical studies undertaken in the field of chronic pain from different backgrounds support the efficacy of ACT for the management of this condition. ACT is a promising and evidence-based approach for the treatment of chronic pain. More research is needed to further validate its

  20. Pharmacological treatment of chronic pelvic ischemia.

    PubMed

    Andersson, Karl-Erik; Nomiya, Masanori; Sawada, Norifumi; Yamaguchi, Osamu

    2014-06-01

    Epidemiological studies have shown that lower urinary tract symptoms, including overactive bladder, commonly occur in both men and women, with an age-related increase in both sexes. Vascular endothelial dysfunction and urological symptoms are common in the metabolic syndrome; they also occur during the human ageing process and are independent risk factors for the development of atherosclerosis and hypertension. Pelvic arterial insufficiency may lead to impaired lower urinary tract perfusion and play an important role in the development of bladder dysfunction such as detrusor overactivity and overactive bladder. It seems reasonable, but has not been definitely established clinically, that chronic ischemia-related bladder dysfunction will progress to bladder underactivity. Studies in experimental models in rabbits and rats have shown that pelvic arterial insufficiency may result in significant bladder ischemia with reduced bladder wall oxygen tension, oxidative stress, increased muscarinic receptor activity, ultrastructural damage, and neurodegeneration. Several types of drug may be able to prevent some of these changes. Even if the α1-adrenoceptor blocker, silodosin, the phosphodiesterase type 5 inhibitor, tadalafil, the β3-α1-adrenoceptor agonist, mirabegron, and the free radical scavenger, melatonin, were unable to prevent the development of neointimal hyperplasia and consequent luminal occlusion in animal models, they all exerted a protecting effect on urodynamic parameters, and on the functional and morphological changes of the bladder demonstrable in vitro. The different mechanisms of action of the drugs suggest that many factors are involved in the pathogenesis of chronic ischemia-induced bladder dysfunction and can be targets for intervention. Since several of the agents tested are used clinically and effectively for relieving lower urinary tract symptoms, the results from animal models of chronic bladder ischemia seem to have translational value

  1. Ghosts in the Machine. Interoceptive Modeling for Chronic Pain Treatment

    PubMed Central

    Di Lernia, Daniele; Serino, Silvia; Cipresso, Pietro; Riva, Giuseppe

    2016-01-01

    Pain is a complex and multidimensional perception, embodied in our daily experiences through interoceptive appraisal processes. The article reviews the recent literature about interoception along with predictive coding theories and tries to explain a missing link between the sense of the physiological condition of the entire body and the perception of pain in chronic conditions, which are characterized by interoceptive deficits. Understanding chronic pain from an interoceptive point of view allows us to better comprehend the multidimensional nature of this specific organic information, integrating the input of several sources from Gifford's Mature Organism Model to Melzack's neuromatrix. The article proposes the concept of residual interoceptive images (ghosts), to explain the diffuse multilevel nature of chronic pain perceptions. Lastly, we introduce a treatment concept, forged upon the possibility to modify the interoceptive chronic representation of pain through external input in a process that we call interoceptive modeling, with the ultimate goal of reducing pain in chronic subjects. PMID:27445681

  2. Chronic Methadone Treatment Shows a Better Cost/Benefit Ratio than Chronic Morphine in Mice

    PubMed Central

    Enquist, Johan; Ferwerda, Madeline; Milan-Lobo, Laura

    2012-01-01

    Chronic treatment of pain with opiate drugs can lead to analgesic tolerance and drug dependence. Although all opiate drugs can promote tolerance and dependence in practice, the severity of those unwanted side effects differs depending on the drug used. Although each opiate drug has its own unique set of pharmacological profiles, methadone is the only clinically used opioid drug that produces substantial receptor endocytosis at analgesic doses. Here, we examined whether moderate doses of methadone carry any benefits over chronic use of equianalgesic morphine, the prototypical opioid. Our data show that chronic administration of methadone produces significantly less analgesic tolerance than morphine. Furthermore, we found significantly reduced precipitated withdrawal symptoms after chronic methadone treatment than after chronic morphine treatment. Finally, using a novel animal model with a degrading μ-opioid receptor we showed that, although endocytosis seems to protect against tolerance development, endocytosis followed by receptor degradation produces a rapid onset of analgesic tolerance to methadone. Together, these data indicated that opioid drugs that promote receptor endocytosis and recycling, such as methadone, may be a better choice for chronic pain treatment than morphine and its derivatives that do not. PMID:22062352

  3. Chronic methadone treatment shows a better cost/benefit ratio than chronic morphine in mice.

    PubMed

    Enquist, Johan; Ferwerda, Madeline; Milan-Lobo, Laura; Whistler, Jennifer L

    2012-02-01

    Chronic treatment of pain with opiate drugs can lead to analgesic tolerance and drug dependence. Although all opiate drugs can promote tolerance and dependence in practice, the severity of those unwanted side effects differs depending on the drug used. Although each opiate drug has its own unique set of pharmacological profiles, methadone is the only clinically used opioid drug that produces substantial receptor endocytosis at analgesic doses. Here, we examined whether moderate doses of methadone carry any benefits over chronic use of equianalgesic morphine, the prototypical opioid. Our data show that chronic administration of methadone produces significantly less analgesic tolerance than morphine. Furthermore, we found significantly reduced precipitated withdrawal symptoms after chronic methadone treatment than after chronic morphine treatment. Finally, using a novel animal model with a degrading μ-opioid receptor we showed that, although endocytosis seems to protect against tolerance development, endocytosis followed by receptor degradation produces a rapid onset of analgesic tolerance to methadone. Together, these data indicated that opioid drugs that promote receptor endocytosis and recycling, such as methadone, may be a better choice for chronic pain treatment than morphine and its derivatives that do not.

  4. Tamsulosin treatment of chronic non-bacterial prostatitis.

    PubMed

    Ye, Z Q; Lan, R Z; Yang, W M; Yao, L F; Yu, X

    2008-01-01

    The efficacy of tamsulosin in the treatment of chronic non-bacterial prostatitis was evaluated in a randomized clinical observation of 105 male outpatients conducted for 90 days. Patients were randomly divided into five groups (n = 21 per group) according to prostatitis type IIIA or IIIB and therapy regimens (tamsulosin, levofloxacin, or tamsulosin plus levofloxacin combination therapy). National Institutes of Health Chronic Prostatitis Symptom Index scores, expressed prostatic massage test and urodynamic urethral pressure and urethral closure pressure tests were performed to evaluate clinical efficacy of the treatments. Scores for pain, urinary symptoms and quality of life were significantly improved by days 45 and 90 after all treatments in both prostatitis categories. Improvements in symptom scores in the combined treatment group were significantly superior to those in the single treatment groups. Tamsulosin and levofloxacin are both effective in the treatment of, and may have an additive effect in, the treatment of non-bacterial prostatitis.

  5. 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…

  6. 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…

  7. Platelet rich plasma treatment for chronic Achilles tendinosis.

    PubMed

    Monto, Raymond Rocco

    2012-05-01

    Chronic Achilles tendinosis is a relatively common but difficult orthopedic condition to treat. In this study, autologous platelet rich plasma (PRP), a concentrated bioactive blood component rich in cytokines and growth factors, was evaluated to determine its potential long-term efficacy in treating chronic cases of Achilles tendinosis resistant to traditional nonoperative management. Thirty patients with chronic Achilles tendinosis who did not respond to a minimum of 6 months of traditional nonoperative treatment modalities were treated with a single ultrasound guided injection of PRP. AOFAS scoring was completed for all patients pretreatment and at 0, 1, 2, 3, 6, 12, and 24 months post-treatment. MRI and/or ultrasound studies were completed for all patients pre-treatment and at 6 months post-treatment. Prior to the PRP treatment all of the patients in this study were considering surgical Achilles repair for their severe symptoms. The average AOFAS score increased from 34 (range, 20 to 60) to 92 (range, 87 to 100) by 3 months after PRP treatment and remained elevated at 88 (range, 76 to 100) at 24 months post-treatment. Pretreatment imaging abnormalities present in the Achilles tendon on MRI and ultrasound studies resolved in 27 of 29 patients at 6 months post-treatment. Clinical success was achieved in 28 of 30 patients. Platelet-rich plasma was used effectively to treat chronic recalcitrant cases of Achilles tendinosis.

  8. Treatment algorithm for chronic lateral ankle instability

    PubMed Central

    Giannini, Sandro; Ruffilli, Alberto; Pagliazzi, Gherardo; Mazzotti, Antonio; Evangelisti, Giulia; Buda, Roberto; Faldini, Cesare

    2014-01-01

    Summary Introduction: ankle sprains are a common sports-related injury. A 20% of acute ankle sprains results in chronic ankle instability, requiring surgery. Aim of this paper is to report the results of a series of 38 patients treated for chronic lateral ankle instability with anatomic reconstruction. Materials and methods: thirty-eight patients were enrolled in the study. Seventeen patients underwent a surgical repair using the Brostrom-modified technique, while the remaining underwent anatomic reconstruction with autologous or allogenic graft. Results: at a mean follow-up of 5 years the AOFAS score improved from 66.1 ± 5.3 to 92.2 ± 5.6. Discussion: the findings of this study confirm that anatomic reconstruction is an effective procedure with satisfactory subjective and objective results which persist at long-term follow-up along with a low complication rate. No differences, in term of clinical and functional outcomes, were observed between the Brostrom-modified repair and the anatomic reconstruction technique. Level of evidence: level IV. PMID:25767783

  9. [Almitrine bismesylate treatment in chronic respiratory insufficiency].

    PubMed

    González Ruiz, J M; Villamor León, J; García-Satué, J L; Sánchez Agudo, L; Calatrava, J M; Carreras, J

    1994-12-01

    This study was designed to evaluate the gasometric and functional respiratory responses in chronic bronchitic patients with chronic respiratory insufficiency (CRI) under ambulatory oxygen therapy (AOT) with almitrine bismesylate (AB). It was a double-blind, placebo-controlled, randomized, prospective study which lasted three months and with a dosage regime of 50-100 mg/day of AB. Fiftyfour patients completed the study (28 in AB and 24 in the placebo (P) groups, respectively). All patients were males, with a mean age or 65 +/- 6.1 years. In the study of pulmonary function only airway resistance (Raw) was changed, with a significant decrease at the third month in the AB group compared with the P group (0.83 +/- 0.31 vs. 1.07 +/- 0.46 kpa/L.S), with a p value of 0.05 (mean +/- SD) and PaO2 which improved from 8.15 +/- 0.88 to 8.81 +/- 2.3 kpa (61.17 +/- 6.6 to 66.10 +/- 10 mmHg), with a p value of 0.05. AB therapy was well tolerated.

  10. Dose-hair concentration relationship and pigmentation effects in patients on low-dose clozapine.

    PubMed

    Kronstrand, R; Roman, M; Hedman, M; Ahlner, J; Dizdar, N

    2007-06-01

    Several hair components have been suggested as possible molecular sites for drug binding and interaction. Of these, keratin and melanin have been investigated in some detail in order to assess the mechanisms by which the binding occurs. Substances that are positively charged at physiological pH may interact by electrostatic forces between their cationic groups and the anionic carboxylic groups on the surface of the melanin polymer. Studies in human subjects with grey hair have shown that various drugs are detectable in both the coloured (melanin rich) and white (melanin free) hair shafts of these individuals. Again this supports the proposition that keratin and hair proteins play an important role in the binding of drugs in hair. However, drugs are often found in significantly higher concentrations in pigmented hair strands than in senile white hair strands. Another interesting question is if the concentration measured in hair reflects the dose taken. Previous reports have both verified and rejected this hypothesis, but most agree that many factors have impact on the incorporation rate, melanin being one. In this study we obtained blood and hair samples from 12 grey haired patients treated with low-dose clozapine as an adjunct medication in their treatment against Parkinson disease. Each patient's hair was divided into a pigmented and a non-pigmented portion and those were analyzed separately. Clozapine and desmethylclozapine were analyzed with LC-MS-MS after extraction of the analytes from hair and plasma. Paired results from the analysis of pigmented and white hair confirmed the preference for binding to pigmented hair for both clozapine and its metabolite. A majority of the incorporated clozapine was found in the pigmented hair but, as drugs could be detected in white hair, binding to hair protein or association with other hair matrix account for a significant part of drug accumulation in hair. High correlations between dose and the measured concentration of

  11. 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

  12. Oculogyric Crisis with Clozapine: A Case Report and Review of Similar Case Reports in the Literature

    PubMed Central

    Nebhinani, Naresh; Avasthi, Ajit; Modi, Manish

    2015-01-01

    Oculogyric crisis (OGC) is a dystonic reaction and commonly caused by typical antipsychotics and rarely occurs with clozapine. Here, we are presenting a case of OGC with clozapine therapy and reviewing the similar cases reported in the literature. PMID:26664086

  13. Outcomes of obese, clozapine-treated inpatients with schizophrenia placed on a six-month diet and physical activity program.

    PubMed

    Wu, Mei-Kuei; Wang, Chin-Kun; Bai, Ya-Mei; Huang, Chih-Yang; Lee, Shin-Da

    2007-04-01

    Patients with schizophrenia treated with clozapine often gain weight. This study evaluated the effects of dietary control and physical activity among obese inpatients with schizophrenia being treated with clozapine. Fifty-three clozapine-treated obese patients with schizophrenia in a veterans hospital in eastern Taiwan who had a body mass index greater than 27 (weight divided by height in meters squared) and who were taking clozapine were randomly assigned to a study group of 28 or a control group of 25. The study group was placed on a diet that reduced calorie intake by 200 to 300 kcal per day (to 1,300 to 1,500 kcal per day for women and to 1,600 to 1,800 kcal per day for men) and a six-month regimen of regular physical activity in which participants used approximately 600 to 750 kcal per week (level walking and walking on stairs for 60 minutes three days per week). Anthropometric, metabolic, and hormonal parameters were measured after three and six months by using anthropometry, an enzyme autoanalyzer, immunoassay, and enzyme-linked immunosorbent assay. Compared with the control group, the study group showed a significant decrease in body weight, body mass index (5.4% reduction), waist circumference (3.3 cm), and hip circumference (3.3 cm) after three months and after six months. Triglyceride and insulin-like growth factor-binding protein-3 (IGFBP-3) decreased significantly only after six months. A program of dietary control and regular physical activity can significantly reduce body weight and improve metabolic profiles of insulin, triglyceride, and IGFBP-3 among obese inpatients taking clozapine for the treatment of schizophrenia.

  14. Autologous epidermal cell suspension: A promising treatment for chronic wounds.

    PubMed

    Zhao, Hongliang; Chen, Yan; Zhang, Cuiping; Fu, Xiaobing

    2016-02-01

    Chronic wounds have become an increasing medical and economic problem of aging societies because they are difficult to manage. Skin grafting is an important treatment method for chronic wounds, which are refractory to conservative therapy. The technique involving epidermal cell suspensions was invented to enable the possibility of treating larger wounds with only a small piece of donor skin. Both uncultured and cultured autologous epidermal cell suspensions can be prepared and survive permanently on the wound bed. A systematic search was conducted of EMBASE, Cochrane Library, PubMed and web of science by using Boolean search terms, from the establishment of the database until May 31, 2014. The bibliographies of all retrieved articles in English were searched. The search terms were: (epithelial cell suspension OR keratinocyte suspension) and chronic and wound. From the included, 6 studies are descriptive interventions and discussed the use of autologous keratinocyte suspension to treat 61 patients' chronic wound. The various methods of preparation of epidermal cell suspension are described. The advantages and shortcomings of different carriers for epidermal cell suspensions are also summarised. Both uncultured and cultured autologous epidermal cell suspensions have been used to treat chronic wounds. Although the limitations of these studies include the small number of patient populations with chronic wounds and many important problems that remain to be solved, autologous epidermal cell suspension is a promising treatment for chronic wounds. Copyright © 2015 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

  15. [Vitaprost plus in the treatment of chronic bacterial prostatitis].

    PubMed

    Lopatkin, N A; Kamalov, A A; Mazo, E B; Kozdoba, A S; Popov, S V; Efremov, E A; Dorofeev, S D; Mel'nik, Ia I; Okhobotov, D A

    2009-01-01

    Our study has demonstrated that compound medicine vitaprost plus in therapy of chronic bacterial prostatitis (CBP) reduces intensity of prostatic inflammation, significantly relieves symptoms of chronic prostatitis and pain syndrome. The absence of unwanted side effects, significant changes in clinical and biochemical blood and urine parameters evidences for good tolerance and safety of the drug. Thus, rectal suppositories vitaprost plus can be recommended for treatment of chronic bacterial prostatitis caused by both gram-positive and gram-negative bacteria in patients of different age and clinical symptoms.

  16. 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

  17. Chronic atypical antipsychotics, but not haloperidol, increase neurogenesis in the hippocampus of adult mouse.

    PubMed

    Chikama, Koji; Yamada, Hidetaka; Tsukamoto, Tatsuo; Kajitani, Kosuke; Nakabeppu, Yusaku; Uchimura, Naohisa

    2017-09-09

    It is suggested that altered neuroplasticity contributes to the pathophysiology of schizophrenia and antipsychotics may exhibit some of their therapeutic efficacies by improving neurogenesis and/or proliferation of neural progenitors. The aim of this study is to investigate whether chronic antipsychotics treatment affect neurogenesis in adult mouse hippocampus. Animals were administered olanzapine, quetiapine, clozapine, risperidone, aripiprazole, or haloperidol via the osmotic minipump for 21 days and then injected with 5-bromo-2'-deoxyuridine (BrdU) to label mitotic cells. BrdU-positive cells in the hippocampus were quantified by stereology. Aripiprazole, quetiapine, clozapine, and olanzapine significantly increased density of BrdU-positive cells in the hippocampus. Interestingly, other antipsychotic drugs had tendency to increasing BrdU-positive cells, whereas haloperidol had propensity to decrease with a marginal significance. These results suggest that differences of neurogenesis among these drugs may, at least in part, account for their pharmacological profiles. Copyright © 2017. Published by Elsevier B.V.

  18. Clozapine and cocaine effects on dopamine and serotonin release in nucleus accumbens during psychostimulant behavior and withdrawal.

    PubMed

    Broderick, Patricia A; Hope, Omotola; Okonji, Catherine; Rahni, David N; Zhou, Yueping

    2004-01-01

    There is an increasing awareness that a psychosis, similar to that of schizophrenic psychosis, can be derived from cocaine addiction. Thus, the prototypical atypical antipsychotic medication, clozapine, a 5-HT(2)/DA(2) antagonist, was studied for its effects on cocaine-induced dopamine (DA) and serotonin (5-HT) release in nucleus accumbens (NAcc) of behaving male Sprague-Dawley laboratory rats with In Vivo Microvoltammetry, while animals' locomotor (forward ambulations), an A(10) behavior, was monitored at the same time with infrared photobeams. Release mechanisms for monoamines were determined by using a depolarization blocker, gamma-butyrolactone (gammaBL). BRODERICK PROBE microelectrodes selectively detected release of DA and 5-HT within seconds and sequentially in A(10) nerve terminals, NAcc. Acute and subacute studies were performed for each treatment group. Acute studies are defined as single injection of drug(s) after a stable baseline of each monoamine and locomotor behavior has been achieved. Subacute studies are defined as 24-h follow-up studies on each monoamine and locomotor behavior, in the same animal at which time, no further drug was administered. Results showed that (1) acute administration of cocaine (10 mg/kg ip) (n=5) significantly increased both DA and 5-HT release above baseline (P<.001) while locomotion was also significantly increased above baseline (P<.001). In subacute studies, DA release decreased significantly below baseline (P<.001) and significant decreases in 5-HT release occurred at the 15-min mark and at each time point during the second part of the hour (P<.05); the maximum decrease in 5-HT was 40% below baseline. Locomotor behavior, on the other hand, increased significantly above baseline (P<.05). (2) Acute administration of clozapine/cocaine (20 and 10 mg/kg ip, respectively; n=6) produced a significant block of the cocaine-induced increase in DA (P<.001) and 5-HT release (P<.001). Cocaine-induced locomotion was blocked

  19. 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

  20. Treatment Options for Chronic Myelogenous Leukemia

    MedlinePlus

    ... a blood vessel in the chest. Donor lymphocyte infusion (DLI) Donor lymphocyte infusion (DLI) is a cancer treatment that may be ... given to the patient through one or more infusions. The lymphocytes see the patient’s cancer cells as ...

  1. Chronic heart failure: pathophysiology, diagnosis and treatment.

    PubMed

    Nicholson, Christopher

    2014-08-01

    Heart failure has significant prevalence in older people: the mean average age of patients with the condition is 77. It has serious prognostic and quality of life implications for patients, as well as health service costs. Diagnosis requires confirmatory investigations and consideration of causative processes. First-line treatment involves education, lifestyle modification, symptom-controlling and disease-modifying medication. Further treatment may include additional medications, cardiac devices and surgery. End of life planning is part of the care pathway.

  2. [Antibacterial therapy in surgical treatment of chronic hepatic abscess].

    PubMed

    Kotenko, O G; Gusev, A V; Korshak, A A; Popov, A O; Grinenko, A V; Fedorov, D A; Grigorian, M S; Petrishche, I I

    2010-01-01

    The results of surgical treatment of 58 patients for chronic hepatic abscess were presented. In patients of the main group hepatic resection was performed and in a control one--sanation and drainage of the abscess cavity. Antibacterial therapy was conducted in patients of both groups before and after operative treatment. The peculiarities and common efficacy of antibacterial therapy depending on the operative treatment kind were noted.

  3. Current concepts in diagnosis and treatment of chronic lymphocytic leukemia

    PubMed Central

    Roliński, Jacek

    2015-01-01

    Chronic lymphocytic leukemia (CLL) is the most commonly diagnosed type of leukemia in Western Europe and North America, and represents about 30% of all leukemias in adults. Chronic lymphocytic leukemia is a disease of the elderly, who are often in poorer general health and burdened with multiple comorbidities. These factors affect the decision making when choosing an appropriate method of treatment. In recent years there has been significant progress in the treatment of chronic lymphocytic leukemia, first due to the introduction of immunochemotherapy with monoclonal antibodies and latterly small molecules, like tyrosine kinase inhibitors targeting B-cell receptor signaling. This article discusses the current diagnostic principles, the most important prognostic factors and therapeutic options, available in first-line treatment and in refractory/resistant disease, including high-risk CLL, both for patients with good and those with poor performance status. It also presents important novel molecules which have been evaluated in clinical trials. PMID:26793019

  4. Non-pharmacological treatment of chronic widespread musculoskeletal pain.

    PubMed

    Hassett, Afton L; Williams, David A

    2011-04-01

    Individuals with chronic widespread pain, including those with fibromyalgia, pose a particular challenge to treatment, given the modest effectiveness of pharmacological agents for this condition. The growing consensus indicates that the best approach to treatment involves the combination of pharmacological and non-pharmacological interventions. Several non-pharmacological interventions, particularly exercise and cognitive-behavioural therapy (CBT), have garnered good evidence of effectiveness as stand-alone, adjunctive treatments for patients with chronic pain. In this article, evidenced-based, non-pharmacological management techniques for chronic widespread pain are described by using two broad categories, exercise and CBT. The evidence for decreasing pain, improving functioning and changing secondary symptoms is highlighted. Lastly, the methods by which exercise and CBT can be combined for a multi-component approach, which is consistent with the current evidence-based guidelines of several American and European medical societies, are addressed.

  5. 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

  6. 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

  7. Chronic fatigue syndrome and the treatment process.

    PubMed

    Mechanic, D

    1993-01-01

    Fatigue is a common complaint in general practice and is often associated with psychiatric and psychosocial problems and demoralization. Although the Centers for Disease Control definition of chronic fatigue syndrome (CFS) excludes pre-existing psychiatric illness, common psychosocial problems short of a clinical disorder (such as irritability, difficulty in thinking, inability to concentrate, depression and sleep disturbance) overlap with the criteria for CFS. Psychological states can affect the course of CFS or become confused in the patient's and doctor's mind with the course of infection. The core dilemma in practice is how aggressively to pursue a possible basis for CFS when it persists in the absence of an identifiable external cause. Possibilities for exploration are numerous and potentially expensive. In practice, the persistence of doctors depends on the patient's illness behaviour, on financial and organizational factors, and on the culture of medical care and practice styles. It is essential to differentiate the appropriate management of CFS from scientific study where intensive investigation may be warranted. In practice doctors should proceed in a manner that conveys concern, supports function, and avoids dysfunctional illness behaviour and inadvertent legitimization and reinforcement of disability.

  8. Assessment and treatment of chronic hand mouthing.

    PubMed

    Roscoe, Eileen M; Iwata, Brian A; Zhou, Liming

    2013-01-01

    Hand mouthing (HM) is a chronic problem in many individuals with intellectual disabilities. Although the prevalence of mouthing has been estimated, data on the frequency, severity, or functions of the behavior were not included. In Study 1, we examined the prevalence and risk of HM. Results obtained from interviews showed that the prevalence of HM in two institutional samples (N = 802) was 12.7%, whereas direct observation yielded a lower estimate of prevalence (8%). Moreover, a large proportion of observed HM (39.1%) was self-injurious in nature. In Study 2, we used modified functional analyses (FAs) to examine the HM of 64 individuals. Results indicated that maintenance by automatic reinforcement accounted for 98.4% of the cases (all but one case). In Study 3, we implemented a progressive series of interventions for HM exhibited by 14 individuals. The following interventions were implemented in sequential order: (a) noncontingent reinforcement (NCR, effective with 6 subjects), (b) either NCR plus differential reinforcement of alternative behavior (DRA) plus response blocking (effective with 5 subjects) or NCR plus response blocking only (effective with 2 subjects), and (c) NCR plus brief manual restraint (effective with 1 subject). © Society for the Experimental Analysis of Behavior.

  9. [The treatment of chronic myeloleukemia with recombinant alfa-2 interferon].

    PubMed

    Strozha, I; Petukhov, V; Bondare, D; Feldmane, G; Duks, A; Teilane, I; Medne, I; Mauritsas, M; Grinberga, L

    1993-01-01

    A trial has been conducted of recombinant alpha 2-interferon (reaferon) used in 32 patients with Ph'[correction of Rh']-positive chronic myeloid leukemia (CML). A chronic stage was in 3, transient in 3 and blast in 1 patients. 25 CML patients were newly diagnosed. The treatment lasted from 2 months to 3 years. Clinicohematological remission was confirmed conventionally and by the degree of Ph'-positive clone reduction. An attempt is made to clarify the mechanism underlying the resistance to reaferon basing on the immunological data (detection of antireaferon neutralizing antibodies). The authors propose a combined treatment (myelosan plus reaferon) of CML which has obvious advantages over myelosan monotherapy.

  10. Easing Chronic Pain: Better Treatments and Medications

    MedlinePlus

    ... in chili peppers used in pain-relieving creams; nerve blocks with drugs or chemicals to interrupt relay of pain messages between the brain and other parts of the body; and enzymes injected into lumbar disks. Physical methods Common treatments include physical therapy, ...

  11. Anti-ICOS Monoclonal Antibody Treatment of Canine Chronic GVHD.

    PubMed

    Graves, Scott S; Parker, Maura H; Stone, Diane; Sale, George E; Pillai, Smitha P S; Johnson, Melissa M; Storb, Rainer

    2017-09-25

    In murine model systems, inducible costimulator (ICOS) signaling has been implicated in the formation of chronic graft-versus-host disease (GVHD). Previously, we showed that chronic GVHD can be reproducibly produced in the dog hematopoietic cell transplantation (HCT) model and that ICOS expression is upregulated on T cells in dogs with chronic GVHD. The goal of the present study was to determine whether administration of a short course of anti-canine ICOS monoclonal antibody (mAb) could alter the rapid and progressive course of chronic GVHD. Five dogs underwent HCT from dog leukocyte antigen mismatched unrelated donors following total body irradiation. Post-grafting immunosuppression consisted of methotrexate (days 1, 3, 6, and 11) and cyclosporine (days -1 through 78). Anti-ICOS mAb (3 injections, 72 hours apart) was administered upon diagnosis of GVHD. One dog failed to respond to anti-ICOS mAb therapy and succumbed to chronic GVHD in a time course similar to control untreated dogs. Overall, anti-ICOS-treated dogs experienced a significant prolongation in survival from the time of diagnosis of chronic GVHD compared to control dogs. Within the limitations of the number of study dogs, we suggest that a short course of anti-ICOS mAb may be useful in the treatment of chronic canine GVHD. Copyright © 2017. Published by Elsevier Inc.

  12. 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

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

    PubMed

    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.

  14. Innovations in chronic anal fissure treatment: A systematic review

    PubMed Central

    Poh, Aaron; Tan, Kok-Yang; Seow-Choen, Francis

    2010-01-01

    A chronic anal fissure is a common perianal condition. This review aims to evaluate both existing and new therapies in the treatment of chronic fissures. Pharmacological therapies such as glyceryl trinitrate (GTN), Diltiazem ointment and Botulinum toxin provide a relatively non-invasive option, but with higher recurrence rates. Lateral sphincterotomy remains the gold standard for treatment. Anal dilatation has no role in treatment. New therapies include perineal support devices, Gonyautoxin injection, fissurectomy, fissurotomy, sphincterolysis, and flap procedures. Further research is required comparing these new therapies with existing established therapies. This paper recommends initial pharmacological therapy with GTN or Diltiazem ointment with Botulinum toxin as a possible second line pharmacological therapy. Perineal support may offer a new dimension in improving healing rates. Lateral sphincterotomy should be offered if pharmacological therapy fails. New therapies are not suitable as first line treatments, though they can be considered if conventional treatment fails. PMID:21160880

  15. [Chronic kidney disease : What is currently available for treatment?

    PubMed

    Fleig, S; Patecki, M; Schmitt, R

    2016-12-01

    Chronic kidney disease is common in the general population with an estimated prevalence of roughly 2 million in Germany. Typically, chronic kidney disease is progressive and in the terminal stage the patients require dialysis or kidney transplantation. In many cases the disease remains silent for a long time but early stages are already associated with increasing morbidity and mortality. Therefore early detection is very important. In recent years several new concepts have been introduced that might help to slow the progression of chronic kidney disease or improve the accompanying risks. Here, we want to provide a nephrologist's perspective on the current guidelines for the treatment and prevention of chronic kidney disease. We summarize which diagnostic approaches are useful for general practitioners and we take a pragmatic look at the existing opportunities for combating renal functional decline. We also shed light on established measures to minimize the risk of comorbidities.

  16. 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

  17. Idelalisib for the Treatment of Chronic Lymphocytic Leukemia

    PubMed Central

    Khan, Maliha

    2014-01-01

    Chronic lymphocytic leukemia is the most common leukemia in the United States. It is a slowly progressive disease, with an 82% five-year survival rate. The treatment strategies are highly individualized with patients in the early and stable stages typically not requiring treatment. However, those with progressive or clinically advanced disease will require treatment. Cytotoxic drugs, such as the alkylating agents, purine nucleoside antagonists, and immunotherapeutic agents, have been the mainstay of chemotherapeutic treatment in CLL. However, given the lack of therapeutic specificity, these medications (especially older ones) have limited tolerability due to side effects. In this paper, we will discuss the data on the use of phosphatidylinositol 3 kinase inhibitor Idelalisib in the management of patients with chronic lymphocytic leukemia. The preclinical and clinical data thus far demonstrate that Idelalisib produces a dramatic and durable response in patients with chronic lymphocytic leukemia and without causing significant toxicity. Moving forward, the ongoing clinical trials will help address the various questions currently being raised regarding the long-term application and safety of Idelalisib. With greater clinical experience following more widespread use of Idelalisib, we will be able to determine the optimal combination therapies in treatment-naïve and relapsed/refractory patients, resulting in more individualized therapeutic strategies for patients with chronic lymphocytic leukemia. PMID:25093123

  18. [Treatment's initiation in chronic inflammatory demyelinating polyradiculopathy (CIDP)].

    PubMed

    Uzenot, D; Azulay, J-P; Pouget, J

    2007-09-01

    Treatment's initiation in chronic inflammatory demyelinating polyradiculopathy (CIDP) remains a difficult medical decision. Only plasma exchanges, intravenous immunoglobulins (IVIg) and corticosteroids are proven effective treatments. Immunosuppressors are actually not first-line treatments in CIDP. Particular CIDP forms are associated with different response to treatments: pure motor CIDP should be treated by IVIg, and corticosteroids should only carefully be used in Lewis-Sumner syndrome. Otherwise, IVIg are first-line treatment in diabetic patients. Patients must be informed of side's effects and expected clinical effects. Early treatment was actually not proved to prevent axonal damages in CIDP patients, and waiting seems to be the best therapeutic option in poorly symptomatic patients. Recently, clinical guidelines were proposed to help clinician in this treatment choice, but there is no consensus about the best dose, duration or administration way to CIDP treatments. Further studies should be performed to clarify these points and to determine immunosuppressor agents place in treatment strategy.

  19. Recent trends in the treatment of chronic hepatitis C.

    PubMed

    Jun, Dae Won; Tak, Won Young; Bae, Si Hyun; Lee, Youn Jae

    2012-03-01

    Pegylated interferon and ribavirin combination therapy is accepted as the standard antiviral treatment for chronic hepatitis C regardless of HCV genotype. This combination therapy achieves higher response rates than previous therapy, but, nevertheless, a large proportion of patients suffer from treatment failure or adverse events. Recent clinical studies of viral kinetics during antiviral treatment have led to the introduction of response-guided therapy, the concept of 'customized therapy depending on viral response', which focuses on modulation of the treatment period depending on the viral response to create a sustained viral response without unnecessary medication and costs. New upcoming direct-acting antivirals (DAAs) maximize response rate, and triple therapy including DAAs along with pegylated interferon and ribavirin combination therapy could soon be the standard therapy. In this article, we reviewed the factors affecting treatment, response guided treatment, retreatment after failure of standard treatment, management of adverse events during treatment, and new treatment options.

  20. Single- vs multiple-dose pharmacokinetics of clozapine in psychiatric patients.

    PubMed

    Choc, M G; Hsuan, F; Honigfeld, G; Robinson, W T; Ereshefsky, L; Crismon, M L; Saklad, S R; Hirschowitz, J; Wagner, R

    1990-04-01

    Clozapine plasma levels were monitored in 16 patients during a series of three consecutive treatments (single dose-multiple dose-single dose). Each patient received a single 75-mg dose (3 x 25 mg) with clozapine tablets, and serial plasma samples were collected over 48 hr after the dose. At 48 hr, a multiple-dose regimen was started, consisting of an initial dose escalation period followed by dosing at a constant regimen for at least 6 days. After the last dose, serial plasma samples were again obtained over 72 hr. Drug was then withheld for at least 7 days, a final single 75-mg dose was given, and plasma sampling was repeated. A subset of the patient population (N = 7) was used to test for a food effect during the single-dose treatments. The pharmacokinetic parameters between the initial and the final single dose periods were not significantly different. Similarly, there were no differences within patients when given the dose after fasting (fed 1 hr after dose) or with a meal. In contrast, the terminal elimination rate differed between the single-dose and the multiple-dose treatments (t1/2 m3 = 7.9 hr single dose and 14.2 hr multiple dose) (P less than 0.05) and the dose-normalized area under the plasma concentration/time curves increased 27% with multiple dosing. Since a previous study in patients (Choc et al., Pharm. Res. 4:402-405, 1987) showed dose proportionality of clozapine plasma concentrations during multiple-dose regimens, the present results cannot be described by Michaelis-Menten kinetics.

  1. Prescribing pattern of clozapine and other antipsychotics for patients with first-episode psychosis: a cross-sectional survey of early intervention teams

    PubMed Central

    Tungaraza, Tongeji E.; Ahmed, Wakil; Chira, Chinonyelum; Turner, Erin; Mayaki, Susan; Nandhra, Harpal Singh; Edwards, Tom; Farooq, Saeed

    2016-01-01

    Objective: To describe the pattern of antipsychotic drug prescribing in patients with first episode psychosis, with more emphasis in the use of clozapine in this group of patients. Method: A cross-sectional survey involving six early intervention service (EIS) teams in the West Midlands was conducted. Data was extracted from case notes and electronic records by clinicians working in each participating team. The pattern of antipsychotic prescribing and the changes that took place after being accepted in EIS, including the use of clozapine, was established. Clinicians involved in the treatment of patients in each team rated the overall clinical response to treatment based on the presence or absence of positive psychotic symptoms. Result: 431 patients with FEP were included in the final analysis. Low antipsychotic discontinuation rate was observed, with the majority (88.2%) still being prescribed antipsychotics. Most (77.3%) were prescribed second-generation antipsychotic drugs, with olanzapine (21.8%) and aripiprazole (19.7%) being the most frequently prescribed antipsychotics. There was low rate use of antipsychotic combinations (7.4%), high dose antipsychotic regime (3.9%), low depot antipsychotic prescribing (9.3%), and clozapine use was low (9.7%). On average, three antipsychotics were tried before clozapine was initiated and it took on average 19.5 months from being accepted into EIS to clozapine being initiated. Conclusion: The majority of patients were prescribed antipsychotics within the guidelines. EIS was associated with an overall low antipsychotic discontinuation. There was also a short waiting time before clozapine was initiated following patients being accepted into EIS. PMID:28348730

  2. Clozapine and quetiapine acutely reduce glucagon-like peptide-1 production and increase glucagon release in obese rats: implications for glucose metabolism and food choice behaviour.

    PubMed

    Smith, Greg C; Vickers, Mark H; Cognard, Emmanuelle; Shepherd, Peter R

    2009-11-01

    Second generation antipsychotic drug (SGA) treatment is associated with detrimental effects on glucose metabolism which is often attributed to the development of obesity and insulin resistance. However, we have recently demonstrated that clozapine and quetiapine also have direct effects of glucose metabolism in animals. This study compares clozapine and quetiapine and investigates the effects of these on the development of obesity and the direct effects of these drugs on glucose metabolism compared with those caused by the obesity per se. Three groups of male Sprague-Dawley rats were fed a high fat/high sugar diet to induce obesity while another three groups were fed a chow diet. One group on each diet was injected daily with vehicle, clozapine or quetiapine and effects on glucose metabolism were monitored. Clozapine and quetiapine treatment did not directly cause obesity or potentiate diet induced obesity but did induce a preference for the high fat/high sugar diet. Neither drug caused a impairment in insulin tolerance over that caused by obesity but both drugs acutely induced impairments in glucose tolerance that were additive with the effects induced by the diet induced obesity. Both drugs caused increases in glucagon levels and a suppression of GLP-1. We investigated two strategies for restoring GLP-1 signalling. The DPP-IV inhibitor sitagliptin only partially restored GLP-1 levels and did not overcome the deleterious effects on glucose tolerance whereas the GLP-1 receptor agonist exendin-4 normalised both glucagon levels and glucose metabolism. Our findings indicate that the clozapine and quetiapine induced impairments in glucose tolerance in rats are independent of insulin resistance caused by obesity and that these defects are linked with a suppression of GLP-1 levels. These studies suggest the need to perform follow up studies in humans to determine whether clozapine and quetiapine induce acute derangements in glucose metabolism and whether GLP-1

  3. [Principles of diagnostics and treatment of chronic appendicitis].

    PubMed

    Sazhin, A V; Mosin, S V; Kodzhoglian, A A; Mirzoian, A T; Laĭpanov, B K; Iuldoshev, A R

    2011-01-01

    Treatment results of 101 patients, operated on with the diagnosis of the chronic appendicitis, were analyzed. Of them, 55 had periodic right iliac pain syndrome, the rest 46 had a history of appendicular abscess or infiltrate. 58 patients were operated on laparoscopically, the rest had traditional open appendectomy. The use of ultrasound and roentgen diagnostics proved to be non-effective. The reliable laparoscopic symptoms of chronic appendicitis were singled out. The laparoscopy provided the correct diagnosis in 93.3% of patients and allowed avoiding the groundless appendectomy in 31.2%. The intraoperative ultrasound is helpful in questionable cases. The diagnostic and treatment algorithm for chronic appendicitis, based on laparoscopic methods, was worked out.

  4. Gabapentin and pregabalin for the treatment of chronic pruritus.

    PubMed

    Matsuda, Kazuki M; Sharma, Divya; Schonfeld, Ariel R; Kwatra, Shawn G

    2016-09-01

    Chronic pruritus is a distressing symptom that is often refractory to treatment. Patients frequently fail topical therapies and oral over-the-counter antihistamines, prompting the clinician to consider alternative therapies such as neuroactive agents. Herein, the use of gabapentin and pregabalin, 2 medications well known for treating neuropathic pain and epilepsy that are occasionally used for relieving chronic pruritus is explored. The findings from original sources published to date to evaluate the use of gabapentin and pregabalin as antipruritic agents are explored. They are found to be promising alternative treatments for the relief of several forms of chronic pruritus, particularly uremic pruritus and neuropathic or neurogenic itch, in patients who fail conservative therapies.

  5. Effects of clozapine, olanzapine and haloperidol on nitric oxide production by lipopolysaccharide-activated N9 cells.

    PubMed

    Hou, Yue; Wu, Chun Fu; Yang, Jing Yu; He, Xiang; Bi, Xiu Li; Yu, Liang; Guo, Tao

    2006-12-30

    Schizophrenia is a devastating illness of unknown etiology and the basis for its treatment rests in the symptomatic response to antipsychotics. It was found that some of the patients with schizophrenia elicited microglia activation. The present study used lipopolysaccharide (LPS)-activated mouse microglial cell line N9 as an in vitro model to mimic microglia activation seen in the patients with schizophrenia. The effects of clozapine, olanzapine and haloperidol on the release of nitric oxide (NO) by LPS-stimulated N9 cells were investigated. The results showed that olanzapine significantly inhibited NO release by LPS-stimulated N9 cells. Clozapine and haloperidol did not show significant effects on this model. The present study suggested that the inhibiting effect of olanzapine on the NO release by LPS-stimulated microglial cells might be a new mechanism through which olanzapine exhibits its therapeutic effect in the treatment of schizophrenia.

  6. A placebo-controlled pilot study of the ampakine CX516 added to clozapine in schizophrenia.

    PubMed

    Goff, D C; Leahy, L; Berman, I; Posever, T; Herz, L; Leon, A C; Johnson, S A; Lynch, G

    2001-10-01

    CX516, a positive modulator of the glutamatergic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor, improves performance in tasks requiring learning and memory in animals. CX516 was added to clozapine in 4-week, placebo-controlled, dose-finding (N = 6) and fixed-dose (N = 13) trials. CX516 was tolerated well and was associated with moderate to large, between-group effect sizes compared with placebo, representing improvement in measures of attention and memory. These preliminary results suggest that CX516 and other "ampakines" hold promise for the treatment of schizophrenia.

  7. Nutritional support treatment for severe chronic hepatitis and posthepatitic cirrhosis.

    PubMed

    Qin, Huimin; Li, Hongtao; Xing, Mingyou; Wu, Chunming; Li, Guojun; Song, Jianxin

    2006-01-01

    The therapeutic effectiveness of nutritional support in the treatment of severe chronic hepatitis and posthepatitic cirrhosis was evaluated. 143 patients with severe chronic hepatitis and 83 with posthepatitic cirrhosis were evaluated with SGA for assessing the nutritional status before the treatment. Patients with severe chronic hepatitis were divided into three groups: group A subject to enteral nutrition (EN) and parenteral nutrition (PN), group B subject to comprehensive treatment (CT)+PN; group C subject to CT+EN. The patients with posthepatitic cirrhosis were divided into two groups: group D receiving CT and group E receiving CT+PN+EN. The function of liver and kidney and nutritional status were monitored to assess the therapy in 6 weeks. The results showed before treatment, over 90 % patients had moderate to severe malnutrition. After nutritional support, the liver function (ALT, T-bil) and nutritional status (TP, TC) in group A was improved significantly as compared with that in groups B and C (P<0.05). Compared with group D, the values of TP and Alb were increased significantly in group E (P<0.05), but the levels of ALT, AST and T-bil had no obvious change. It was suggested that most patients with severe chronic hepatitis or posthepatitic cirrhosis had malnutrition to varying degrees. The nutritional support treatment could obviously improve the nutritional status of these patients, and was helpful to ameliorate the liver function of the patients with severe chronic hepatitis. Among the methods of nutritional support treatment, PN combined with EN had the best effectiveness.

  8. 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.

  9. Clozapine-associated cardiac dysfunction during a gastroenteritis outbreak

    PubMed Central

    Szema, Anthony M.; Marboe, Charles; Fritz, Paul; Nguyen, Tram N.B.

    2016-01-01

    We report that two young adult patients who were initiated with clozapine for severe psychosis during a hospital-wide gastroenteritis outbreak went into severe shock. Neither patient had troponin elevation. Each required left ventricular assist device support for myocarditis. Endomyocardial biopsy revealed lymphocytic myocarditis in one patient and eosinophilic myocarditis in the other. The former patient expired. Polymerase chain reaction testing was negative for Coxsackie virus. These two patients illustrate that myocarditis can occur at usual incipient doses and that there may be an epidemiologic risk associated with gastroenteritis. Although the white blood cell (WBC) count is expected to decrease with clozapine, these patients had persistently elevated WBC counts. In conclusion, physicians should exercise caution when prescribing clozapine, especially for those with diarrhea. PMID:27987278

  10. Chronic amantadine treatment enhances the sexual behaviour of male rats.

    PubMed

    Ferraz, Marcia Martins Dias; Fontanella, Julia Cordeiro; Damasceno, Fabio; Silva de Almeida, Olga Maria Martins; Ferraz, Marcos Rochedo

    2007-04-01

    The acute administration of amantadine (AMA), a dopaminomimetic and NMDA glutamatergic receptor antagonist also used as an anti-Parkinsonian agent, stimulates male rat sexual behaviour. However it remains unclear whether long term AMA supplementation might also provoke a similar increase in male rat sexual conduct. In the present study, male rats were administered AMA (5-50 mg/kg/day) or vehicle daily for 21 days and their sexual response was monitored weekly. Chronic treatment with AMA effectively increased the sexual response of male rats, similarly to what had been observed before with acute amantadine treatment. The main effect of chronic AMA treatment occurs in arousal and in ejaculatory response, whilst the excitatory component was not affected. The 21-day treatment with AMA did not lead to tolerance, suggesting that perhaps AMA could be used in male human patients to prevent sexual inhibition caused by anti-depressant and anti-psychotic agents.

  11. Alitretinoin for the treatment of severe chronic hand eczema

    PubMed Central

    King, Thomas; McKenna, John; Alexandroff, Anton B

    2014-01-01

    Chronic hand eczema is a common and often debilitating condition. Alitretinoin, a 9-cis-retinoic acid and pan-retinoic acid agonist, is a new and effective systemic treatment for chronic hand eczema, which provides another treatment option. A “clear” or “almost clear” response can be achieved in up to half of patients within a 24-week course of treatment. Even higher rates of remission can be obtained with a longer duration of treatment. Alitretinoin has a favorable overall profile of adverse effects; however, female patients who are at risk of becoming pregnant should follow a strict pregnancy-prevention program due to the teratogenic effects of this drug. PMID:25525339

  12. In-vivo administration of clozapine affects behaviour but does not reverse dendritic spine deficits in the 14-3-3ζ KO mouse model of schizophrenia-like disorders.

    PubMed

    Jaehne, Emily J; Ramshaw, Hayley; Xu, Xiangjun; Saleh, Eiman; Clark, Scott R; Schubert, Klaus Oliver; Lopez, Angel; Schwarz, Quenten; Baune, Bernhard T

    2015-11-01

    Clozapine is an atypical antipsychotic drug used in the treatment of schizophrenia, which has been shown to reverse behavioural and dendritic spine deficits in mice. It has recently been shown that deficiency of 14-3-3ζ has an association with schizophrenia, and that a mouse model lacking this protein displays several schizophrenia-like behavioural deficits. To test the effect of clozapine in this mouse model, 14-3-3ζ KO mice were administered clozapine (5mg/kg) for two weeks prior to being analysed in a test battery of cognition, anxiety, and despair (depression-like) behaviours. Following behavioural testing brain samples were collected for analysis of specific anatomical defects and dendritic spine formation. We found that clozapine reduced despair behaviour of 14-3-3ζ KO mice in the forced swim test (FST) and altered the behaviour of wild types and 14-3-3ζ KO mice in the Y-maze task. In contrast, clozapine had no effects on hippocampal laminar defects or decreased dendritic spine density observed in 14-3-3ζ KO mice. Our results suggest that clozapine may have beneficial effects on clinical behaviours associated with deficiencies in the 14-3-3ζ molecular pathway, despite having no effects on morphological defects. These findings may provide mechanistic insight to the action of this drug.

  13. Treatment of Chronic Anger Through Cognitive and Relaxation Controls

    ERIC Educational Resources Information Center

    Novaco, Raymond W.

    1976-01-01

    The study examined the extent to which cognitive self-control processes and relaxation techniques could be therapeutically applied to chronic anger problems. The cognitive treatment was implemented by self-instruction procedures. The cognitive coping procedures involved the use of self-statements for the management of anger and cognitive…

  14. [Gentos in the treatment of chronic abacterial prostatitis].

    PubMed

    Loran, O B; Pushkar', D Iu; Tedeev, V V; Nosovitskiĭ, P B

    2003-01-01

    Gentos was given to 46 patients with chronic abacterial prostatitis. The results of the treatment were analysed for 39 of them. Compared to control group, efficacy of gentos was 64.5-71.8% versus 53.6%. It can be used both as monotherapy and in combination with other modalities. Side effects of gentos were not registered.

  15. Treatment of Chronic Anger Through Cognitive and Relaxation Controls

    ERIC Educational Resources Information Center

    Novaco, Raymond W.

    1976-01-01

    The study examined the extent to which cognitive self-control processes and relaxation techniques could be therapeutically applied to chronic anger problems. The cognitive treatment was implemented by self-instruction procedures. The cognitive coping procedures involved the use of self-statements for the management of anger and cognitive…

  16. Entecavir: a new treatment option for chronic hepatitis B.

    PubMed

    Zoulim, Fabien

    2006-05-01

    Because of the slow kinetics of viral clearance and the spontaneous genetic variability of hepatitis B virus (HBV), antiviral therapy of chronic hepatitis B remains a clinical challenge. Despite the recent development of lamivudine, adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic HBV infection, there is still a major need for new antiviral compounds. Entecavir, a guanosine analog, has been recently approved in US for the therapy of chronic hepatitis B and its registration is expected soon in Europe. Extensive studies have been performed to characterize its antiviral activity in enzymatic and tissue culture models, as well as in animal models of HBV infection. In clinical trails, entecavir administration was associated with a significantly more potent viral suppression compared to lamivudine, and a significant advantage in terms of biochemical and histological improvement compared to lamivudine. Entecavir was tolerated as well as lamivudine in these phase III trials. No case of resistance was detected after two years of therapy in nucleoside naive patients. Treatment of patients with lamivudine failure requires a higher dosage of entecavir and induces a significant decline in viraemia levels. However, 10% of these patients developed entecavir resistance after two years of therapy. The availability of entecavir as a new treatment option is providing clinicians more choice to keep both viral replication and liver disease under control. This provides new hope for improved treatment concepts for chronic HBV infection.

  17. Long term treatment of chronic Lyme arthritis with benzathine penicillin.

    PubMed Central

    Cimmino, M A; Accardo, S

    1992-01-01

    The cases are reported of two patients with chronic Lyme arthritis resistant to the recommended antibiotic regimens who were cured by long term treatment with benzathine penicillin. It is suggested that the sustained therapeutic levels of penicillin were effective either by the inhibition of germ replication or by lysis of the spirochaetes when they were leaving their sanctuaries. PMID:1417107

  18. [Halotherapy in the combined treatment of chronic bronchitis patients].

    PubMed

    Maev, E Z; Vinogradov, N V

    1999-06-01

    Halotherapy proved to be a highly effective method in a complex sanatorium treatment of patients with chronic bronchitis. Its use promotes more rapid liquidation of clinical manifestations of disease, improves indices of vent function of lungs, especially those values that characterize bronchial conduction (volume of forced exhalations per second, index Tiffno), increases tolerance to physical load, normalizes indices of reduced immunity and leads to increasing the effectiveness of patient treatment in sanatorium.

  19. Clozapine and anemia: a 2-year follow-up study.

    PubMed

    Lee, Jimmy; Bies, Robert; Bhaloo, Amaal; Powell, Valerie; Remington, Gary

    2015-12-01

    Clozapine's association with agranulocytosis led to the implementation of stringent and mandatory hematologic monitoring guidelines in most countries. Although other hematologic aberrations such as eosinophilia and neutropenia have been previously described, clozapine's impact on the erythroid lineage has not been studied. There is a suspicion that a higher rate of anemia is observed in patients receiving clozapine; therefore, we hypothesized that there would be a higher rate of anemia in patients receiving clozapine therapy. All individuals initiated on clozapine at our center from 2009 to 2010 were recruited. Information on age, gender, medical comorbidities, and smoking status was extracted from the medical records. Data from complete blood counts over a 2-year follow-up period were extracted, with anemia defined as a hemoglobin value below 120 g/L for women and 130 g/L for men. Time to anemia event was calculated and Cox regression was employed to identify predictors of anemia. We found a high incidence of anemia in the first 2 years following clozapine initiation; of the 94 individuals (68 men, 26 women) recruited, 23 (24.5%) developed anemia. Higher baseline hemoglobin level (hazard ratio [HR] = 0.86, P = .002) and smoking status (HR = 0.21, P = .021) were identified as significant protective factors against anemia in men but not in women (HR = 0.92, P = .184, and HR = 0.52, P = .467 for baseline hemoglobin and smoking, respectively). Although smoking appears to lower the risk of anemia, we believe this is due to smoking's up-regulation of hemoglobin levels. Further studies are warranted in light of the present findings; for example, we cannot exclude the possibility that anemia was an epiphenomenon, characterizing instead a population with severe mental illness. © Copyright 2015 Physicians Postgraduate Press, Inc.

  20. 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.

  1. Hematological clozapine monitoring with a point-of-care device: a randomized cross-over trial.

    PubMed

    Nielsen, Jimmi; Thode, Dorrit; Stenager, Elsebeth; Andersen, Kristian Øllegaard; Sondrup, Ulla; Hansen, Tine N; Munk, Anne Marie; Lykkegaard, Signe; Gosvig, Annette; Petrov, Igor; le Quach, Phuong

    2012-06-01

    Clozapine remains the drug of choice for patients with treatment-resistant schizophrenia, who show a response rate of about 50% despite their unresponsiveness to other antipsychotics. Although treatment with clozapine can lead to considerable savings on bed days, the drug is underutilized for several reasons, perhaps most importantly because of the mandatory hematological monitoring. The Chempaq Express Blood Counter (Chempaq XBC) is a point-of-care device providing counts of white blood cells (WBC) and granulocytes based on a capillary blood sampling. A randomized cross-over trial design was used comparing capillary blood sampling using a point-of-care device with traditional venous blood sampling. Patients were randomized to two sequences starting with either capillary or venous blood sampling followed by a repeated sequence. Primary outcome was measured on a 10-cm visual analog scale. Eighty-five patients were included in the test. Eight (9.4%) dropped out before completion. Patients indicated that they found capillary blood monitoring less painful than venous sampling (VAS ratings: 0.55 cm 25-75 percentiles: 0.1-1.4 cm vs. 1.75 cm 25-75 percentiles: 0.7-2.6, p<0.001). They also felt less inconvenienced by the point-of-care method than the traditional blood sampling, which involved traveling to the laboratory clinical (0.3 cm 25-75 percentiles: 0.05-0.7 vs. 2.3 cm 25-75 percentiles: 0.75-4.5, p<0.001). For hematological monitoring of clozapine patients a point-of-care device based on capillary blood sampling is better tolerated than traditional venous blood sampling.

  2. 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.

  3. Combined approach in the treatment of chronic anal fissures.

    PubMed

    Vershenya, S; Klotz, J; Joos, A; Bussen, D; Herold, A

    2015-03-01

    This study was designed to evaluate the healing and complications rates in surgically and conservatively treated patients with chronic anal fissure. Conservative treatment consisted of nitrate or diltiazem ointment. In case of surgery, fissurectomy was performed. In total, 340 patients were included in the study. Among them, 162 patients had surgery and 178 patients had conservative treatment. The healing rate at surgically treated group of patients varied between 95 and 98% depending on previous treatment. Group treated with nitrate ointment and group treated with diltiazem ointment showed, respectively 62% and 52% healing rates. Difference between ointments was not statistically significant. Average healing time was between 105 and 123 days and complication rates were between 1.7 and 5.4%. The surgical treatment showed much higher healing rates and thus should recommended as primary treatment option for the chronic anal fissure, especially if there are chronic secondary lesions already present. In case of conservative treatment, either nitrate or diltiazem ointment could be used with similar efficacy.

  4. Prescribing clozapine and rifampicin: clinical impact of their interaction

    PubMed Central

    Parker, Caroline

    2016-01-01

    The predictable pharmacokinetic drug interaction between clozapine and rifampicin is listed in most standard reference texts but little detail is given or emphasis on its clinical significance. The interaction is based on theoretical knowledge of both drugs; to date just two case reports have been published. This article describes a third case demonstrating the significance of this interaction. This was potentially devastating for the patient who required an extended psychiatric admission. The enzyme induction was so potent that the dose of clozapine had to be increased approximately sixfold. Careful management of this significant interaction is essential for effective patient care. PMID:27280037

  5. 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.

  6. Predicting work status following interdisciplinary treatment for chronic pain.

    PubMed

    Vowles, Kevin E; Gross, Richard T; Sorrell, John T

    2004-08-01

    The effectiveness of interdisciplinary treatments for chronic pain is well established. In general, these treatments decrease psychosocial distress and increase physical abilities. Further, return to work rates following interdisciplinary treatment tend to be quite high. Previous studies have highlighted a number of factors that individually influence return to work rates; however, there is a need for more comprehensive and unified models that allow an evaluation of the inter-relations among these factors. The present investigation examined how demographic and treatment outcome variables interacted to influence post-treatment return to work rates in a sample of individuals with chronic pain following interdisciplinary treatment. Results indicated that patient age, lifting ability, pain duration, depression level, and reported disability were individually related to return to work; however, when these variables were evaluated relative to one another, level of depression and patient age had the best ability to predict post-treatment work status. These results add to the literature by specifically highlighting post-treatment factors that best discriminate patients who had returned to work from those that had not. Furthermore, they provide evidence that general emotional distress is perhaps the most important predictor of work status following treatment.

  7. [Non-sedative antihistaminics in the treatment of chronic urticaria].

    PubMed

    Negro, J M; Sarrió, F; Miralles, J C; García Sellés, F J; López Sánchez, J D; Pagán, J a; Hernándéz, J

    1995-01-01

    Antihistamines are the drugs of choice in the symptomatic relief of chronic idiopathic urticaria; however, the usefulness of classic antihistamines has been limited by side effects. In the 1980s a new class of antihistamines has been developed that maintains effectiveness and produces less side effects (eg anticholinergic side effects, daytime sedation, etc). This review analyzes each of the new nonsedating antihistamines commercially available in Spain (astemizole, ebastine, cetirizine, loratadine and terfenadine) and evaluates its clinical efficacy and safety in the treatment of chronic idiopathic urticaria.

  8. Chronic migraine: current pathophysiologic concepts as targets for treatment.

    PubMed

    Vargas, Bert B

    2009-02-01

    Chronic daily headache (CDH) affects approximately 4% of the population and exerts a significant degree of disability on its sufferers. Chronic migraine (CM) is a subset of CDH that represents migraine without aura occurring on 15 or more days per month for at least 3 months. Although numerous risk factors are associated with the development of CM, the pathophysiology governing its genesis is largely unknown. The role of neurotransmitters, such as glutamate, as well as disruptions of antinociceptive systems and structures, are implicated in CM and are supported by the fact that treatments targeting these abnormalities are effective.

  9. Effective Treatment of Chronic Radiation Proctitis Using Radiofrequency Ablation

    PubMed Central

    Zhou, Chao; Adler, Desmond C.; Becker, Laren; Chen, Yu; Tsai, Tsung-Han; Figueiredo, Marisa; Schmitt, Joseph M.; Fujimoto, James G.

    2009-01-01

    Endoscopic argon plasma coagulation and bipolar electrocautery are currently preferred treatments for chronic radiation proctitis, but ulcerations and strictures frequently occur. Radiofrequency ablation (RFA) has been successful for mucosal ablation in the esophagus. Here we report the efficacy of RFA with the BarRx Halo90 system in three patients with bleeding from chronic radiation proctitis. In all cases, the procedure was well tolerated and hemostasis was achieved after 1 or 2 RFA sessions. Re-epithelialization of squamous mucosa was observed over areas of prior hemorrhage. No stricturing or ulceration was seen on follow-up up to 19 months after RFA treatment. Real-time endoscopic optical coherence tomography (EOCT) visualized epithelialization and subsurface tissue microvasculature pre- and post-treatment, demonstrating its potential for follow-up assessment of endoscopic therapies. PMID:20593010

  10. Treatment preferences of psychotherapy patients with chronic PTSD.

    PubMed

    Markowitz, John C; Meehan, Kevin B; Petkova, Eva; Zhao, Yihong; Van Meter, Page E; Neria, Yuval; Pessin, Hayley; Nazia, Yasmin

    2016-03-01

    Patient treatment preference may moderate treatment effect in major depressive disorder (MDD) studies. Little research has addressed preference in posttraumatic stress disorder (PTSD); almost none has assessed actual patients' PTSD psychotherapy preferences. From a 14-week trial of chronic PTSD comparing prolonged exposure, relaxation therapy, and interpersonal psychotherapy, we report treatment preferences of the 110 randomized patients, explore preference correlates, and assess effects on treatment outcome. Patients recruited between 2008 and 2013 with chronic DSM-IV PTSD (Clinician-Administered PTSD Scale [CAPS] score ≥ 50) received balanced, scripted psychotherapy descriptions prerandomization and indicated their preferences. Analyses assessed relationships of treatment attitudes to demographic and clinical factors. We hypothesized that patients randomized to preferred treatments would have better outcomes, and to unwanted treatment worse outcomes. Eighty-seven patients (79%) voiced treatment preferences or disinclinations: 29 (26%) preferred prolonged exposure, 29 (26%) preferred relaxation therapy, and 56 (50%) preferred interpersonal psychotherapy (Cochran Q = 18.46, P < .001), whereas 29 (26%) were disinclined to prolonged exposure, 18 (16%) to relaxation therapy, and 3 (3%) to interpersonal psychotherapy (Cochran Q = 22.71, P < .001). Several baseline clinical variables correlated with treatment preferences. Overall, treatment preference/disinclination did not predict change in CAPS score, treatment response, or dropout. Comorbidly depressed patients receiving unwanted treatment had worse final CAPS scores. These exploratory findings are the first relating patients' PTSD psychotherapy preferences to outcome. Despite explanations emphasizing prolonged exposure's greater empirical support, patients significantly preferred interpersonal psychotherapy. Preference subtly affected psychotherapy outcome; depression appeared an important moderator of the effect

  11. Double-Blind, Randomized, Placebo-Controlled Trial of Metoclopramide for Hypersalivation Associated With Clozapine.

    PubMed

    Kreinin, Anatoly; Miodownik, Chanoch; Mirkin, Vitaly; Gaiduk, Yulia; Yankovsky, Yan; Bersudsky, Yuly; Lerner, Paul P; Bergman, Joseph; Lerner, Vladimir

    2016-06-01

    Hypersalivation is a frequent, disturbing, and uncomfortable adverse effect of clozapine therapy that frequently leads to noncompliance. The aim of this study was to examine the efficacy of metoclopramide (dopamine D2 antagonist, antiemetic medication) as an option for management of hypersalivation associated with clozapine (HAC). A 3-week, double-blind, placebo-controlled trial was conducted in university-based research clinics from January 2012 to May 2014, on 58 inpatients treated with clozapine who were experiencing hypersalivation. The subjects were randomly divided into placebo and metoclopramide groups. The starting dose was 10 mg/d. Participants who did not respond were up-titrated 10 mg/d weekly to a total of 30 mg/d during the third week. The number of placebo capsules was increased accordingly up to 3 capsules per day. Primary outcome was the change from baseline to the end of study in the severity of hypersalivation as measured with the Nocturnal Hypersalivation Rating Scale and the Drooling Severity Scale. Secondary outcomes included Clinical Global Impression of Improvement scale and adverse effect scales. Significant improvement on the Nocturnal Hypersalivation Rating Scale was demonstrated in the metoclopramide group from the end of the second week (P < 0.004), and on the Drooling Severity Scale (P < 0.02) in the third week. Clinical Global Impression-Improvement scale scores revealed major improvement. Twenty subjects (66.7%) treated with metoclopramide reported significant decline or total disappearance of HAC in comparison to 8 patients (28.6%) who received placebo (P = 0.031). No adverse effects to metoclopramide were reported. Metoclopramide was found to be safe and effective for the treatment of HAC.

  12. 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.

  13. 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

  14. Adult chronic sleepwalking and its treatment based on polysomnography.

    PubMed

    Guilleminault, Christian; Kirisoglu, Ceyda; Bao, Gang; Arias, Viola; Chan, Allison; Li, Kasey K

    2005-05-01

    Adult sleepwalking affects 2.5% of the general population and may lead to serious injuries. Fifty young adults with chronic sleepwalking were studied prospectively. Clinical evaluation, questionnaires from patients and bed partners, and polysomnography were obtained on all subjects in comparison with 50 age-matched controls. Subjects were examined for the presence of psychiatric anxiety, depression and any other associated sleep disorder. Isolated sleepwalking or sleepwalking with psychiatric disorders was treated with medication. All other patients with other sleep disorders were treated only for their associated problem. Prospective follow-up lasted 12 months after establishment of the most appropriate treatment. Patients with only sleepwalking, treated with benzodiazepines, dropped out of follow-up testing and reported persistence of sleepwalking, as did patients with psychiatric-related treatment. Chronic sleepwalkers frequently presented with sleep-disordered breathing (SDB). All these patients were treated only for their SDB, using nasal continuous positive airway pressure (CPAP). All nasal CPAP-compliant patients had control of sleepwalking at all stages of follow-up. Non-compliant nasal CPAP patients had persistence of sleepwalking. They were offered surgical treatment for SDB. Those successfully treated with surgery also had complete resolution of sleepwalking. Successful treatment of SDB, which is frequently associated with chronic sleepwalking, controlled the syndrome in young adults.

  15. 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.

  16. Chronic hepatitis B therapy: available drugs and treatment guidelines.

    PubMed

    Caviglia, G P; Abate, M L; Pellicano, R; Smedile, A

    2015-06-01

    There are currently several drugs approved for the treatment of chronic hepatitis B including recombinant interferons, such as interferon-α and its pegylated formulation, and the nucleos(t)ide analogues, such as lamivudine, adefovir, telbivudine, entecavir and tenofovir. Pegylated-interferon is an immune-modulatory agent that works mainly by enhancing the innate immune response while nucleos(t)ide analogues are oral drugs with direct inhibition of viral replication. Each agent has its own advantages and drawbacks. Pegylated-Interferon treatment has a finite duration without induction of drug resistance but only a limited number of patients achieve a sustained virological response to therapy. On the other hand, the care with nucleos(t)ide analogues requires a long-term treatment with a potential risk of induction of drug resistance, but higher rates of viral replication suppression are achieved. Nevertheless, second generation nucleos(t)ide analogues, such as Entecavir and Tenofovir, have both high genetic barrier to resistance and potent antiviral action. This review describes the mechanisms of antiviral activity and the efficacy of viral suppression of the different available drugs for chronic hepatitis B treatment, considering the recent clinical guidelines for an optimal management of chronic HBV infection.

  17. Response to acupuncture treatment in horses with chronic laminitis.

    PubMed

    Faramarzi, Babak; Lee, Dongbin; May, Kevin; Dong, Fanglong

    2017-08-01

    There is a need for evidence-based scientific research to address the question of the effectiveness of acupuncture in improving clinical signs of laminitis in horses. The objective of this study was to compare lameness levels before and after 2 acupuncture treatments in horses with chronic laminitis. Twelve adult horses with chronic laminitis received 2 acupuncture treatments 1 week apart. The points were treated using dry needling, hemo-acupuncture, and aqua-acupuncture. Lameness level was objectively evaluated using an inertial sensor-based lameness evaluation system (Lameness Locator), as well as routine examinations following American Association of Equine Practitioners scoring before the first and 1 week after the second acupuncture treatment. Data were analyzed using Wilcoxon signed-rank test and P-values < 0.05 were considered statistically significant. Both the Lameness Locator (P = 0.0269) and routine lameness examination (P = 0.0039) showed a significant reduction in lameness severity. Our results support using acupuncture, along with other treatment options, in treating chronic equine laminitis.

  18. Sulodexide in the treatment of chronic venous disease.

    PubMed

    Andreozzi, Giuseppe Maria

    2012-04-01

    Chronic venous disease encompasses a range of venous disorders, including those involving the lower limbs resulting from venous hypertension. The spectrum of chronic venous disease signs and symptoms shows variable severity, ranging from mild (aching, pain, and varicose veins) to severe (venous ulcers). The pathophysiology of chronic venous disease is characterized by venous hypertension, which triggers endothelial dysfunction and inflammation leading to microcirculatory and tissue damage, and eventually to varicose veins and venous ulcers. Sulodexide is an orally active mixture of glycosaminoglycan (GAG) polysaccharides with established antithrombotic and profibrinolytic activity. The agent is used in the treatment of a number of vascular disorders with increased risk of thrombosis, including intermittent claudication, peripheral arterial occlusive disease and post-myocardial infarction. Sulodexide differs from heparin because it is orally bioavailable and has a longer half-life and a smaller effect on systemic clotting and bleeding. An increasing body of preclinical evidence shows that sulodexide also exerts anti-inflammatory, endothelial-protective, and pleiotropic effects, supporting its potential efficacy in the treatment of chronic venous disease. Clinical studies of sulodexide have shown that the agent is associated with significant improvements in the clinical signs and symptoms of venous ulcers, and is therefore a recommended therapy in combination with local wound care and bandages for patients with persistent venous leg ulcers. Preliminary evidence supports the use of sulodexide in the prevention of recurrent deep venous thrombosis. Sulodexide was generally safe and well tolerated in clinical trials, without hemorrhagic complications. Sulodexide therefore appears to be a favorable option for the treatment of all stages of chronic venous disease and for the prevention of disease progression.

  19. Evaluation and treatment of gout as a chronic disease.

    PubMed

    Perez-Ruiz, Fernando; Herrero-Beites, Ana Maria

    2012-11-01

    Gout is a disease caused by deposition of monosodium urate crystals in tissues. One of the limitations for successful treatment of gout is to consider it as an intermittent disease rather than a chronic inflammatory disease which, if improperly treated, leads to chronic clinical manifestations. In addition, gout is linked to increased cardiovascular morbidity and mortality.Urate-lowering therapy comprises both nonpharmacologic and pharmacologic interventions, but most patients will need urate-lowering drugs to achieve target therapeutic serum urate levels. Reaching target serum urate levels is associated with improvement in clinical outcomes, including a reduction of acute inflammation episodes, resolution of tophi, and improvement in health-related quality of life perception.A number of urate-lowering drugs are available but a number of patients fail to achieve or maintain therapeutic serum urate levels and go on to develop refractory chronic gout. For such patients, efforts have been made to develop new treatments (e.g., febuxostat or pegloticase).This review intends to increase the awareness of gout as a chronic deposition disease, and show that efforts should be made to properly control serum urate levels in order to achieve complete disappearance of urate crystal deposition.

  20. 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.

  1. Chronic pain: the burden of disease and treatment innovations.

    PubMed

    Monti, S; Caporali, R

    2015-10-23

    Musculoskeletal conditions are the most frequent cause of chronic pain and affect around 1 in 5 adults in Europe. When chronic pain occurs, it becomes disease itself, with substantial clinical, social and economic impact. Efficacy and tolerability problems are encountered with all therapeutic strategies available to treat musculoskeletal pain. This often limits effective analgesia and patients' long term compliance, with the result that chronic pain is persistently underestimated and undertreated. Tapentadol is a novel, centrally acting analgesic that has been recently commercialized for the treatment of chronic pain. This new molecule, by combining two distinct mechanisms of action, μ-opioid receptor agonism (MOR) and noradrenaline reuptake inhibition (NRI), introduces a new pharmacological class called MOR-NRI. Several studies demonstrated promising results in the management of both nociceptive and neuropathic pain and good tolerability profile, particularly concerning side effects, compared to traditional opioids. This novel analgesic represents a possible therapeutic option also in the rheumatologic field, particularly in the treatment of osteoarthritis and low back pain.

  2. Treatment of refractory chronic cluster headache by chronic occipital nerve stimulation.

    PubMed

    Fontaine, Denys; Christophe Sol, Jean; Raoul, Sylvie; Fabre, Nelly; Geraud, Gilles; Magne, Christine; Sakarovitch, Charlotte; Lanteri-Minet, Michel

    2011-07-01

    Greater occipital nerve stimulation (ONS) has been recently proposed to treat severe chronic cluster headache patients (CCH) refractory to medical treatment. We report the results of a French multidisciplinary cohort study. Thirteen CCH patients were operated and data were collected prospectively. All of them suffered from CCH according to the International Headache Society classification, lasting for more than 2 years, refractory to pharmacological prophylactic treatment with adequate trials, with at least one daily attack. Chronic ONS was delivered through a subcutaneous occipital electrode connected to an implanted generator, in order to induce paraesthesias perceived locally in the lower occipital region. After surgery (mean follow-up 14,6 months), the mean attack frequency and intensity decreased by 68% and 49%, respectively. At last follow-up, 10/13 patients were considered as responders (improvement >50%). Prophylactic treatment could be stopped or reduced in 8/13 cases. Local infection occurred in one patient, leading to hardware removal. Our data confirmed the results of the 36 similar cases reported in the literature, suggesting that ONS may act as a prophylactic treatment in chronic CH. Considering their respective risks, ONS should be proposed before deep brain stimulation in severe refractory CCH patients.

  3. Release behaviour of clozapine matrix pellets based on percolation theory.

    PubMed

    Aguilar-de-Leyva, Angela; Sharkawi, Tahmer; Bataille, Bernard; Baylac, Gilles; Caraballo, Isidoro

    2011-02-14

    The release behaviour of clozapine matrix pellets was studied in order to investigate if it is possible to explain it applying the concepts of percolation theory, previously used in the understanding of the release process of inert and hydrophilic matrix tablets. Thirteen batches of pellets with different proportions of clozapine/microcrystalline cellulose (MCC)/hydroxypropylmethyl cellulose (HPMC) and different clozapine particle size fractions were prepared by extrusion-spheronisation and the release profiles were studied. It has been observed that the distance to the excipient (HPMC) percolation threshold is important to control the release rate. Furthermore, the drug percolation threshold has a big influence in these systems. Batches very close to the drug percolation threshold, show a clear effect of the drug particle size in the release rate. However, this effect is much less evident when there is a bigger distance to the drug percolation threshold, so the release behaviour of clozapine matrix pellets is possible to be explained based on the percolation theory.

  4. Non-invasive physical treatments for chronic/recurrent headache.

    PubMed

    Bronfort, G; Nilsson, N; Haas, M; Evans, R; Goldsmith, C H; Assendelft, W J J; Bouter, L M

    2004-01-01

    Non-invasive physical treatments are often used to treat common types of chronic/recurrent headache. To quantify and compare the magnitude of short- and long-term effects of non-invasive physical treatments for chronic/recurrent headaches. We searched the following databases from their inception to November 2002: MEDLINE, EMBASE, BIOSIS, CINAHL, Science Citation Index, Dissertation Abstracts, CENTRAL, and the Specialised Register of the Cochrane Pain, Palliative Care and Supportive Care review group. Selected complementary medicine reference systems were searched as well. We also performed citation tracking and hand searching of potentially relevant journals. We included randomized and quasi-randomized controlled trials comparing non-invasive physical treatments for chronic/recurrent headaches to any type of control. Two independent reviewers abstracted trial information and scored trials for methodological quality. Outcomes data were standardized into percentage point and effect size scores wherever possible. The strength of the evidence of effectiveness was assessed using pre-specified rules. Twenty-two studies with a total of 2628 patients (age 12 to 78 years) met the inclusion criteria. Five types of headache were studied: migraine, tension-type, cervicogenic, a mix of migraine and tension-type, and post-traumatic headache. Ten studies had methodological quality scores of 50 or more (out of a possible 100 points), but many limitations were identified. We were unable to pool data because of study heterogeneity. For the prophylactic treatment of migraine headache, there is evidence that spinal manipulation may be an effective treatment option with a short-term effect similar to that of a commonly used, effective drug (amitriptyline). Other possible treatment options with weaker evidence of effectiveness are pulsating electromagnetic fields and a combination of transcutaneous electrical nerve stimulation [TENS] and electrical neurotransmitter modulation. For the

  5. An overview of treatment approaches for chronic pain management.

    PubMed

    Hylands-White, Nicholas; Duarte, Rui V; Raphael, Jon H

    2017-01-01

    Pain which persists after healing is expected to have taken place, or which exists in the absence of tissue damage, is termed chronic pain. By definition chronic pain cannot be treated and cured in the conventional biomedical sense; rather, the patient who is suffering from the pain must be given the tools with which their long-term pain can be managed to an acceptable level. This article will provide an overview of treatment approaches available for the management of persistent non-malignant pain. As well as attempting to provide relief from the physical aspects of pain through the judicious use of analgesics, interventions, stimulations, and irritations, it is important to pay equal attention to the psychosocial complaints which almost always accompany long-term pain. The pain clinic offers a biopsychosocial approach to treatment with the multidisciplinary pain management programme; encouraging patients to take control of their pain problem and lead a fulfilling life in spite of the pain.

  6. Chronic Lymphocytic Leukemia: An Update on Current Treatment Approaches.

    PubMed

    Rozman, C; Montserrat, E

    1997-01-01

    During the last two decades, important progress has been made in the understanding of the biology, natural history, and prognosis of chronic lymphocytic leukemia (CLL). In addition, new and more effective treatment modalities are changing the objectives of treatment in patients with CLL. In this regard, the purine analogues offer great promise and fludarabine is already considered the treatment of choice for patients failing standard therapies. The role of purine analogues either alone or combined with other agents as front-line therapy is being actively investigated. Certain situations (e.g, autoimmune cytopenias, hypersplenism) require special treatment approaches (e.g., corticosteroids, splenectomy). Transplants of hemopoietic progenitor cells are also increasingly performed. As a result of these advances, treatment of subjects with CLL can be decided on the basis of the individual risk of each patient and the possibility of curing some of them may become a realistic objective.

  7. [Efficacy of antacids in the treatment of chronic gastritis].

    PubMed

    Maev, I V; Dicheva, D T; Lebedeva, E G

    2010-01-01

    This article presents main principles of chronic gastritis treatment. Therapeutic abilities and possible side-effects due to components of antacids are analyzed. Special attention is paid to antisecretory and cytoprotective activity of Pepsan-R, which contains haiasulen (the main active component of chamomilla) and dimeticon. The authors of the article emphasize opportunity of using Pepsan-R in case of heartburn, gastric pain, abdominal distention during pregnancy and lactation.

  8. [Treatment of main chronic diseases in childhood from birth].

    PubMed

    Casimir, G

    2015-09-01

    Children suffering from chronic diseases are very quickly diagnosed by neonatal screening and follow-up of the mother during the pregnancy. Early screening and diagnosis are essential to obtain continuous improvement of the prognosis in term of treatment and psychosocial outcome. Multidisciplinary teams are now well organized to treat all the complications of the disease. Registers at national and international levels allow professionals to compare themselves and to evaluate the improvement of clinical status and mid-life expectancy.

  9. Studies on Aplysia neurons suggest treatments for chronic human disorders.

    PubMed

    Abrams, Thomas W

    2012-09-11

    For decades, the marine snail Aplysia has proven to be a powerful system for analyzing basic neurobiological mechanisms, particularly cellular and molecular mechanisms of neural plasticity. Three new findings on Aplysia may be relevant for the understanding and treatment of chronic human disorders. This research on this simple molluscan nervous system may lead to new therapeutic approaches for spinal cord injury, Fragile X syndrome, and genetic learning deficits more generally.

  10. Chronic hepatitis C: This and the new era of treatment

    PubMed Central

    Bertino, Gaetano; Ardiri, Annalisa; Proiti, Maria; Rigano, Giuseppe; Frazzetto, Evelise; Demma, Shirin; Ruggeri, Maria Irene; Scuderi, Laura; Malaguarnera, Giulia; Bertino, Nicoletta; Rapisarda, Venerando; Di Carlo, Isidoro; Toro, Adriana; Salomone, Federico; Malaguarnera, Mariano; Bertino, Emanuele; Malaguarnera, Michele

    2016-01-01

    Over the last years it has started a real revolution in the treatment of chronic hepatitis C. This occurred for the availability of direct-acting antiviral agents that allow to reach sustained virologic response in approximately 90% of cases. In the near future further progress will be achieved with the use of pan-genotypic drugs with high efficacy but without side effects. PMID:26807205

  11. The treatment of chronic pain with psychotropic drugs

    PubMed Central

    Merskey, H.; Hester, R. A.

    1972-01-01

    The treatment is described of thirty patients with chronic nervous system lesion causing intractable pain. Moderately good relief of pain was obtained with a combination of phenothiazines (especially pericyazine), antidepressant drugs and antihistamines. The theoretical implications of this are discussed and it is suggested that the drugs in question act partly by virtue of an effect on the multisynaptic neuronal systems whose activities are related to the experience of pain. PMID:4404064

  12. 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.

  13. 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.

  14. General Approach to Treatment of Chronic Myelomonocytic Leukemia

    MedlinePlus

    ... Growth Factors for Treating Chronic Myelomonocytic Leukemia Radiation Therapy for Chronic Myelomonocytic Leukemia Surgery for Chronic Myelomonocytic ... Cancer Information Cancer Prevention & Detection Cancer Basics ...

  15. Severe chronic venous insufficiency: primary treatment with sclerofoam.

    PubMed

    Bergan, John J; Pascarella, Luigi

    2005-03-01

    Venous insufficiency, for practical purposes, can be divided into primary venous insufficiency and chronic venous insufficiency. The latter is characterized by advanced skin changes of hyperpigmentation, edema, ulceration, scarring from healed ulcers or open ulcerations. These are summarized in the CEAP classification as Classes 4, 5 and 6. Pretreatment evaluation is done with a standing ultrasound reflux examination. Thorough mapping of the extremity reflux is desirable. Physiologic tests of venous function, such as plethysmography, are unnecessary. Treatment is directed at closing refluxing axial veins as well as controlling those perforating veins with outward flow. Varicose veins contribute to axial reflux and must be obliterated. Arterial occlusive disease may complicate venous ulceration in as many as 15% of cases. Initial treatment of severe chronic venous insufficiency is usually carried out by controlling the edema with elastic bandaging or nonelastic support, such as the Unna boot or the CircAid dressing. Surgical intervention has been successful but the advent of foam sclerotherapy has proven to be an attractive alternative to surgery and has added a new tool for the treatment of severe chronic venous insufficiency. In this preliminary experience, the results are quite satisfactory and the technique has been shown to be effective, pain-free, inexpensive, with very little morbidity. Guidelines for obtaining sclerosants for use in foam sclerotherapy legally are provided.

  16. 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.

  17. Comparative neurochemical changes associated with chronic administration of typical and atypical neuroleptics: implications in tardive dyskinesia.

    PubMed

    Bishnoi, Mahendra; Kumar, Anil; Chopra, Kanwaljit; Kulkarni, Shrinivas K

    2007-02-01

    An important goal of current neuroleptic research is to develop antipsychotic compounds with the low incidence of extrapyramidal side effects. The therapeutic success and less side-effect of atypical anti-psychotics such as clozapine and risperidone has focused the attention on the role of receptor systems other than dopaminergic system in the pathophysiology of neuroleptics-associated extrapyramidal side effects. The present study compares the effect of chronic administration of typical and atypical antipsychotics on neurochemical profile in rat forebrain. The study was planned to study changes in extracellular levels of norepinephrine, dopamine and serotonin in forebrain region of brain and tried to correlate them with hyperkinetic motor activities (vacuous chewing movements (VCM's), tongue protrusions and facial jerking) in rats, hall mark of chronic extrapyramidal side-effect of neuroleptic therapy tardive dyskinesia. Chronic administration of haloperidol (1 mg/kg) and chlorpromazine (5 mg/kg) resulted in significant increase in orofacial hyperkinetic movements where as clozapine and risperidone showed less significant increase in orofacial hyperkinetic movements as compared to control. There were also significant decrease in the extracellular levels of neurotransmitters dopamine, norepinephrine and serotonin in fore-brain as measured by HPLC/ED after chronic administration of haloperidol and chlorpromazine. Chronic administration of atypical neuroleptics clozapine and risperidone resulted in the decrease in extracellular concentration of dopamine and norepinephrine but the effect was less significant as compared to typical drugs. However, treatment with atypical neuroleptics resulted in 3 fold increase in serotonin levels as compared to forebrain of control rats. Typical and atypical neuroleptics showed varying effects on neurotransmitters, especially serotonin which may account for the difference in their profile of side effects (Tardive dyskinesia).

  18. 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

  19. Treatment of Chronic Migraine with Focus on Botulinum Neurotoxins

    PubMed Central

    Schaefer, Sara M.; Gottschalk, Christopher H.; Jabbari, Bahman

    2015-01-01

    Migraine is the most common neurological disorder, and contributes to disability and large healthcare costs in the United States and the world. The treatment of migraine until recently has focused on medications, both abortive and prophylactic, but treatment of chronic migraine has been revolutionized with the introduction of botulinum toxin injection therapy. In this review, we explore the current understanding of migraine pathophysiology, and the evolution of the use of botulinum toxin therapy including proposed pathophysiological mechanisms through animal data. We also discuss the similarities and differences between three injection techniques. PMID:26184313

  20. Treatment of Chronic Migraine with Focus on Botulinum Neurotoxins.

    PubMed

    Schaefer, Sara M; Gottschalk, Christopher H; Jabbari, Bahman

    2015-07-14

    Migraine is the most common neurological disorder, and contributes to disability and large healthcare costs in the United States and the world. The treatment of migraine until recently has focused on medications, both abortive and prophylactic, but treatment of chronic migraine has been revolutionized with the introduction of botulinum toxin injection therapy. In this review, we explore the current understanding of migraine pathophysiology, and the evolution of the use of botulinum toxin therapy including proposed pathophysiological mechanisms through animal data. We also discuss the similarities and differences between three injection techniques.

  1. Full mouth versus quadrant treatment in chronic periodontitis.

    PubMed

    Sagar, Anjana

    2014-08-01

    The aim of this review is to discuss the evidence for the management of chronic periodontitis, including methods of non-surgical therapy such as full mouth disinfection, full mouth debridement and conventional quadrant-by-quadrant therapy. Manual searches of Medline and Embase databases provided the relevant studies. Multiple randomised controlled trials (RCTs) selected for the paper failed to show any significant differences between the quadrant-wise treatment and full mouth debridement and modalities. This review demonstrates that there is no known difference in treatment outcomes between full mouth debridement and traditional quadrant therapy. Further RCTs are necessary to assess clinical effectiveness of chemical adjunct use.

  2. Laparoscopic treatment of lower abdominal pain related to chronic appendicitis.

    PubMed

    Pandza, Haris; Custović, Samir; Cović, Ranko; Delibegovic, Samir

    2008-01-01

    The appendicitis is one of the most common entities that could be met at surgical department. Chronic pelvic pain of right iliac fossa is common and it causes disability and distress and results in significant costs to health services. Often, investigation by laparoscopy reveals no obvious cause for pain. There are several possible explanations for chronic pelvic pain including undetected irritable bowel syndrome, the vascular hypothesis where pain is thought to arise from dilated pelvic veins in which blood flow is markedly reduced and altered spinal cord and brain processing of stimuli in women with chronic pelvic pain. As the pathophysiology of chronic pelvic pain is not well understood, its treatment is often unsatisfac