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Sample records for atypical antipsychotics improves

  1. [Atypical antipsychotics and metabolic syndrome].

    PubMed

    Baranyi, Andreas; Yazdani, Renè; Haas-Krammer, Alexandra; Stepan, Alexandra; Kapfhammer, Hans-Peter; Rothenhäusler, Hans-Bernd

    2007-01-01

    The introduction of atypical antipsychotics in psychopharmacology represented a major advance in the treatment of psychotic disorders. However, there have been numerous studies that certain atypical antipsychotics may be associated with a greater risk of metabolic abnormalities than others, including weight gain, hyperlipidemia and new-onset typ 2 diabetes mellitus. A G-Protein beta3 subunit Gen (C825T) polymorphism, an increased carbohydrate metabolism and dyshormonism are discussed as pathogenetic mechanisms. High risk patients (adiposity, hyperlipidaemia, hyperglycaemia, preexisting diabetes) should maintain an antipsychotic agent with a favourable side effect profile. In these cases a periodical diabetes screening and blood lipid controls are required. Clinicans must balance the significant benefits of atypical antipsychotics against the risk of metabolic disturbances. In this article recent findings are reviewed.

  2. Novel antipsychotics: issues and controversies. Typicality of atypical antipsychotics.

    PubMed Central

    Stip, E

    2000-01-01

    The typicality of atypical antipsychotic drugs remains debatable. Preclinical studies and findings from randomized, controlled and open trials of clozapine, olanzapine, risperidone, quetiapine, sertindole, ziprasidone and a substituted benzamide were examined. A MEDLINE search was conducted using key words, including "extrapyramidal side effects," "cognition," "schizophrenia" and the generic drug names. Over 140 articles from peer-reviewed journals were reviewed, some of which were based on a meta-analysis. New-generation neuroleptic agents were found to have greater efficacy on the negative symptoms of schizophrenia and to cause fewer unwanted extrapyramidal side effects (EPS) than the traditional antipsychotic drugs. On one hand, atypical neuroleptic agents could be strictly defined as any neuroleptic agent with antipsychotic effects at a dosage that does not cause extrapyramidal side effects. Thus, clozapine is regarded as the "standard" atypical antipsychotic drug. On the other hand, typicality is about dimension rather than category, and we suggest the use of the term "spectrum of atypicality." For example, an emphasis is placed on quetiapine to illustrate where a new compound fits in this spectrum. Although dose-related, atypicality may be more a question of prescription attitude than of a specific characteristic of a compound. The degree to which a new compound is clinically superior to another atypical antipsychotic drug, in terms of improving positive, negative or affective symptoms, cognitive function and long-term outcome, will require further a priori hypotheses based on conceptual frameworks that are clinically meaningful. In addition, the results from industry-sponsored trials should be more comparable to those obtained from investigator-leading trials. Finally, the patient characteristics that define a patient's response to a specific antipsychotic drug are unknown. PMID:10740987

  3. Atypical Antipsychotic Medication Improves Aggression, but Not Self-Injurious Behaviour, in Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Ruedrich, S. L.; Swales, T. P.; Rossvanes, C.; Diana, L.; Arkadiev, V.; Lim, K.

    2008-01-01

    Objective: Atypical antipsychotic medications have largely supplanted their typical counterparts, both for psychosis and for the treatment of aggression and/or self-injurious behaviour (SIB), in persons with intellectual disabilities (ID). However, with the exception of risperidone, little systematic research supports their use in such persons.…

  4. Low-Dose Atypical Antipsychotic Risperidone Improves the 5-Year Outcome in Alzheimer's Disease Patients with Sleep Disturbances.

    PubMed

    Yin, You; Liu, Yan; Zhuang, Jianhua; Pan, Xiao; Li, Peng; Yang, Yuechang; Li, Yan-Peng; Zhao, Zheng-Qing; Huang, Liu-Qing; Zhao, Zhong-Xin

    2015-01-01

    Sleep disturbances (SD) accelerate the progression of Alzheimer's disease (AD) and increase the stress of caregivers. However, the long-term outcome of disturbed nocturnal sleep/wake patterns in AD and on increased stress of spousal caregivers is unclear. This study assessed the 5-year effect of nocturnal SD on the long-term outcome in AD patients. A total of 156 donepezil-treated mild-moderate AD patients (93 AD + SD and 63 AD - SD as a control group) were recruited. The AD + SD patients were formed into 4 subgroups according to the preferences of spousal caregivers for treatment with atypical antipsychotics (0.5-1 mg risperidone, n = 22), non-benzodiazepine hypnotic (5-10 mg zolpidem tartrate, n = 33), melatonin (2.55 mg, n = 9), or no-drug treatment (n = 29). SD were evaluated by polysomnography, sleep scale, and cognitive scale examinations. Moreover, all spousal caregivers of AD patients were assessed using a series of scales, including sleep, anxiety, mood, and treatment attitude scales. Our data showed that nocturnal sleep/wake disturbances were significantly associated with lower 5-year outcomes for AD patients, earlier nursing home placement, and more negative emotions of spousal caregivers. Treatment with low-dose atypical antipsychotic risperidone improved the 5-year outcome in AD + SD patients. In conclusion, low-dose atypical antipsychotic risperidone improves the 5-year outcome in AD patients with SD. Moreover, improvement of nocturnal sleep problems in AD patients will also bring better emotional stability for AD caregivers.

  5. Atypical and Typical Antipsychotics in the Schools

    ERIC Educational Resources Information Center

    Noggle, Chad A.; Dean, Raymond S.

    2009-01-01

    The use of antipsychotic medications within the school-age population is rapidly increasing. Although typical antipsychotics may be used in rare cases, this influx is largely secondary to the availability of the atypical antipsychotics. Reduction of possible adverse effects and increased efficacy represent the primary basis for the atypical…

  6. 'Atypical' antipsychotics: where does ziprasidone fit?

    PubMed

    Remington, Gary

    2002-01-01

    Identified as the prototype of 'atypicality', clozapine heralded a new generation of antipsychotics intent on providing greater efficacy than 'typical' antipsychotics, while diminishing the risk of D2-related side effects such as extrapyramidal symptoms and hyperprolactinemia. Ziprasidone is the most recent in this new class of antipsychotics to enter the clinical market. PMID:19811011

  7. Atypical antipsychotics: sedation versus efficacy.

    PubMed

    Kane, John M; Sharif, Zafar A

    2008-01-01

    Many patients with schizophrenia or bipolar disorder experience disturbances in their sleep-wake cycle, which may be a result of the disorder itself, of pharmacotherapy, or of a comorbid sleep disorder. These sleep disruptions can seriously impair patients' functioning as well as their quality of life. Therefore, accurate assessment of sleep problems is essential to appropriately treat patients and promote symptomatic remission. Sedating antipsychotics may ameliorate sleep disturbances, as well as agitation or other behavioral emergencies; however, these agents may also sedate patients to the point of dissatisfaction with the medication and/or impaired functioning, which may, in turn, increase treatment noncompliance and nonadherence. Using short-term adjunctive medications, such as benzo-diazepines or hypnotic agents, with a nonsedating antipsychotic to alleviate sleep disturbances is a reasonable treatment option for patients with schizophrenia or bipolar disorder. Overall, the pharma-cokinetics and pharmacodynamics of atypical antipsychotics are important factors to consider in the risk-benefit analysis, as are dosing strategies and individual patient factors, and clinicians must decide which agents are most appropriate for which patients. PMID:18484805

  8. New onset diabetes and atypical antipsychotics.

    PubMed

    Liebzeit, K A; Markowitz, J S; Caley, C F

    2001-02-01

    As a class, the atypical antipsychotics are the first line treatment choice for the psychopharmacologic management of psychotic disorders. Emerging evidence currently suggests that at least two of the atypical antipsychotics, clozapine and olanzapine, and possibly quetiapine may be associated with the risk of new onset diabetes or serum glucose dyscontrol. Computerized Medline and Current Contents searches from years 1966 through June 2000 were undertaken to retrieve all pertinent studies and case reports of typical and atypical antipsychotics and glucose-insulin problems. Historically, both schizophrenia and the older antipsychotics medications have been reported to be associated with a similar risk for causing disruptions in serum glucose control. Additionally, diabetes has well recognized associations with a number of medical disorders such as cardiovascular disease; it is therefore worthy of attention. Hypothesized mechanisms for antipsychotic induced diabetes ranges from the antagonism of several neurotransmitter receptors to insulin resistance. A total of thirty-five cases of induced or exacerbated diabetes are presently available in the published literature; the vast majority of cases implicate clozapine (n=20) and olanzapine (n=15). In multiple cases, diabetic ketoacidosis has been the presenting symptom; daily atypical antipsychotic doses have been within acceptable ranges and were not considered to be excessive.

  9. Atypical antipsychotics in first admission schizophrenia: medication continuation and outcomes.

    PubMed

    Mojtabai, Ramin; Lavelle, Janet; Gibson, P Joseph; Bromet, Evelyn J

    2003-01-01

    This study compares the effects of atypical and conventional antipsychotic medications on treatment continuation and outcomes in a first admission sample of patients with schizophrenia treated in usual practice settings. In a sample of 189 participants with a research diagnosis of DSM-IV schizophrenia drawn from the Suffolk County Mental Health Project, we compared the effects of atypical and conventional agents on change of medication, medication gaps, and rehospitalization. For these analyses we used the method of survival analysis for recurrent events, in which the episodes of treatment rather than individual subjects are the units of analysis. In addition, we compared improvement in positive and negative symptoms from intake to 24- or 48-month followups for subjects who stayed on one type of medication or changed to atypicals from conventional antipsychotics. Atypical agents were associated with lower risk of medication change, medication gaps, and rehospitalization. Both conventional and atypical agents were associated with improvement of positive symptoms at followup, but only subjects on atypical agents at followup experienced a significant improvement in negative symptoms. We conclude that in usual practice settings, as in randomized clinical trials, atypical agents are associated with improved treatment continuation and outcomes.

  10. Olanzapine versus other atypical antipsychotics for schizophrenia

    PubMed Central

    Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Duggan, Lorna; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second generation (“atypical”) antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of olanzapine differs from that of other second generation antipsychotics. Objectives To evaluate the effects of olanzapine compared to other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. Search methods 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. 2. Reference searching We inspected the reference of all identified studies for more trials. 3. Personal contact We contacted the first author of each included study for missing information. 4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. Selection criteria We included all randomised trials that used at least single-blind (rater-blind) design, comparing oral olanzapine with oral forms of amisulpride, aripiprazole, clozapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. Main results The review currently includes 50 studies and 9476 participants which provided data for six comparisons (olanzapine compared to amisulpride, aripiprazole

  11. Clinical pharmacology of atypical antipsychotics: an update

    PubMed Central

    Mauri, M.C.; Paletta, S.; Maffini, M.; Colasanti, A.; Dragogna, F.; Di Pace, C.; Altamura, A.C.

    2014-01-01

    This review will concentrate on the clinical pharmacology, in particular pharmacodynamic data, related to atypical antipsychotics, clozapine, risperidone, paliperidone, olanzapine, que¬tiapine, amisulpride, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone and cariprazine. A summary of their acute pharmacokinetics properties are also reported. Four new second-generation antipsychotics are available: iloperidone, asenapine, lurasidone and in the next future cariprazine. Similar to ziprasidone and aripiprazole, these new agents are advisable for the lower propensity to give weight gain and metabolic abnormalities in comparison with older second-generation antipsychotics such as olanzapine or clozapine. Actually lurasidone seems to be best in terms of minimizing unwanted alterations in body weight and metabolic variables. Therapeutic drug monitoring is not strictly necessary for all of the new antipsychotic drugs because there are no unequivocal data supporting a relationship between plasma drug levels and clinical outcomes or side effects. The exception can be represented by clozapine for which plasma levels of 350-420 ng/ml are reported to be associated with an increased probability of a good clinical response. Also for olanzapine an established therapeutic range (20-50 ng/ml) is proposed to yield an optimal response and minimize side effects. PMID:26417330

  12. Atypical antipsychotics to treat the neuropsychiatric symptoms of dementia

    PubMed Central

    Lee, Philip E; Gill, Sudeep S; Rochon, Paula

    2006-01-01

    Neuropsychiatric symptoms are common in older adults with dementia and can be associated with a rapid decline in cognitive and functional status. This article reviews the current literature supporting the use of atypical antipsychotic medications in this population. Among the currently available atypical antipsychotics, risperidone and olanzapine have been the most widely studied in double-blind, randomized, placebo-controlled clinical trials. Despite the common use of other atypical antipsychotic medications, their efficacy and safety in older adults with dementia has not been as extensively studied. Some controversy surrounds the use of atypical antipsychotic agents in older adults with the suggestion that they may increase the incidence of stroke or even death. Despite the potential for increased risk of harm from the use of these medications, atypical antipsychotics are often effective in treating troublesome neuropsychiatric symptoms refractory to other treatments. Whenever possible, these atypical antipsychotic drug treatments should be combined with non-pharmacological treatments to limit the need and dose of antipsychotic drugs and constant monitoring for potential harms should be maintained. The choice of which atypical antipsychotic agent can be guided by the nature and severity of the target symptom and the medication least likely to cause harm to the patient. PMID:19412500

  13. Risperidone versus other atypical antipsychotics for schizophrenia

    PubMed Central

    Komossa, Katja; Rummel-Kluge, Christine; Schwarz, Sandra; Schmid, Franziska; Hunger, Heike; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second-generation (“atypical”) antipsychotics (SGAs) have become the first line drug treatment for people with schizophrenia. The question as to whether and if so how much the effects of the various SGAs differ is a matter of debate. In this review we examined how the efficacy and tolerability of risperidone differs from that of other SGAs. Objectives To evaluate the effects of risperidone compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. Search methods 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. 2. Reference searching We inspected the references of all identified studies for more trials. 3. Personal contact We contacted the first author of each included study for missing information. 4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. Selection criteria We included all randomised, blinded trials comparing oral risperidone with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated risk ratio (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis 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 45 blinded RCTs with 7760 participants. The number of RCTs available for each comparison varied: four studies compared risperidone with amisulpride, two with aripiprazole, 11 with clozapine, 23 with olanzapine, eleven with

  14. Amisulpride versus other atypical antipsychotics for schizophrenia

    PubMed Central

    Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; da Mota Neto, Joaquim I Silveira; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of amisulpride differs from that of other second generation antipsychotics. Objectives To evaluate the effects of amisulpride compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE and PsycINFO. We updated this search in July 2012 and added 47 new trials to the awaiting classification section. Selection criteria We included randomised, at least single-blind, trials comparing oral amisulpride with oral forms of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses. Data collection and analysis We extracted data independently. For continuous data we calculated weighted mean differences (MD), for dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. Main results The review currently includes ten short to medium term trials with 1549 participants on three comparisons: amisulpride versus olanzapine, risperidone and ziprasidone. The overall attrition rate was considerable (34.7%) with no significant difference between groups. Amisulpride was similarly effective as olanzapine and risperidone and more effective than ziprasidone (leaving the study early due to inefficacy: n=123, 1 RCT, RR 0.21 CI 0.05 to 0.94, NNT 8 CI 5 to 50

  15. Ziprasidone versus other atypical antipsychotics for schizophrenia

    PubMed Central

    Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schwarz, Sandra; Bhoopathi, Paranthaman Sethupathi; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second generation (‘atypical’) antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various new generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of ziprasidone differs from that of other second generation antipsychotics. Objectives To evaluate the effects of ziprasidone compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Group Specialised Register (April 2007) and references of all identified studies for further trial citations. We contacted pharmaceutical companies and authors of trials for additional information. This search was updated July 2012, 254 citations added to awaiting classification section. Selection criteria We included all randomised, at least single-blind, controlled trials comparing oral ziprasidone with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone or zotepine in people with schizophrenia or schizophrenia-like psychoses. Data collection and analysis We extracted data independently. For continuous data, we calculated weighted mean differences (MD) for dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. Main results The review currently includes nine randomised controlled trials (RCTs) with 3361 participants. The overall rate of premature study discontinuation was very high (59.1%). Data for the comparisons of ziprasidone with amisulpride, clozapine, olanzapine, quetiapine and risperidone were available. Ziprasidone was a less acceptable treatment than olanzapine (leaving the studies early for any

  16. Hepatic Safety of Atypical Antipsychotics: Current Evidence and Future Directions.

    PubMed

    Slim, Mahmoud; Medina-Caliz, Inmaculada; Gonzalez-Jimenez, Andres; Cabello, M Rosario; Mayoral-Cleries, Fermin; Lucena, M Isabel; Andrade, Raul J

    2016-10-01

    The newer atypical antipsychotic agents (AAPs) represent an attractive therapeutic option for a wide range of psychotic disorders, including schizophrenia and bipolar mania, because of the reduced risk of disabling extrapyramidal symptoms. However, their growing use has raised questions about their tolerability over the endocrine, metabolic, and cardiovascular axes. Indeed, atypical antipsychotic drugs are associated, to differing extents, with mild elevation of aminotransferases related to weight gain, AAP-induced metabolic syndrome, and nonalcoholic fatty liver disease. Although the hepatic safety of new AAPs seems improved over that of chlorpromazine, they can occasionally cause idiosyncratic liver injury with varying phenotypes and, rarely, lead to acute liver failure. However, AAPs are a group of heterogeneous, chemically unrelated compounds with distinct pharmacological and pharmacokinetic properties and substantially different safety profiles, which precludes the notion of a class effect for hepatotoxicity risk and highlights the need for an individualized therapeutic approach. We discuss the current evidence on the hepatotoxicity potential of AAPs, the emerging underlying mechanisms, and the limitations inherent to this group of drugs for both establishing a proper causality assessment and developing strategies for risk management. PMID:27449495

  17. Current status of atypical antipsychotics for the treatment of fibromyalgia.

    PubMed

    Rico-Villademoros, F; Calandre, E P; Slim, M

    2014-06-01

    The treatment of fibromyalgia requires pharmacological and nonpharmacological therapies. The pharmacological treatment of fibromyalgia is limited to a few drugs that have been demonstrated to be moderately effective in some but not all dimensions of the disease. Therefore, the search for new drugs to treat this condition is warranted. Atypical antipsychotics offered an attractive alternative because they had been shown to be active against several key symptoms of fibromyalgia. The results of open-label studies, however, appear to indicate that atypical antipsychotics are poorly tolerated in patients with fibromyalgia, and only quetiapine XR has been studied in randomized controlled trials. Quetiapine XR has demonstrated effectiveness in treating comorbid major depression, anxiety and sleep disturbance. However, in two randomized controlled trials, quetiapine XR was not differentiated from placebo and failed to demonstrate noninferiority to amitriptyline in terms of improving overall symptomatology. The effect of quetiapine XR on pain and its usefulness as part of a combination pharmacological regimen should be further evaluated. Overall, the use of quetiapine (initiated at a low dose and slowly titrated) in fibromyalgia should be limited to patients with comorbid major depression or patients who are currently receiving other treatments and have unresolved and disabling depressive and/or anxiety symptoms.

  18. Hepatic Safety of Atypical Antipsychotics: Current Evidence and Future Directions.

    PubMed

    Slim, Mahmoud; Medina-Caliz, Inmaculada; Gonzalez-Jimenez, Andres; Cabello, M Rosario; Mayoral-Cleries, Fermin; Lucena, M Isabel; Andrade, Raul J

    2016-10-01

    The newer atypical antipsychotic agents (AAPs) represent an attractive therapeutic option for a wide range of psychotic disorders, including schizophrenia and bipolar mania, because of the reduced risk of disabling extrapyramidal symptoms. However, their growing use has raised questions about their tolerability over the endocrine, metabolic, and cardiovascular axes. Indeed, atypical antipsychotic drugs are associated, to differing extents, with mild elevation of aminotransferases related to weight gain, AAP-induced metabolic syndrome, and nonalcoholic fatty liver disease. Although the hepatic safety of new AAPs seems improved over that of chlorpromazine, they can occasionally cause idiosyncratic liver injury with varying phenotypes and, rarely, lead to acute liver failure. However, AAPs are a group of heterogeneous, chemically unrelated compounds with distinct pharmacological and pharmacokinetic properties and substantially different safety profiles, which precludes the notion of a class effect for hepatotoxicity risk and highlights the need for an individualized therapeutic approach. We discuss the current evidence on the hepatotoxicity potential of AAPs, the emerging underlying mechanisms, and the limitations inherent to this group of drugs for both establishing a proper causality assessment and developing strategies for risk management.

  19. Use of atypical antipsychotics in the elderly: a clinical review

    PubMed Central

    Gareri, Pietro; Segura-García, Cristina; Manfredi, Valeria Graziella Laura; Bruni, Antonella; Ciambrone, Paola; Cerminara, Gregorio; De Sarro, Giovambattista; De Fazio, Pasquale

    2014-01-01

    The use of atypical antipsychotic drugs in the elderly has become wider and wider in recent years; in fact, these agents have novel receptor binding profiles, good efficacy with regard to negative symptoms, and reduced extrapyramidal symptoms. However, in recent years, the use of both conventional and atypical antipsychotics has been widely debated for concerns about their safety in elderly patients affected with dementia and the possible risks for stroke and sudden death. A MEDLINE search was made using the words elderly, atypical antipsychotics, use, schizophrenia, psychosis, mood disorders, dementia, behavioral disorders, and adverse events. Some personal studies were also considered. This paper reports the receptor binding profiles and the main mechanism of action of these drugs, together with their main use in psychiatry and the possible adverse events in elderly people. PMID:25170260

  20. Improvement of cognitive flexibility and cingulate blood flow correlates after atypical antipsychotic treatment in drug-naive patients with first-episode schizophrenia.

    PubMed

    Pardo, Bernardo M; Garolera, Maite; Ariza, Mar; Pareto, Deborah; Salamero, Manel; Valles, Vicenç; Delgado, Luis; Alberni, Joan

    2011-12-30

    The aim of this study was to examine the changes in cognitive flexibility and associated cerebral blood flow in the anterior cingulate lobe of drug-naive patients with first-episode schizophrenia who were treated with atypical antipsychotics for 6 weeks. Single photon emission computed tomography (SPECT) images were obtained from 8 healthy subjects both at rest and while performing the flexibility subtest of the TAP (Test for Attentional Performance). SPECT images were obtained in parallel from 8 first-episode drug-naive schizophrenic patients while they were performing the same task both before and after 6 weeks of neuroleptic treatment. In the control group, an increase in the perfusion indices of the dorsal section of the anterior cingulate gyrus was observed in the activation condition. Task performance was altered and the level of perfusion of the brain region related to the task execution was significantly decreased in the patients at baseline. After treatment, there was a significant improvement in both task performance and the level of perfusion of the dorsal section of the anterior cingulate. We conclude that treatment with second-generation neuroleptics improves cognitive flexibility, and there was a relationship between such improvements and normalization of perfusion indices of the involved brain areas.

  1. Pharmacological management of atypical antipsychotic-induced weight gain.

    PubMed

    Baptista, Trino; ElFakih, Yamily; Uzcátegui, Euderruh; Sandia, Ignacio; Tálamo, Eduardo; Araujo de Baptista, Enma; Beaulieu, Serge

    2008-01-01

    Excessive bodyweight gain was reported during the 1950s as an adverse effect of typical antipsychotic drug treatment, but the magnitude of bodyweight gain was found to be higher with the atypical antipsychotic drugs that were introduced after 1990. Clozapine and olanzapine produce the greatest bodyweight gain, ziprasidone and aripiprazole have a neutral influence, and quetiapine and risperidone cause an intermediate effect. In the CATIE study, the percentage of patients with bodyweight gain of >7% compared with baseline differed significantly between the antipsychotic drugs, i.e. 30%, 16%, 14%, 12% and 7% for olanzapine, quetiapine, risperidone, perphenazine (a typical antipsychotic) and ziprasidone, respectively (p<0.001). Appetite stimulation is probably a key cause of bodyweight gain, but genetic polymorphisms modify the bodyweight response during treatment with atypical antipsychotics. In addition to nutritional advice, programmed physical activity, cognitive-behavioural training and atypical antipsychotic switching, pharmacological adjunctive treatments have been assessed to counteract excessive bodyweight gain. In some clinical trials, nizatidine, amantadine, reboxetine, topiramate, sibutramine and metformin proved effective in preventing or reversing atypical antipsychotic-induced bodyweight gain; however, the results are inconclusive since few randomized, placebo-controlled clinical trials have been conducted. Indeed, most studies were short-term trials without adequate statistical power and, in the case of metformin, nizatidine and sibutramine, the results are contradictory. The tolerability profile of these agents is adequate. More studies are needed before formal recommendations on the use of these drugs can be made. Meanwhile, clinicians are advised to use any of these adjunctive treatments according to their individual pharmacological and tolerability profiles, and the patient's personal and family history of bodyweight gain and metabolic dysfunction.

  2. The use of atypical antipsychotics in the management of schizophrenia

    PubMed Central

    Campbell, M; Young, P I; Bateman, D N; Smith, J M; Thomas, S H L

    1999-01-01

    Long-term drug treatment of schizophrenia with conventional antipsychotics has limitations: an estimated quarter to one third of patients are treatment-resistant; conventional antipsychotics have only a modest impact upon negative symptoms (poverty of thought, social withdrawal and loss of affect); and adverse effects, particularly extrapyramidal symptoms (EPS). Newer, so-called atypical, antipsychotics such as olanzapine, risperidone, sertindole and clozapine (an old drug which was re-introduced in 1990) are claimed to address these limitations. Atypical agents are, at a minimum, at least as effective as conventional drugs such as haloperidol. They also cause substantially fewer extrapyramidal symptoms. However, some other adverse effects are more common than with conventional drugs. For example, clozapine carries a significant risk of serious blood disorders, for which special monitoring is mandatory; it also causes troublesome drowsiness and increased salivation more often than conventional agents. Some atypical agents cause more weight gain or QT prolongation than older agents. The choice of therapy is, therefore, not straightforward. At present, atypical agents represent an advance for patients with severe or intolerable EPS. Most published evidence exists to support the use of clozapine, which has also been shown to be effective in schizophrenia refractory to conventional agents. However, the need for compliance with blood count monitoring and its sedative properties make careful patient selection important. The extent of any additional direct benefit offered by atypical agents on negative symptoms is not yet clear. The lack of a depot formulation for atypical drugs may pose a significant practical problem. To date, only two double-blind studies in which atypical agents were compared directly have been published. Neither provides compelling evidence for the choice of one agent over another. Atypical agents are many times more expensive than conventional drugs

  3. Comparative effectiveness of atypical antipsychotics in schizophrenia: what have real-world trials taught us?

    PubMed

    Attard, Azizah; Taylor, David M

    2012-06-01

    Real-world, effectiveness studies add an important new dimension to the evaluation of the benefits of individual antipsychotics. Efficacy studies have already shown the unique effectiveness of clozapine, and suggested improved outcomes for olanzapine compared with some atypical antipsychotics and a reduced tendency to produce acute and chronic movement disorders for atypical compared with typical drugs. Recent effectiveness studies largely confirm these prior observations. The CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness), CUtLASS (Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study) and SOHO (Schizophrenia Outpatient Health Outcomes) programmes confirmed the superiority of clozapine over other antipsychotics; CATIE and SOHO also confirmed olanzapine as probably the second most effective antipsychotic. Effectiveness studies have confirmed the high incidence of adverse metabolic effects with clozapine, olanzapine and (with less certainty) quetiapine but the ZODIAC (Ziprasidone Observational Study of Cardiac Outcomes) study found no excess cardiovascular events or deaths for olanzapine compared with ziprasidone. Prior observations on reduced frequency of movement disorders for second-generation versus first-generation antipsychotics were also largely (but not uniformly) supported. Overall, recent real-world studies have done much to confirm prior observations from efficacy-based randomized, controlled trials.

  4. Comparative effectiveness of atypical antipsychotics in schizophrenia: what have real-world trials taught us?

    PubMed

    Attard, Azizah; Taylor, David M

    2012-06-01

    Real-world, effectiveness studies add an important new dimension to the evaluation of the benefits of individual antipsychotics. Efficacy studies have already shown the unique effectiveness of clozapine, and suggested improved outcomes for olanzapine compared with some atypical antipsychotics and a reduced tendency to produce acute and chronic movement disorders for atypical compared with typical drugs. Recent effectiveness studies largely confirm these prior observations. The CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness), CUtLASS (Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study) and SOHO (Schizophrenia Outpatient Health Outcomes) programmes confirmed the superiority of clozapine over other antipsychotics; CATIE and SOHO also confirmed olanzapine as probably the second most effective antipsychotic. Effectiveness studies have confirmed the high incidence of adverse metabolic effects with clozapine, olanzapine and (with less certainty) quetiapine but the ZODIAC (Ziprasidone Observational Study of Cardiac Outcomes) study found no excess cardiovascular events or deaths for olanzapine compared with ziprasidone. Prior observations on reduced frequency of movement disorders for second-generation versus first-generation antipsychotics were also largely (but not uniformly) supported. Overall, recent real-world studies have done much to confirm prior observations from efficacy-based randomized, controlled trials. PMID:22668246

  5. Economics of atypical antipsychotics in bipolar disorder: a review of the literature.

    PubMed

    Fleurence, Rachael L; Dixon, Julia M; Revicki, Dennis A

    2006-01-01

    Economic evaluations are increasingly being used by policy makers to evaluate the relative costs and benefits of healthcare interventions. These analyses provide economic and clinical evidence to decision makers seeking to make recommendations on treatment alternatives for patients. This article describes the economic evidence on the atypical antipsychotics currently approved for the treatment of bipolar disorder. This area remains under-researched. A literature search identified only six relevant studies of atypical antipsychotics in bipolar disorder: two retrospective database analyses, three economic analyses alongside clinical trials and one cost-effectiveness analysis. Based on the limited available studies, there appears to be no significant difference in healthcare resource use between olanzapine, quetiapine, risperidone and valproate semisodium (divalproex sodium; an antiepileptic drug and a standard treatment for mania associated with bipolar disorder). While a cost-effectiveness study for the UK found haloperidol (a conventional antipsychotic) to be more cost effective than atypical antipsychotics, these results must be considered with caution because of the non-inclusion of adverse effects in the model. No economic data are available for aripiprazole, clozapine or ziprasidone in bipolar disorder. Until more economic evidence becomes available, the economic implications of atypical antipsychotic treatment in patients with bipolar disorder are unlikely to significantly impact on prescribing and treatment patterns. Future economic studies evaluating atypical antipsychotics in bipolar disorder should address the issue of long-term costs and effectiveness to reflect the chronic nature of the disease, the variety of health states that patients may experience and the range of treatments they may receive. A better understanding of the complex interplay between effectiveness, safety, quality of life, adherence and resource use should ultimately contribute to

  6. Atypical Antipsychotics and Metabolic Syndrome in Patients with Schizophrenia: Risk Factors, Monitoring, and Healthcare Implications

    PubMed Central

    Riordan, Henry J.; Antonini, Paola; Murphy, Michael F.

    2011-01-01

    Background Metabolic syndrome is a leading cause of morbidity and mortality in patients with schizophrenia, with a prevalence rate double that of nonpsychiatric populations. Given the amount of evidence suggesting a link between atypical antipsychotic medications and metabolic syndrome, several agencies have recommended regular clinical monitoring of weight, symptoms of hyperglycemia, and glucose in chronically medicated patients with schizophrenia. Objectives To summarize the current literature on atypical antipsychotic-induced metabolic syndrome in patients with schizophrenia, outline some of the molecular mechanisms behind this syndrome, identify demographic and disease-related risk factors, and describe cost-effective methods for surveillance. Discussion The differential prevalence of metabolic syndrome associated with various atypical antipsychotic medications has been evidenced across numerous studies, with higher effects seen for certain antipsychotic medications on weight gain, waist circumference, fasting triglyceride level, and glucose levels. Given the association of these symptoms, all atypical antipsychotic medications currently include a warning about the risk of hyperglycemia and diabetes, as well as suggestions for regular monitoring. Despite this, very little data are available to support adherence to these monitoring recommendations. Lack of awareness and resources, diffusion of responsibility, policy implementation, and organizational structure have all been implicated. Conclusion The treatment of schizophrenia involves a balance in terms of risks and benefits. Failing to treat because of risk for complications from metabolic syndrome may place the patient at a higher risk for more serious health outcomes. Supporting programs aimed at increasing monitoring of simple laboratory and clinical measures associated with metabolic syndrome may decrease important risk factors, improve patients' quality of life, and reduce healthcare costs. PMID:25126357

  7. Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis

    PubMed Central

    Geddes, John; Freemantle, Nick; Harrison, Paul; Bebbington, Paul

    2000-01-01

    Objective To develop an evidence base for recommendations on the use of atypical antipsychotics for patients with schizophrenia. Design Systematic overview and meta-regression analyses of randomised controlled trials, as a basis for formal development of guidelines. Subjects 12 649 patients in 52 randomised trials comparing atypical antipsychotics (amisulpride, clozapine, olanzapine, quetiapine, risperidone, and sertindole) with conventional antipsychotics (usually haloperidol or chlorpromazine) or alternative atypical antipsychotics. Main outcome measures Overall symptom scores. Rate of drop out (as a proxy for tolerability) and of side effects, notably extrapyramidal side effects. Results For both symptom reduction and drop out, there was substantial heterogeneity between the results of trials, including those evaluating the same atypical antipsychotic and comparator drugs. Meta-regression suggested that dose of conventional antipsychotic explained the heterogeneity. When the dose was ⩽12 mg/day of haloperidol (or equivalent), atypical antipsychotics had no benefits in terms of efficacy or overall tolerability, but they still caused fewer extrapyramidal side effects. Conclusions There is no clear evidence that atypical antipsychotics are more effective or are better tolerated than conventional antipsychotics. Conventional antipsychotics should usually be used in the initial treatment of an episode of schizophrenia unless the patient has previously not responded to these drugs or has unacceptable extrapyramidal side effects. PMID:11099280

  8. Hospitalization and cost after switching from atypical to typical antipsychotics in schizophrenia patients in Thailand

    PubMed Central

    Boonlue, Tuanthon; Subongkot, Suphat; Dilokthornsakul, Piyameth; Kongsakon, Ronnachai; Pattanaprateep, Oraluck; Suanchang, Orabhorn; Chaiyakunapruk, Nathorn

    2016-01-01

    Background Several clinical practice guidelines suggest using atypical over typical antipsychotics in patients diagnosed with schizophrenia. Nevertheless, cost-containment policy urged restricting usage of atypical antipsychotics and switching from atypical to typical antipsychotics. Objective This study aimed to evaluate clinical and economic impacts of switching from atypical to typical antipsychotics in schizophrenia patients in Thailand. Methods From October 2010 through September 2013, a retrospective cohort study was performed utilizing electronic database of two tertiary hospitals. Schizophrenia patients aged 18 years or older and being treated with atypical antipsychotics were included. Patients were classified as atypical antipsychotic switching group if they switched to typical antipsychotics after 180 days of continual atypical antipsychotics therapy. Outcomes were schizophrenia-related hospitalization and total health care cost. Logistic and Poisson regression were used to evaluate the risk of hospitalization, and generalized linear model with gamma distribution was used to determine the health care cost. All analyses were adjusted by employing propensity score and multivariable analyses. All cost estimates were adjusted according to 2013 consumer price index and converted to US$ at an exchange rate of 32.85 Thai bahts/US$. Results A total of 2,354 patients were included. Of them, 166 (7.1%) patients switched to typical antipsychotics. The adjusted odds ratio for schizophrenia-related hospitalization in atypical antipsychotic switching group was 1.87 (95% confidence interval [CI] 1.23–2.83). The adjusted incidence rate ratio was 2.44 (95% CI 1.57–3.79) for schizophrenia-related hospitalizations. The average total health care cost was lower in patients with antipsychotic switching (−$64; 95% CI −$459 to $332). Conclusion Switching from atypical to typical antipsychotics is associated with an increased risk of schizophrenia-related hospitalization

  9. Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review

    PubMed Central

    Umar, Musa Usman; Abdullahi, Aminu Taura

    2016-01-01

    A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect. PMID:27335511

  10. Off-label indications for atypical antipsychotics: A systematic review

    PubMed Central

    Fountoulakis, Konstantinos N; Nimatoudis, Ioannis; Iacovides, Apostolos; Kaprinis, George

    2004-01-01

    Introduction With the introduction of newer atypical antipsychotic agents, a question emerged, concerning their use as complementary pharmacotherapy or even as monotherapy in mental disorders other than psychosis. Material and method MEDLINE was searched with the combination of each one of the key words: risperidone, olanzapine and quetiapine with key words that refered to every DSM-IV diagnosis other than schizophrenia and other psychotic disorders, bipolar disorder and dementia and memory disorders. All papers were scored on the basis of the JADAD index. Results The search returned 483 papers. The selection process restricted the sample to 59 papers concerning Risperidone, 37 concerning Olanzapine and 4 concerning Quetiapine (100 in total). Ten papers (7 concerning Risperidone and 3 concerning Olanzapine) had JADAD index above 2. Data suggest that further research would be of value concerning the use of risperidone in the treatment of refractory OCD, Pervasive Developmental disorder, stuttering and Tourette's syndrome, and the use of olanzapine for the treatment of refractory depression and borderline personality disorder. Discussion Data on the off-label usefulness of newer atypical antipsychotics are limited, but positive cues suggest that further research may provide with sufficient hard data to warrant the use of these agents in a broad spectrum of psychiatric disorders, either as monotherapy, or as an augmentation strategy. PMID:14975068

  11. Type 2 diabetes in children and adolescents on atypical antipsychotics.

    PubMed

    Pramyothin, Pornpoj; Khaodhiar, Lalita

    2015-08-01

    Youth receiving treatment with antipsychotics are particularly susceptible to weight gain, type 2 diabetes (T2D), and associated metabolic disorders, which is directly associated with excess morbidity and mortality in this vulnerable population. The risk of T2D is 2- to 3-fold that of the general population, starts early in the course of treatment, and reflects the effects of weight gain in conjunction with direct effects of antipsychotics on the hypothalamus, pancreatic beta cells, and insulin-sensitive peripheral tissues. Close monitoring with early intervention through lifestyle intervention, switching away from antipsychotics with deleterious metabolic effects, and adjunctive treatment with metformin are modalities available to mitigate weight gain and improve cardiometabolic health in these patients. Despite rapidly advancing knowledge in the field, patient's access to metabolic screening and quality care remains limited. Efforts must be made to broaden reach of early cardiometabolic intervention among these patients in order to avert serious cardiovascular disease burden in the future.

  12. Amisulpride a selective dopamine antagonist and atypical antipsychotic: results of a meta-analysis of randomized controlled trials.

    PubMed

    Leucht, Stefan

    2004-03-01

    The pharmacological profiles of the atypical antipsychotics, clozapine, olanzapine, quetiapine and risperidone, all show a combined serotonin (5-HT2) and dopamine type-2 (D2) receptor antagonism. Amisulpride, a highly selective dopamine D2/D3 receptor antagonist that binds preferentially to receptors in the mesolimbic system, is also an 'atypical' antipsychotic despite having a different receptor-affinity profile. A meta-analysis of 18 clinical trials was undertaken to compare the efficacy and safety of amisulpride with conventional antipsychotics. The improvement in mental state was assessed using the Brief Psychiatric Rating Scale (BPRS) or the Scale for the Assessment of Negative Symptoms (SANS). In a pooled analysis of 10 studies of acutely ill patients, amisulpride was significantly more effective than conventional neuroleptics with regard to improvement of global symptoms. Amisulpride is, to date, the only atypical antipsychotic for which several studies on patients suffering predominantly from negative symptoms have been published. In four such studies, amisulpride was significantly superior to placebo. Three small studies with conventional neuroleptics as a comparator showed only a trend in favour of amisulpride in this regard. Amisulpride was associated with fewer extrapyramidal side-effects and fewer drop-outs due to adverse events than conventional neuroleptics. These results clearly show that amisulpride is an 'atypical' antipsychotic, and they cast some doubt on the notion that combined 5-HT2-D2 antagonism is the only reason for the high efficacy against negative symptoms and fewer extrapyramidal side-effects.

  13. A potential mechanism underlying atypical antipsychotics-induced lipid disturbances.

    PubMed

    Cai, H L; Tan, Q Y; Jiang, P; Dang, R L; Xue, Y; Tang, M M; Xu, P; Deng, Y; Li, H D; Yao, J K

    2015-10-20

    Previous findings suggested that a four-protein complex, including sterol-regulatory element-binding protein (SREBP), SREBP-cleavage-activating protein (SCAP), insulin-induced gene (INSIG) and progesterone receptor membrane component 1 (PGRMC1), within the endoplasmic reticulum appears to be an important regulator responsible for atypical antipsychotic drug (AAPD)-induced lipid disturbances. In the present study, effects of typical antipsychotic drug and AAPDs as well as treatment outcome of steroid antagonist mifepristone (MIF) on the PGRMC1/INSIG/SCAP/SREBP pathway were investigated in rat liver using real-time quantitative polymerase chain reaction (qPCR) and western blot analysis. In addition, serum triacylglycerol, total cholesterol, free fatty acids and various hormones including progesterone, corticosterone and insulin were measured simultaneously. Following treatment with clozapine or risperidone, both lipogenesis and cholesterogenesis were enhanced via inhibition of PGRMC1/INSIG-2 and activation of SCAP/SREBP expressions. Such metabolic disturbances, however, were not demonstrated in rats treated with aripiprazole (ARI) or haloperidol (HAL). Moreover, the add-on treatment of MIF was effective in reversing the AAPD-induced lipid disturbances by upregulating the expression of PGRMC1/INSIG-2 and subsequent downregulation of SCAP/SREBP. Taken together, our findings suggest that disturbances in lipid metabolism can occur at an early stage of AAPD treatment before the presence of weight gain. Such metabolic defects can be modified by an add-on treatment of steroid antagonist MIF enhancing the PGRMC1 pathway. Thus, it is likely that PGRMC1/INSIG-2 signaling may be a therapeutic target for AAPD-induced weight gain.

  14. Attentional and emotional functioning in schizophrenia patients treated with conventional and atypical antipsychotic drugs

    PubMed Central

    Kucharska-Pietura, Katarzyna; Tylec, Aneta; Czernikiewicz, Andrzej; Mortimer, Ann

    2012-01-01

    Summary Background Effectiveness of antipsychotics in treating emotional and cognitive deficits in schizophrenia still remains controversial. The aim of our study was to assess emotional and cognitive functioning in schizophrenic inpatients currently treated with typical antipsychotics (perphenazine, perazine, fluphenazine, and haloperidol) and in another group of schizophrenic inpatients currently on atypical antipsychotics (olanzapine, risperidone, amisulpride, and quetiapine). Material/Methods One hundred patients with DSM-IV schizophrenia or schizoaffective disorders (39 treated using typical antipsychotics and 61 treated with atypical antipsychotics) under naturalistic treatment conditions, and 50 healthy controls were given the following: Test of Everyday Attention, Facial Emotion Recognition Test, Facial Memory Recognition Test, and “Reading the mind in the eyes” Test. Results Patients with a diagnosis of schizophrenia revealed the following deficits: facial emotion perception, empathy/theory of mind, visual selective attention/speed, attentional switching, and auditory-verbal working memory. Our results show a significant difference between schizophrenic and healthy controls in all tasks, with schizophrenic patients performing worse than controls. Interestingly, our patients on atypical neuroleptics performed similarly compared to schizophrenic patients treated with conventional neuroleptics on all tasks provided. There were some significant relationships between emotional and cognitive deficits and clinical variables. Conclusions Our findings remain consistent with other recent studies in which atypical antipsychotics did not show a clear advantage over typical antipsychotics on both emotional and cognitive functioning. PMID:22207119

  15. How do we choose between atypical antipsychotics? The advantages of amisulpride.

    PubMed

    Mortimer, Ann M

    2004-03-01

    Clinician choice of an atypical antipsychotic may depend on a number of factors such as perceived efficacy, tolerability and cost. It is also important that the choice of treatment takes into consideration the previous response to treatment, experience of side-effects and personal clinical characteristics. The receptor-affinity profiles of the atypical antipsychotics differ; with the exception of amisulpride, a selective D2/D3 antagonist, all the atypical antipsychotics exhibit a greater affinity for the serotonin-2A receptors than dopamine receptors. However, there is no evidence that the variation in receptor affinities is relevant to efficacy. Indeed, the crucial factor may be fast dissociation from low affinity for the D2 receptor. Tolerability also varies between the atypical antipsychotics and the side-effect profile may be related to the receptor-affinity profile of the individual drugs. Extrapyramidal side-effects are generally less of a problem with most atypical drugs than with conventional drugs, but weight gain, loss of glycaemic control, sedation and hyperprolactinaemia remain problematic in some patients. Amisulpride is effective for the treatment of both positive and negative symptoms, and is well tolerated with regard to weight gain, glucose tolerance and sedation. In two clinical trials, the AMIRIS and SOLIANOL studies, amisulpride demonstrated clear advantages over some other atypical antipsychotics with respect to negative symptoms, depressive symptoms and weight gain.

  16. Off-label use of atypical antipsychotics: cause for concern?

    PubMed

    McKean, Andrew; Monasterio, Erik

    2012-05-01

    Licensed indications for medicines were designed to regulate the claims that can be made about a medicine by a pharmaceutical company. Off-label prescribing (i.e. prescribing a drug for an indication outside of that for which it is licensed) is legal and an integral part of medical practice. In psychiatry, off-label prescribing is common and gives clinicians scope to treat patients who are refractory to standard therapy or where there is no licensed medication for an indication. However, efficacy or safety of such off-label use may not be established. There is a growing list of licensed indications for atypical antipsychotics (AAP) beyond schizophrenia and bipolar affective disorder, and also more evidence for other indications where pharmaceutical companies have not obtained a license. Pharmaceutical companies have promoted AAPs for off-label indications to increase sales and consequently have been fined by the US FDA for this. Since the 1990s, AAP use has expanded considerably, for example, the off-label use of quetiapine alone accounted for an estimated 17% of the AAP spend in New Zealand in 2010. There are a number of potential problems with the expanded use of AAPs outside of schizophrenia and related psychoses. A larger population will be exposed to their adverse effects, which include weight gain, type 2 diabetes mellitus, sudden cardiac death and increased mortality rates in the elderly with dementia. There are also concerns with the abuse of these agents, in particular quetiapine. Given that an increasing percentage of the population is being treated with these agents, off-label prescribing of AAPs is a cause for concern; they have a propensity to cause significant side effects and their efficacy and long-term safety for most off-label indications remains largely unknown, and therefore the risks and benefits of their use should be carefully weighed up prior to prescribing these agents off-label. PMID:22448598

  17. [Social cognition and atypical antipsychotic agents in the treatment of persons with schizophrenia: preliminary data from a naturalistic study].

    PubMed

    Mazza, M; Tozzini, C; Giosué, P; De Risio, A; Palmucci, M; Roncone, R; Casacchia, M

    2003-01-01

    Schizophrenia is a chronic disorder that begins in adolescence or in early adulthood. In schizophrenic disorder there are relevant deficits in social interaction. The aim of this study was to evaluate the efficacy of atypical antipsychotic drugs compared to a conventional antipsychotic in the treatment of psychotic symptoms and on cognitive functions of a group of people affected by schizophrenia. Effects of novel antipsychotic drugs on social functioning improvement, regarded as improvement in the ability to represent mental states, were thoroughly assessed. Our study was conducted in the form of naturalistic observation of a sample of 45 people affected by schizophrenia treated with haloperidol, clozapine and risperidone. Our results show that after one year of treatment there were significant positive results in social competence abilities in the group of people being treated with risperidone. Theses results may have a relevant impact on the improvement of quality of life in people affected by schizophrenia.

  18. [Assessment of metabolic impairments inducted by atypical antipsychotics among schizophrenic patients].

    PubMed

    Gauthé, M; Goldberger, C; Olié, J P; Lôo, H; Gury, C; Poirier, M F

    2005-01-01

    Conventional and atypical antipsychotics are known to induce weight gain, cause glucose and lipid impairments among schizophrenic patients. These impairments contribute to the intrinsic risk factors linked to the psychiatric pathology (sedentary state, nicotin addiction, diabetes) increasing numbers of cardiovascular complications. We propose to study ponderal modifications and presence of metabolic abnormalities in a population of schizophrenic patients treated by conventional or atypical antipsychotics, depending on the received treatment; 32 patients, whose schizophrenia diagnosis had been previously made, were consecutively included over a 4 months period. They were divided into three groups: patients treated by conventional antipsychotics (n = 6), by atypical antipsychotics (n = 16) or by a combination of both (n = 10); 6 patients (18%) display overweight problems, 4 patients (12.5%) got hypertriglyceridemia and 4 other patients (12.5%) have hypercholesterolemia. No particular drug could be directly targeted, partly because of the restricted size of our sample, but the patients presenting metabolism impairment were treated by atypical antipsychotic. The observance of these abnormalities is reflected in publications and lead to some antipsychotic treatments monitoring rules. PMID:15971636

  19. Tardive dyskinesia in patients treated with atypical antipsychotics: case series and brief review of etiologic and treatment considerations

    PubMed Central

    Kim, Jungjin; MacMaster, Eric; Schwartz, Thomas L

    2014-01-01

    Tardive dyskinesia (TD) is a disfiguring side-effect of antipsychotic medications that is potentially irreversible in affected patients. Newer atypical antipsychotics are felt by many to have a lower risk of TD. As a result, many clinicians may have developed a false sense of security when prescribing these medications. We report five cases of patients taking atypical antipsychotics who developed TD, review the risk of TD, its potential etiologic mechanisms, and treatment options available. The goal of this paper is to alert the reader to continue to be diligent in obtaining informed consent and monitoring for the onset of TD in patients taking atypical antipsychotics. PMID:24744806

  20. Management of atypical antipsychotic-induced weight gain in schizophrenic patients with topiramate.

    PubMed

    Lin, Yi-Hsiung; Liu, Chia-Yih; Hsiao, Mei-Chun

    2005-10-01

    Patients treated with atypical antipsychotic drugs commonly gain excess weight. Because obesity is associated with considerable morbidity and decreased life expectancy, treatment of weight gain in these patients is critical. Topiramate, a fairly new anticonvulsant, promotes bodyweight loss in healthy obese subjects, patients with bipolar disorder, and patients with eating disorder. However, there are very few reports about the efficacy of topiramate for weight management in schizophrenic patients. We present the cases of three Taiwanese patients with schizophrenia whose bodyweight increased as a result of atypical antipsychotics treatment, then was controlled by topiramate without aggravation of their psychotic symptoms.

  1. Monitoring Metabolic Side Effects of Atypical Antipsychotics in People with an Intellectual Disability

    ERIC Educational Resources Information Center

    Teeluckdharry, Sadira; Sharma, Sujit; O'Rourke, Elizabeth; Tharian, Priyanka; Gondalekar, Anjali; Nainar, Feroz; Roy, Meera

    2013-01-01

    This audit was undertaken prospectively to examine the compliance of a group of psychiatrists against guidelines they developed for monitoring the onset of metabolic syndrome, a potential side effect of antipsychotic medication, especially second generation or atypical ones. Phase 1 of the audit was to set standards by a questionnaire survey of…

  2. Using Functional Analysis Methodology to Evaluate Effects of an Atypical Antipsychotic on Severe Problem Behavior

    ERIC Educational Resources Information Center

    Danov, Stacy E.; Tervo, Raymond; Meyers, Stephanie; Symons, Frank J.

    2012-01-01

    The atypical antipsychotic medication aripiprazole was evaluated using a randomized AB multiple baseline, double-blind, placebo-controlled design for the treatment of severe problem behavior with 4 children with intellectual and developmental disabilities. Functional analysis (FA) was conducted concurrent with the medication evaluation to…

  3. Characterization of typical and atypical antipsychotic drugs based on in vivo occupancy of serotonin2 and dopamine2 receptors.

    PubMed

    Stockmeier, C A; DiCarlo, J J; Zhang, Y; Thompson, P; Meltzer, H Y

    1993-09-01

    Atypical antipsychotic drugs related to clozapine may be distinguishable from typical antipsychotic drugs by having a greater potency in vitro at serotonin2 (5-HT2) receptors relative to dopamine2 (D2) receptors. The in vivo potencies of 10 typical and 10 putative atypical antipsychotic drugs in occupying D2 and 5-HT2 receptors in rat brain are reported here. There is no significant difference in the average potency of the two groups of antipsychotic drugs in preventing the in vivo binding of N-[3H] methylspiperone to 5-HT2 receptors in the cortex. However, the average potency of the atypical antipsychotic drugs is about 8-fold less than typical antipsychotic drugs in preventing N-[3H] methylspiperone binding to D2 receptors in the striatum. Thus, all of the atypical antipsychotic drugs that are clozapine-like have a greater relative affinity in vivo for the 5-HT2 than the D2 receptor. As a group, the typical antipsychotic drugs tend to be equipotent at both receptors. The average relative potency of the group of typical antipsychotic drugs at 5-HT2 vs. D2 receptors is essentially equal when examined in vivo vs. in vitro. Atypical antipsychotic drugs are slightly but significantly more potent in vivo at D2 receptors in the olfactory tubercle than the striatum. For only the typical antipsychotic drugs, the in vivo and in vitro potencies in occupying D2 receptors are correlated with their average clinical dosage. Thus, the relative in vivo potency of clozapine-related drugs at 5-HT2 vs. D2 receptors may help identify these compounds as atypical antipsychotic drugs.

  4. Evaluation of Paraoxonase, Arylesterase and Malondialdehyde Levels in Schizophrenia Patients Taking Typical, Atypical and Combined Antipsychotic Treatment

    PubMed Central

    Güneş, Mehmet; Camkurt, Mehmet Akif; Bulut, Mahmut; Demir, Süleyman; İbiloğlu, Aslıhan Okan; Kaya, Mehmet Cemal; Atlı, Abdullah; Kaplan, İbrahim; Sir, Aytekin

    2016-01-01

    Objective Human serum paraoxonase (PON1) prevents lipids from peroxidation and functions as an antioxidant mechanism. Malonyldialdehyde (MDA) is the final product of lipid peroxidation and can be used as an indicator of oxidative stress. The aim of this study was to investigate PON1, MDA, and arylesterase (ARY) levels in schizophrenic patients who are taking typical, atypical, or combined (typical and atypical) antipsychotic drug treatment, with respect to those of healthy controls. Methods We evaluated 41 patients (11 taking typical antipsychotics, 19 taking atypical antipsychotics, 11 taking combined anti-psychotics) and 43 healthy controls. Results MDA levels were higher in schizophrenic patients taking typical antipsychotics compared with healthy controls (p=0.001). ARY levels were higher in patients taking atypical antipsychotics compared with healthy controls (p=0.005). PON1 activity was similar in all groups. Conclusion Our results indicate that treatment with typical antipsychotic drugs could be related to increased MDA levels; and antipsychotic medication may increase PON1 levels in schizophrenic patients. PMID:27776386

  5. The newer, 'atypical' antipsychotic drugs--their development and current therapeutic use.

    PubMed Central

    Kendrick, T

    1999-01-01

    General practitioners (GPs) need to become more aware of a new generation of antipsychotic drugs that are 'atypical' in that, unlike traditional neuroleptics, they do not cause extrapyramidal side-effects; they may also be more effective against both the positive and negative symptoms of schizophrenia by their actions on various neurotransmitter pathways in the brain. This is a non-systematic review of the development of these new drugs and outlines how they are currently being used. It includes information found from an electronic search of the databases MEDLINE (from 1966 to June 1998) and EMBASE (from 1980 to January 1998) using the combined search terms 'antipsychotic agents', 'atypical', and 'schizophrenia'. PMID:10756621

  6. Misuse of atypical antipsychotics in conjunction with alcohol and other drugs of abuse.

    PubMed

    Malekshahi, Tara; Tioleco, Nina; Ahmed, Nahima; Campbell, Aimee N C; Haller, Deborah

    2015-01-01

    Non-medical use of atypical antipsychotics by substance abusers has been reported in the literature, although no detailed studies exist. Among 429 addiction treatment inpatients screened, 73 (17.0%) reported misuse of antipsychotics with alcohol, opioids, cocaine, methamphetamine and/or cannabis; 39 (9.1%) within the past year. Of past year misusers, 25 (64.1%) were interviewed. Most were male (76.0%), non-Caucasian (56.0%), and polysubstance abusers (84.0%). Quetiapine, the most abused drug (96.0%), was obtained primarily from doctors (52.0%) and family/friends (48.0%). Reasons for use included to "recover" from other substances (66.7%), "enhance" the effects of other substances (25.0%), and "experiment" (20.8%). The most frequently reported positive effect was "feeling mellow" (75.0%); negative effects were consistent with antipsychotic use (e.g., feeling thirsty, trouble concentrating). Compared to a normative sample of inpatient substance abusers, ASI composite scores were higher. Findings suggest that physicians should assess for use/misuse of atypical antipsychotics among patients with addiction. PMID:25216812

  7. Psychopharmacology of chronic pain: a focus on antidepressants and atypical antipsychotics.

    PubMed

    Khouzam, Hani Raoul

    2016-01-01

    Chronic pain is considered one of the most prevalent causes of costly and disabling medical conditions. This review will define chronic pain and its categories and then will summarize the effectiveness and side effects associated with the use of various antidepressants, including the tricyclics, the selective serotonin reuptake inhibitors, the serotonin norepinephrine reuptake inhibitors, other miscellaneous antidepressants and the atypical antipsychotics in the treatment of chronic pain. PMID:26821680

  8. Psychosocial processes influencing weight management among persons newly prescribed atypical antipsychotic medications.

    PubMed

    Xiao, S; Baker, C; Oyewumi, L K

    2012-04-01

    The purpose was to generate a theory of the psychosocial processes influencing weight management among persons newly prescribed atypical antipsychotic medications. A grounded theory research design was used to guide the study. Semi-structured interviews were the method of data collection, and analysis was performed using constant comparison. Using theoretical sampling, a sample of 11 participants with first-episode psychosis prescribed atypical antipsychotics for at least 8 weeks, and five participants with a diagnosis of chronic schizophrenia prescribed atypical antipsychotic medication for at least 3 years were recruited from an outpatient psychiatric programme. Contextual factors influencing weight management were: accessibility to resources, unstructured lifestyle, and others' perception of weight. Conditions influencing weight management were: rapid weight gain, insatiable hunger and lack of motivation boosters. Participants' early responses to weight gain included discontinuing medications, choosing lower-calorie foods, using walking in daily activities as exercise, accepting weight gain and trying to manage weight but giving up. The consequences revealed from data analysis were contemplating weight management and not trying, as the barriers to weight management exceeded the facilitators. The theoretical framework developed in this study can assist with the understanding and management of weight gain among this unique population. PMID:22074295

  9. Pharmacogenomics can improve antipsychotic treatment in schizophrenia.

    PubMed

    Xu, Qingqing; Wu, Xi; Xiong, Yuyu; Xing, Qinghe; He, Lin; Qin, Shengying

    2013-06-01

    Schizophrenia is a widespread mental disease with a prevalence of about 1% in the world population, and heritability of up to 80%. Drug therapy is an important approach to treating the disease. However, the curative effect of antipsychotic is far from satisfactory in terms of tolerability and side effects. Many studies have indicated that about 30% of the patients exhibit little or no improvements associated with antipsychotics. The response of individual patients who are given the same dose of the same drug varies considerably. In addition, antipsychotic drugs are often accompanied by adverse drug reactions (ADRs), which can cause considerable financial loss in addition to the obvious societal harm. So, it is strongly recommended that personalized medicine should be implemented both to improve drug efficacy and to minimize adverse events and toxicity. There is therefore a need for pharmacogenomic studies into the factors affecting response of schizophrenia patients to antipsychotic drugs to provide informed guidance for clinicians. Individual differences in drug response is due to a combination of many complex factors including ADEM (absorption, distribution, metabolism, excretion) process, transporting, binding with receptor and intracellular signal transduction. Pharmacogenetic and pharmacogenomic studies have successfully identified genetic variants that contribute to this interindividual variability in antipsychotics response. In addition, epigenetic factors such as methylation of DNA and regulation by miRNA have also been reported to play an important role in the complex interactions between the multiple genes and environmental factors which influence individual drug response phenotypes in patients. In this review, we will focus on the latest research on polymorphisms of candidate genes that code for drug metabolic enzymes (CYP2D6, CYP1A2, CYP3A4, etc.), drug transporters (mainly ABCB1) and neurotransmitter receptors (dopamine receptors and serotonin

  10. Do atypical antipsychotics really enhance smoking reduction more than typical ones?: the effects of antipsychotics on smoking reduction in patients with schizophrenia.

    PubMed

    Wu, Bo-Jian; Chen, Hsing-Kang; Lee, Shin-Min

    2013-06-01

    Whether atypical antipsychotics (AAs) can enhance smoking reduction in schizophrenic patients remains controversial because of methodological limitations in existing studies. This study explored whether certain types of antipsychotics predict smoking reduction in schizophrenic patients. Three hundred eight smoking, predominantly male schizophrenic patients (271/308 [88.9%]) participated in an 8-week open-label study with antismoking medications (high-dose, low-dose nicotine transdermal patch and bupropion). Antipsychotics were classified into (1) typical antipsychotics (TAs) and (2) AAs, including multiacting receptor-targeted antipsychotics (clozapine, olanzapine, and quetiapine), serotonin-dopamine antagonists (risperidone), D2/D3 receptor antagonists (amisulpride), and partial dopamine receptor agonists (aripiprazole). A general linear model was used to explore whether types of antipsychotic predict changes in the number of cigarettes smoked per day (CPD) and the score of the Fagerstrom Test for Nicotine Dependence (FTND) while controlling for confounding factors. The type of antipsychotic (TAs or AAs) was not significantly associated with smoking cessation (n = 21; χ = 1.8; df = 4; P = 0.77). Regarding smoking reduction, the type of antipsychotic was significantly predictive of a change in the CPD (P = 0.027; partial eta square = 0.055) and FTND scores (P = 0.002; partial eta square = 0.073). The 95% confidence intervals of the estimated means of change in the CPD and FTND scores did not contain zero only among subjects on TAs or clozapine.These findings suggest that TAs and clozapine enhance smoking reduction compared with nonclozapine atypical antipsychotics in schizophrenic patients. The mechanisms underlying the effects of various antipsychotics on smoking reduction remain unclear and warrant future study.

  11. Typical and atypical antipsychotic medications differentially affect two nondeclarative memory tasks in schizophrenic patients: a double dissociation.

    PubMed

    Beninger, Richard J; Wasserman, James; Zanibbi, Katherine; Charbonneau, Danielle; Mangels, Jennifer; Beninger, Bruce V

    2003-06-01

    Nondeclarative memory (NDM) has subtypes associated with different brain regions; learning of a probabilistic classification task is impaired by striatal damage and learning of a gambling task is impaired by ventromedial prefrontocortical damage. Typical and atypical antipsychotic medications differentially affect immediate early gene expression in the striatum and frontal cortex in normal rats. This suggested the hypothesis that schizophrenic patients treated with typical antipsychotics will have impaired probabilistic classification learning (PCL) and that similar patients treated with atypical antipsychotics will have impaired learning of the gambling task. Groups of schizophrenia patients treated with typical or atypical antipsychotics did not differ from each other on the Brief Psychiatric Rating Scale (BPRS), Mini Mental State Exam (MMSE) or a number of indexes of the Wisconsin Card Sorting Task (WCST) but performed worse than normal controls on these instruments. In the first study, patients treated with typicals (n=20) but not atypicals (n=20) or normal controls (n=32) were impaired in probabilistic classification. In the second study, those treated with atypicals (n=18) but not typicals (n=18) or normal controls (n=18) were impaired in the gambling task. Results suggest that typical and atypical antipsychotics differentially affect nondeclarative memory mediated by different brain regions. PMID:12729880

  12. Atypical antipsychotics alter cholesterol and fatty acid metabolism in vitro[S

    PubMed Central

    Canfrán-Duque, Alberto; Casado, María E.; Pastor, Óscar; Sánchez-Wandelmer, Jana; de la Peña, Gema; Lerma, Milagros; Mariscal, Paloma; Bracher, Franz; Lasunción, Miguel A.; Busto, Rebeca

    2013-01-01

    Haloperidol, a typical antipsychotic, has been shown to inhibit cholesterol biosynthesis by affecting Δ7-reductase, Δ8,7-isomerase, and Δ14-reductase activities, which results in the accumulation of different sterol intermediates. In the present work, we investigated the effects of atypical or second-generation antipsychotics (SGA), such as clozapine, risperidone, and ziprasidone, on intracellular lipid metabolism in different cell lines. All the SGAs tested inhibited cholesterol biosynthesis. Ziprasidone and risperidone had the same targets as haloperidol at inhibiting cholesterol biosynthesis, although with different relative activities (ziprasidone > haloperidol > risperidone). In contrast, clozapine mainly affected Δ24-reductase and Δ8,7-isomerase activities. These amphiphilic drugs also interfered with the LDL-derived cholesterol egress from the endosome/lysosome compartment, thus further reducing the cholesterol content in the endoplasmic reticulum. This triggered a homeostatic response with the stimulation of sterol regulatory element-binding protein (SREBP)-regulated gene expression. Treatment with SGAs also increased the synthesis of complex lipids (phospholipids and triacylglycerides). Once the antipsychotics were removed from the medium, a rebound in the cholesterol biosynthesis rate was detected, and the complex-lipid synthesis further increased. In this condition, apolipoprotein B secretion was also stimulated as demonstrated in HepG2 cells. These effects of SGAs on lipid homeostasis may be relevant in the metabolic side effects of antipsychotics, especially hypertriglyceridemia. PMID:23175778

  13. Cognitive Impairment in Schizophrenia, Neurotransmitters and the New Atypical Antipsychotic Aripiprazole.

    PubMed

    Topolov, Mariyan K; Getova, Damianka P

    2016-03-01

    Cognition is a group of mental processes that includes the capacity to perceive, think, learn and to study, and the capacity of the brain to analyze information and program adaptive behaviour. Although there has been an appreciable evolution in the therapy of psychoses in the last twenty-five years, cognitive disturbances still persist in spite of antipsychotic treatment. The cognitive decay disrupts the ability of clinically diagnosed patients with psychoses, mainly schizophrenia, to learn and to memorize skills that are useful for their family and social relationships. Moreover, cognitive deficiency is often considered to be crucial for further rehabilitation. In atypical antipsychotics there are big differences in the effects on cognitive functions. Some clinical studies demonstrate the benefits of a third generation of antipsychotics on cognitive functions in patients treated for mental illnesses. In the present study we have reviewed many articles investigating the influence of aripiprazole on cognition in human and animal subjects. Aripiprazole is a third generation antipsychotic drug that possesses a unique pharmacodynamic profile, which in conjunction with recently published scientific data on the drugs' influence on antidepressant, anxiolytic and cognitive functions, suggests a highly positive future potential for restorative cognitive treatment and ongoing healthy function. The data included in the review will contribute to determining the potential benefits of aripiprazole on memory and training processes. PMID:27383873

  14. The effects of race and criminal justice involvement on access to atypical antipsychotic medications among persons with schizophrenia.

    PubMed

    Van Dorn, Richard A; Swanson, Jeffrey W; Swartz, Marvin S; Elbogen, Eric B

    2005-06-01

    This study examined the impact of race and arrest history on the likelihood of being prescribed, and maintaining an atypical antipsychotic prescription for 90 or more days among patients with schizophrenia in the community. Participants were 224 adults with schizophrenia-spectrum disorders receiving services in public-sector mental health systems in North Carolina. The data used for this report were from a subsample of a larger group of participants being followed in an observational study and consisted of individuals who were prescribed either an atypical or conventional antipsychotic medication for 90 or more days. The purpose of the analyses presented here was to investigate differences in the likelihood of being prescribed an atypical antipsychotic by demographic and other characteristics. Logistic regression analysis indicated that African American patients were significantly less likely to receive atypical antipsychotics than their white counterparts, even when controlling for key clinical and demographic variables. However, white patients with a history of arrest were no more likely than black patients to receive atypical antipsychotics; that is, minority racial status and criminal involvement each functioned to limit patients' access to the novel medications. Implications for equal access to mental health services, in this case, effective psychopharmacologic treatment, are discussed.

  15. Olanzapine, an atypical antipsychotic, increases rates of punished responding in pigeons.

    PubMed

    Benvenga, M J; Leander, J D

    1995-05-01

    The effects of olanzapine [LY 170053; 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2, 3b] [1,5]benzodiazepine), a potential atypical antipsychotic, were determined in pigeons whose keypeck responding was punished. These effects were compared to the anxiolytic agents chlordiazepoxide and pentobarbital, and to other antipsychotic agents. Keypeck behavior was maintained under a multiple FR30 FR30 schedule, signalled by white and red stimulus lights, respectively. Each component of the schedule alternated every 3 min with a 30-s timeout. During the white keylight component, responding was maintained by food presentation. During the red keylight component, responding was maintained by food and simultaneously suppressed by electric shock presentation, with response rates being only about 5% of those during the white stimulus light. Olanzapine (0.01-1.0 mg/kg) increased punished responding at doses below those which had an effect on unpunished responding. Clozapine (0.01-1.0 mg/kg), ritanserin (0.1-3.0 mg/kg), and, to a lesser extent, risperidone (0.1-1.0 mg/kg) were also effective at increasing punished responding. Generally, the maximum effect seen with olanzapine was equal to that seen with ritanserin, and it exceeded that seen with clozapine. However, these effects were generally less than those seen with chlordiazepoxide and pentobarbital. Haloperidol (0.01-0.1 mg/kg) was completely without effect on punished responding, while it caused decreases in unpunished behavior. These results provide further evidence that olanzapine has a profile in behavioral tests unlike the typical antipsychotic haloperidol. Moreover, this profile is similar to clozapine, a clinically effective antipsychotic with an atypical profile. PMID:7544900

  16. Use of atypical antipsychotic drugs for schizophrenia in Maine Medicaid following a policy change.

    PubMed

    Soumerai, Stephen B; Zhang, Fang; Ross-Degnan, Dennis; Ball, Daniel E; LeCates, Robert F; Law, Michael R; Hughes, Tom E; Chapman, Daniel; Adams, Alyce S

    2008-01-01

    More than one-third of Medicaid programs and Medicare Part D plans use prior authorization (PA) policies to control the use of atypical antipsychotics (AAs). We used Medicaid and Medicare claims data to investigate how Maine's PA policy affected AA use, treatment discontinuities, and spending among schizophrenia patients initiating AA therapy. Patients initiating AAs during Maine's policy experienced a 29 percent greater risk of treatment discontinuity than patients initiating AAs before the policy took effect; no change occurred in a comparison state. AA spending was slightly lower in both states. Observed increases in treatment discontinuities without cost savings suggest that AAs should be exempt from PA for patients with severe mental illnesses.

  17. The Long-Term Effects of Conventional and Atypical Antipsychotics in Patients With Probable Alzheimer’s Disease

    PubMed Central

    Lopez, Oscar L.; Becker, James T.; Chang, Yue-Fang; Sweet, Robert A.; Aizenstein, Howard; Snitz, Beth; Saxton, Judith; McDade, Eric; Kamboh, M. Ilyas; DeKosky, Steven T.; Reynolds, Charles F.; Klunk, William E.

    2014-01-01

    Objective The authors sought to determine the effects of conventional and atypical antipsychotic use on time to nursing home admission and time to death in a group of outpatients with mild to moderate probable Alzheimer’s disease. Method The authors examined time to nursing home admission and time to death in 957 patients with the diagnosis of probable Alzheimer’s disease who had at least one follow-up evaluation (mean follow-up time, 4.3 years [SD=2.7]; range, 0.78–18.0 years) using Cox proportional hazard models adjusted for age, gender, education level, dementia severity, hypertension, diabetes mellitus, heart disease, extrapyramidal signs, depression, psychosis, aggression, agitation, and dementia medication use. Results A total of 241 patients (25%) were exposed to antipsychotics at some time during follow-up (conventional, N=138; atypical, N=95; both, N=8). Nursing home admission (63% compared with 23%) and death (69% compared with 34%) were more frequent in individuals taking conventional than atypical antipsychotics. In amodel that included demographic and cognitive variables, hypertension, diabetes mellitus, heart disease, incident strokes, and extrapyramidal signs, only conventional antipsychotic use was associated with time to nursing home admission. However, the association was no longer significant after adjustment for psychiatric symptoms. Psychosis was strongly associated with nursing home admission and time to death, but neither conventional nor atypical antipsychotics were associated with time to death. Conclusions The use of antipsychotic medications, both conventional and atypical, was not associated with either time to nursing home admission or time to death after adjustment for relevant covariates. Rather, it was the presence of psychiatric symptoms, including psychosis and agitation, that was linked to increased risk of institutionalization and death after adjustment for exposure to antipsychotics. PMID:23896958

  18. Cinnarizine has an atypical antipsychotic profile in animal models of psychosis.

    PubMed

    Dall'Igna, Oscar P; Tort, Adriano B L; Souza, Diogo O; Lara, Diogo R

    2005-07-01

    Cinnarizine, a drug known as a calcium channel blocker, is currently used for the treatment of migraine and vertigo. Induction of extrapyramidal signs by cinnarizine has been reported in the elderly, which is related to its moderate antagonistic properties at dopamine D2 receptors, resembling the mechanism of action of most antipsychotic drugs. Despite this effect, cinnarizine has never been tested as a putative antipsychotic drug. Here we evaluate the potential effect of cinnarizine in two pharmacological models of psychosis, namely amphetamine- and MK-801-induced hyperlocomotion, as well as its ability to induce catalepsy. Cinnarizine significantly counteracted MK-801 (0.25 mg/kg) and amphetamine (5mg/kg) locomotor effects at doses as low as 20mg/kg, having no incremental effect at 60 or 180 mg/kg. Regarding side-effects, cinnarizine induced no catalepsy in mice at the effective dose of 20 mg/kg, inducing only mild catalepsy at the doses of 60 and 180 mg/kg. Based on these results and on the antagonist effect of cinnarizine on dopamine D2 receptors, we suggest that it has a potential antipsychotic effect with an atypical profile that should be evaluated clinically. PMID:15982988

  19. Minimizing cardiovascular adverse effects of atypical antipsychotic drugs in patients with schizophrenia.

    PubMed

    Khasawneh, Fadi T; Shankar, Gollapudi S

    2014-01-01

    The use of atypical antipsychotic agents has rapidly increased in the United States and worldwide in the last decade. Nonetheless, many health care practitioners do not appreciate the significance of the cardiovascular side effects that may be associated with their use and the means to minimize them. Thus, atypical antipsychotic medications can cause cardiovascular side effects such as arrhythmias and deviations in blood pressure. In rare cases, they may also cause congestive heart failure, myocarditis, and sudden death. Patients with schizophrenia have a higher risk of cardiovascular mortality than healthy individuals, possibly because of excessive smoking, the underlying disorder itself, or a combination of both factors. Increased awareness of these potential complications can allow pharmacists and physicians to better manage and monitor high risk patients. Accurate assessments are very important to avoid medications from being given to patients inappropriately. Additionally, monitoring patients regularly via blood draws and checking blood pressure, heart rate, and electrocardiogram can help catch any clinical problems and prevent further complications. Finally, patient and family-member education, which pharmacists in particular can play key roles in, is central for the management and prevention of side effects, which is known to reflect positively on morbidity and mortality in these patients. PMID:24649390

  20. Atypical Antipsychotics for Older Adults: Are They Safe and Effective As We Once Thought?

    PubMed Central

    Jeste, Dilip V.; Maglione, Jeanne E.

    2015-01-01

    Summary The initial enthusiasm for atypical antipsychotics as being safe and effective for treating older adults with psychotic disorders has diminished. Despite multiple short-term double-blind trials, these drugs have not been approved by the FDA for the most common form of psychosis in this population – i.e., psychosis associated with dementia. On the contrary, these drugs have received FDA warnings for adverse cerebrovascular events and mortality in these patients. Our pragmatic clinical trial failed to show evidence of either safety or effectiveness of the four most commonly prescribed atypical antipsychotics in middle-aged and older patients with different psychotic disorders – schizophrenia as well as psychosis associated with mood disorders, dementia or PTSD. A reconsideration of the common use of these medications, especially off-label use, in older patients is warranted. Unfortunately, there are no evidence-based alternatives to these agents in the target population. Wider employment of psychosocial interventions, cautious and limited use of medications, shared decision making, and greater research on developing better treatments are the order of the day. PMID:24236673

  1. Behavioral and Metabolic Effects of the Atypical Antipsychotic Ziprasidone on the Nematode Caenorhabditis elegans

    PubMed Central

    Gubert, Priscila; Aguiar, Gabriel Costa; Mourão, Tácito; Bridi, Jessika Cristina; Barros, Alexandre Guimarães; Soares, Félix Alexandre; Romano-Silva, Marco Aurélio

    2013-01-01

    Atypical antipsychotics are associated with metabolic syndrome, primarily associated with weight gain. The effects of Ziprasidone, an atypical antipsychotic, on metabolic syndrome has yet to be evaluated. Here in, we evaluated lipid accumulation and behavioral changes in a new experimental model, the nematode Caenorhabditis elegans (C. elegans). Behavioral parameters in the worms were evaluated 24 h after Ziprasidone treatment. Subsequently, lipid accumulation was examined using Nile red, LipidTox green and BODIPY labeling. Ziprasidone at 40 µM for 24 h effectively decreased the fluorescence labeling of all markers in intestinal cells of C. elegans compared to control (0.16% dimethyl sulfoxide). Ziprasidone did not alter behaviors related to energetic balance, such as pharynx pumping, defecation cycles and movement. There was, however, a reduction in egg-production, egg-laying and body-length in nematodes exposed to Ziprasidone without any changes in the progression of larval stages. The serotoninergic pathway did not appear to modulate Ziprasidone’s effects on Nile red fluorescence. Additionally, Ziprasidone did not alter lipid accumulation in daf-16 or crh-1 deletion mutants (orthologous of the transcription factors DAF-16 and CREB, respectively). These results suggest that Ziprasidone alters reproductive behavior, morphology and lipid reserves in the intestinal cells of C. elegans. Our results highlight that the DAF-16 and CREB transcription factors are essential for Ziprasidone-induced fat store reduction. PMID:24069346

  2. A Comparative Study of Sexual Dysfunction due to Typical and Atypical Antipsychotics in Remitted Bipolar-I Disorder

    PubMed Central

    Nagaraj, Anil Kumar M.; Nizamie, Haque S.; Akhtar, Sayeed; Sinha, Baxi Neeraj P.; Goyal, Nishant

    2004-01-01

    In the remitted phase of bipolar I disorder, sexual dysfunction is commonly due to drugs used in the treatment rather than the disease itself. There are very few studies, especially in the Indian population, addressing the frequency of sexual dysfunction due to antipsychotics in bipolar I disorder. Hence this study was done to determine the sexual dysfunction due to antipsychotics and to compare the same among typical and atypical antipsychotics. A cross sectional study with 108 male patients of remitted bipolar I disorder (DSM-IV), chosen by purposive sampling technique was done. Psychopathology was assessed using the Brief Psychiatric Rating Scale, Structured Interview Guide for the Hamilton Depression Rating Scale and Young Mania Rating Scale. Sexual side effects due to antipsychotics were assessed using the Udvalg for Kliniske ndersogelser (UKU) side effect rating scale. The total sample size was divided into two groups of those on typical antipsychotics (n = 53) and atypical antipsychotics (n = 55). The two groups were compared for sexual dysfunction using Chi-square test. Results showed dysfunction in at least one phase of the sexual response cycle, comprising of desire, arousal and orgasm, was present in 66% of the sample population. Erectile dysfunction was present in 42% of the sample population and it was the most common type of sexual dysfunction reported. It was also significantly different across the two groups (p = 0.025). There was no significant difference in other aspects of sexual dysfunction across the two groups. In conclusion patients of Bipolar I disorder experience sexual side effects of antipsychotics frequently. Erectile dysfunction is the most common sexual dysfunction among men and this is significantly higher with typical than atypical antipsychotics. PMID:21224908

  3. Atypical antipsychotic use is an independent predictor for the increased mean platelet volume in patients with schizophrenia: A preliminary study

    PubMed Central

    Semiz, Murat; Yücel, Hasan; Kavakçı, Önder; Yıldırım, Osman; Zorlu, Ali; Yılmaz, Mehmet Birhan; Küçükdurmaz, Zekeriya; Canan, Fatih

    2013-01-01

    Background: Cardiovascular diseases, cardiovascular risk factors, and mortality due to these situations are more frequently encountered in schizophrenic patients when compared with the general population. The mean platelet volume (MPV) is a surrogate biomarker of the platelet activity and an useful prognostic test in cardiometabolic diseases. The aim of this study was to investigate what influenced MPV levels in patients with schizophrenia. Materials and Methods: We evaluated hospital records of 60 hospitalized schizophrenia patients. Thirty age- and sex-matched healthy control subjects were also included as a control group. Results: MPV levels were significantly higher in patients who were on atypical antipsychotic drugs than in patients who were not using any drug (9.2 ± 0.8 vs. 8.6 ± 0.8 fL, P = 0.016) and also higher than control group (9.2 ± 0.8 vs. 8.1 ± 0.9 fL, P < 0.001). Furthermore, patients who were not using antipsychotics had higher MPV than control group (8.6 ± 0.8 vs. 8.1 ± 0.9 fL, P = 0.036). Atypical antipsychotic use [Odds ratio (OR) =6.152, 95% confidence interval (CI,) P = 0.003)] and platelet distribution width (OR = 0.989, 95% CI, P = 0.032) were associated with high MPV levels in univariate analysis. In multivariate logistic regression model, only atypical antipsychotics use (OR = 6.152, 95% CI, P = 0.003) was found to be independent predictor of high MPV levels after adjustment of other potential confounders (age, gender, presence of hypertension, diabetes mellitus, hyperlipidemia, and smoking). Conclusion: MPV seems to be influenced not only by schizophrenia itself but also by atypical antipsychotic drugs. It might be concluded that schizophrenic patients are under increased risk for cardiometabolic diseases and risk factors and this risk is higher in patients on atypical antipsychotic treatment. PMID:24516487

  4. Long-term cost-effectiveness of atypical antipsychotics in the treatment of adults with schizophrenia in the US

    PubMed Central

    O’Day, Ken; Rajagopalan, Krithika; Meyer, Kellie; Pikalov, Andrei; Loebel, Antony

    2013-01-01

    Background The purpose of this study was to evaluate the long-term cost-effectiveness (including hospitalizations and cardiometabolic consequences) of atypical antipsychotics among adults with schizophrenia. Methods A 5-year Markov cohort cost-effectiveness model, from a US payer perspective, was developed to compare lurasidone, generic risperidone, generic olanzapine, generic ziprasidone, aripiprazole, and quetiapine extended-release. Health states included in the model were patients: on an initial atypical antipsychotic; switched to a second atypical antipsychotic; and on clozapine after failing a second atypical antipsychotic. Incremental cost-effectiveness ratios (ICERs) assessed incremental cost/hospitalization avoided. Effectiveness inputs included discontinuations, hospitalizations, weight change, and cholesterol change from comparative clinical trials for lurasidone and for aripiprazole, and the Clinical Antipsychotic Trials of Intervention Effectiveness for other comparators. Atypical antipsychotic-specific relative risk of diabetes obtained from a retrospective analysis was used to predict cardiometabolic events per Framingham body mass index risk equation. Mental health costs (relapsing versus nonrelapsing patients) and medical costs associated with cardiometabolic consequences (cardiovascular events and diabetes management) were obtained from published sources. Atypical antipsychotic costs were estimated from Red Book® prices at dose(s) reported in clinical data sources used in the model (weighted average dose of lurasidone and average dose for all other comparators). Costs and outcomes were discounted at 3%, and model robustness was tested using one-way and probabilistic sensitivity analyses. Results Ziprasidone, olanzapine, quetiapine extended-release, and aripiprazole were dominated by other comparators and removed from the comparative analysis. ICER for lurasidone versus risperidone was $25,884/relapse-related hospitalization avoided. At a $50

  5. Tardive Dyskinesia and Intellectual Disability: An Examination of Demographics and Topography in Adults with Dual Diagnosis and Atypical Antipsychotic Use

    ERIC Educational Resources Information Center

    Fodstad, Jill C.; Bamburg, Jay W.; Matson, Johnny L.; Mahan, Sara; Hess, Julie A.; Neal, Daniene; Holloway, Jodie

    2010-01-01

    Atypical antipsychotic medications are commonly used in large-scale residential care facilities for adults with developmental disabilities. While the benefits of this class of psychotropics are noted, debate exists whether the side effect profile of these medications outweigh their therapeutic benefit, especially in those who use them long-term.…

  6. Why Research on the Pharmacogenetics of Atypical Antipsychotic-Induced Weight Gain in Individuals with Intellectual Disabilities Is Warranted

    ERIC Educational Resources Information Center

    Sleister, Heidi M.; Valdovinos, Maria Gabriela

    2011-01-01

    Weight gain is an often-observed side effect of atypical antipsychotics (AAPs) and is particularly significant in individuals with intellectual disabilities (ID). The majority of individuals treated with AAPs will gain at least 10% of their initial body weight over the course of therapy (Umbricht & Kane, 1996). One's genetic constitution is an…

  7. Molecular study of weight gain related to atypical antipsychotics: clinical implications of the CYP2D6 genotype.

    PubMed

    Nussbaum, Laura Alexandra; Dumitraşcu, Victor; Tudor, Anca; Grădinaru, Raluca; Andreescu, Nicoleta; Puiu, Maria

    2014-01-01

    Atypical antipsychotics, especially some of them, influence cellular lipogenesis, being associated with metabolic side effects including weight gain. Due to the increasing use of atypical antipsychotics in children and adolescents, their metabolic and endocrine adverse effects are of particular concern especially within this pediatric population that appears to be at greater risk. Genetic factors with a possible influence on atypical antipsychotics adverse effects include CYP2D6 polymorphisms. Our study, performed in 2009-2014, with a two-year enrolment period during which we recruited children and adolescents with a diagnosis of schizophrenia or bipolar disorder on treatment with the antipsychotics (Risperidone, Aripiprazole or Olanzapine), included 81 patients, aged between 9 and 20 years, median age being 15.74 years. The gender percentage was 54% girls/46% boys. The CYP2D6 genotyping was performed after enrolment of the last patient. Based on the CYP2D6 genotype, three activity groups were identified and compared and we found that the patients with wt/*4 genotype, intermediary metabolizer (carrier of one functional and one non-functional allele) have significantly higher weight gain values than the patients who did not exhibit allele *4. The CYP2D6 genotype in children and adolescents with schizophrenia and bipolar disorder, proved to be a good predictor for the response to atypical antipsychotics and the side effects registered. The significant correlations between the CYP2D6 polymorphisms and the weight gain/BMI (body mass index) increase, as major side effects induced by antipsychotics proved the fact that the pharmacogenetic screening is needed in the future clinical practice, allowing for individualized, tailored treatment, especially for at-risk individuals. PMID:25329115

  8. Antioxidant properties of atypical antipsychotic drugs used in the treatment of schizophrenia.

    PubMed

    Sadowska-Bartosz, Izabela; Galiniak, Sabina; Bartosz, Grzegorz; Zuberek, Mariusz; Grzelak, Agnieszka; Dietrich-Muszalska, Anna

    2016-10-01

    The aim of this study was to compare the antioxidant activities of six atypical antipsychotic drugs: clozapine (CLZ), quetiapine, olanzapine (OLA), risperidone, ziprasidone, aripiprazole (ARI), as well as a typical antipsychotic drug, haloperidol. Several tests of antioxidant activity were used: protection of thiol groups against oxidation by peroxynitrite (PN) and 3-morpholinosydnonimine (SIN-1, generator of PN), oxidation of dihydrorhodamine 123 by PN, SIN-1 and hypochlorite (NaOCl), bleaching of fluorescein fluorescence by PN, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH, generator of peroxyl radicals) and NaOCl, radical-scavenging activity with respect to 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) radical, 2,2-diphenyl-1-picrylhydrazyl free radical and the Ferric Reducing Antioxidant Potential. In most of the tests, OLA showed the highest antioxidant activity, followed by CLZ and in some cases ARI, other compounds being much less active or not active. OLA and CLZ exerted limited toxicity on mouse neuroblastoma Neuro-2A (N2A) cells and protected the cells against the toxic action of SIN-1, AAPH and NaOCl in the physiologically relevant concentration range of these oxidants. Both drugs reduced the PN-induced nitration of intracellular proteins. Given that schizophrenia is associated with oxidative and nitrosative stress, the direct antioxidant activity OLA and CLZ may contribute to the therapeutic action of these compounds. PMID:27449251

  9. The impact of newer atypical antipsychotics on patient-reported outcomes in schizophrenia.

    PubMed

    Awad, A George; Voruganti, Lakshmi N P

    2013-08-01

    Over the past two decades there has been increasing interest in including patients' self-reports in the management of their illness. Among the many reasons for such recent interest has been a rising consumer movement over the past few decades, which has led patients, their caregivers and their families to press for more meaningful sharing with physicians in the clinical decision-making process, with the clear expectations of better therapies and improved outcomes. Patients as consumers of services, their views, attitudes towards healthcare, as well as their level of satisfaction with care, have become increasingly recognized. The recent interest by the US Food and Drug Administration (FDA), as well as other regulatory agencies, in patient-reported outcomes (PROs) in the process of developing and testing new antipsychotics, has also added more impetus. It is clear that including patients in the decision-making process about the management of their psychiatric conditions also broadens the concept of 'recovery', by empowering patients to be active participants and gives a clear message that successful treatment in schizophrenia is more than a symptomatic improvement, but also includes improved functional status. Additionally, the recent interest in personalized medicine puts the patient in the centre of such development. Since 2004, when we published our review about the impact of new antipsychotics on quality of life in CNS Drugs, a number of newer antipsychotics have been introduced and include ziprasidone, aripiprazole, paliperidone, asenapine, iloperidone and lurasidone. The current review is based on 31 selected publications that cover the years 2004-2012, and deals with the impact of such newer antipsychotics on specific domains of PROs, such as subjective tolerability, quality of life, medication preference, satisfaction and social functioning. Most of the available data deal with ziprasidone, aripiprazole and paliperidone. Though the great majority of the

  10. Blonanserin, a novel atypical antipsychotic agent not actively transported as substrate by P-glycoprotein.

    PubMed

    Inoue, Tomoko; Osada, Kenichi; Tagawa, Masaaki; Ogawa, Yuriko; Haga, Toshiaki; Sogame, Yoshihisa; Hashizume, Takanori; Watanabe, Takashi; Taguchi, Atsushi; Katsumata, Takashi; Yabuki, Masashi; Yamaguchi, Noboru

    2012-10-01

    Although blonanserin, a novel atypical antipsychotic agent with dopamine D(2)/serotonin 5-HT(2A) antagonistic properties, displays good brain distribution, the mechanism of this distribution has not been clarified. P-glycoprotein [(P-gp) or multidrug resistance protein 1 (MDR1)] is an efflux transporter expressed in the brain and plays an important role in limiting drug entry into the central nervous system (CNS). In particular, P-gp can affect the pharmacokinetics and efficacy of antipsychotics, and exacerbate or soothe their adverse effects. In this study, we conducted in vitro and in vivo experiments to determine whether blonanserin is a P-gp substrate. Risperidone and its active metabolite 9-hydroxyrisperidone, both of which are P-gp substrates, were used as reference drugs. Affinity of blonanserin, risperidone, and 9-hydroxyrisperidone for P-gp was evaluated by in vitro transcellular transport across LLC-PK1, human MDR1 cDNA-transfected LLC-PK1 (LLC-MDR1), and mouse Mdr1a cDNA-transfected LLC-PK1 (LLC-Mdr1a). In addition, pharmacokinetic parameters in the brain and plasma (B/P ratio) of test compounds were measured in mdr1a/1b knockout (KO) and wild-type (WT) mice. The results of in vitro experiments revealed that P-gp does not actively transport blonanserin as a substrate in humans or mice. In addition, blonanserin displayed comparable B/P ratios in KO and WT mice, whereas B/P ratios of risperidone and 9-hydroxyrisperidone differed markedly in these animals. Our results indicate that blonanserin is not a P-gp substrate and therefore its brain distribution is unlikely to be affected by this transporter.

  11. Can Atypical Antipsychotic Augmentation Reduce Subsequent Treatment Failure More Effectively Among Depressed Patients with a Higher Degree of Treatment Resistance? A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Wang, Hee Ryung; Woo, Young Sup; Ahn, Hyeong Sik; Ahn, Il Min; Kim, Hyun Jung; Bahk, Won-Myong

    2015-01-01

    Background: Atypical antipsychotic augmentation was demonstrated to be efficacious in treatment-resistant depression (TRD) in previous meta-analyses. We investigate whether there are differences in the effect size of atypical antipsychotic augmentation in major depressive disorder according to the degree of treatment resistance. Methods: A comprehensive search of four databases identified 11 randomized controlled trials. The 11 trials, which included 3 341 participants, were pooled using a random-effects meta-analysis. Results: Atypical antipsychotic augmentation of antidepressant therapy showed superior efficacy compared to antidepressant monotherapy in TRD in terms of both response and remission rates (response, risk ratio [RR] = 1.38, 95% confidence interval [CI] = 1.25 to 1.53; remission, RR = 1.62, 95% CI = 1.42 to 1.85). In addition, regarding response rates in the TRD trials, atypical antipsychotic augmentation exhibited significantly different effect sizes according to the degree of treatment resistance (TRD 1: RR = 1.24; TRD 2: RR = 1.37; TRD 2–4: RR = 1.58). In non-TRD trials, atypical antipsychotic augmentation failed to show superior efficacy over antidepressant monotherapy in terms of remission rates (RR = 0.89; 95% CI = 0.69 to 1.14). Atypical antipsychotic augmentation of antidepressant therapy exhibits greater effect size in patients with a higher degree of treatment resistance. Conclusions: This finding strengthens the rationale for considering atypical antipsychotic augmentation among depressed patients with multiple previous treatment failures in clinical practice. The efficacy of atypical antipsychotic augmentation for non-TRD seems to be different from that for TRD and, thus, further studies of non-TRD populations are needed. PMID:25770098

  12. Atypical charles bonnet syndrome.

    PubMed

    Arun, Priti; Jain, Rajan; Tripathi, Vaibhav

    2013-10-01

    Charles Bonnet syndrome (CBS) is not uncommon disorder. It may not present with all typical symptoms and intact insight. Here, a case of atypical CBS is reported where antipsychotics were not effective. Patient improved completely after restoration of vision.

  13. Atypical antipsychotic medications in the management of disruptive behaviors in children: safety guidelines and recommendations.

    PubMed

    McKinney, Cliff; Renk, Kimberly

    2011-04-01

    Use of atypical antipsychotic medications (AAMs) in the treatment of disruptive behavior (DB) in children and adolescents has increased dramatically worldwide. However, with exception of using risperidone (i.e., for the management of irritability associated with autism, manic and mixed episodes associated with bipolar I disorder, and schizophrenia) and aripiprazole (i.e., for manic and mixed episodes associated with bipolar I disorder and schizophrenia), the Food and Drug Administration (FDA) has not approved the use of AAMs in children and adolescents. Although research on use of these medications in children and adolescents has increased, mechanisms of action and long-term outcomes remain poorly understood or unknown. Particularly concerning is that use of these medications in children and adolescents may impact cognitive, social, and physical development, as side effects may interfere with activities in their educational setting, peer networks, and recreational settings. Overall, AAMs frequently are prescribed off label, control DB through sedation rather than targeting actual causes of DB, and lead to many negative side effects with unknown long-term effects. Reconsidering the use of AAMs in managing DB is encouraged strongly.

  14. A novel insulin sensitizer drug candidate-BGP-15-can prevent metabolic side effects of atypical antipsychotics.

    PubMed

    Literati-Nagy, Zsuzsanna; Tory, Kálmán; Literáti-Nagy, Botond; Kolonics, Attila; Vígh, László; Vígh, László; Mandl, József; Szilvássy, Zoltán

    2012-10-01

    Atypical antipsychotic drugs (AAPD) are widely used to treat severe psychiatric disorders, have well documented metabolic side effects such as disturbances in glucose metabolism, insulin resistance and weight gain. It has been shown that BGP-15, a hydroxylamine derivative with insulin sensitizing activity can prevent AAPD provoked fat accumulation in adipocyte cultures, and insulin resistance in animal experiments and in healthy volunteers. The aim of this study was to compare the preventive effect of BGP-15 with conventional oral antidiabetics on metabolic side effects of AAPDs. We found that BGP-15 that does not belong to either conventional insulin sensitizers or oral antidiabetics, is able to counteract insulin resistance and weight gain provoked by antipsychotic agents in rats while rosiglitazone and metformin were not effective in the applied doses. Our results confirm that BGP-15 is a promising new drug candidate to control the metabolic side effects of atypical antipsychotics. Data indicate that this rat model is suitable to analyze the metabolic side effects of AAPDs and the protective mechanism of BGP-15.

  15. Lipidomics Reveals Early Metabolic Changes in Subjects with Schizophrenia: Effects of Atypical Antipsychotics

    PubMed Central

    McEvoy, Joseph; Baillie, Rebecca A.; Zhu, Hongjie; Buckley, Peter; Keshavan, Matcheri S.; Nasrallah, Henry A.; Dougherty, George G.; Yao, Jeffrey K.; Kaddurah-Daouk, Rima

    2013-01-01

    There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs), including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease. PMID:23894336

  16. Do Atypical Antipsychotics Have Antisuicidal Effects? A Hypothesis-Generating Overview

    PubMed Central

    Pompili, Maurizio; Baldessarini, Ross J.; Forte, Alberto; Erbuto, Denise; Serafini, Gianluca; Fiorillo, Andrea; Amore, Mario; Girardi, Paolo

    2016-01-01

    Modern antipsychotic drugs are employed increasingly in the treatment of mood disorders as well as psychoses, stimulating interest in their possible contributions to altering suicidal risk. Clozapine remains the only treatment with an FDA-recognized indication for reducing suicidal risk (in schizophrenia). We carried out a systematic, computerized search for reports of studies involving antipsychotic drug treatment and suicidal behaviors. A total of 19 reports provide data with preliminary support for potential suicide risk-reducing effects of olanzapine, quetiapine, ziprasidone, aripiprazole, and asenapine in addition to clozapine, and provide some support for antipsychotic drug treatment in general. These preliminary findings encourage further testing of antipsychotics for effects on suicidal behavior, making use of explicit, pre-planned assessments of suicidal behavior. PMID:27727180

  17. Effectiveness and cost of atypical versus typical antipsychotic treatment in a nationwide cohort of patients with schizophrenia in Germany.

    PubMed

    Stargardt, Tom; Edel, Marc-Andreas; Ebert, Andreas; Busse, Reinhard; Juckel, Georg; Gericke, Christian A

    2012-10-01

    This study investigates the effectiveness and cost of typical versus atypical antipsychotics in a nationwide German cohort of patients with schizophrenia. The study sample consisted of patients insured with 4 sickness funds (n = 8,610) who were followed up for 12 months after hospital discharge with a diagnosis of schizophrenia in 2003. Multivariate regression models were fitted to assess the relationship between outcome variables (rehospitalization, bed-days, prescriptions against adverse effects, cost) and medication type, sex, age, and severity. Severity was assessed by prior bed-days due to schizophrenia during 2000 to 2002. Risk of rehospitalization did not differ between groups but within each group severity (P = 0.0003). Males (P = 0.0016) and patients younger than 35 years (P < 0.0001) had a higher risk of rehospitalization. Number of bed-days was lower for treatment with typicals compared with atypicals (P < 0.0001); furthermore, bed-days depended on severity of disease (P < 0.0001). Prescriptions of drugs against extrapyramidal symptoms, anxiety, and agitation were higher for patients treated with typicals (P < 0.0001 for each). Mean predicted treatment cost per year was € 6442 for atypicals versus € 4443 for typicals (P < 0.0001). This study does not support unconditional superiority of atypicals over typicals, neither in terms of effectiveness nor in terms of cost. PMID:22926592

  18. The HSP co-inducer BGP-15 can prevent the metabolic side effects of the atypical antipsychotics.

    PubMed

    Literáti-Nagy, Zsuzsanna; Tory, Kálmán; Literáti-Nagy, Botond; Kolonics, Attila; Török, Zsolt; Gombos, Imre; Balogh, Gábor; Vígh, László; Horváth, Ibolya; Mandl, József; Sümegi, Balázs; Hooper, Philip L; Vígh, László

    2012-07-01

    Weight gain and dysfunction of glucose and lipid metabolism are well-known side effects of atypical antipsychotic drugs (AAPD). Here, we address the question whether a heat-shock protein (HSP) co-inducer, insulin sensitizer drug candidate, BGP-15, can prevent AAPD-induced glucose, lipid, and weight changes. We also examined how an AAPD alters HSP expression and whether BGP-15 alters that expression. Four different experiments are reported on the AAPD BGP-15 interventions in a human trial of healthy men, a rodent animal model, and an in vitro adipocyte cell culture system. Olanzapine caused rapid insulin resistance in healthy volunteers and was associated with decreased level of HSP72 in peripheral mononuclear blood cells. Both changes were restored by the administration of BGP-15. In Wistar rats, weight gain and insulin resistance induced by clozapine were abolished by BGP-15. In 3T3L1 adipocytes, clozapine increased intracellular fat accumulation, and BGP-15 inhibited this process. Taken together, our results indicate that BGP-15 inhibits multiple metabolic side effects of atypical antipsychotics, and this effect is likely to be related to its HSP co-inducing ability.

  19. Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro

    SciTech Connect

    Sárvári, Anitta K.; Veréb, Zoltán; Uray, Iván P.; Fésüs, László; Balajthy, Zoltán

    2014-08-08

    Highlights: • Antipsychotics modulate the expression of adipogenic genes in human adipocytes. • Secretion of proinflammatory cytokine IL8 and MCP-1 is induced by antipsychotics. • Adipocyte-dependent inflammatory abnormality could develop during chronic treatment. • Infiltrated macrophages would further enhance proinflammatory cytokine production. - Abstract: Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin

  20. State of the art of drug treatment of schizophrenia and the future position of the novel/atypical antipsychotics.

    PubMed

    Möller, H J

    2000-10-01

    Neuroleptic medication is the most important part of the treatment regimen for schizophrenic patients. The efficacy of neuroleptics in the acute and long-term treatment of schizophrenia is very well proven and the effect size is comparatively high. After more than 40 years of clinical practice with the classical neuroleptics, several more or less generally accepted rules for the management of drug treatment in schizophrenia have been established. The paper aims to describe these standards, discussing, among other things, developments which have appeared in the last 10 to 20 years, e.g. the tendency to a lower daily dose during acute treatment and the tendency to alternative strategies during long-term treatment. The paper especially also takes into consideration the benefits of the novel/atypical antipsychotics as compared to the classical neuroleptics, which will change the current treatment standards under several aspects--a change which is already ongoing. The novel/atypical antipsychotics will be much better accepted by patients, thus leading to increased compliance, will be associated with a better quality of life and will possibly change the long-term outcome of schizophrenic patients in a very important manner. It should be considered that the so-called novel/atypical neuroleptics do not constitute a homogeneous group but are a group of individual drugs, each with their own advantages and disadvantages. As was the situation with the classical neuroleptics, the physician also has to choose the most adequate drug under consideration of the risk/benefit profile of each drug in relation to the disposition of the individual patient. PMID:12607217

  1. Pyrrolo[1,3]benzothiazepine-based atypical antipsychotic agents. Synthesis, structure-activity relationship, molecular modeling, and biological studies.

    PubMed

    Campiani, Giuseppe; Butini, Stefania; Gemma, Sandra; Nacci, Vito; Fattorusso, Caterina; Catalanotti, Bruno; Giorgi, Gianluca; Cagnotto, Alfredo; Goegan, Mara; Mennini, Tiziana; Minetti, Patrizia; Di Cesare, M Assunta; Mastroianni, Domenico; Scafetta, Nazzareno; Galletti, Bruno; Stasi, M Antonietta; Castorina, Massimo; Pacifici, Licia; Ghirardi, Orlando; Tinti, Ornella; Carminati, Paolo

    2002-01-17

    The prototypical dopamine and serotonin antagonist (+/-)-7-chloro-9-(4-methylpiperazin-1-yl)-9,10-dihydropyrrolo[2,1-b][1,3]benzothiazepine (5) was resolved into its R and S enantiomers via crystallization of the diastereomeric tartaric acid salts. Binding studies confirmed that the (R)-(-)-enantiomer is a more potent D(2) receptor antagonist than the (S)-(+)-enantiomer, with almost identical affinity at the 5-HT(2) receptor ((S)-(+)-5, log Y = 4.7; (R)-(-)-5, log Y = 7.4). These data demonstrated a significant stereoselective interaction of 5 at D(2) receptors. Furthermore, enantiomer (S)-(+)-5 (ST1460) was tested on a panel of receptors; this compound showed an intriguing binding profile characterized by high affinity for H(1) and the alpha(1) receptor, a moderate affinity for alpha(2) and D(3) receptors, and low affinity for muscarinic receptors. Pharmacological and biochemical investigation confirmed an atypical pharmacological profile for (S)-(+)-5. This atypical antipsychotic lead has low propensity to induce catalepsy in rat. It has minimal effect on serum prolactin levels, and it has been selected for further pharmacological studies. (S)-(+)-5 increases the extracellular levels of dopamine in the rat striatum after subcutaneous administration. By use of 5 as the lead compound, a novel series of potential atypical antipsychotics has been developed, some of them being characterized by a stereoselective interaction at D(2) receptors. A number of structure-activity relationships trends have been identified, and a possible explanation is advanced in order to account for the observed stereoselectivity of the enantiomer of (+/-)-5 for D(2) receptors. The molecular structure determination of the enantiomers of 5 by X-ray diffraction and molecular modeling is reported. PMID:11784139

  2. Clinical pharmacokinetics of atypical antipsychotics: a critical review of the relationship between plasma concentrations and clinical response.

    PubMed

    Mauri, Massimo C; Volonteri, Lucia S; Colasanti, Alessandro; Fiorentini, Alessio; De Gaspari, Ilaria F; Bareggi, Silvio R

    2007-01-01

    In the past, the information about the dose-clinical effectiveness of typical antipsychotics was not complete and this led to the risk of extrapyramidal adverse effects. This, together with the intention of improving patients' quality of life and therapeutic compliance, resulted in the development of atypical or second-generation antipsychotics (SGAs). This review will concentrate on the pharmacokinetics and metabolism of clozapine, risperidone, olanzapine, quetiapine, amisulpride, ziprasidone, aripiprazole and sertindole, and will discuss the main aspects of their pharmacodynamics. In psychopharmacology, therapeutic drug monitoring studies have generally concentrated on controlling compliance and avoiding adverse effects by keeping long-term exposure to the minimal effective blood concentration. The rationale for using therapeutic drug monitoring in relation to SGAs is still a matter of debate, but there is growing evidence that it can improve efficacy, especially when patients do not respond to therapeutic doses or when they develop adverse effects. Here, we review the literature concerning the relationships between plasma concentrations of SGAs and clinical responses by dividing the studies on the basis of the length of their observation periods. Studies with clozapine evidenced a positive relationship between plasma concentrations and clinical response, with a threshold of 350-420 ng/mL associated with good clinical response. The usefulness of therapeutic drug monitoring is well established because high plasma concentrations of clozapine can increase the risk of epileptic seizures. Plasma clozapine concentrations seem to be influenced by many factors such as altered cytochrome P450 1A4 activity, age, sex and smoking. The pharmacological effects of risperidone depend on the sum of the plasma concentrations of risperidone and its 9-hydroxyrisperidone metabolite, so monitoring the plasma concentrations of the parent compound alone can lead to erroneous

  3. Efficacy of Atypical Antipsychotic Medication in the Management of Behaviour Problems in Children with Intellectual Disabilities and Borderline Intelligence: A Systematic Review

    ERIC Educational Resources Information Center

    Unwin, Gemma L.; Deb, Shoumitro

    2011-01-01

    The use of medications to manage problem behaviours is widespread. However, robust evidence to support their use seems to be lacking. The aim was to review research evidence into the efficacy of atypical antipsychotic medication in managing problem behaviour in children with intellectual disabilities and borderline intelligence. A systematic…

  4. Risk of mortality (including sudden cardiac death) and major cardiovascular events in atypical and typical antipsychotic users: a study with the general practice research database.

    PubMed

    Murray-Thomas, Tarita; Jones, Meghan E; Patel, Deven; Brunner, Elizabeth; Shatapathy, Chetan C; Motsko, Stephen; Van Staa, Tjeerd P

    2013-01-01

    Objective. Antipsychotics have been associated with increased cardiac events including mortality. This study assessed cardiac events including mortality among antipsychotic users relative to nonusers. Methods. The General Practice Research Database (GPRD) was used to identify antipsychotic users, matched general population controls, and psychiatric diseased nonusers. Outcomes included cardiac mortality, sudden cardiac death (SCD), all-cause mortality (excluding suicide), coronary heart disease (CHD), and ventricular arrhythmias (VA). Sensitivity analyses were conducted for age, dose, duration, antipsychotic type, and psychiatric disease. Results. 183,392 antipsychotic users (115,491 typical and 67,901 atypical), 544,726 general population controls, and 193,920 psychiatric nonusers were identified. Nonusers with schizophrenia, dementia, or bipolar disorder had increased risks of all-cause mortality compared to general population controls, while nonusers with major depression had comparable risks. Relative to psychiatric nonusers, the adjusted relative ratios (aRR) of all-cause mortality in antipsychotic users was 1.75 (95% CI: 1.64-1.87); cardiac mortality 1.72 (95% CI: 1.42-2.07); SCD primary definition 5.76 (95% CI: 2.90-11.45); SCD secondary definition 2.15 (95% CI: 1.64-2.81); CHD 1.16 (95% CI: 0.94-1.44); and VA 1.16 (95% CI: 1.02-1.31). aRRs of the various outcomes were lower for atypical versus typical antipsychotics (all-cause mortality 0.83 (95% CI: 0.80-0.85); cardiac mortality 0.89 (95% CI: 0.82-0.97); and SCD secondary definition 0.76 (95% CI: 0.55-1.04). Conclusions. Antipsychotic users had an increased risk of cardiac mortality, all-cause mortality, and SCD compared to a psychiatric nonuser cohort.

  5. Geographic variation in efficacy of atypical antipsychotics for the acute treatment of schizophrenia - an individual patient data meta-analysis.

    PubMed

    Mattila, Taina; Wohlfarth, Tamar; Koeter, Maarten; Storosum, Jitschak; van den Brink, Wim; de Haan, Lieuwe; Leufkens, Hubertus; Denys, Damiaan

    2014-07-01

    Generalizability of efficacy results from medication trials across geographic regions is disputed. Geographic differences in factors such as patient characteristics, treatment practices and disease definitions might lead to differences in effect sizes across regions. This study examined geographic variation in efficacy results of schizophrenia trials with atypical antipsychotics using individual-patient data meta-analysis. Twenty-two studies including in total 5233 patients from three regions (North America, Europe, and the rest of the world) were included in the random effects meta-analysis. The effect size in North American patients was smaller in terms of mean change from baseline and in terms of responders (Hedge׳s G=0.37, 95% CI 0.28-0.46; OR 1.71, 95% CI 1.35-2.17) as compared to patients in Europe (Hedge׳s G=0.56, 95% CI 0.34-0.79; OR 2.25, 95% CI 1.62-3.12) and the rest of the world (Hedge׳s G=0.53, 95% CI 0.12-0.75; OR 2.61, 95% CI 1.66-4.17). The differences were not statistically significant. The observed differences remained when the confounding effect of unequal distribution of compounds was controlled for by analyzing separately the compounds that were studied across all three regions. Based on these results it cannot be excluded that there are differences in efficacy results of atypical antipsychotics trials across geographic regions. The observed trend towards differential efficacy across geographic regions warrants further examination of the determinants of these differences.

  6. Factors associated with non evidence-based prescribing of antipsychotics

    PubMed Central

    Connolly, Anne

    2014-01-01

    Objectives: Non evidence-based prescribing of antipsychotics is common in the UK and internationally with high doses and polypharmacy the norm. These practices often remain even after systematic attempts are made to change. We aimed to establish which factors are linked to antipsychotic prescribing quality so we can identify and target patients for interventions to improve quality and allow us to understand further the drivers of non evidence-based prescribing. Objectives: A cross-sectional survey with a collection of factors potentially affecting antipsychotic prescribing quality outcomes was carried out in eight secondary care units in England. Participants were inpatients prescribed regular antipsychotics on the day of the survey. Antipsychotic dose, polypharmacy, type and route were the main outcome measures. Objectives: Data were collected for 1198 patients. Higher total dose was associated with greater weight, higher number of previous admissions, longer length of admission, noncompliance with medication and use of an atypical antipsychotic. A lower total dose was associated with clozapine use. Polypharmacy was associated with not being a patient at the South London and Maudsley NHS Trust centre, the subject having a forensic history, a greater number of previous admissions and higher total dose. Younger age, not being detained under a Mental Health Act section, atypical antipsychotic use and oral route were predictors of antipsychotic monotherapy. Atypical antipsychotic use was associated with oral route, higher total dose, being administered only one antipsychotic, having had fewer previous antipsychotics and no anticholinergic use. Use of the oral route was associated with not being sectioned under the Mental Health Act, atypical antipsychotic use, younger age, non-schizophrenia diagnosis, fewer previous admissions and a lower total dose. Objectives: In patients with chronic illness who are detained, heavier, noncompliant, not taking clozapine and on a

  7. Atypical antipsychotics: from potassium channels to torsade de pointes and sudden death.

    PubMed

    Titier, Karine; Girodet, Pierre-Olivier; Verdoux, Hélène; Molimard, Mathieu; Bégaud, Bernard; Haverkamp, Wilhelm; Lader, Malcolm; Moore, Nicholas

    2005-01-01

    Syncope and sudden death are features of schizophrenia that can be attributed to ischaemic heart disease, the use of antipsychotics (because of proarrhythmia or other reasons such as pharyngeal dyskinesia) or the psychiatric disease itself. Cases have been described with most antipsychotics and have led to the withdrawal, temporary suspension from the market or restricted use of antipsychotics, such as sultopride, droperidol, sertindole or thioridazine. Reviewing the available data shows that all antipsychotics tested affect the cardiac potassium channel, with the concentration that produces 50% inhibition (IC50) ranging from 1 nmol/L (haloperidol) to 6 micromol/L (olanzapine). Experimental in vitro or in vivo electrophysiological studies have shown a dose-dependent increase in the duration of the action potential with various degrees of indicators of serious arrhythmogenicity. However, this does not always translate clinically into an increased duration of the QT interval or increased risk of torsade de pointes or sudden death in clinical trials or pharmacoepidemiological studies. In turn, QT prolongation in clinical trials does not always translate to an increased risk of torsade de pointes or sudden death. The reasons for these apparent discrepancies are unclear and could be related to insufficiently powered field studies, low plasma and tissue drug concentrations with reference to in vitro data or drug effects on other receptors or ion channels that have a protective effect. Alternatively, risks that were not apparent from preclinical or clinical data could be related to the use of the drug in high-risk patients, metabolic interactions or other factors that would only be encountered in large postmarketing populations. The assessment of cardiovascular safety, both preclinical and during premarketing clinical trials, needs to be supported by appropriately powered pharmacoepidemiology studies.

  8. (S)-amisulpride as a discriminative stimulus in C57BL/6 mice and its comparison to the stimulus effects of typical and atypical antipsychotics.

    PubMed

    Donahue, Timothy J; Hillhouse, Todd M; Webster, Kevin A; Young, Richard; De Oliveira, Eliseu O; Porter, Joseph H

    2014-07-01

    Amisulpride, a substituted benzamide derivative, exerts atypical antipsychotic and antidepressant clinical effects and its (S)-stereoisomer is thought to underlie these actions. In the present study, male C57BL/6 mice were trained to discriminate (S)-amisulpride (10mg/kg, s.c.) from vehicle in a two-lever drug discrimination task for food reward. The (S)-amisulpride stimulus was rapidly acquired and was shown to be dose-related, time dependent (effective between 30 and 120min) and stereoselective: (S)-amisulpride (ED50=1.77mg/kg; 4.2µmol/kg) was about three times more potent than rac-amisulpride (ED50=4.94mg/kg; 13.4µmol/kg) and ten times more potent than (R)-amisulpride (ED50=15.84mg/kg; 42.9µmol/kg). In tests of stimulus generalization, the (S)-amisulpride stimulus generalized completely to sulpiride (ED50=12.67mg/kg; 37.1µmol/kg), a benzamide analog that also is purported to be an atypical antipsychotic, but did not fully generalize to the typical antipsychotic drug haloperidol (maximum of 45% drug-lever responding) nor to the atypical antipsychotic drugs clozapine (partial substitution of 65% drug-lever responding) or aripiprazole (~30% drug-lever responding). These results demonstrated that (S)-amisulpride appears to exert a unique discriminative stimulus effect that is similar to other benzamides, but which differs from other structural classes of antipsychotic drugs.

  9. Differences among conventional, atypical and novel putative D(2)/5-HT(1A) antipsychotics on catalepsy-associated behaviour in cynomolgus monkeys.

    PubMed

    Auclair, Agnès L; Kleven, Mark S; Barret-Grévoz, Catherine; Barreto, Martine; Newman-Tancredi, Adrian; Depoortère, Ronan

    2009-11-01

    Typical antipsychotics such as haloperidol exert their therapeutic effects via blockade of dopamine (DA) D(2) receptors, leading to extrapyramidal symptoms (EPS) in humans and catalepsy in rodents. In contrast, atypical antipsychotics and new generation D(2)/5-HT(1A) antipsychotics have low cataleptogenic potential. However, there has been no systematic comparative study on the effects of these different classes of antipsychotics in non-human primates, a species displaying a more sophisticated repertoire of behavioural/motor activity than rats. Once weekly, six young adult female non-haloperidol-sensitised cynomolgus monkeys were treated i.m. with a test compound and videotaped to score catalepsy-associated behaviour (CAB: static postures, unusual positions and crouching). Haloperidol, risperidone, olanzapine, nemonapride and remoxipride induced, to different extents, an increase in unusual positions (a response akin to dystonia), some crouching and static postures. In contrast, clozapine, quetiapine, ziprasidone and aripiprazole produced much lower or no unusual positions; clozapine also produced marked increases in static postures and crouching. Among novel D(2)/5-HT(1A) antipsychotics, SLV313 and F15063 augmented the number of unusual positions, albeit at doses 16-63 times higher than those of haloperidol for approximately the same score. SSR181507 and bifeprunox produced moderate static postures, little crouching and negligible unusual positions. These data provide the first comparative analysis in cynomolgus monkeys of EPS liability of conventional, atypical and novel D(2)/5-HT(1A) antipsychotics. They indicate that the latter are less prone than haloperidol to produce CAB, and provide a basis for comparison with rodent catalepsy studies. PMID:19464324

  10. Efficacy, quality of life, and acceptability outcomes of atypical antipsychotic augmentation treatment for treatment-resistant depression: protocol for a systematic review and network meta-analysis

    PubMed Central

    2014-01-01

    Background Major depressive disorder (MDD) is a debilitating and costly mental disorder. Although commercially available antidepressants have proliferated over the last 20 years, a substantial number of patients either do not respond adequately to these drugs or are unable to tolerate their adverse effects. One common approach has been to augment conventional antidepressants with an adjunctive agent, but the optimal selection of atypical antipsychotic agents for adjunctive treatment of treatment-resistant depression (TRD) remains controversial. Methods/Design An electronic literature search of PubMed, the Cochrane Library, Embase, Web of Science, LiLACS, CINAHL, and PsycINFO for studies will be conducted with no restrictions on language, publication year, or publication type. Several clinical trial registry agencies, pharmaceutical company websites, and FDA reports will also be reviewed. Randomized clinical trials (RCTs) with atypical antipsychotic augmentation treatment for treatment-resistant depression will be considered. Data will be independently extracted by two reviewers. Traditional pairwise meta-analyses will be performed for RCTs that directly compare different treatment arms. Then, Bayesian network meta-analyses will be performed to compare the relative efficacy and acceptability of different atypical antipsychotic agents (and doses). A sensitivity analysis will be performed by excluding studies classified as a small sample size, having a high placebo effect. Discussion This systematic review and network meta-analysis will comparatively analyze the efficacy, quality of life, and acceptability profiles of atypical antipsychotic medications used for the adjunctive treatment of TRD. The findings should provide clinically relevant implications for comprehensively understanding the risk–benefit profiles of these adjunctive treatments. Systematic review registration PROSPERO CRD 42014009666. PMID:25373601

  11. Pharmacological profiles in rats of novel antipsychotics with combined dopamine D2/serotonin 5-HT1A activity: comparison with typical and atypical conventional antipsychotics.

    PubMed

    Bardin, Laurent; Auclair, Agnès; Kleven, Mark S; Prinssen, Eric P M; Koek, Wouter; Newman-Tancredi, Adrian; Depoortère, Ronan

    2007-03-01

    Combining antagonist/partial agonist activity at dopamine D2 and agonist activity at serotonin 5-HT1A receptors is one of the approaches that has recently been chosen to develop new generation antipsychotics, including bifeprunox, SSR181507 and SLV313. There have been, however, few comparative data on their pharmacological profiles. Here, we have directly compared a wide array of these novel dopamine D2/5-HT1A and conventional antipsychotics in rat models predictive of antipsychotic activity. Potency of antipsychotics to antagonize conditioned avoidance, methylphenidate-induced behaviour and D-amphetamine-induced hyperlocomotion correlated with their affinity at dopamine D2 receptors. Potency against ketamine-induced hyperlocomotion was independent of affinity at dopamine D2 or 5-HT1A receptors. Propensity to induce catalepsy, predictive of occurrence of extrapyramidal side effects, was inversely related to affinity at 5-HT1A receptors. As a result, preferential D2/5-HT1A antipsychotics displayed a large separation between doses producing 'antipsychotic-like' vs. cataleptogenic actions. These data support the contention that 5-HT1A receptor activation greatly reduces or prevents the cataleptogenic potential of novel antipsychotics. They also emphasize that interactions at 5-HT1A and D2 receptors, and the nature of effects (antagonism or partial agonism) at the latter has a profound influence on pharmacological activities, and is likely to affect therapeutic profiles.

  12. Comparative efficacy between clozapine and other atypical antipsychotics on depressive symptoms in patients with schizophrenia: Analysis of the CATIE Phase 2E data

    PubMed Central

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

    2014-01-01

    Background The comparative antidepressant effects of clozapine and other atypical antipsychotics for schizophrenia remain elusive, leading us to examine this question using the data from the Clinical Antipsychotic Trials of Interventions Effectiveness phase 2E. Methods Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone because of inadequate efficacy were randomly assigned to open-label treatment with clozapine (n=49) or double-blind treatment with another atypical antipsychotic not previously received in the trial (olanzapine [n=19], quetiapine [n=15], or risperidone [n=16]). The primary outcome was the Calgary Depression Scale for Schizophrenia (CDSS) total score. Antidepressant effects of clozapine and the other atypical antipsychotics were compared in patients with chronic schizophrenia and those with a major depressive episode (MDE) at baseline (i.e. ≥6 on the CDSS), using mixed models. Results No differences in the baseline CDSS total scores were found between the treatment groups regardless of presence of an MDE. Clozapine was more effective than quetiapine in antidepressant effects for chronic schizophrenia (p<.01 for the whole sample and p=.01 for those with an MDE), and comparable to olanzapine and risperidone. Conclusion The present findings suggest clozapine demonstrates superior antidepressant effects to quetiapine and comparable effects to olanzapine and risperidone in chronic schizophrenia regardless of presence of MDE. Given the indication of clozapine for treatment-resistant schizophrenia (TRS) and the negative impacts of depressive symptoms on clinical outcomes in schizophrenia, further research is warranted to investigate antidepressant effects of clozapine in TRS with an MDE. PMID:25556080

  13. Atypical antipsychotics as add-on treatment in late-life depression

    PubMed Central

    Cakir, Sibel; Senkal, Zeynep

    2016-01-01

    Background Second-generation antipsychotics (SGAs) have been used in the augmentation of treatment-resistant depression. However, little is known about their effectiveness, tolerability, and adverse events in the treatment of late-life depression, which were the aim of this study. Methods The retrospective data of patients aged >65 years who had a major depressive episode with inadequate response to antidepressant treatment and had adjuvant SGA treatment were analyzed. The outcome measures were the number of the patients who continued to use SGAs in the fourth and twelfth weeks, adverse events, and changes in symptoms of depression. Results Thirty-five patients were screened: 21 (60%) had quetiapine, twelve (34.28%) had aripiprazole, and two (5.71%) had olanzapine adjuvant treatment. The mean age was 72.17±5.02 years, and 65.7% of the patients were women. The mean daily dose was 85.71±47.80 mg for quetiapine, 3.33±1.23 mg for aripiprazole, and 3.75±1.76 mg for olanzapine. The Geriatric Depression Scale scores of all patients were significantly decreased in the fourth week and were significant in the aripiprazole group (P=0.02). Of the 35 patients, 23 (65.7%) patients discontinued the study within 12 weeks. The frequency of adverse events was similar in all SGAs, and the most common were sedation, dizziness, constipation, and orthostatic hypotension with quetiapine, and akathisia and headache because of aripiprazole. Conclusion This study indicates that dropout ratio of patients with SGAs is high, and a subgroup of patients with late-life depression may benefit from SGAs. Effectiveness is significant in aripiprazole, and adverse events of SGAs were not serious but common in elderly patients. PMID:27672315

  14. The atypical antipsychotic clozapine selectively inhibits interleukin 8 (IL-8)-induced neutrophil chemotaxis.

    PubMed

    Capannolo, Marta; Fasciani, Irene; Romeo, Stefania; Aloisi, Gabriella; Rossi, Mario; Bellio, Pierangelo; Celenza, Giuseppe; Cinque, Benedetta; Cifone, Maria Grazia; Scarselli, Marco; Maggio, Roberto

    2015-03-01

    Clozapine is the most effective antipsychotic to date, but its benefits are counterbalanced by the risk of severe hematological effects. In this study, we analyzed whether clozapine inhibits polymorphonuclear (PMN) leukocyte chemotaxis. We found that clozapine, within the therapeutic concentration range, potently and selectively inhibits PMN chemotaxis induced by interleukin 8 (IL-8), a chemokine inducing neutrophil migration. The effect was not due to its action at dopamine, serotonin and muscarinic receptors, or to a direct antagonism to IL-8 receptors. Furthermore, clozapine did not inhibit PMN chemotaxis by its presumed toxic mechanism. In fact, after an overnight incubation in cell culture, the drug did not increase the physiological PMN apoptosis. An interference of clozapine with the autocrine release of leukotriene B4 (LTB4), a secondary chemoattractant secreted by neutrophils in response to the primary chemoattractant IL-8, was hypothesized. In agreement with this hypothesis, clozapine attenuated the IL-8-induced release of LTB4 in PMNs. A series of experiments with an antagonist of the LTB4 receptor, U75302, and an inhibitor of LTB4 synthesis, zileuton, provided support to this conjecture. Intriguingly MK-571, an inhibitor of the multi-drug resistance protein MRP4, playing a pivotal role in effluxing LTB4, completely blocked PMN chemotaxis induced by IL-8, but gave conflicting results when tested for its ability to reduce LTB4 release, increasing LTB4 efflux by itself but reducing the release when in combination with IL-8. The reduction of PMN chemotaxis due to clozapine could predispose patients to infections. Whether this effect is a prelude to clozapine agranulocytosis requires further investigation.

  15. Atypical antipsychotics as add-on treatment in late-life depression

    PubMed Central

    Cakir, Sibel; Senkal, Zeynep

    2016-01-01

    Background Second-generation antipsychotics (SGAs) have been used in the augmentation of treatment-resistant depression. However, little is known about their effectiveness, tolerability, and adverse events in the treatment of late-life depression, which were the aim of this study. Methods The retrospective data of patients aged >65 years who had a major depressive episode with inadequate response to antidepressant treatment and had adjuvant SGA treatment were analyzed. The outcome measures were the number of the patients who continued to use SGAs in the fourth and twelfth weeks, adverse events, and changes in symptoms of depression. Results Thirty-five patients were screened: 21 (60%) had quetiapine, twelve (34.28%) had aripiprazole, and two (5.71%) had olanzapine adjuvant treatment. The mean age was 72.17±5.02 years, and 65.7% of the patients were women. The mean daily dose was 85.71±47.80 mg for quetiapine, 3.33±1.23 mg for aripiprazole, and 3.75±1.76 mg for olanzapine. The Geriatric Depression Scale scores of all patients were significantly decreased in the fourth week and were significant in the aripiprazole group (P=0.02). Of the 35 patients, 23 (65.7%) patients discontinued the study within 12 weeks. The frequency of adverse events was similar in all SGAs, and the most common were sedation, dizziness, constipation, and orthostatic hypotension with quetiapine, and akathisia and headache because of aripiprazole. Conclusion This study indicates that dropout ratio of patients with SGAs is high, and a subgroup of patients with late-life depression may benefit from SGAs. Effectiveness is significant in aripiprazole, and adverse events of SGAs were not serious but common in elderly patients.

  16. The atypical antipsychotics clozapine and olanzapine promote down-regulation and display functional selectivity at human 5-HT7 receptors

    PubMed Central

    Andressen, K W; Manfra, O; Brevik, C H; Ulsund, A H; Vanhoenacker, P; Levy, F O; Krobert, K A

    2015-01-01

    Background and Purpose Classically, ligands of GPCRs have been classified primarily upon their affinity and efficacy to activate a signal transduction pathway. Recent reports indicate that the efficacy of a particular ligand can vary depending on the receptor-mediated response measured (e.g. activating G proteins, other downstream responses, internalization). Previously, we reported that inverse agonists induce both homo- and heterologous desensitization, similar to agonist stimulation, at the Gs-coupled 5-HT7 receptor. The primary objective of this study was to determine whether different inverse agonists at the 5-HT7 receptor also induce internalization and/or degradation of 5-HT7 receptors. Experimental Approach HEK293 cells expressing 5-HT7(a, b or d) receptors were pre-incubated with 5-HT, clozapine, olanzapine, mesulergine or SB269970 and their effects upon receptor density, AC activity, internalization, recruitment of β-arrestins and lysosomal trafficking were measured. Key Results The agonist 5-HT and three out of four inverse agonists tested increased internalization independently of β-arrestin recruitment. Among these, only the atypical antipsychotics clozapine and olanzapine promoted lysosomal sorting and reduced 5-HT7 receptor density (∼60% reduction within 24 h). Inhibition of lysosomal degradation with chloroquine blocked the clozapine- and olanzapine-induced down-regulation of 5-HT7 receptors. Incubation with SB269970 decreased both 5-HT7(b) constitutive internalization and receptor density but increased 5-HT7(d) receptor density, indicating differential ligand regulation among the 5-HT7 splice variants. Conclusions and Implications Taken together, we found that various ligands differentially activate regulatory processes governing receptor internalization and degradation in addition to signal transduction. Thus, these data extend our understanding of functional selectivity at the 5-HT7 receptor. PMID:25884989

  17. National trends in off-label use of atypical antipsychotics in children and adolescents in the United States.

    PubMed

    Sohn, Minji; Moga, Daniela C; Blumenschein, Karen; Talbert, Jeffery

    2016-06-01

    The objectives of the study were as follows: to examine the national trend of pediatric atypical antipsychotic (AAP) use in the United States; to identify primary mental disorders associated with AAPs; to estimate the strength of independent associations between patient/provider characteristics and AAP use. Data are from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. First, average AAP prescription rates among 4 and 18-year-old patients between 1993 and 2010 were estimated. Second, data from 2007 to 2010 were combined and analyzed to identify primary mental disorders related to AAP prescription. Third, a multivariate logistic regression model was developed having the presence of AAP prescription as the dependent variable and patient/provider characteristics as explanatory variables. Adjusted odds ratios (AORs) with associated 95% confidence intervals (CIs) were estimated. Outpatient visits including an AAP prescription among 4 to 18-year-old patients significantly increased between 1993 and 2010 in the United States, and over 65% of those visits did not have diagnoses for US Food and Drug Administration-approved AAP indications. During 2007 to 2010, the most common mental disorder was attention-deficit hyperactivity disorder, accounting for 24% of total pediatric AAP visits. Among visits with attention-deficit hyperactivity disorder diagnosis, those with Medicaid as payer (AOR 1.66, 95% CI 1.01-2.75), comorbid mental disorders (e.g., psychoses AOR 3.34, 95% CI 1.35-8.26), and multiple prescriptions (4 or more prescriptions AOR 4.48, 95% CI 2.08-9.64) were more likely to have an AAP prescription. The off-label use of AAPs in children and adolescents is prevalent in the United States. Our study raises questions about the potential misuse of AAPs in the population. PMID:27281081

  18. Effect of in utero exposure to the atypical anti-psychotic risperidone on histopathological features of the rat placenta.

    PubMed

    Singh, K P; Singh, Manoj K; Gautam, Shrikant

    2016-04-01

    For clinical management of different forms of psychosis, both classical and atypical anti-psychotic drugs (APDs) are available. These drugs are widely prescribed, even during pregnancy considering their minimal extra-pyramidal side effects and teratogenic potential compared to classical APDs. Among AAPDs, risperidone (RIS) is a first-line drug of choice by physicians. The molecular weight of RIS is 410.49 g/mol; hence, it can easily cross the placental barrier and enter the foetal bloodstream. It is not known whether or not AAPDs like RIS may affect the developing placenta and foetus adversely. Reports on this issue are limited and sketchy. Therefore, this study has evaluated the effects of maternal exposure to equivalent therapeutic doses of RIS on placental growth, histopathological and cytoarchitectural changes, and to establish a relationship between placental dysfunction and foetal outcomes. Pregnant rats (n = 24) were exposed to selected doses (0.8, 1.0 and 2.0 mg/kg) of RIS from gestation days 6-21. These dams were sacrificed; their placentas and foetuses were collected, morphometrically examined and further processed for histopathological examination. This study revealed that in utero exposure to equivalent therapeutic doses of RIS during organogenesis-induced placental dystrophy (size and weight), disturbed cytoarchitectural organization (thickness of different placental layers), histopathological lesions (necrosis in trophoblast with disruption of trophoblastic septa and rupturing of maternal-foetal interface) and intrauterine growth restriction of the foetuses. It may be concluded that multifactorial mechanisms might be involved in the dysregulation of structure and function of the placenta and of poor foetal growth and development. PMID:27256515

  19. Pyrrolo[1,3]benzothiazepine-based serotonin and dopamine receptor antagonists. Molecular modeling, further structure-activity relationship studies, and identification of novel atypical antipsychotic agents.

    PubMed

    Campiani, Giuseppe; Butini, Stefania; Fattorusso, Caterina; Catalanotti, Bruno; Gemma, Sandra; Nacci, Vito; Morelli, Elena; Cagnotto, Alfredo; Mereghetti, Ilario; Mennini, Tiziana; Carli, Miriana; Minetti, Patrizia; Di Cesare, M Assunta; Mastroianni, Domenico; Scafetta, Nazzareno; Galletti, Bruno; Stasi, M Antonietta; Castorina, Massimo; Pacifici, Licia; Vertechy, Mario; Di Serio, Stefano; Ghirardi, Orlando; Tinti, Ornella; Carminati, Paolo

    2004-01-01

    Recently we reported the pharmacological characterization of the 9,10-dihydropyrrolo[1,3]benzothiazepine derivative (S)-(+)-8 as a novel atypical antipsychotic agent. This compound had an optimum pK(i) 5-HT(2A)/D(2) ratio of 1.21 (pK(i) 5-HT(2A) = 8.83; pK(i) D(2) = 7.79). The lower D(2) receptor affinity of (S)-(+)-8 compared to its enantiomer was explained by the difficulty in reaching the conformation required to optimally fulfill the D(2) pharmacophore. With the aim of finding novel atypical antipsychotics we further investigated the core structure of (S)-(+)-8, synthesizing analogues with specific substituents; the structure-activity relationship (SAR) study was also expanded with the design and synthesis of other analogues characterized by a pyrrolo[2,1-b][1,3]benzothiazepine skeleton, substituted on the benzo-fused ring or on the pyrrole system. On the 9,10-dihydro analogues the substituents introduced on the pyrrole ring were detrimental to affinity for dopamine and for 5-HT(2A) receptors, but the introduction of a double bond at C-9/10 on the structure of (S)-(+)-8 led to a potent D(2)/5-HT(2A) receptor ligand with a typical binding profile (9f, pK(i) 5-HT(2A)/D(2) ratio of 1.01, log Y = 8.43). Then, to reduce D(2) receptor affinity and restore atypicality on unsaturated analogues, we exploited the effect of specific substitutions on the tricyclic system of 9f. Through a molecular modeling approach we generated a novel series of potential atypical antipsychotic agents, with optimized 5HT(2A)/D(2) receptor affinity ratios and that were easier to synthesize and purify than the reference compound (S)-(+)-8. A number of SAR trends were identified, and among the analogues synthesized and tested in binding assays, 9d and 9m were identified as the most interesting, giving atypical log Y scores respectively 4.98 and 3.18 (pK(i) 5-HT(2A)/D(2) ratios of 1.20 and 1.30, respectively). They had a multireceptor affinity profile and could be promising atypical agents

  20. Length of mechanical restraint following haloperidol injections versus oral atypical antipsychotics for the initial treatment of acute schizophrenia: a propensity-matched analysis from the Japanese diagnosis procedure combination database.

    PubMed

    Nakamura, Mitsuhiro; Yasunaga, Hideo; Haraguchi, Tadashi; Ando, Shuntaro; Sugihara, Toru; Horiguchi, Hiromasa; Ohe, Kazuhiko; Matsuda, Shinya; Fushimi, Kiyohide

    2013-10-30

    Differences in effectiveness between haloperidol injection and oral atypical antipsychotics in the acute-phase treatment of schizophrenia are not well examined. We retrospectively investigated whether these treatment options affected the length of mechanical restraint. We used the Japanese Diagnosis Procedure Combination Database to identify schizophrenia patients who were involuntarily hospitalized and receiving mechanical restraint between July and December, 2006-2009. Data included patient demographics, use of antipsychotics, and number of days on which patients underwent mechanical restraint. Propensity score matching was performed to compare the number of days of mechanical restraint between the haloperidol injection group and the oral atypical antipsychotics group. We used survival analysis to examine whether the initial difference in treatment affected the number of days of mechanical restraint. Cox regression was performed to compare the concurrent effects of various factors. Among 1731 eligible patients, 574 were treated with haloperidol injections and 420 with atypical antipsychotics. Matching produced 274 patients in each group. Cox regression analysis showed that the initial therapeutic agents did not significantly affect the number of days of mechanical restraint. The results indicate that atypical antipsychotics were as effective as haloperidol injections in the acute-phase treatment of schizophrenia.

  1. The role of 5-HT7 receptor antagonism in the amelioration of MK-801-induced learning and memory deficits by the novel atypical antipsychotic drug lurasidone.

    PubMed

    Horisawa, Tomoko; Nishikawa, Hiroyuki; Toma, Satoko; Ikeda, Atsushi; Horiguchi, Masakuni; Ono, Michiko; Ishiyama, Takeo; Taiji, Mutsuo

    2013-05-01

    Lurasidone is a novel atypical antipsychotic with high affinity for dopamine D2, serotonin 5-HT7 and 5-HT2A receptors. We previously reported that lurasidone and the selective 5-HT7 receptor antagonist, SB-656104-A improved learning and memory deficits induced by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist, in the rat passive avoidance test. In this study, we first examined the role of the 5-HT7 receptor antagonistic activity of lurasidone in its pro-cognitive effect to ameliorate MK-801-induced deficits in the rat passive avoidance test. The 5-HT7 receptor agonist, AS19, (2S)-(+)-5-(1,3,5-trimethylpyrazol-4-yl)-2-(dimethylamino) tetralin, (3 mg/kg, s.c.) completely blocked the attenuating effects of lurasidone (3 mg/kg, p.o.), highlighting the importance of 5-HT7 receptor antagonism in the pro-cognitive effect of lurasidone. AS19 (3 mg/kg, s.c.) also blocked the ameliorating effect of SB-656104-A (10 mg/kg, i.p.) in the same experimental paradigm. To further extend our observation, we next tested whether 5-HT7 receptor antagonism still led to the amelioration of MK-801-induced deficits when combined with D2 and 5-HT2A receptor antagonists, and found that SB-656104-A (10 mg/kg, i.p.) significantly ameliorated MK-801-induced deficits even in the presence of the D2 receptor antagonist raclopride (0.1 mg/kg, s.c.) and 5-HT2A receptor antagonist ketanserin (1 mg/kg, s.c.). Taken together, these results suggest that the 5-HT7 receptor antagonistic activity of lurasidone plays an important role in its effectiveness against MK-801-induced deficits, and may contribute to its pharmacological actions in patients with schizophrenia.

  2. Meta-analysis on the efficacy and tolerability of the augmentation of antidepressants with atypical antipsychotics in patients with major depressive disorder.

    PubMed

    Wen, X J; Wang, L M; Liu, Z L; Huang, A; Liu, Y Y; Hu, J Y

    2014-07-01

    We assessed the efficacy and tolerability of the augmentation of antidepressants (ATDs) with atypical antipsychotics (AAPs) to treat patients with major depressive disorder. A retrograde study to identify relevant patient data included databases of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Database of Abstracts of Reviews of Effects. Data from 17 trials, involving 3807 participants, were identified. The remission rate (RR) and overall response rate (ORR) of adjunctive treatment with AAPs were significantly higher than placebo treatment: RR=1.90 (95%CI=1.61-2.23, z=7.74, P<0.00001) and ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001). We found that the short-term (4 weeks) treatment [ORR=1.70 (95%CI=0.98-2.95, Z=1.89, P=0.06)] was significantly different from the long-term (6-12 weeks) treatment [ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001)]. No significant difference in ORR was observed between groups with or without sedative drugs. The discontinuation rate due to adverse effects was higher for adjunctive treatment with AAPs: ORR=3.32 (95%CI=2.35-4.70, z=6.78, P<0.00001). These results demonstrate that the augmentation of ATDs with AAPs (olanzapine, quetiapine, aripiprazole, and risperidone) was more effective than a placebo in improving response and remission rates, although associated with a higher discontinuation rate due to adverse effects.

  3. Improving antipsychotic agent use in nursing homes: development of an algorithm for treating problem behaviors in dementia.

    PubMed

    Smith, Marianne; Schultz, Susan K; Seydel, Linda L; Reist, Jeffrey; Kelly, Michael; Weckmann, Michelle; Weckman, Michelle; Gryzlak, Brian; Carnahan, Ryan

    2013-05-01

    Many issues related to safety and quality care emerge from reports that nearly one in three nursing home residents is treated with antipsychotic medication, a rate that exceeds levels that led to nursing home reform more than 2 decades ago. Atypical antipsychotic medications have become the mainstay of treatment for behavioral problems among residents with dementia, despite federal "black box" warnings about health risks and research demonstrating their limited effectiveness. The purpose of this article is to briefly describe a dissemination research project designed to increase appropriate antipsychotic prescribing for older adults with dementia. A step-wise problem-solving algorithm designed to reduce unnecessary psychotropic medication use is described. Formative evaluation results provided by nursing home personnel are reviewed. Discussion focuses on nursing home culture as an important influence on the adoption of evidence-based practices and changes needed to promote use of behavioral interventions in dementia care and reduction of reliance on antipsychotic medications. PMID:23506127

  4. Association between the HTR2C rs1414334 C/G gene polymorphism and the development of the metabolic syndrome in patients treated with atypical antipsychotics

    PubMed Central

    Rico-Gomis, José María; Triano-García, Irene; Mahecha-García, Luis Fabián; García-Monsalve, Ana; Navarro-Ruiz, Andrés; Villagordo-Peñalver, Berta; Jiménez-Abril, Jessica; Martínez-Hortelano, Alicia; Gil-Guillén, Vicente Francisco

    2016-01-01

    Few studies have assessed the association between the rs1414334 C/G polymorphism in the HTR2C gene and the development of the metabolic syndrome in patients treated with atypical antipsychotics. To provide further evidence, a cross-sectional study was conducted in Spain between 2012 and 2013 in 166 patients with these characteristics. In these patients, the association between the polymorphism and the presence of the metabolic syndrome was determined by implementing binary logistic regression models adjusted for variables associated with the metabolic syndrome. We did not confirm previous claims that the C allele of the polymorphism was linked to the metabolic syndrome: the association was in the opposite direction and non-significant. This conclusion held after taking gender and lifestyle variables into account. PMID:27441116

  5. The atypical antipsychotic, olanzapine, potentiates ghrelin-induced receptor signaling: An in vitro study with cells expressing cloned human growth hormone secretagogue receptor.

    PubMed

    Tagami, Keita; Kashiwase, Yohei; Yokoyama, Akinobu; Nishimura, Hitomi; Miyano, Kanako; Suzuki, Masami; Shiraishi, Seiji; Matoba, Motohiro; Ohe, Yuichiro; Uezono, Yasuhito

    2016-08-01

    The growth hormone secretagogue receptor (GHS-R) belongs to Gαq-coupled G protein-coupled receptor (GPCR) that mediates growth hormone release, food intake, appetite, glucose metabolism and body composition. Ghrelin has been identified as an endogenous ligand for GHS-R, and it is the only orexigenic peptide found in the peripheral organs. Olanzapine, an atypical antipsychotic agent that binds to and inhibits the activation of GPCR for several neurotransmitters, has metabolic side effects such as excessive appetite and weight gain. Recently, studies have revealed that the orexigenic mechanism of olanzapine is mediated via GHS-R signaling, although the precise mechanisms have not been clarified. In this study, we investigated the effect of olanzapine on ghrelin-mediated GHS-R signaling by using an electrical impedance-based receptor biosensor assay system (CellKey™). Olanzapine at concentrations of 10(-7) and 10(-6)mol/L enhanced ghrelin-induced (10(-10)-10(-8)mol/L) GHS-R activation. A Ca(2+) imaging assay revealed that olanzapine (10(-7) and 10(-6)mol/L) enhanced ghrelin (10(-7) M)-induced GHS-R activity. In contrast, haloperidol (an antipsychotic agent) failed to enhance this ghrelin-mediated GHS-R activation, as demonstrated by both the CellKey™ and Ca(2+) imaging assays. Together, these results suggest that olanzapine, but not haloperidol, promotes appetite by enhancing ghrelin-mediated GHS-R signaling. PMID:26775231

  6. A cost-effectiveness analysis of off-label atypical antipsychotic treatment in children and adolescents with ADHD who have failed stimulant therapy.

    PubMed

    Sohn, Minji; Talbert, Jeffery; Moga, Daniela C; Blumenschein, Karen

    2016-09-01

    The objectives of this study are: (1) to estimate the expected health outcomes of atypical antipsychotics (AAPs) and other non-stimulant attention-deficit/hyperactivity disorder (ADHD) medications and (2) to evaluate the cost-effectiveness of AAPs compared to other non-stimulant ADHD medications. We used decision analysis to compare three alternatives for treating children and adolescents with ADHD who failed initial stimulant treatment: (1) AAPs, (2) a selective norepinephrine reuptake inhibitor (atomoxetine), and (3) selective α2-adrenergic agonists (clonidine and guanfacine). Probability estimates and quality-adjusted life year (QALY) weights were derived from a literature review. Cost-effectiveness was estimated using the expected health outcomes derived from the decision analysis and expected costs from the literature. The study was conducted from the third-party payer perspective, and the study period was 1 year. One-way deterministic sensitivity analysis and a Monte Carlo simulation were performed. Over the course of 1 year of ADHD pharmacotherapy, the highest QALY was for clonidine/guanfacine (expected QALY = 0.95) followed by atomoxetine (expected QALY = 0.94). Atypical antipsychotics yielded the lowest health outcome with an expected QALY of 0.84. In the cost-effectiveness analysis, the AAP strategy was dominated as it was less effective and more costly than other two strategies. Compared to clonidine/guanfacine, AAPs provided lower QALYs (0.11 QALY lost) at an additional cost of $2186 on average. Compared to atomoxetine, AAPs resulted in 0.10 QALYs lost at an additional cost of $2186. In this decision analysis model, AAPs provide lower expected health outcomes than other ADHD medications in children and adolescents who failed prior stimulant therapy. Furthermore, AAPs were not a cost-effective option. PMID:27143026

  7. [Prescription of traditional neuroleptics in the remission period for schizophrenic patients with excess of body mass caused by atypical antipsychotics].

    PubMed

    Danilov, D S; Tiul'pin, Iu G

    2007-01-01

    A sample included 61 patients, 53 men and 8 women, with ICD-10 episodic schizophrenia in the remission after treatment with atypical neuroleptics (risperidon, olanzapine, clozapine). All patients were featured by therapeutically caused excess of body mass (obesity of different degrees) that hampered the further treatment. In 31 cases (the main group) atypical neuroleptics were substituted for traditional drugs that exerted lesser influence on body mass. Haloperidol (mean dosage 4,1 mg daily) was administered to 17 patients and trifluoperazine (mean dosage 7,1 mg daily) to 14 patients. Other 30 patients (a control group) continued to receive atypical neuroleptics. Between group differences of patient's mental and somatic state were assessed using quantitative scales. It was shown that the substitution of atypical neuroleptics for traditional neuroleptic drugs allowed to stop further body mass gain and even decreased it without significant influence on psychopathological symptoms and other side-effects in patients with excess of body mass.

  8. Synthesis and biological investigation of new equatorial (β) stereoisomers of 3-aminotropane arylamides with atypical antipsychotic profile.

    PubMed

    Stefanowicz, Jacek; Słowiński, Tomasz; Wróbel, Martyna Zofia; Herold, Franciszek; Gomółka, Anna Edyta; Wesołowska, Anna; Jastrzębska-Więsek, Magdalena; Partyka, Anna; Andres-Mach, Marta; Czuczwar, Stanisław Jerzy; Łuszczki, Jarogniew Jacek; Zagaja, Mirosław; Siwek, Agata; Nowak, Gabriel; Żołnierek, Maria; Bączek, Tomasz; Ulenberg, Szymon; Belka, Mariusz; Turło, Jadwiga

    2016-09-15

    A series of novel 3β-aminotropane derivatives containing a 2-naphthalene or a 2-quinoline moiety was synthesised and evaluated for their affinity for 5-HT1A, 5-HT2A and D2 receptors. Their affinity for the receptors was in the nanomolar to micromolar range. p-Substitution (6c, 6f, 6i, 6l, 6o), as well as substitution with chlorine atoms (6g, 6h, 6i), led to a significant increase in binding affinity for D2 receptors with compounds 6f (Ki=0.6nM), 6c and 6i (Ki=0.4nM), having the highest binding affinities. m-Substituted derivatives were the most promising ligands in terms of 5-HT2A receptor binding affinity whereas 2-quinoline derivatives (10a, 10b) displayed the highest affinity for 5-HT1AR and were the most selective ligands with Ki=62.7nM and Ki=30.5nM, respectively. Finally, the selected ligands 6b, 6d, 6e, 6g, 6h, 6k, 6n and 6o, with triple binding activity for the D2, 5-HT1A and 5-HT2A receptors, were subjected to in vivo tests, such as those for induced hypothermia, climbing behaviour and the head twitch response, in order to determine their pharmacological profile. The tested ligands presented neither agonist nor antagonist properties for the 5-HT1A receptors in the induced hypothermia and lower lip retraction (LLR) tests. All tested compounds displayed antagonistic activity against 5-HT2A, with 6n and 6o being the most active. Four (6b, 6k, 6n and 6o) out of eight tested compounds could be classified as D2 antagonists. Additionally, evaluation of metabolic stability was performed for selected ligands, and introduction of halogen atoms into the benzene ring of 6h, 6k, 6n and 6o improved their metabolic stability. The project resulted in the selection of the lead compounds 6n and 6o, which had antipsychotic profiles, combining dopamine D2-receptor and 5-HT2A antagonism and metabolic stability. PMID:27377863

  9. Norzotepine, a major metabolite of zotepine, exerts atypical antipsychotic-like and antidepressant-like actions through its potent inhibition of norepinephrine reuptake.

    PubMed

    Shobo, M; Kondo, Y; Yamada, H; Mihara, T; Yamamoto, N; Katsuoka, M; Harada, K; Ni, K; Matsuoka, N

    2010-06-01

    The antipsychotic drug zotepine [ZTP; 2-[(8-chlorodibenzo[b,f]thiepin-10-yl)oxy]-N,N-dimethylethan-1-amine] is known to have not only atypical antipsychotic effects but also antidepressive effects in schizophrenia patients. Norzotepine [norZTP; N-desmethylzotepine, 2-[(8-chlorodibenzo[b,f]thiepin-10-yl)oxy]-N-methylethan-1-amine] has been postulated to be a major metabolite of ZTP in humans. Here, we characterized norZTP through several in vitro studies and in animal models of psychosis, depression, and extrapyramidal symptoms (EPS) and compared the pharmacological profiles with those of ZTP. Although both compounds showed similar overall neurotransmitter receptor binding profiles, norZTP showed 7- to 16-fold more potent norepinephrine reuptake inhibition than ZTP. In a pharmacokinetic study, both ZTP and norZTP showed good brain permeability when administered individually in mice, although norZTP was not detected in either plasma or brain after intraperitoneal injection of ZTP. In the methamphetamine-induced hyperlocomotion test in mice, norZTP and ZTP showed similar antipsychotic-like effects at doses above 1 mg/kg i.p. In contrast, unlike ZTP, norZTP did not induce catalepsy up to 10 mg/kg i.p. norZTP significantly antagonized the hypothermia induced by reserpine [(3beta,16beta,17alpha,18beta,20alpha)-11,17-dimethoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]yohimban-16-carboxylic acid methyl ester], suggesting in vivo inhibition of the norepinephrine transporter. In the forced-swim test, norZTP exerted an antidepressant-like effect at the effective doses for its antipsychotic action, whereas ZTP neither antagonized reserpine-induced hypothermia nor showed antidepressant-like effect. These results collectively demonstrate that norZTP exerts more potent inhibitory action than ZTP on norepinephrine transporters both in vitro and in vivo, presumably accounting for its antidepressant-like effect and low EPS propensity. Given that norZTP is the major metabolite observed in

  10. Downregulation of 5-HT7 Serotonin Receptors by the Atypical Antipsychotics Clozapine and Olanzapine. Role of Motifs in the C-Terminal Domain and Interaction with GASP-1.

    PubMed

    Manfra, Ornella; Van Craenenbroeck, Kathleen; Skieterska, Kamila; Frimurer, Thomas; Schwartz, Thue W; Levy, Finn Olav; Andressen, Kjetil Wessel

    2015-07-15

    The human 5-HT7 serotonin receptor, a G-protein-coupled receptor (GPCR), activates adenylyl cyclase constitutively and upon agonist activation. Biased ligands differentially activate 5-HT7 serotonin receptor desensitization, internalization and degradation in addition to G protein activation. We have previously found that the atypical antipsychotics clozapine and olanzapine inhibited G protein activation and, surprisingly, induced both internalization and lysosomal degradation of 5-HT7 receptors. Here, we aimed to determine the mechanism of clozapine- and olanzapine-mediated degradation of 5-HT7 receptors. In the C-terminus of the 5-HT7 receptor, we identified two YXXΦ motifs, LR residues, and a palmitoylated cysteine anchor as potential sites involved in receptor trafficking to lysosomes followed by receptor degradation. Mutating either of these sites inhibited clozapine- and olanzapine-mediated degradation of 5-HT7 receptors and also interfered with G protein activation. In addition, we tested whether receptor degradation was mediated by the GPCR-associated sorting protein-1 (GASP-1). We show that GASP-1 binds the 5-HT7 receptor and regulates the clozapine-mediated degradation. Mutations of the identified motifs and residues, located in or close to Helix-VIII of the 5-HT7 receptor, modified antipsychotic-stimulated binding of proteins (such as GASP-1), possibly by altering the flexibility of Helix-VIII, and also interfered with G protein activation. Taken together, our data demonstrate that binding of clozapine or olanzapine to the 5-HT7 receptor leads to antagonist-mediated lysosomal degradation by exposing key residues in the C-terminal tail that interact with GASP-1. PMID:25706089

  11. Cost-effectiveness model comparing olanzapine and other oral atypical antipsychotics in the treatment of schizophrenia in the United States

    PubMed Central

    Furiak, Nicolas M; Ascher-Svanum, Haya; Klein, Robert W; Smolen, Lee J; Lawson, Anthony H; Conley, Robert R; Culler, Steven D

    2009-01-01

    Background Schizophrenia is often a persistent and costly illness that requires continued treatment with antipsychotics. Differences among antipsychotics on efficacy, safety, tolerability, adherence, and cost have cost-effectiveness implications for treating schizophrenia. This study compares the cost-effectiveness of oral olanzapine, oral risperidone (at generic cost, primary comparator), quetiapine, ziprasidone, and aripiprazole in the treatment of patients with schizophrenia from the perspective of third-party payers in the U.S. health care system. Methods A 1-year microsimulation economic decision model, with quarterly cycles, was developed to simulate the dynamic nature of usual care of schizophrenia patients who switch, continue, discontinue, and restart their medications. The model captures clinical and cost parameters including adherence levels, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment discontinuation by reason, treatment-emergent adverse events, suicide, health care resource utilization, and direct medical care costs. Published medical literature and a clinical expert panel were used to develop baseline model assumptions. Key model outcomes included mean annual total direct cost per treatment, cost per stable patient, and incremental cost-effectiveness values per QALY gained. Results The results of the microsimulation model indicated that olanzapine had the lowest mean annual direct health care cost ($8,544) followed by generic risperidone ($9,080). In addition, olanzapine resulted in more QALYs than risperidone (0.733 vs. 0.719). The base case and multiple sensitivity analyses found olanzapine to be the dominant choice in terms of incremental cost-effectiveness per QALY gained. Conclusion The utilization of olanzapine is predicted in this model to result in better clinical outcomes and lower total direct health care costs compared to generic risperidone, quetiapine, ziprasidone, and aripiprazole. Olanzapine

  12. Improving physical health for people taking antipsychotic medication in the Community Learning Disabilities Service.

    PubMed

    Hall, Ian; Shah, Amar

    2016-01-01

    Adherence with antipsychotic monitoring guidelines is notoriously low nationally. Without active monitoring and measures to improve metabolic abnormalities, more patients may develop related morbidity and mortality. An audit highlighted antipsychotic monitoring in this learning disability service in London did not match guideline recommendations. People with intellectual disability also experience health inequalities. Psychiatrists are well placed to provide advice and assistance that is suitable for those with complex communication, behaviour, and social needs. The QI team tested ideas to increase rates of antipsychotic reviews. The focus was the follow up monitoring of all universal measures recommended by NICE 2014, collected at 2-weekly intervals. We trialled interventions in four broad categories; Intervention 1: to make monitoring more structured and planned; Intervention 2: to increase staff and patient awareness of healthy eating and exercise programs; Intervention 3: to increase the collection of diet and exercise histories from patients; Intervention 4: to improve the uptake of blood tests. The interventions created an improvement in monitoring. There are lessons in the methodology for others carrying out similar projects. PMID:27335645

  13. Blonanserin Augmentation of Atypical Antipsychotics in Patients with Schizophrenia-Who Benefits from Blonanserin Augmentation?: An Open-Label, Prospective, Multicenter Study

    PubMed Central

    Woo, Young Sup; Park, Joo Eon; Kim, Do-Hoon; Sohn, Inki; Hwang, Tae-Yeon; Park, Young-Min; Jon, Duk-In; Jeong, Jong-Hyun

    2016-01-01

    Objective The purpose of this study was to investigate the efficacy and tolerability of atypical antipsychotics (AAPs) with augmentation by blonanserin in schizophrenic patients. Methods aA total of 100 patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP were recruited in this 12-week, open-label, non-comparative, multicenter study. Blonanserin was added to their existing AAP regimen, which was maintained during the study period. Efficacy was primarily evaluated using the Positive and Negative Syndrome Scale (PANSS) at baseline and at weeks 2, 4, 8, and 12. Predictors for PANSS response (≥20% reduction) were investigated. Results The PANSS total score was significantly decreased at 12 weeks of blonanserin augmentation (-21.0±18.1, F=105.849, p<0.001). Moreover, 51.0% of participants experienced a response at week 12. Premature discontinuation of blonanserin occurred in 17 patients (17.0%); 4 of these patients dropped out due to adverse events. The patients who benefited the most from blonanserin were those with severe symptoms despite a treatment with a higher dose of AAP. Conclusion Blonanserin augmentation could be an effective strategy for patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP. PMID:27482249

  14. Analysis of eighteen antidepressants, four atypical antipsychotics and active metabolites in serum by liquid chromatography: a simple tool for therapeutic drug monitoring.

    PubMed

    Frahnert, Christine; Rao, Marie Luise; Grasmäder, Katja

    2003-08-25

    Therapeutic drug monitoring necessitates efficient, fast and reliable analytical methods validated by external quality control. We therefore devised an isocratic reversed-phase HPLC method with ultraviolet detection and optimised this to quantify mirtazapine, reboxetine, moclobemide, venlafaxine, O-desmethylvenlafaxine, paroxetine, fluvoxamine, fluoxetine, norfluoxetine, sertraline, citalopram, amitriptyline, nortriptyline, imipramine, desipramine, doxepin, nordoxepin, clomipramine, norclomipramine, trimipramine, mianserine, maprotiline, normaprotiline, amisulpride, clozapine, norclozapine, quetiapine, risperidone and 9-OH-risperidone in human serum. After solid-phase extraction of the drugs and metabolites, the chromatographic separation was achieved on a Nucleosil 100-Protect 1 column with acetonitrile-potassium dihydrogenphosphate buffer as mobile phase. The method was validated for therapeutic and toxic serum ranges. A linear relationship (r>0.998) was obtained between the concentration and the detector signal. Recoveries were between 75 and 99% for the drugs and metabolites. The accuracy of the quality control samples, expressed as percent recovery, ranged from 91 to 118%; intra- and inter-assay-relative standard deviations were 0.9-10.2% and 0.9-9.7%, respectively. Additional external quality control is carried out since 3 years. This method is applicable to rapidly and effectively analyze serum or plasma samples for therapeutic drug monitoring of about 30 antidepressants and atypical antipsychotics. PMID:12888196

  15. Antipsychotic treatment of schizophrenia: an update.

    PubMed

    Bruijnzeel, Dawn; Suryadevara, Uma; Tandon, Rajiv

    2014-10-01

    The primary objectives in the treatment of schizophrenia are to reduce the frequency and severity of psychotic exacerbation, ameliorate a broad range of symptoms, and improve functional capacity and quality of life. Treatment includes pharmacotherapy and a range of psychosocial interventions. Antipsychotics are the cornerstone of pharmacological treatment for schizophrenia. The sixty-five antipsychotics available in the world are classified into two major groups: first-generation (conventional) agents (FGAs) and second-generation (atypical) agents (SGAs). Whereas clozapine is found to be more efficacious than other agents among otherwise treatment-refractory schizophrenia patients, other differences in efficacy between antipsychotic agents are minor. There are, however, pronounced differences in adverse effect profiles among the 65 antipsychotic medications. Although the 14 SGAs differ "on average" from the 51 FGAs in terms of being associated with a lower risk of EPS and greater risk of metabolic side-effects, substantial variation within the two classes with regard to both risks and other relevant clinical properties undermines the categorical distinction between SGAs and FGAs. Choice of antipsychotic medication should be based on prior treatment response, individual preference, medical history and individual patient vulnerabilities. An individualized treatment approach with ongoing risk-benefit monitoring and collaborative decision-making is outlined. Even as rapid neuroscience advances promise revolutionary improvements in the future, a thoughtful and disciplined approach can provide enhanced outcomes for all schizophrenia patients today.

  16. Safety and tolerability of antipsychotics: focus on amisulpride

    PubMed Central

    Juruena, Mario F; de Sena, Eduardo Pondé; de Oliveira, Irismar Reis

    2010-01-01

    The introduction of the atypical antipsychotic drugs represents an important advance in the treatment of schizophrenia, because the therapeutic efficacy, tolerability, and safety profiles of these agents seem to be superior to that of the classical neuroleptics. As would be predicted from the pharmacologic profile of a pure D2/D3 receptor blocker, amisulpride is an atypical antipsychotic agent, effective for positive and negative symptoms, which can bring about additional improvement in the social functioning and quality of life of patients with schizophrenia. Amisulpride is effective in acute schizophrenia as determined by Clinical Global Impression scores. The major concern regarding the safety of the atypical antipsychotics is related to their propensity to induce weight gain and alter glucose and lipid metabolism. Amisulpride has one of the lowest potentials for weight gain of all the antipsychotic agents, and is associated with clearly lower use of antiparkinsonian medication and with fewer dropouts due to adverse events than conventional antipsychotics. Amisulpride is well tolerated with regard to anxiety and insomnia, and not notably different from placebo. Amisulpride has a pronounced prolactin-elevating effect which appears to be independent of dosage and duration of administration. Hyperprolactinemia rapidly reverses following amisulpride discontinuation. Amisulpride benefits patients with negative symptoms, and is the only antipsychotic to demonstrate efficacy in patients with predominantly negative symptoms. Amisulpride maintains its efficacy when used for medium/long-term treatment, as demonstrated in studies of up to 12 months. In terms of relevance of the effects, superiority is observed for quality of life, social adaptation, and functioning, as measured by the Quality of Life and Functional Status Questionnaire scales. In conclusion, amisulpride is an antipsychotic agent with proven efficacy and good tolerability. Moreover, this drug can help

  17. Improving physical health monitoring for patients with chronic mental health problems who receive antipsychotic medications.

    PubMed

    Abdallah, Nihad; Conn, Rory; Latif Marini, Abdel

    2016-01-01

    Physical health monitoring is an integral part of caring for patients with mental health problems. It is proven that serious physical health problems are more common among patients with severe mental health illness (SMI), this monitoring can be challenging and there is a need for improvement. The project aimed at improving the physical health monitoring among patients with SMI who are receiving antipsychotic medications. The improvement process focused on ensuring there is a good communication with general practitioners (GPs) as well as patient's education and education of care home staff. GP letters requesting physical health monitoring were updated; care home staff and patients were given more information about the value of regular physical health monitoring. There was an improvement in patients' engagement with the monitoring and the monitoring done by GPs was more adherent to local and national guidelines and was communicated with the mental health service.

  18. Improving physical health monitoring for patients with chronic mental health problems who receive antipsychotic medications

    PubMed Central

    Abdallah, Nihad; Conn, Rory; Latif Marini, Abdel

    2016-01-01

    Physical health monitoring is an integral part of caring for patients with mental health problems. It is proven that serious physical health problems are more common among patients with severe mental health illness (SMI), this monitoring can be challenging and there is a need for improvement. The project aimed at improving the physical health monitoring among patients with SMI who are receiving antipsychotic medications. The improvement process focused on ensuring there is a good communication with general practitioners (GPs) as well as patient's education and education of care home staff. GP letters requesting physical health monitoring were updated; care home staff and patients were given more information about the value of regular physical health monitoring. There was an improvement in patients' engagement with the monitoring and the monitoring done by GPs was more adherent to local and national guidelines and was communicated with the mental health service. PMID:27559474

  19. Improving physical health monitoring for patients with chronic mental health problems who receive antipsychotic medications.

    PubMed

    Abdallah, Nihad; Conn, Rory; Latif Marini, Abdel

    2016-01-01

    Physical health monitoring is an integral part of caring for patients with mental health problems. It is proven that serious physical health problems are more common among patients with severe mental health illness (SMI), this monitoring can be challenging and there is a need for improvement. The project aimed at improving the physical health monitoring among patients with SMI who are receiving antipsychotic medications. The improvement process focused on ensuring there is a good communication with general practitioners (GPs) as well as patient's education and education of care home staff. GP letters requesting physical health monitoring were updated; care home staff and patients were given more information about the value of regular physical health monitoring. There was an improvement in patients' engagement with the monitoring and the monitoring done by GPs was more adherent to local and national guidelines and was communicated with the mental health service. PMID:27559474

  20. A long-term, phase 2, multicenter, randomized, open-label, comparative safety study of pomaglumetad methionil (LY2140023 monohydrate) versus atypical antipsychotic standard of care in patients with schizophrenia

    PubMed Central

    2013-01-01

    significantly greater in the SOC group at 24-week endpoint (P = .004). LY2140023 and SOC groups had comparable negative symptom improvement at 24-week endpoint (P = .444). Conclusion These data provide further evidence that the potential antipsychotic LY2140023 monohydrate, with a glutamatergic mechanism of action, may have a unique tolerability profile characterized by a low association with some adverse events such as extrapyramidal symptoms and weight gain that may characterize currently available dopaminergic antipsychotics. Trials registration A Long-term, Phase 2, Multicenter, Randomized, Open-label, Comparative Safety Study of LY2140023 Versus Atypical Antipsychotic Standard of Care in Patients with DSM-IV-TR Schizophrenia ClinicalTrials.gov identifier: NCT00845026. PMID:23694720

  1. Atypical Antipsychotics in the Treatment of Acute Bipolar Depression with Mixed Features: A Systematic Review and Exploratory Meta-Analysis of Placebo-Controlled Clinical Trials

    PubMed Central

    Fornaro, Michele; Stubbs, Brendon; De Berardis, Domenico; Perna, Giampaolo; Valchera, Alessandro; Veronese, Nicola; Solmi, Marco; Ganança, Licínia

    2016-01-01

    Evidence supporting the use of second generation antipsychotics (SGAs) in the treatment of acute depression with mixed features (MFs) associated with bipolar disorder (BD) is scarce and equivocal. Therefore, we conducted a systematic review and preliminary meta-analysis investigating SGAs in the treatment of acute BD depression with MFs. Two authors independently searched major electronic databases from 1990 until September 2015 for randomized (placebo-) controlled trials (RCTs) or open-label clinical trials investigating the efficacy of SGAs in the treatment of acute bipolar depression with MFs. A random-effect meta-analysis calculating the standardized mean difference (SMD) between SGA and placebo for the mean baseline to endpoint change in depression as well as manic symptoms score was computed based on 95% confidence intervals (CI). Six RCTs and one open-label placebo-controlled studies (including post-hoc reports) representing 1023 patients were included. Participants received either ziprasidone, olanzapine, lurasidone, quetiapine or asenapine for an average of 6.5 weeks across the included studies. Meta-analysis with Duval and Tweedie adjustment for publication bias demonstrated that SGA resulted in significant improvements of (hypo-)manic symptoms of bipolar mixed depression as assessed by the means of the total scores of the Young Mania Rating Scale (YMRS) (SMD −0.74, 95% CI −1.20 to −0.28, n SGA = 907, control = 652). Meta-analysis demonstrated that participants in receipt of SGA (n = 979) experienced a large improvement in the Montgomery–Åsberg Depression Rating Scale (MADRS) scores (SMD −1.08, 95% CI −1.35 to −0.81, p < 0.001) vs. placebo (n = 678). Publication and measurement biases and relative paucity of studies. Overall, SGAs appear to offer favorable improvements in MADRS and YMRS scores vs. placebo. Nevertheless, given the preliminary nature of the present report, additional original studies are required to allow more reliable and

  2. Combined serotonin (5-HT)1A agonism, 5-HT(2A) and dopamine D₂ receptor antagonism reproduces atypical antipsychotic drug effects on phencyclidine-impaired novel object recognition in rats.

    PubMed

    Oyamada, Yoshihiro; Horiguchi, Masakuni; Rajagopal, Lakshmi; Miyauchi, Masanori; Meltzer, Herbert Y

    2015-05-15

    Subchronic administration of an N-methyl-D-aspartate receptor (NMDAR) antagonist, e.g. phencyclidine (PCP), produces prolonged impairment of novel object recognition (NOR), suggesting they constitute a hypoglutamate-based model of cognitive impairment in schizophrenia (CIS). Acute administration of atypical, e.g. lurasidone, but not typical antipsychotic drugs (APDs), e.g. haloperidol, are able to restore NOR following PCP (acute reversal model). Furthermore, atypical APDs, when co-administered with PCP, have been shown to prevent development of NOR deficits (prevention model). Most atypical, but not typical APDs, are more potent 5-HT(2A) receptor inverse agonists than dopamine (DA) D2 antagonists, and have been shown to enhance cortical and hippocampal efflux and to be direct or indirect 5-HT(1A) agonists in vivo. To further clarify the importance of these actions to the restoration of NOR by atypical APDs, sub-effective or non-effective doses of combinations of the 5-HT(1A) partial agonist (tandospirone), the 5-HT(2A) inverse agonist (pimavanserin), or the D2 antagonist (haloperidol), as well as the combination of all three agents, were studied in the acute reversal and prevention PCP models of CIS. Only the combination of all three agents restored NOR and prevented the development of PCP-induced deficit. Thus, this triple combination of 5-HT(1A) agonism, 5-HT(2A) antagonism/inverse agonism, and D2 antagonism is able to mimic the ability of atypical APDs to prevent or ameliorate the PCP-induced NOR deficit, possibly by stimulating signaling cascades from D1 and 5-HT(1A) receptor stimulation, modulated by D2 and 5-HT(2A) receptor antagonism. PMID:25448429

  3. Reducing the rates of prescribing high-dose antipsychotics and polypharmacy on psychiatric inpatient and intensive care units: results of a 6-year quality improvement programme

    PubMed Central

    Taylor, David

    2015-01-01

    Background: There is no conclusive evidence that either high doses or combinations of antipsychotics are more effective than standard doses or monotherapy alone. Nonetheless, prescription of both remains prevalent in the UK. In 2006 the South London and Maudsley NHS Foundation Trust (SLAM) participated in a national survey of prescription of antipsychotic medications, organized by the Prescribing Observatory for Mental Health. Over half of the patients on SLAM inpatient or psychiatric intensive care units were prescribed a high-dose antipsychotic or a combination of antipsychotics. Prescribing high-dose antipsychotics and polypharmacy in SLAM was found to be among the highest in the UK. Aim: To assess the impact of a 6-year quality improvement programme aimed at reducing the rates of prescribing high-dose antipsychotics and polypharmacy on SLAM inpatients and psychiatric intensive care units. Results: There was a significant reduction between baseline and final survey in the rates of prescription of both high-dose antipsychotics and polypharmacy on SLAM inpatients and intensive care units (58% versus 10% p < 0.0001 and 57% versus 16%, p < 0.0001 respectively). The proportion of patients at final survey prescribed a high-dose antipsychotic and a combination was substantially lower in SLAM than in the national sample (10% versus 28%, p < 0.0001 and 16% versus 38%, p < 0.0001 respectively). Clinical implications: A sustained change in the prescribing culture of an organization can be achieved through a targeted improvement programme. PMID:25653825

  4. Valid grounds for the switch of original antipsychotics with generics.

    PubMed

    Ruzić, Klementina; Dadić-Hero, Elizabeta; Knez, Rajna; Medved, Paola; Graovac, Mirjana

    2010-03-01

    Patients' non-compliance in treatments, such as irregular taking of medication, represents an enormous problem with psychiatric patients in general. This difficulty occurs especially in patients suffering from chronic mental illnesses such as schizophrenia. There are not any significant differences in the efficacy of reducing the positive symptoms in schizophrenia between the conventional and the atypical antipsychotics. However, the effects which are manifested in negative schizophrenia symptoms or in the patients' cognitive functioning, favour the atypical antipsychotics. When it comes to adding the subjective well-being of the patients and their improvement of the quality of life, then, the advantages of atypical antipsychotics are unquestionable. New trends in medicine are increasingly impinge on the pharmacoeconomy, which aims at reducing treatment cost. This trend is getting progressively stronger in the world and as such, it certainly will not bypass Croatia. Pharmacists and General Practice doctors (GP) are permitted, by the law, to replace the original medicament prescribed by a specialist doctor, with a cheaper one from the same generic group of medicaments, with a purpose of cutting down the treatment costs. Is there always a valid justification for such practice, and should it become a rule for all the patients out there? This is a case report of a patient who suffers from paranoid schizophrenia. He has been on a treatment with atypical antipsychotics and has kept in a good and stable remission for the past seven years. His therapy consisted of olanzapine in a dose of 15 mg in the evening, throughout the whole period of his 7-year remission. A month ago, his GP doctor self- initially prescribed a generic olanzapine. The impact of this decision on to the mental state of the patient as well as his trust in the treatment itself is described in this report. PMID:20305601

  5. Public-academic partnerships: a program to improve the quality of antipsychotic prescribing in a community mental health system.

    PubMed

    Brunette, Mary F; de Nesnera, Alexander; Swain, Karin; Riera, Erik G; Lotz, Doris; Bartels, Stephen J

    2011-09-01

    State mental health authorities can use public-academic partnerships to create professional roles in which leaders can track trends, identify problems, and carry out quality improvement projects to address key issues. Leaders with positions in both academic institutions and state mental health authorities ensure access to resources, technical expertise, and key relationships to improve quality. The authors describe a public-academic partnership in New Hampshire and a quality improvement program it carried out. The program encourages providers at community mental health centers to adopt prescribing practices that limit the cardiometabolic side effects of antipsychotic medicines.

  6. Long-acting injectable antipsychotics in the elderly: guidelines for effective use.

    PubMed

    Masand, Prakash S; Gupta, Sanjay

    2003-01-01

    are reduced dramatically with atypical antipsychotics compared with traditional agents, the development of long-acting atypical antipsychotic formulations has been pursued. Of the atypical antipsychotics, risperidone is the first agent to be approved in a long-acting injectable formulation. Unpublished clinical data have revealed that patients treated with long-acting injectable risperidone (25mg, 50mg or 75mg) are more likely to show significant clinical improvement than placebo. In addition, hospitalisation rates decreased continuously and significantly during 1 year of treatment for patients who received long-acting injectable risperidone.Long-acting injectable antipsychotic medication should be considered for older patients for whom long-term treatment is indicated. The choice of which drug to use should be based on patients' history of response and personal preference, clinician's previous experience and pharmacokinetic properties.

  7. Efficacy of newer generation antipsychotics in the treatment of schizophrenia.

    PubMed

    Tandon, R; Jibson, M D

    2003-01-01

    The advent of the newer 'atypical' antipsychotic medications has revolutionized the pharmacologic treatment of schizophrenia and other psychotic disorders. In contrast to the older conventional antipsychotic agents, atypical medications have a broader spectrum of efficacy (greater efficacy in negative, cognitive, and mood symptoms) and a lower risk of extrapyramidal symptoms (EPS) and tardive dyskinesia. Due to concerns surrounding hematological safety and other adverse effects, clozapine is used principally in patients refractory to treatment with other antipsychotic agents. The other three universally available atypical agents (risperidone, olanzapine, and quetiapine) collectively constitute about 70% of all antipsychotic prescriptions in the USA. Despite the broad popularity of these medications and their rapid adoption in general clinical practice, there are limited data on how they compare to each other with regards to their overall efficacy and also as to their efficacy in specific symptom domains. To address this question, two separate analyses were undertaken. First, all published, short-term, randomized, controlled clinical trials of these agents in schizophrenia and schizoaffective disorder were reviewed and the extent of improvement across these agents was compared. While the amount of improvement with a particular agent across its different studies varied, the average improvement was similar for the agents for all efficacy parameters considered. Secondly, all randomized, controlled clinical trials directly comparing two or more of these agents in patients with schizophrenia or schizoaffective disorder were analyzed. Only three such trials (all industry sponsored) were identified; while there were differences in methodology and small differences in efficacy on a minority of measures on which comparisons were undertaken, the preponderance of data suggested no differences in efficacy. While data thus far do not support assertions of differential efficacy

  8. Survey on schizophrenia treatment in Mexico: perception and antipsychotic prescription patterns

    PubMed Central

    Apiquian, Rogelio; Fresán, Ana; de la Fuente-Sandoval, Camilo; Ulloa, Rosa-Elena; Nicolini, Humberto

    2004-01-01

    Background Since the introduction of antipsychotics, especially the so called atypicals, the treatment of schizophrenia has shown important improvements. At the present time, it is preferred to label clozapine and other antipsychotics sharing similar profiles as second-generation antipsychotics (SGAs). These medications have been proposed by some experts as a first line treatment for schizophrenia. It is critical to have reliable data about antipsychotic prescription in Mexico and to create management guidelines based on expert meetings and not only on studies carried out by the pharmaceutical industry. Only this approach will help to make the right decisions for the treatment of schizophrenia. Methods A translated version of Rabinowitz's survey was used to evaluate antipsychotic prescription preferences and patterns in Mexican psychiatrists. The survey questionnaire was sent by mail to 200 psychiatrists from public institutions and private practice in Mexico City and Guadalajara, Mexico. Results Recommendations for antipsychotics daily doses at different stages of the treatment of schizophrenia varied widely. Haloperidol was considered as the first choice for the treatment of positive symptoms. On the contrary, risperidone was the first option for negative symptoms. For a patient with a high susceptibility for developing extrapyramidal symptoms (EPS), risperidone was the first choice. It was also considered that SGAs had advantages over typical antipsychotics in the management of negative symptoms, cognitive impairment and fewer EPS. Besides, there was a clear tendency for prescribing typical antipsychotics at higher doses than recommended and inadequate doses for the atypical ones. Conclusions Some of the obstacles for the prescription of SGAs include their high cost, deficient knowledge about their indications and dosage, the perception of their being less efficient for the treatment of positive symptoms and the resistance of some Mexican physicians to change

  9. Novel antipsychotics and severe hyperlipidemia.

    PubMed

    Meyer, J M

    2001-08-01

    Newer atypical antipsychotics demonstrate superior effectiveness, with a diminished incidence of extrapyramidal side effects compared with older typical antipsychotics, but they have been associated with the development of obesity and new-onset diabetes. A small number of reports documenting modest hypertriglyceridemia related to newer antipsychotics have implicated fluperlapine, clozapine, and, most recently, olanzapine. This study summarizes the results of 14 cases of severe hypertriglyceridemia (>600 mg/dL) associated with olanzapine and quetiapine therapy occurring among inpatients at Oregon State Hospital, including 7 patients whose serum triglyceride levels exceeded 1,000 mg/ dL. Four of these patients also developed new-onset diabetes. Nine cases occurred during the first 8 months of treatment, with three cases identified within 3 months of commencing olanzapine or quetiapine therapy. Weight gain in olanzapine and quetiapine groups was modest (12.3 lb and 8.5 lb, respectively) and did not correlate with the severity of hypertriglyceridemia. Biochemical causes for severe hypertriglyceridemia associated with novel antipsychotics are unclear, but clinical monitoring of serum lipids must be added to the concerns about the metabolic consequences of therapy with certain newer antipsychotic agents. PMID:11476120

  10. Antipsychotic Drugs on Maternal Behavior in Rats

    PubMed Central

    Li, Ming

    2015-01-01

    Rat maternal behavior is a complex social behavior. Many clinically used antipsychotic drugs, including the typical drug haloperidol and atypical drugs clozapine, risperidone, olanzapine, quetiapine, aripiprazole and amisulpride, all disrupt active maternal responses (e.g. pup retrieval, pup licking and nest building) to various extents. In this review, I present a summary of recent studies on the behavioral effects and neurobiological mechanisms of antipsychotic action on maternal behavior in rats. I argue that antipsychotic drugs at the clinical relevant doses disrupt active maternal responses primarily by suppressing maternal motivation. Atypical drug-induced sedation also contributes to their disruptive effects, especially that on pup nursing. Among many potential receptor mechanisms, dopamine D2 receptors and serotonin 5-HT2A/2C receptors are shown to be critically involved in the mediation of the maternal disruptive effects of antipsychotic drugs, with D2 receptors contributing more to typical antipsychotic-induced disruptions, while 5-HT2A/2C receptors contributing more to atypical drug-induced disruption. The nucleus accumbens shell-related reward circuitry is an essential neural network in the mediation of the behavioral effects of antipsychotic drugs on maternal behavior. This research not only helps to understand the extent and mechanisms of impacts of antipsychotic medications on human maternal care, but also is important for enhancing our understanding of the neurochemical basis of maternal behavior. It is also valuable for understanding the complete spectrum of therapeutic and side-effects of antipsychotic treatment. This knowledge may facilitate the development of effective intervening strategies to help patients coping with such undesirable effects. PMID:26221833

  11. Screening for the metabolic side effects of antipsychotic medication: findings of a 6-year quality improvement programme in the UK

    PubMed Central

    Barnes, T R E; Bhatti, S F; Adroer, R; Paton, C

    2015-01-01

    Objectives To increase the frequency and quality of screening for the metabolic syndrome in people prescribed continuing antipsychotic medication. Design An audit-based, quality improvement programme (QIP) with customised feedback to participating mental health services after each audit, including benchmarked data on their relative and absolute performance against an evidence-based practice standard and the provision of bespoke change interventions. Setting Adult, assertive outreach, community psychiatric services in the UK. Participants 6 audits were conducted between 2006 and 2012. 21 mental health Trusts participated in the baseline audit in 2006, submitting data on screening for 1966 patients, while 32 Trusts participated in the 2012 audit, submitting data on 1591 patients. Results Over the 6 years of the programme, there was a statistically significant increase in the proportion of patients for whom measures for all 4 aspects of the metabolic syndrome had been documented in the clinical records in the previous year, from just over 1 in 10 patients in 2006 to just over 1 in 3 by 2012. The proportion of patients with no evidence of any screening fell from almost ½ to 1 in 7 patients over the same period. Conclusions The findings suggest that audit-based QIPs can help improve clinical practice in relation to physical healthcare screening. Nevertheless, they also reveal that only a minority of community psychiatric patients prescribed antipsychotic medication is screened for the metabolic syndrome in accordance with best practice recommendations, and therefore potentially remediable causes of poor physical health remain undetected and untreated. PMID:26428329

  12. Antipsychotics--the future of schizophrenia treatment.

    PubMed

    Beaumont, G

    2000-01-01

    Schizophrenia is a debilitating mental disorder affecting up to five in every thousand people. Although specialist psychiatrists are initially responsible for treating patients suffering from acute schizophrenia, the current structure of mental healthcare in the U.K. puts the onus for the delivery of maintenance therapy of discharged patients on to the general practitioner. It is crucial, therefore, that the general practitioner is aware of all available therapies for the effective, long-term, community-based treatment of patients with schizophrenia. The so-called typical antipsychotics effectively treat the positive but not the negative symptoms of schizophrenia, and up to 40% of patients are nonresponders. These antipsychotics, however, are associated with high levels of extrapyramidal side-effects (EPS), which are the main cause of patient non-compliance and their subsequent relapse and hospital readmission. Clozapine, the first atypical antipsychotic, may cause severe agranulocytosis and patients must undergo regular haematological monitoring, which is both costly and a factor unlikely to foster patient compliance. In contrast, newly developed atypical antipsychotics, such as olanzapine and quetiapine, are not only efficacious in treating the symptoms of schizophrenia, but also give rise to fewer EPS and are generally better tolerated than clozapine. In particular, olanzapine and quetiapine are not associated with severe agranulocytosis. Atypical antipsychotics, therefore, have the potential to enhance patient compliance and thus ease the general practitioner's problems of providing long-term and effective treatment for patients with schizophrenia. PMID:16422033

  13. Biomarkers for antipsychotic therapies.

    PubMed

    Pich, Emilio Merlo; Vargas, Gabriel; Domenici, Enrico

    2012-01-01

    Molecular biomarkers for antipsychotic treatments have been conceptually linked to the measurements of dopamine functions, mostly D(2) receptor occupancy, either by imaging using selective PET/SPECT radioactive tracers or by assessing plasma prolactin levels. A quest for novel biomarkers was recently proposed by various academic, health service, and industrial institutions driven by the need for better treatments of psychoses. In this review we conceptualize biomarkers within the Translational Medicine paradigm whose goal was to provide support to critical decision-making in drug discovery. At first we focused on biomarkers as outcome measure of clinical studies by searching into the database clinicaltrial.gov. The results were somewhat disappointing, showing that out of 1,659 antipsychotic trials only 18 used a biomarker as an outcome measure. Several of these trials targeted plasma lipids as sentinel marker for metabolic adverse effects associated with the use of atypical antipsychotics, while only few studies were aimed to new disease specific biological markers. As an example of a mechanistic biomarker, we described the work done to progress the novel class of glycine transporter inhibitors as putative treatment for negative symptoms of schizophrenia. We also review how large-scale multiplex biological assays were applied to samples from tissues of psychiatric patients, so to learn from changes of numerous analytes (metabolic products, lipids, proteins, RNA transcripts) about the substrates involved in the disease. We concluded that a stringent implementation of these techniques could contribute to the endophenotypic characterization of patients, helping in the identification of key biomarkers to drive personalized medicine and new treatment development. PMID:23129338

  14. Facial affect processing deficits in schizophrenia: A meta-analysis of antipsychotic treatment effects

    PubMed Central

    Kempton, Matthew J; Mehta, Mitul A

    2015-01-01

    Social cognition, including emotion processing, is a recognised deficit observed in patients with schizophrenia. It is one cognitive domain which has been emphasised as requiring further investigation, with the efficacy of antipsychotic treatment on this deficit remaining unclear. Nine studies met our criteria for entry into a meta-analysis of the effects of medication on facial affect processing, including data from 1162 patients and six antipsychotics. Overall we found a small, positive effect (Hedge’s g = 0.13, 95% CI 0.05 to 0.21, p = 0.002). In a subgroup analysis this was statistically significant for atypical, but not typical, antipsychotics. It should be noted that the pooled sample size of the typical subgroup was significantly lower than the atypical. Meta-regression analyses revealed that age, gender and changes in symptom severity were not moderating factors. For the small, positive effect on facial affect processing, the clinical significance is questionable in terms of treating deficits in emotion identification in schizophrenia. We show that antipsychotic medications are poor at improving facial affect processing compared to reducing symptoms. This highlights the need for further investigation into the neuropharmacological mechanisms associated with accurate emotion processing, to inform treatment options for these deficits in schizophrenia. PMID:25492885

  15. Antipsychotic agents and QT changes.

    PubMed Central

    Welch, R; Chue, P

    2000-01-01

    Recently, antipsychotic medications of the novel or atypical classes have received increased attention because of concerns with respect to potential lengthening of the QT interval, yet the currently available and commonly prescribed conventional antipsychotics are significantly more cardiotoxic, particularly agents in the butyrophenone and phenothiazine classes. Lengthening of the QT interval can be associated with a fatal paroxysmal ventricular arrhythmia known as torsades de pointes. The specific duration of the QT interval at which the risk of an adverse cardiac event is greatest, is not established. There is not only significant variation in the applied definition of an abnormal interval, but the maximal QT interval in healthy volunteers is greater than the currently accepted standards. The QT interval is influenced by normal physiological and pathologic factors, but the mechanisms remain unclear. Using recombinant technology, haloperidol and sertindole have been demonstrated to be high-affinity antagonists of a human cardiac potassium channel encoded by the human ether-a-go-go-related gene. Pimozide, however, has been shown to act principally through calcium channel antagonism, and chlorpromazine may affect sodium channels. Nevertheless, it is possible that these effects are significant only in the presence of predisposing factors, either genetic or acquired. Despite proven efficacy in clinical trials and subsequent supervised use in Europe, a number of recently developed antipsychotic medications are not available to patients in North America. Yet, conventional antipsychotic medications that would not be approved by current safety standards continue to be widely used. PMID:10740988

  16. [Schizophrenia, diabetes mellitus and antipsychotics].

    PubMed

    Gury, C

    2004-01-01

    and subjected to many flaws: concomitant diseases not taken into account, diabetes status evaluated by drug consumption, unknown diabetes status before antipsychotic treatment, etc. In the few prospective studies performed, no significant differences between the atypical versus typical antipsychotics were evidenced for new cases of diabetes. Moreover, in general population, the glucose tolerance impairment is underdiagnosed and it is estimated that people with a glucose tolerance impairment have a 5-10% annual risk of type II diabetes. Thus, this concern has to be replaced among the world epidemic increase of diabetes and in a population of patients whose the disease itself and life style are risk factors for diabetes. Some studies have explored the pathophysiological mechanisms that could support a diabetogenic effect of antipsychotics. Although it does not seem to be a direct effect of antipsychotics on insulin secretion by pancreatic cells, body weight increase has been evidence for both typical and atypical antipsychotics. However, it remains unclear whether this weight increase is responsible for a visceral adiposity, which is a risk factor better fitted to the cardiovascular mortality tha the body weight itself. Other hypotheses involving an effect on the leptin, which regulates the appetite, have been proposed. In waiting of new prospective controlled studies, and without denying the impact of antipsychotics on the glucose and lipid metabolisms (on the weight increase, for example), it should be recognized that the benefit/risk ratio remains largely in favour of the treatment, particularly for the atypical antipsychotics, more effective and better tolerated at the neurological level than the conventional antipsychotics. One of the benefits of the mainly articles in professional media about this concern is to draw attention on the metabolism disorders in schizophrenic patients, which are important risk factor of their frequent cardiovascular surmortality

  17. Monitoring and managing metabolic effects of antipsychotics: a cluster randomized trial of an intervention combining evidence-based quality improvement and external facilitation

    PubMed Central

    2013-01-01

    Background Treatment of psychotic disorders consists primarily of second generation antipsychotics, which are associated with metabolic side effects such as overweight/obesity, diabetes, and dyslipidemia. Evidence-based clinical practice guidelines recommend timely assessment and management of these conditions; however, research studies show deficits and delays in metabolic monitoring and management for these patients. This protocol article describes the project ‘Monitoring and Management for Metabolic Side Effects of Antipsychotics,’ which is testing an approach to implement recommendations for these practices. Methods/Design This project employs a cluster randomized clinical trial design to test effectiveness of an evidence-based quality improvement plus facilitation intervention. Eligible study sites were VA Medical Centers with ≥300 patients started on a new antipsychotic prescription in a six-month period. A total of 12 sites, matched in pairs based on scores on an organizational practice survey, were then randomized within pairs to intervention or control conditions. Study participants include VA employees involved in metabolic monitoring and management of patients treated with antipsychotics at participating sites. The intervention involves researchers partnering with clinical stakeholders to facilitate tailoring of local implementation strategies to address barriers to metabolic side-effect monitoring and management. The intervention includes a Design Phase (initial site visit and subsequent development of a local implementation plan); Implementation Phase (guided by an experienced external facilitator); and a Sustainability Phase. Evaluation includes developmental, implementation-focused, progress-focused and interpretative formative evaluation components, as well as summative evaluation. Evaluation methods include surveys, qualitative data collection from provider participants, and quantitative data analysis of data for all patients prescribed a new

  18. Receptor mechanisms of antipsychotic drug action in bipolar disorder - focus on asenapine.

    PubMed

    Reynolds, Gavin P

    2011-12-01

    , although the lower propensity for weight gain shown by asenapine which, like olanzapine, binds to these receptors, indicates that other protective receptor mechanisms, or subtle differences in the 5-HT2C receptor-mediated effects, may be important. Of other peripheral and central effects, the pharmacological basis of sedation (H1 receptors) and postural hypotension (alpha1 adrenoceptors) are rather better understood. The relative benefits of atypical antipsychotics like asenapine can be understood from their receptor pharmacology, and this understanding is key to the future development of improved treatment for bipolar disorder.

  19. Environmental enrichment improves behavioral outcome in the AY-9944 model of childhood atypical absence epilepsy.

    PubMed

    Stewart, Lee S; Cortez, Miguel A; Snead, O Carter

    2012-08-01

    Atypical absence seizures are drug resistant in the majority of children with Lennox-Gastaut syndrome and herald a poor neurodevelopmental outcome. Here we studied the effects of environmental enrichment, enriched housing conditions designed to stimulate sensory and motor systems in the brain, on behavioral outcome in mice treated with the cholesterol biosynthesis inhibitor AY-9944 (AY), a clinically relevant model of atypical absence epilepsy. Beginning at postnatal day (P) 2, C3H mice were treated with AY (7.5 mg/kg) every 6 days until P20 and then weaned into enriched or standard cages. After 30 days (∼P50), AY mice from the enriched housing condition exhibited less behavioral hyperactivity and anxiety, improved olfactory recognition, and spatial learning, but no significant reduction in the number of ictal discharges in comparison with their non-enriched cohorts. The beneficial effects of environmental enrichment in AY model were in some behavioral tests gender-specific in favor of males suggesting that other, possibly hormonally mediated mechanisms, may interact with the therapeutic effects of enrichment. Taken together, these data provide a starting point to derive clinical occupational therapies for improving behavioral outcome in cases of intractable childhood seizures.

  20. Half a century of antipsychotics and still a central role for dopamine D2 receptors.

    PubMed

    Kapur, Shitij; Mamo, David

    2003-10-01

    A review of the history of antipsychotics reveals that while the therapeutic effects of chlorpromazine and reserpine were discovered and actively researched almost concurrently, subsequent drug development has been restricted to drugs acting on postsynaptic receptors rather than modulation of dopamine release. The fundamental property of atypical antipsychotics is their ability to produce an antipsychotic effect in the absence of extrapyramidal side effects (EPS) or prolactin elevation. Modulation of the dopamine D2 receptor remains both necessary and sufficient for antipsychotic drug action, with affinity to the D2-receptor being the single most important discriminator between a typical and atypical drug profile. Most antipsychotics, including atypical antipsychotics, show a dose-dependent threshold of D2 receptor occupancy for their therapeutic effects, although the precise threshold is different for different drugs. Some atypical antipsychotics do not appear to reach the threshold for EPS and prolactin elevation, possibly accounting for their atypical nature. To link the biological theories of antipsychotics to their psychological effects, a hypothesis is proposed wherein psychosis is a state of aberrant salience of stimuli and ideas, and antipsychotics, via modulation of the mesolimbic dopamine system, dampen the salience of these symptoms. Thus, antipsychotics do not excise psychosis: they provide the neurochemical platform for the resolution of symptoms. Future generations of antipsychotics may need to move away from a "one-size-fits-all polypharmacy-in-a-pill" approach to treat all the different aspects of schizophrenia. At least in theory a preferred approach would be the development of specific treatments for the different dimensions of schizophrenia (e.g., positive, negative, cognitive, and affective) that can be flexibly used and titrated in the service of patients' presenting psychopathology. PMID:14642968

  1. Half a century of antipsychotics and still a central role for dopamine D2 receptors.

    PubMed

    Kapur, Shitij; Mamo, David

    2003-10-01

    A review of the history of antipsychotics reveals that while the therapeutic effects of chlorpromazine and reserpine were discovered and actively researched almost concurrently, subsequent drug development has been restricted to drugs acting on postsynaptic receptors rather than modulation of dopamine release. The fundamental property of atypical antipsychotics is their ability to produce an antipsychotic effect in the absence of extrapyramidal side effects (EPS) or prolactin elevation. Modulation of the dopamine D2 receptor remains both necessary and sufficient for antipsychotic drug action, with affinity to the D2-receptor being the single most important discriminator between a typical and atypical drug profile. Most antipsychotics, including atypical antipsychotics, show a dose-dependent threshold of D2 receptor occupancy for their therapeutic effects, although the precise threshold is different for different drugs. Some atypical antipsychotics do not appear to reach the threshold for EPS and prolactin elevation, possibly accounting for their atypical nature. To link the biological theories of antipsychotics to their psychological effects, a hypothesis is proposed wherein psychosis is a state of aberrant salience of stimuli and ideas, and antipsychotics, via modulation of the mesolimbic dopamine system, dampen the salience of these symptoms. Thus, antipsychotics do not excise psychosis: they provide the neurochemical platform for the resolution of symptoms. Future generations of antipsychotics may need to move away from a "one-size-fits-all polypharmacy-in-a-pill" approach to treat all the different aspects of schizophrenia. At least in theory a preferred approach would be the development of specific treatments for the different dimensions of schizophrenia (e.g., positive, negative, cognitive, and affective) that can be flexibly used and titrated in the service of patients' presenting psychopathology.

  2. Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management.

    PubMed

    Haddad, Peter M; Wieck, Angelika

    2004-01-01

    Hyperprolactinaemia is an important but neglected adverse effect of antipsychotic medication. It occurs frequently with conventional antipsychotics and some atypical antipsychotics (risperidone and amisulpride) but is rare with other atypical antipsychotics (aripiprazole, clozapine, olanzapine, quetiapine, ziprasidone). For this reason the terms 'prolactin-sparing' and 'prolactin-raising' are more useful than 'atypical' and 'conventional' when considering the effect of antipsychotic drugs on serum prolactin. During antipsychotic treatment prolactin levels can rise 10-fold or more above pretreatment values. In a recent study approximately 60% of women and 40% of men treated with a prolactin-raising antipsychotic had a prolactin level above the upper limit of the normal range. The distinction between asymptomatic and symptomatic hyperprolactinaemia is important but is often not made in the literature. Some symptoms of hyperprolactinaemia result from a direct effect of prolactin on target tissues but others result from hypogonadism caused by prolactin disrupting the normal functioning of the hypothalamic-pituitary-gonadal axis. Symptoms of hyperprolactinaemia include gynaecomastia, galactorrhoea, sexual dysfunction, infertility, oligomenorrhoea and amenorrhoea. These symptoms are little researched in psychiatric patients. Existing data suggest that they are common but that clinicians underestimate their prevalence. For example, well conducted studies of women treated with conventional antipsychotics have reported prevalence rates of approximately 45% for oligomenorrhoea/amenorrhoea and 19% for galactorrhoea. An illness-related under-function of the hypothalamic-pituitary-gonadal axis in female patients with schizophrenia may also contribute to menstrual irregularities. Long-term consequences of antipsychotic-related hypogonadism require further research but are likely and include premature bone loss in men and women. There are conflicting data on whether

  3. Financial incentives to improve adherence to antipsychotic maintenance medication in non-adherent patients: a cluster randomised controlled trial.

    PubMed Central

    Priebe, Stefan; Bremner, Stephen A; Lauber, Christoph; Henderson, Catherine; Burns, Tom

    2016-01-01

    BACKGROUND: Poor adherence to long-term antipsychotic injectable (LAI) medication in patients with psychotic disorders is associated with a range of negative outcomes. No psychosocial intervention has been found to be consistently effective in improving adherence. OBJECTIVES: To test whether or not offering financial incentives is effective and cost-effective in improving adherence and to explore patient and clinician experiences with such incentives. DESIGN: A cluster randomised controlled trial with economic and nested qualitative evaluation. The intervention period lasted for 12 months with 24 months' follow-up. The unit of randomisation was mental health teams in the community. SETTING: Community teams in secondary mental health care. PARTICIPANTS: Patients with a diagnosis of schizophrenia, schizoaffective psychosis or bipolar illness, receiving ≤ 75% of their prescribed LAI medication. In total, 73 teams with 141 patients (intervention n = 78 and control n = 63) were included. INTERVENTIONS: Participants in the intervention group received £15 for each LAI medication. Patients in the control group received treatment as usual. MAIN OUTCOME MEASURES: PRIMARY OUTCOME: adherence to LAI medication (the percentage of received out of those prescribed). SECONDARY OUTCOMES: percentage of patients with at least 95% adherence; clinical global improvement; subjective quality of life; satisfaction with medication; hospitalisation; adverse events; and costs. Qualitative evaluation: semistructured interviews with patients in the intervention group and their clinicians. RESULTS: PRIMARY OUTCOME: outcome data were available for 131 patients. Baseline adherence was 69% in the intervention group and 67% in the control group. During the intervention period, adherence was significantly higher in the intervention group than in the control group (85% vs. 71%) [adjusted mean difference 11.5%, 95% confidence interval (CI) 3.9% to 19.0%; p = 0.003]. Secondary outcome

  4. A preliminary analysis of association between the down-regulation of microRNA-181b expression and symptomatology improvement in schizophrenia patients before and after antipsychotic treatment.

    PubMed

    Song, Hong-tao; Sun, Xin-yang; Zhang, Liang; Zhao, Lin; Guo, Zhong-min; Fan, Hui-min; Zhong, Ai-fang; Niu, Wei; Dai, Yun-hua; Zhang, Li-yi; Shi, Zheng; Liu, Xiao-ping; Lu, Jim

    2014-07-01

    Despite the growing evidences on the relation of altered expression of miRNAs and schizophrenia, most schizophrenia subjects have an extensive antipsychotic treatment history and the pharmacological effects on miRNA expression are largely unknown. This study aimed to investigate the change of plasma microRNA-181b level and improvement of symptomatology before and after six-week antipsychotic treatment in schizophrenia patients, and explore their association. A total of 20 schizophrenia patients absent of antipsychotics and 20 age-and gender-matched normal controls were enrolled, and tested for 9 schizophrenia-associated microRNA (miR-30e, miR-34a, miR-181b, miR-195, miR-346, miR-432, miR-7, miR-132 and miR-212) expression levels in plasma using quantitative RT-PCR and for symptomatology improvement using Positive And Negative Syndrome Scale (PANSS) before and after treatment (olanzapine, quetiapine, ziprasidone and risperidone) for the patients only. Compared with the normal control group, the expression levels of miRNA-181b, miRNA-30e, miRNA-34a and miRNA-7 of the patients group were significantly higher (p < 0.05). Compared with those before treatment in the patient group, the symptomatology scores were significantly lower (p < 0.001), and the expression level of microRNA-181b was significantly down-regulated after treatment (p < 0.05). The change of miRNA-181b expression was positively correlated with the improvement of negative symptoms and lack of response symptoms (r = 0.502 and 0.557, P < 0.05, accounting for 20.2% and 26.4% respectively), and their therapeutic effects with OR being 11.283 and 5.119 respectively. We conclude that miRNA-181b, miRNA-30e, miRNA-34a and miRNA-7 are probably involved in pathogenesis of SZ, and the significant down-regulation of miRNA-181b expression predicts improvement of negative symptoms to treatment, and thus can serve as a potential plasmamolecular marker for antipsychotic responses.

  5. Hypothermia following antipsychotic drug use

    PubMed Central

    Wegewijs, Michelle A.; Loonen, Anton J. M.; Beers, Erna

    2007-01-01

    Objective Hypothermia is an adverse drug reaction (ADR) of antipsychotic drug (APD) use. Risk factors for hypothermia in ADP users are unknown. We studied which risk factors for hypothermia can be identified based on case reports. Method Case reports of hypothermia in APD-users found in PUBMED or EMBASE were searched for risk factors. The WHO international database for Adverse Drug Reactions was searched for reports of hypothermia and APD use. Results The literature search resulted in 32 articles containing 43 case reports. In the WHO database, 480 reports were registered of patients developing hypothermia during the use of APDs which almost equals the number of reports for hyperthermia associated with APD use (n = 524). Hypothermia risk seems to be increased in the first days following start or dose increase of APs. APs with strong 5-HT2 antagonism seem to be more involved in hypothermia; 55% of hypothermia reports are for atypical antipsychotics. Schizophrenia was the most prevalent diagnosis in the case reports. Conclusion Especially in admitted patients who are not able to control their own environment or physical status, frequent measurements of body temperature (with a thermometer that can measure low body temperatures) must be performed in order to detect developing hypothermia. PMID:17401555

  6. Antipsychotic drugs and obesity

    PubMed Central

    Correll, Christoph U.; Lencz, Todd; Malhotra, Anil K.

    2011-01-01

    Mechanisms underlying antipsychotic cardiometabolic adverse effects are incompletely understood. This hampers the identification of high-risk patients, low-risk antipsychotics and preventive/ameliorative treatments. Recent clinical, molecular, and genetic data suggest that i) antipsychotic-naïve samples provide the greatest power for mechanistic studies; ii) weight and metabolic effects can be discordant, pointing to overlapping and distinct mechanisms; iii) antipsychotics affect satiety and energy homeostasis signaling; iv) the specific peptides mediating these effects are unknown but likely overlap with those involved in idiopathic obesity; and v) single nucleotide polymorphisms in genes encoding known neurotransmitter receptors and metabolic proteins are promising pharmacogenomic targets for countering adverse affects. However, sophisticated molecular studies and genome-wide association studies, ideally in antipsychotic-naïve/first episode samples, are needed to further advance the field. PMID:21185230

  7. A Non-Interventional Naturalistic Study of the Prescription Patterns of Antipsychotics in Patients with Schizophrenia from the Spanish Province of Tarragona

    PubMed Central

    Aguado, Víctor; Rico, Guillem; Labad, Javier; de Pablo, Joan; Vilella, Elisabet

    2015-01-01

    Background The analysis of prescribing patterns in entire catchment areas contributes to global mapping of the use of antipsychotics and may improve treatment outcomes. Objective To determine the pattern of long-term antipsychotic prescription in outpatients with schizophrenia in the province of Tarragona (Catalonia-Spain). Methods A naturalistic, observational, retrospective, non-interventional study based on the analysis of registries of computerized medical records from an anonymized database of 1,765 patients with schizophrenia treated between 2011 and 2013. Results The most used antipsychotic was risperidone, identified in 463 (26.3%) patients, followed by olanzapine in 249 (14.1%), paliperidone in 225 (12.7%), zuclopenthixol in 201 (11.4%), quetiapine in 141 (8%), aripiprazole in 100 (5.7%), and clozapine in 100 (5.7%). Almost 8 out of 10 patients (79.3%) were treated with atypical or second-generation antipsychotics. Long-acting injectable (LAI) formulations were used in 44.8% of patients. Antipsychotics were generally prescribed in their recommended doses, with clozapine, ziprasidone, LAI paliperidone, and LAI risperidone being prescribed at the higher end of their therapeutic ranges. Almost 7 out of 10 patients (69.6%) were on antipsychotic polypharmacy, and 81.4% were on psychiatric medications aside from antipsychotics. Being prescribed quetiapine (OR 14.24, 95% CI 4.94–40.97), LAI (OR 9.99, 95% CI 6.45–15.45), psychiatric co-medications (OR 4.25, 95% CI 2.72–6.64), and paliperidone (OR 3.13, 95% CI 1.23–7.92) were all associated with an increased likelihood of polypharmacy. Being prescribed risperidone (OR 0.54, 95% CI 0.35–0.83) and older age (OR 0.98, 95% CI 0.97–0.99) were related to a low polypharmacy probability. Conclusions Polypharmacy is the most common pattern of antipsychotic use in this region of Spain. Use of atypical antipsychotics is extensive. Most patients receive psychiatric co-medications such as anxiolytics or

  8. Second-generation antipsychotics and extrapyramidal adverse effects.

    PubMed

    Divac, Nevena; Prostran, Milica; Jakovcevski, Igor; Cerovac, Natasa

    2014-01-01

    Antipsychotic-induced extrapyramidal adverse effects are well recognized in the context of first-generation antipsychotic drugs. However, the introduction of second-generation antipsychotics, with atypical mechanism of action, especially lower dopamine receptors affinity, was met with great expectations among clinicians regarding their potentially lower propensity to cause extrapyramidal syndrome. This review gives a brief summary of the recent literature relevant to second-generation antipsychotics and extrapyramidal syndrome. Numerous studies have examined the incidence and severity of extrapyramidal syndrome with first- and second-generation antipsychotics. The majority of these studies clearly indicate that extrapyramidal syndrome does occur with second-generation agents, though in lower rates in comparison with first generation. Risk factors are the choice of a particular second-generation agent (with clozapine carrying the lowest risk and risperidone the highest), high doses, history of previous extrapyramidal symptoms, and comorbidity. Also, in comparative studies, the choice of a first-generation comparator significantly influences the results. Extrapyramidal syndrome remains clinically important even in the era of second-generation antipsychotics. The incidence and severity of extrapyramidal syndrome differ amongst these antipsychotics, but the fact is that these drugs have not lived up to the expectation regarding their tolerability. PMID:24995318

  9. Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI) and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder

    PubMed Central

    Umehara, Hidehiro; Numata, Shusuke; Tajima, Atsushi; Nishi, Akira; Nakataki, Masahito; Imoto, Issei; Sumitani, Satsuki; Ohmori, Tetsuro

    2016-01-01

    Background Selective serotonin reuptake inhibitors (SSRI) are established first-line pharmacological treatments for obsessive-compulsive disorder (OCD), while antipsychotics are used as an augmentation strategy for SSRI in OCD patients who have either no response or a partial response to SSRI treatment. The goal of the present study was to identify genetic variants and pathways that are associated with the long-term clinical response of OCD patients to SSRI or SSRI with antipsychotics. Methods We first performed a genome-wide association study of 96 OCD patients to examine genetic variants contributing to the response to SSRI or SSRI with antipsychotics. Subsequently, we conducted pathway-based analyses by using Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i-GSEA4GWAS) to examine the combined effects of genetic variants on the clinical response in OCD. Results While we failed to detect specific genetic variants associated with clinical responses to SSRI or to SSRI with an atypical antipsychotic at genome-wide levels of significance, we identified 8 enriched pathways for the SSRI treatment response and 5 enriched pathways for the treatment response to SSRI with an antipsychotic medication. Notably, the calcium signaling pathway was identified in both treatment responses. Conclusions Our results provide novel insight into the molecular mechanisms underlying the variability in clinical response to SSRI and SSRI with antipsychotics in OCD patients. PMID:27281126

  10. Catechol-O-Methyltransferase Val158Met Polymorphism and Clinical Response to Antipsychotic Treatment in Schizophrenia and Schizo-Affective Disorder Patients: a Meta-Analysis

    PubMed Central

    Huang, Eric; Zai, Clement C.; Lisoway, Amanda; Maciukiewicz, Malgorzata; Felsky, Daniel; Tiwari, Arun K.; Bishop, Jeffrey R.; Ikeda, Masashi; Molero, Patricio; Ortuno, Felipe; Porcelli, Stefano; Samochowiec, Jerzy; Mierzejewski, Pawel; Gao, Shugui; Crespo-Facorro, Benedicto; Pelayo-Terán, José M; Kaur, Harpreet; Kukreti, Ritushree; Meltzer, Herbert Y.; Lieberman, Jeffrey A.; Potkin, Steven G.; Müller, Daniel J.

    2016-01-01

    Background: The catechol-O-methyltransferase (COMT) enzyme plays a crucial role in dopamine degradation, and the COMT Val158Met polymorphism (rs4680) is associated with significant differences in enzymatic activity and consequently dopamine concentrations in the prefrontal cortex. Multiple studies have analyzed the COMT Val158Met variant in relation to antipsychotic response. Here, we conducted a meta-analysis examining the relationship between COMT Val158Met and antipsychotic response. Methods: Searches using PubMed, Web of Science, and PsycInfo databases (03/01/2015) yielded 23 studies investigating COMT Val158Met variation and antipsychotic response in schizophrenia and schizo-affective disorder. Responders/nonresponders were defined using each study’s original criteria. If no binary response definition was used, authors were asked to define response according to at least 30% Positive and Negative Syndrome Scale score reduction (or equivalent in other scales). Analysis was conducted under a fixed-effects model. Results: Ten studies met inclusion criteria for the meta-analysis. Five additional antipsychotic-treated samples were analyzed for Val158Met and response and included in the meta-analysis (ntotal=1416). Met/Met individuals were significantly more likely to respond than Val-carriers (P=.039, ORMet/Met=1.37, 95% CI: 1.02–1.85). Met/Met patients also experienced significantly greater improvement in positive symptoms relative to Val-carriers (P=.030, SMD=0.24, 95% CI: 0.024–0.46). Posthoc analyses on patients treated with atypical antipsychotics (n=1207) showed that Met/Met patients were significantly more likely to respond relative to Val-carriers (P=.0098, ORMet/Met=1.54, 95% CI: 1.11–2.14), while no difference was observed for typical-antipsychotic-treated patients (n=155) (P=.65). Conclusions: Our findings suggest that the COMT Val158Met polymorphism is associated with response to antipsychotics in schizophrenia and schizo-affective disorder

  11. A Qualitative Study of Antipsychotic Medication Experiences of Youth

    PubMed Central

    Murphy, Andrea L.; Gardner, David M.; Kisely, Steve; Cooke, Charmaine; Kutcher, Stan P.; Hughes, Jean

    2015-01-01

    Objective: To explore the lived experience of youth who are prescribed antipsychotics. Methods: We conducted an interpretive phenomenology study of young people with recent experience of taking antipsychotics. Youth were interviewed and a staged approach was used for data analysis of transcriptions. We collected approximately 13 hours of audio from 18 youth aged 13 to 26 years between January and August of 2010. Results: Ambivalence was significant and antipsychotic adverse effects frequently tempered benefits. Both illness and antipsychotics had significant impacts on physical and mental wellbeing with adverse effects on relationships and functioning in various contexts (e.g., school). Stigma related to both antipsychotics and illness was also prominent. Participants’ limited knowledge about their antipsychotics and pressure to conform within their youth culture and context affected decisions on starting, adhering to, and persisting with treatment. Conclusions: The lived experience of youth taking antipsychotics is complex and the benefits (e.g., symptom improvement) and consequences (e.g., adverse effects) associated with antipsychotics affect all facets of life. More research is needed to better understand youth priorities in treatment decisions and whether youth who demonstrate substantive gaps in their knowledge about antipsychotics are truly given the opportunity to be informed and engage in management decisions including whether to initiate, persist with, and discontinue treatments. PMID:26336383

  12. [Atypical depression].

    PubMed

    Escande, M; Boucard, J

    1999-04-01

    The principal atypical aspects of depressive disease are: minor and attenued aspects, monosymptomatic and atypical aspects (food disorders and sleep disorders), masqued aspects (somatoform, anxious, characterial and addict disorders), atypical aspects of child (anxious nevrotical disorder), pseudo-demented and characterial aspects of aged subjects. Facing to these aspects, the diagnosis of depression is evoqued on: the recent and fast advent of these disorders, their morning predominance, their recurrent character, the state of attenued depressive symptoms (anhedonia), the positive responsiveness to treatment.

  13. Pharmacogenetics of Antipsychotics

    PubMed Central

    Brandl, Eva J; Kennedy, James L; Müller, Daniel J

    2014-01-01

    Objective: During the past decades, increasing efforts have been invested in studies to unravel the influence of genetic factors on antipsychotic (AP) dosage, treatment response, and occurrence of adverse effects. These studies aimed to improve clinical care by predicting outcome of treatment with APs and thus allowing for individualized treatment strategies. We highlight most important findings obtained through both candidate gene and genome-wide association studies, including pharmacokinetic and pharmacodynamic factors. Methods: We reviewed studies on pharmacogenetics of AP response and adverse effects published on PubMed until early 2012. Owing to the high number of published studies, we focused our review on findings that have been replicated in independent studies or are supported by meta-analyses. Results: Most robust findings were reported for associations between polymorphisms of the cytochrome P450 system, the dopamine and the serotonin transmitter systems, and dosage, treatment response, and adverse effects, such as AP-induced weight gain or tardive dyskinesia. These associations were either detected for specific medications or for classes of APs. Conclusion: First promising and robust results show that pharmacogenetics bear promise for a widespread use in future clinical practice. This will likely be achieved by developing algorithms that will include many genetic variants. However, further investigation is warranted to replicate and validate previous findings, as well as to identify new genetic variants involved in AP response and for replication of existing findings. PMID:24881126

  14. Switching antipsychotics: Imaging the differential effect on the topography of postsynaptic density transcripts in antipsychotic-naïve vs. antipsychotic-exposed rats.

    PubMed

    de Bartolomeis, Andrea; Marmo, Federica; Buonaguro, Elisabetta F; Latte, Gianmarco; Tomasetti, Carmine; Iasevoli, Felice

    2016-10-01

    The postsynaptic density (PSD) has been regarded as a functional switchboard at the crossroads of a dopamine-glutamate interaction, and it is putatively involved in the pathophysiology of psychosis. Indeed, it has been demonstrated that antipsychotics may modulate several PSD transcripts, such as PSD-95, Shank, and Homer. Despite switching antipsychotics is a frequent strategy to counteract lack of efficacy and/or side effect onset in clinical practice, no information is available on the effects of sequential treatments with different antipsychotics on PSD molecules. The aim of this study was to evaluate whether a previous exposure to a typical antipsychotic and a switch to an atypical one may affect the expression of PSD transcripts, in order to evaluate potential neurobiological correlates of this common clinical practice, with specific regards to putative synaptic plasticity processes. We treated male Sprague-Dawley rats intraperitoneally for 15days with haloperidol or vehicle, then from the sixteenth day we switched the animals to amisulpride or continued to treat them with vehicle or haloperidol for 15 additional days. In this way we got six first treatment/second treatment groups: vehicle/vehicle, vehicle/haloperidol, vehicle/amisulpride, haloperidol/vehicle, haloperidol/haloperidol, haloperidol/amisulpride. In this paradigm, we evaluated the expression of brain transcripts belonging to relevant and interacting PSD proteins, both of the Immediate-Early Gene (Homer1a, Arc) and the constitutive classes (Homer1b/c and PSD-95). The major finding was the differential effect of amisulpride on gene transcripts when administered in naïve vs. antipsychotic-pretreated rats, with modifications of the ratio between Homer1a/Homer1b transcripts and differential effects in cortex and striatum. These results suggest that the neurobiological effects on PSD transcripts of amisulpride, and possibly of other antipsychotics, may be greatly affected by prior antipsychotic

  15. Inhibition of the reward system by antipsychotic treatment.

    PubMed

    Juckel, Georg

    2016-03-01

    The mesolimbic dopaminergic reward system is responsible for the negative affective symptomatology of schizophrenia, which may be related to a low dopamine tonus within the ventral striatum. The monetary incentive delay (MID) task can be used to study the response of the ventral striatum to incentive stimuli. We show that activation of the ventral striatum is low in patients with schizophrenia, and that this low activation is related to primary and secondary negative symptoms induced by neuroleptics, also known as antipsychotics. Switching from first-(typical) to second-generation (atypical) antipsychotics increased activation of the ventral striatum due to less blocking of dopamine D2 receptors. This and similar studies show that functional magnetic resonance imaging (fMRI) tasks are suitable to investigate important aspects of antipsychotic mechanisms.

  16. Inhibition of the reward system by antipsychotic treatment

    PubMed Central

    Juckel, Georg

    2016-01-01

    The mesolimbic dopaminergic reward system is responsible for the negative affective symptomatology of schizophrenia, which may be related to a low dopamine tonus within the ventral striatum. The monetary incentive delay (MID) task can be used to study the response of the ventral striatum to incentive stimuli. We show that activation of the ventral striatum is low in patients with schizophrenia, and that this low activation is related to primary and secondary negative symptoms induced by neuroleptics, also known as antipsychotics. Switching from first-(typical) to second-generation (atypical) antipsychotics increased activation of the ventral striatum due to less blocking of dopamine D2 receptors. This and similar studies show that functional magnetic resonance imaging (fMRI) tasks are suitable to investigate important aspects of antipsychotic mechanisms. PMID:27069385

  17. Aggresiveness in institutionalised schizophrenic patients and the selection of antipsychotics.

    PubMed

    Ruzić, Klementina; Francisković, Tanja; Suković, Zoran; Hero, Elizabeta Dadić; Roncević-Grzeta, Ika; Graovac, Mirjana; Palijan, Tija Zarković

    2011-01-01

    The selection of antipsychotics as medications used primarily for treating schizophrenia and disorders similar to schizophrenia is an important aspect of the treatment of forensicpatients. This study examines the effect of antipsychotics selection (typical or atipycal) on the level of aggressiveness, side effects and the hospitalisation length. The research is conducted on 98 psychiatric patients diagnosed with schizophrenia or similar disorders (F 20-F 29) in two forensic psychiatric institutions. The patients committed aggressive criminal offence in state of insanity. The patients are currently treated in inpatient psychiatric institutions. The research was conducted by using the Aggressiveness Questionnaire (AG-87), the Simpson-Angus Scale for the assessment of extrapyramidal side effects, the Barnes Akathisia Rating Scale for the assesment of akathisia and the Abnormal Involuntary Movement Scale. The results show no significant difference between the groups of patients treated with typical and atypical antipsychotics in all the variables.

  18. Can transcranial electrical stimulation improve learning difficulties in atypical brain development? A future possibility for cognitive training.

    PubMed

    Krause, Beatrix; Cohen Kadosh, Roi

    2013-10-01

    Learning difficulties in atypical brain development represent serious obstacles to an individual's future achievements and can have broad societal consequences. Cognitive training can improve learning impairments only to a certain degree. Recent evidence from normal and clinical adult populations suggests that transcranial electrical stimulation (TES), a portable, painless, inexpensive, and relatively safe neuroenhancement tool, applied in conjunction with cognitive training can enhance cognitive intervention outcomes. This includes, for instance, numerical processing, language skills and response inhibition deficits commonly associated with profound learning difficulties and attention-deficit hyperactivity disorder (ADHD). The current review introduces the functional principles, current applications and promising results, and potential pitfalls of TES. Unfortunately, research in child populations is limited at present. We suggest that TES has considerable promise as a tool for increasing neuroplasticity in atypically developing children and may be an effective adjunct to cognitive training in clinical settings if it proves safe. The efficacy and both short- and long-term effects of TES on the developing brain need to be critically assessed before it can be recommended for clinical settings. PMID:23770059

  19. Trends in the use and cost of antipsychotics among older adults from 2007 to 2013: a repeated cross-sectional study

    PubMed Central

    Foster, Paul D.; Camacho, Ximena; Vigod, Simone; Yao, Zhan; Juurlink, David N.; Paterson, J. Michael; Mamdani, Muhammad M.; Martins, Diana; Gomes, Tara

    2016-01-01

    Background: Recently, several new atypical antipsychotic agents have been introduced in Ontario, and regulatory warnings have been issued regarding use of atypical antipsychotics in older adults. We sought to establish the impact of newer atypical antipsychotics on prescribing rates and costs. Methods: We performed a population-based cross-sectional study of Ontario adults aged 65 years or more using atypical antipsychotics from Jan. 1, 2007, to Mar. 31, 2013. These people have universal access to publicly funded drugs through the Ontario Health Insurance Plan and the Ontario Drug Benefit. We conducted time-series analysis to assess the impact of the introduction of new atypical antipsychotics on rates of use of atypical antipsychotics and associated expenditures. Results: Rates of atypical antipsychotic use increased following the introduction of new agents in 2009, from 27.6 users per 1000 older adults in the third quarter of 2009 to 29.1 users per 1000 older adults at the end of the study period (p = 0.04). Although prescribing rates for the newer atypical agents (paliperidone, ziprasidone and aripiprazole) remained low relative to their older counterparts (risperidone, olanzapine and quetiapine), rates of aripiprazole use rose to 1.0 user per 1000 older adults by the end of the study period. The proportion of prescriptions that were for brand-name agents fell from 57.5% in the second quarter of 2007 to 6.1% in the second quarter of 2009, and then rose to 11.7% by the end of the study period. By the first quarter of 2013, newer atypical antipsychotic agents were used by 4.4% of atypical antipsychotic users but accounted for 14.1% ($1.2 million of $8.5 million) of atypical antipsychotic expenditures. Interpretation: Although the overall prevalence of use of new atypical antipsychotic agents remains low, their introduction has led to increased prescribing of this class of drugs in older adults. Given the potential cost implications, further study of these trends

  20. Olanzapine (LY170053, 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine), but not the novel atypical antipsychotic ST2472 (9-piperazin-1-ylpyrrolo[2,1-b][1,3]benzothiazepine), chronic administration induces weight gain, hyperphagia, and metabolic dysregulation in mice.

    PubMed

    Coccurello, Roberto; Caprioli, Antonio; Conti, Roberto; Ghirardi, Orlando; Borsini, Franco; Carminati, Paolo; Moles, Anna

    2008-09-01

    A mouse model of atypical antipsychotic-associated adverse effects was used to compare the liability to induce weight gain, food intake, and metabolic alterations after chronic olanzapine (OL; LY170053, 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno-[2,3-b][1,5] benzodiazepine) and ST2472 (ST; 9-piperazin-1-ylpyrrolo[2,1-b][1,3]benzothiazepine) administration. By adding two equipotent doses (3 and 6 mg/kg) of either OL or ST to a high-sweet, high-fat (HS-HF) diet, mice were allowed to self-administer drugs up to 50 days. Body weight and food intake were evaluated daily. Locomotor activity was recorded over 48 h at two different time points. Dyslipidemia was measured by central visceral obesity. Blood serum levels of insulin (IN), glucose (Glu), triglycerides (TGs), nonesterified fatty acids (NEFAs), cholesterol (Ch), and ketone (Ke) bodies were quantified. OL treatment at 3 mg/kg enhanced body weight, whereas at the highest dose, the increase became evident only during the last 10 days of treatment. OL (3 mg/kg) increased HS-HF intake over time, whereas the highest dose reduced intake during the second 10 and final 10 days of administration. Both compounds induced nocturnal hypomotility at the highest dose. In contrast to ST, 3 mg/kg OL elevated serum levels of IN, Glu, TG, NEFA, Ch, and Ke, whereas 6 mg/kg OL elevated those of Glu, TG, and Ch. In contrast, ST did not affect weight gain, food intake, and metabolic markers. Given the similarities between OL-induced obesogenic effects and medical reports, this study further supports the view that ST may represent a new class of agents characterized by a low propensity to induce side effects with promising clinical safety.

  1. [Antipsychotics and hyperpolactinaemia: pathophysiology, clinical relevance, diagnosis and therapy].

    PubMed

    Riecher-Rössler, Anita; Schmid, Christoph; Bleuer, Stefan; Birkhäuser, Martin

    2009-01-01

    Hyperprolactinaemia is a frequent but often neglected side effect of typical, but also of many atypical antipsychotics such as amisulpiride, risperidone or ziprasidone. Besides galactorrhoea, potential consequences are suppression of the hypothalamic-pituitary-gonadal axis with hypogonadism, sexual dysfunction, infertility and in women also irregularities of the menstrual cycle and amenorrhoea. Potential long term consequences are mainly osteopenia and osteoporosis with an enhanced risk of fractures. Hyperprolactinaemia, if not clearly caused by a prolactin inducing antipsychotic, should always be thoroughly investigated. Ideally, prolactin should be measured before starting a patient on a new antipsychotic. Furthermore, before neuroleptic treatment is begun, and also in regular intervals after that, patients should be asked about potential clinical signs of hyperprolactinaemia. Hyperprolactinaemia which is clearly due to antipsychotics but without clinical symptoms only requires regular controls of bone mineral density. However, if clinical symptoms occur, switching to a prolactin sparing antipsychotic may be necessary. In these cases fertility is often regained and the women concerned have to be informed about the enhanced risk of pregnancy and counselled regarding contraception. If switching is not possible, estradiol has to be substituted in women. Also in men with hypogonadism hormonesubstitution (with testosterone) is usually indicated. Generally hyperprolactinaemia in psychiatric patients should be taken more seriously in the future.

  2. Factors affecting cognitive remediation response in schizophrenia: the role of COMT gene and antipsychotic treatment.

    PubMed

    Bosia, Marta; Zanoletti, Andrea; Spangaro, Marco; Buonocore, Mariachiara; Bechi, Margherita; Cocchi, Federica; Pirovano, Adele; Lorenzi, Cristina; Bramanti, Placido; Smeraldi, Enrico; Cavallaro, Roberto

    2014-06-30

    Cognitive remediation is the best available tool to treat cognitive deficits in schizophrenia and has evidence of biological validity; however results are still heterogeneous and significant predictors are lacking. Previous studies showed that cognitive remediation is able to induce changes in PFC function and dopaminergic transmission and thus the study of possible sources of variability at these levels (i.e. antipsychotic treatments and genetic variability) might help to gain a deeper understanding of neurobiological correlates and translate into optimization and personalization of interventions. In the present study, we analyzed the interaction between pharmacological treatment (clozapine vs typical/atypical D2 blockers) and COMT rs4680 polymorphism on cognitive changes after cognitive remediation therapy, in a sample of 98 clinically stabilized patients with schizophrenia. The General Linear Model showed a significant interaction of pharmacological treatment and COMT polymorphism on the improvement in "Symbol Coding" subtest, a global measure of speed of processing. Post-hoc analysis revealed a significant difference between COMT genotypes, when treated with D2 blockers, with worse results among Val/Val patients. These preliminary results suggest that genetic variability, influencing prefrontal dopamine, might affect individual capacity to improve with different patterns, depending on antipsychotic treatment. PMID:24656901

  3. Factors affecting cognitive remediation response in schizophrenia: the role of COMT gene and antipsychotic treatment.

    PubMed

    Bosia, Marta; Zanoletti, Andrea; Spangaro, Marco; Buonocore, Mariachiara; Bechi, Margherita; Cocchi, Federica; Pirovano, Adele; Lorenzi, Cristina; Bramanti, Placido; Smeraldi, Enrico; Cavallaro, Roberto

    2014-06-30

    Cognitive remediation is the best available tool to treat cognitive deficits in schizophrenia and has evidence of biological validity; however results are still heterogeneous and significant predictors are lacking. Previous studies showed that cognitive remediation is able to induce changes in PFC function and dopaminergic transmission and thus the study of possible sources of variability at these levels (i.e. antipsychotic treatments and genetic variability) might help to gain a deeper understanding of neurobiological correlates and translate into optimization and personalization of interventions. In the present study, we analyzed the interaction between pharmacological treatment (clozapine vs typical/atypical D2 blockers) and COMT rs4680 polymorphism on cognitive changes after cognitive remediation therapy, in a sample of 98 clinically stabilized patients with schizophrenia. The General Linear Model showed a significant interaction of pharmacological treatment and COMT polymorphism on the improvement in "Symbol Coding" subtest, a global measure of speed of processing. Post-hoc analysis revealed a significant difference between COMT genotypes, when treated with D2 blockers, with worse results among Val/Val patients. These preliminary results suggest that genetic variability, influencing prefrontal dopamine, might affect individual capacity to improve with different patterns, depending on antipsychotic treatment.

  4. Neuroprotective treatment strategies for poststroke mood disorders: A minireview on atypical neuroleptic drugs and selective serotonin re-uptake inhibitors.

    PubMed

    Yulug, Burak

    2009-09-28

    In our minireview we summarize the neuroprotective effect of atypical antipsychotic and selective serotonin re-uptake inhibitors after cerebral ischemia. In regard of increasing rate of poststroke mood disorders and current evidences indicating to an increased rate of cerebrovascular accidents after neuroleptic usage by the elderly population we also reviewed the clinical relevance of the neuroprotective and mood stabilizing effect of atypical antipsychotic agents in the light of basic pathophysiology of stroke.

  5. Research on antipsychotics in India

    PubMed Central

    Avasthi, Ajit; Aggarwal, Munish; Grover, Sandeep; Khan, Mohd Khalid Rasheed

    2010-01-01

    Antipsychotic as a class of medications became available for treatment of various psychiatric disorders in the early 1950’s. Over the last 60 years many antipsychotics have become available. In line with the west, Indian researchers have evaluated the efficacy of antipsychotics in various conditions. Additionally, researchers have also evaluated the important safety and tolerability issues. Here, we review data originating from India in the form of drug trials, effectiveness, usefulness, safety and tolerability of antipsychotics. Additionally, data with respect to other important treatment related issues is discussed. PMID:21836703

  6. [Effect of antipsychotic amisulpride on immune reactivity].

    PubMed

    Idova, G V; Al'perina, E L; Lobacheva, O A; Zhukova, E N; Cheĭdo, M A; Meniavtseva, T A; Vetlugina, T P

    2013-01-01

    The effect of atypical antipsychotic solian (amisulpride), binding predominantly to dopamine D2/D3-receptors, on the immune reactivity has been studied in mice of the CBA strain with different psychoemotional states (aggressive and submissive behavior). In addition, the effect of solian on the expression of various CD-markers of lymphocytes in has been analyzed in vitro for patients with schizophrenia diagnosis. Chronic (10 days) administration of solian in mice at a dose of 5.0 mg/kg resulted in a significant suppression of the immune response to T-dependent antigen (sheep red blood cells). This effect was manifested in animals with both psychoemotional states, but was more expressed in aggressive animals. In the in vitro system, solian produced opposite effects on the expression of surface CD receptors in lymphocytes of patients with schizophrenia. It is suggested that solian does not only affects immune function through D2 receptors of the brain, but also directly influences immunocompetent cells.

  7. Atypical Cities

    ERIC Educational Resources Information Center

    DiJulio, Betsy

    2011-01-01

    In this creative challenge, Surrealism and one-point perspective combine to produce images that not only go "beyond the real" but also beyond the ubiquitous "imaginary city" assignment often used to teach one-point perspective. Perhaps the difference is that in the "atypical cities challenge," an understanding of one-point perspective is a means…

  8. Egis-11150: a candidate antipsychotic compound with procognitive efficacy in rodents.

    PubMed

    Gacsályi, István; Nagy, Katalin; Pallagi, Katalin; Lévay, György; Hársing, László G; Móricz, Krisztina; Kertész, Szabolcs; Varga, Péter; Haller, József; Gigler, Gábor; Szénási, Gábor; Barkóczy, József; Bíró, Judit; Spedding, Michael; Antoni, Ferenc A

    2013-01-01

    Classical antipsychotics, e.g. haloperidol, chlorpromazine, are potent at controlling the positive symptoms of schizophrenia but frequently elicit extrapyramidal motor side-effects. The introduction of atypical antipsychotics such as risperidone, olanzapine and clozapine has obviated this problem, but none of the current drugs seem to improve the cognitive deficits accompanying schizophrenia. Thus there is an unmet need for agents that not only suppress the psychotic symptoms but also ameliorate the impairment of cognition. Here, we report the preclinical properties of a candidate antipsychotic, Egis-11150, that shows marked pro-cognitive efficacy. Egis-11150 displayed high affinity for adrenergic α(1), α(2c), 5-HT(2A) 5-HT₇, moderate affinity for adrenergic α(2a) and D₂ receptors. It was a functional antagonist on all of the above receptors, with the exception of 5-HT₇ receptors, where it was an inverse agonist. Phencyclidine-induced hypermotility in mice and inhibition of conditioned avoidance response in rats were assessed to estimate efficacy against the positive and social withdrawal test in rats was used to predict efficacy against the negative symptoms of schizophrenia. Passive-avoidance learning, novel object recognition and radial maze tests in rats were used to assess pro-cognitive activity, while phencyclidine-induced disruption of prepulse inhibition in mice was examined to test for effects on attention. Egis-11150 (0.01-0.3 mg/kg, ip.) was effective in all of the preclinical models of schizophrenia examined. Moreover, a robust pro-cognitive profile was apparent. In summary, work in preclinical models indicates that Egis-11150 is a potential treatment for controlling the psychosis as well as the cognitive dysfunction in schizophrenia. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

  9. Did FDA Decisionmaking Affect Anti-Psychotic Drug Prescribing in Children?: A Time-Trend Analysis

    PubMed Central

    Wang, Bo; Franklin, Jessica M.; Eddings, Wesley; Landon, Joan; Kesselheim, Aaron S.

    2016-01-01

    Background Following Food and Drug Administration (FDA) approval, many drugs are prescribed for non-FDA-approved (“off-label”) uses. If substantial evidence supports the efficacy and safety of off-label indications, manufacturers can pursue formal FDA approval through supplemental new drug applications (sNDAs). We evaluated the effect of FDA determinations on pediatric sNDAs for antipsychotic drugs on prescribing of these products in children. Methods Retrospective, segmented time-series analysis using new prescription claims during 2003–2012 for three atypical antipsychotics (olanzapine, quetiapine, ziprasidone). FDA approved the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but did not approve the sNDA for pediatric use of ziprasidone. Results During the months before FDA approval of its pediatric sNDA, new prescriptions of olanzapine decreased for both children and adults. After FDA approval, the increase in prescribing trends was similar for both age groups (P = 0.47 for schizophrenia and bipolar disorder; P = 0.37 for other indications). Comparable decreases in use of quetiapine were observed between pediatrics and adults following FDA approval of its pediatric sNDA (P = 0.88; P = 0.63). Prescribing of ziprasidone decreased similarly for pediatric and adult patients after FDA non-approval of its pediatric sNDA (P = 0.61; P = 0.79). Conclusions The FDA’s sNDA determinations relating to use of antipsychotics in children did not result in changes in use that favored the approved sNDAs and disfavored the unapproved sNDA. Improved communication may help translate the agency’s expert judgments to clinical practice. PMID:27032095

  10. Atypical parkinsonism: an update

    PubMed Central

    Stamelou, Maria; Hoeglinger, Guenter U.

    2013-01-01

    Purpose of review This update discusses novel aspects on genetics, diagnosis, and treatments of atypical parkinsonism published over the past 2 years. Recent findings A genome-wide association study identified new genetic risk factors for progressive supranuclear palsy and new genetic conditions presenting with atypical parkinsonism have been described. The clinical criteria for diagnosis of corticobasal degeneration have been revised, and for progressive supranuclear palsy are under revision. Novel molecular techniques to identify possible biomarkers, as in other neurodegenerative disorders, have started being studied on atypical parkinsonian conditions, and although preliminary results seem promising, further studies are urgently warranted. Therapeutic trials based on disease-specific targets have shown no clinical improvement. Summary The knowledge obtained recently on atypical parkinsonian conditions points out the major deficits in this field. With the expanding phenotypical spectrum of atypical parkinsonian conditions, the early identification of patients has become difficult. The inability of conventional methods to identify these disorders earlier and better than clinicians, and the recent failure of promising therapeutic compounds, highlight the fact that the lack of biomarkers is probably the greatest limitation for developing treatments for these disorders. Thus, current and future research in this direction will be crucial. PMID:23812308

  11. Antidepressant, Antipsychotic, and Hallucinogen Drugs for the Treatment of Psychiatric Disorders: A Convergence at the Serotonin-2A Receptor.

    PubMed

    Howland, Robert H

    2016-07-01

    Antidepressant, atypical antipsychotic, and hallucinogen drugs mediate their actions in part by interactions with the serotonin-2A (5HT2A) receptor. Serotonergic hallucinogen drugs, such as psilocybin, bind most potently as agonists at the 5HT2A receptor, producing profound changes in perception, mood, and cognition. Some of these drugs have been or are currently being investigated in small Phase 2 studies for depression, alcoholism, smoking cessation, anxiety, and posttraumatic stress disorder. However, unlike the synergistic effects of combining antidepressant and atypical antipsychotic drugs, the potential therapeutic effects of hallucinogen drugs may be attenuated by the concurrent use of these medications because antidepressant and atypical antipsychotic drugs desensitize and/or down-regulate 5HT2A receptors. This finding has important implications for optimizing the potential therapeutic use of hallucinogen drugs in psychiatry. [Journal of Psychosocial Nursing and Mental Health Services, 54(7), 21-24.]. PMID:27362381

  12. Prototypical antipsychotic drugs protect hippocampal neuronal cultures against cell death induced by growth medium deprivation

    PubMed Central

    Bastianetto, Stéphane; Danik, Marc; Mennicken, Françoise; Williams, Sylvain; Quirion, Rémi

    2006-01-01

    Background Several clinical studies suggested that antipsychotic-based medications could ameliorate cognitive functions impaired in certain schizophrenic patients. Accordingly, we investigated the effects of various dopaminergic receptor antagonists – including atypical antipsychotics that are prescribed for the treatment of schizophrenia – in a model of toxicity using cultured hippocampal neurons, the hippocampus being a region of particular relevance to cognition. Results Hippocampal cell death induced by deprivation of growth medium constituents was strongly blocked by drugs including antipsychotics (10-10-10-6 M) that display nM affinities for D2 and/or D4 receptors (clozapine, haloperidol, (±)-sulpiride, domperidone, clozapine, risperidone, chlorpromazine, (+)-butaclamol and L-741,742). These effects were shared by some caspases inhibitors and were not accompanied by inhibition of reactive oxygen species. In contrast, (-)-raclopride and remoxipride, two drugs that preferentially bind D2 over D4 receptors were ineffective, as well as the selective D3 receptor antagonist U 99194. Interestingly, (-)-raclopride (10-6 M) was able to block the neuroprotective effect of the atypical antipsychotic clozapine (10-6 M). Conclusion Taken together, these data suggest that D2-like receptors, particularly the D4 subtype, mediate the neuroprotective effects of antipsychotic drugs possibly through a ROS-independent, caspase-dependent mechanism. PMID:16573831

  13. Cannabidiol exhibits anxiolytic but not antipsychotic property evaluated in the social interaction test.

    PubMed

    Almeida, Valéria; Levin, Raquel; Peres, Fernanda Fiel; Niigaki, Suzy T; Calzavara, Mariana B; Zuardi, Antônio W; Hallak, Jaime E; Crippa, José A; Abílio, Vanessa C

    2013-03-01

    Cannabidiol (CBD), a non-psychotomimetic compound of the Cannabis sativa, has been reported to have central therapeutic actions, such as antipsychotic and anxiolytic effects. We have recently reported that Spontaneously Hypertensive Rats (SHRs) present a deficit in social interaction that is ameliorated by atypical antipsychotics. In addition, SHRs present a hyperlocomotion that is reverted by typical and atypical antipsychotics, suggesting that this strain could be useful to study negative symptoms (modeled by a decrease in social interaction) and positive symptoms (modeled by hyperlocomotion) of schizophrenia as well as the effects of potential antipsychotics drugs. At the same time, an increase in social interaction in control animals similar to that induced by benzodiazepines is used to screen potential anxiolytic drugs. The aim of this study was to investigate the effects of CBD on social interaction presented by control animals (Wistar) and SHRs. The lowest dose of CBD (1mg/kg) increased passive and total social interaction of Wistar rats. However, the hyperlocomotion and the deficit in social interaction displayed by SHRs were not altered by any dose of CBD. Our results do not support an antipsychotic property of cannabidiol on symptoms-like behaviors in SHRs but reinforce the anxiolytic profile of this compound in control rats.

  14. A controlled, mirror-image study of second-generation antipsychotics in the treatment of schizophrenia.

    PubMed

    Taylor, David; Hayhurst, Karen; Kerwin, Robert

    2007-05-01

    Second-generation antipsychotics are now treatments of choice in many countries. In this study, we aimed to compare hospital stay and admissions to hospital in patients switching from first-generation (conventional) to second-generation (atypical) antipsychotics with patients switching from one first-generation drug to another. This was a retrospective, 6-year, controlled mirror-image study conducted in an acute general psychiatry services in an inner-city area. Subjects were consisted of patients diagnosed with schizophrenia or schizoaffective disorder receiving continuous prescription of antipsychotics over at least a 6-year period between 1994 and 2002. The main outcome measures were number of days spent in hospital and number of admissions to hospital. In 36 patients switched from first to second-generation antipsychotics, total number of days spent in hospital increased, from a mean of 90 days in the 3 years before switching, to a mean of 200 days in the 3 years after (P<0.001). Mean number of admissions did not change significantly (1.61 before vs. 1.44 after, P=0.360). In 36 matched control patients, switching between first-generation antipsychotic drugs, mean number of days in hospital fell from 64 to 50 (P=0.189) and number of admissions was virtually unchanged (1.42 before vs. 1.03 after, P=0.202). Mean days in hospital were significantly increased in the second-generation antipsychotic group compared with the first-generation antipsychotic (control) group (P<0.001). Switching from first to second-generation antipsychotics resulted in an important increase in number of days spent in hospital. Switching from one first-generation antipsychotic drug to another did not significantly affect number of days in hospital. PMID:17414738

  15. Investigation into effects of antipsychotics on ectonucleotidase and adenosine deaminase in zebrafish brain.

    PubMed

    Seibt, Kelly Juliana; Oliveira, Renata da Luz; Bogo, Mauricio Reis; Senger, Mario Roberto; Bonan, Carla Denise

    2015-12-01

    Antipsychotic agents are used for the treatment of psychotic symptoms in patients with several brain disorders, such as schizophrenia. Atypical and typical antipsychotics differ regarding their clinical and side-effects profile. Haloperidol is a representative typical antipsychotic drug and has potent dopamine receptor antagonistic functions; however, atypical antipsychotics have been developed and characterized an important advance in the treatment of schizophrenia and other psychotic disorders. Purine nucleotides and nucleosides, such as ATP and adenosine, constitute a ubiquitous class of extracellular signaling molecules crucial for normal functioning of the nervous system. Indirect findings suggest that changes in the purinergic system, more specifically in adenosinergic activity, could be involved in the pathophysiology of schizophrenia. We investigated the effects of typical and atypical antipsychotics on ectonucleotidase and adenosine deaminase (ADA) activities, followed by an analysis of gene expression patterns in zebrafish brain. Haloperidol treatment (9 µM) was able to decrease ATP hydrolysis (35%), whereas there were no changes in hydrolysis of ADP and AMP in brain membranes after antipsychotic exposure. Adenosine deamination in membrane fractions was inhibited (38%) after haloperidol treatment when compared to the control; however, no changes were observed in ADA soluble fractions after haloperidol exposure. Sulpiride (250 µM) and olanzapine (100 µM) did not alter ectonucleotidase and ADA activities. Haloperidol also led to a decrease in entpd2_mq, entpd3 and adal mRNA transcripts. These findings demonstrate that haloperidol is an inhibitor of NTPDase and ADA activities in zebrafish brain, suggesting that purinergic signaling may also be a target of pharmacological effects promoted by this drug.

  16. Improvement of diagnostic agreement among pathologists in resolving an "atypical glands suspicious for cancer" diagnosis in prostate biopsies using a novel "Disease-Focused Diagnostic Review" quality improvement process.

    PubMed

    Shah, Rajal B; Leandro, Gioacchino; Romerocaces, Gloria; Bentley, James; Yoon, Jiyoon; Mendrinos, Savvas; Tadros, Yousef; Tian, Wei; Lash, Richard

    2016-10-01

    One of the major goals of an anatomic pathology laboratory quality program is to minimize unwarranted diagnostic variability and equivocal reporting. This study evaluated the utility of Miraca Life Sciences' "Disease-Focused Diagnostic Review" (DFDR) quality program in improving interobserver diagnostic reproducibility associated with classification of "atypical glands suspicious for adenocarcinoma" (ATYP) in prostate biopsies. Seventy-one selected prostate biopsies with a focus of ATYP were reviewed by 8 pathologists. Participants were blinded to the original diagnosis and were first asked to classify the ATYP as benign, atypical, or limited adenocarcinoma. DFDR comprised a "theoretical consensus" (in which pathologists first reached consensus on the morphological features they considered relevant for the diagnosis of limited prostatic adenocarcinoma), a didactic review including relevant literature, and "practical consensus" (pathologists performed joint microscopic sessions, reconciling each other's observations and positions evaluating a separate unique slide set). Participants were finally asked to reclassify the original 71 ATYP cases based on knowledge gleaned from DFDR. Pre- and post-DFDR interobserver reproducibility of overall diagnostic agreement was assessed. Interobserver reproducibility measured by Fleiss κ values of pre- and post-DFDR was 0.36 and 0.59, respectively (P=.006). Post-DFDR, there were significant improvement for "100% concordance" (P=.011) and reduction for "no consensus" (P=.0004) categories. Despite a lower pre-DFDR reproducibility for non-uropathology fellowship-trained (n=3, κ=0.38) versus uropathology fellowship-trained (n=5, κ=0.43) pathologists, both groups achieved similarly high post-DFDR κ levels (κ=0.58 and 0.56, respectively). DFDR represents an effective tool to formally achieve diagnostic consensus and reduce variability associated with critical diagnoses in an anatomic pathology practice.

  17. Effects of antipsychotic D2 antagonists on long-term potentiation in animals and implications for human studies.

    PubMed

    Price, Rae; Salavati, Bahar; Graff-Guerrero, Ariel; Blumberger, Daniel M; Mulsant, Benoit H; Daskalakis, Zafiris J; Rajji, Tarek K

    2014-10-01

    In people with schizophrenia, cognitive abilities - including memory - are strongly associated with functional outcome. Long-term potentiation (LTP) is a form of neuroplasticity that is believed to be the physiological basis for memory. It has been postulated that antipsychotic medication can impair long-term potentiation and cognition by altering dopaminergic transmission. Thus, a systematic review was performed in order to assess the relationship between antipsychotics and D2 antagonists on long-term potentiation. The majority of studies on LTP and antipsychotics have found that acute administration of antipsychotics was associated with impairments in LTP in wild-type animals. In contrast, chronic administration and acute antipsychotics in animal models of schizophrenia were not. Typical and atypical antipsychotics and other D2 antagonists behaved similarly, with the exception of clozapine and olanzapine. Clozapine caused potentiation independent of tetanization, while olanzapine facilitated tetanus-induced potentiation. These studies are limited in their ability to model the effects of antipsychotics in patients with schizophrenia as they were largely performed in wild-type animals as opposed to humans with schizophrenia, and assessed after acute rather than chronic treatment. Further studies using patients with schizophrenia receiving chronic antipsychotic treatment are needed to better understand the effects of these medications in this population.

  18. Methodological Issues in Current Antipsychotic Drug Trials

    PubMed Central

    Leucht, Stefan; Heres, Stephan; Hamann, Johannes; Kane, John M.

    2008-01-01

    Every year numerous reports on antipsychotic drug trials are being published in neuropsychiatric journals, adding new information to our knowledge in the field. The information however is often hard for the reader to interpret, sometimes contradictory to comparable available studies and leaves more questions open than it actually answers. Although the overall quality of the studies is rather good, there are manifold options for further improvement in the conception, conduct, and reporting of antipsychotic drug trials. In this survey, we address methodological challenges such as the limited generalizability of outcomes due to patient selection and sample size; the vague or even lacking definition of key outcome parameters such as response, remission or relapse, insufficient blinding techniques, the pitfalls of surrogate outcomes and their assessment tools; the varying complex statistical approaches; and the challenge of balancing various ways of reporting outcomes. The authors present practical examples to highlight the current problems and propose a concrete series of suggestions on how to further optimize antipsychotic drug trials in the future. PMID:18234700

  19. Antipsychotics--history of development and field of indication, new wine--old glassess.

    PubMed

    Jašović-Gašić, Miroslava; Vuković, Olivera; Pantović, Maja; Cvetić, Tijana; Marić-Bojović, Nadja

    2012-10-01

    More than half a century ago, Delay and colleagues have discovered, quite accidentally, that antihistamine (chlorpromazine) relieves psychotic symptoms. This discovery prompted further investigation through a series of performed experiments aimed to elucidate the antipsychotic mechanism of action. Initial results have shown that antipsychotic drugs in experimental animals lead to "neuroleptic effect" (indifference). However, not until the end of 1960s, it becomes clear that all previously known antipsychotics block dopamine receptors, particularly postsynaptic D2 receptors. The next three decades marked the development and application of these so-called classic neuroleptics in the treatment of psychotic patients. During the nineteen nineties, as a result of ongoing efforts to achieve greater efficiency and reduce the scope of side effects, novel antipsychotics were synthesized (second generation antipsychotics--SGA). As a result the notion of serotonin-dopamine antagonist (SDA) was formulated. According to one of the hypothesis, "new", so called atypical antipsychotic drugs strongly block the serotonin (5-HT2), and weakly block the dopamine (D2) receptors. Yet, there is still a debate as to the molecular basis of atypicality, whether it is in dopaminergic and serotonergic antagonism of neurotransmission or it lays exclusively in the modulation of dopaminergic system and dissociation rate at the level of D2 receptors in specific brain regions. Although the synthesis and use of antipsychotics in clinical practice have radically changed not only the basic approach to the patient, but also the quality of life of millions of people, the question remains whether this is just "old wine in new glasses".

  20. Hunger and negative alliesthesia to aspartame and sucrose in patients treated with antipsychotic drugs and controls.

    PubMed

    Khazaal, Y; Chatton, A; Claeys, F; Ribordy, F; Khan, R; Zullino, D

    2009-12-01

    The present study explores sweet stimuli effects on hunger and negative alliesthesia in patients treated with antipsychotic drugs and controls. Those phenomena were examined in relation to previous weight gain, eating and weight-related cognitions and type of sweet stimuli: aspartame or sucrose. Alliesthesia is delayed in participants who gained weight regardless of cross group differences. A similar reduction of hunger was observed after the intake of two kinds of sweet stimuli (aspartame or sucrose) whereas alliesthesia measures were not affected. Whereas atypical antipsychotic drug-induced weight gain is linked to delayed satiety, the phenomenon is similar in magnitude in non-psychiatric controls who gained weight.

  1. Antipsychotic medication for early episode schizophrenia

    PubMed Central

    Bola, John; Kao, Dennis; Soydan, Haluk; Adams, Clive E

    2014-01-01

    compared to placebo. One trial suggested a higher rehospitalisation rate for those receiving chlorpromazine compared to placebo (n=80, RR 2.29 CI 1.3 to 4.0, NNH 2.9). However, a higher attrition in the placebo group is likely to have introduced a survivor bias into this comparison, as this difference becomes non-significant in a sensitivity analysis on intent-to-treat participants (n=127, RR 1.69 CI 0.9 to 3.0). One study contributes data to a comparison of trifluoperazine to psychotherapy on long-term health in favour of the trifluoperazine group (n=92, MD 5.8 CI 1.6 to 0.0); however, data from this study are also likely to contain biases due to selection and attrition. One other study contributes data to a comparison of typical antipsychotic medication to psychosocial treatment on six-week outcome measures of global psychopathology (n=89, MD 0.01 CI −0.6 to 0.6) and global improvement (n=89, MD −0.03 CI −0.5 to 0.4), indicating no between-group differences. On the whole, there is very little useable data in the few studies meeting inclusion criteria. Authors’ conclusions With only a few studies meeting inclusion criteria, and with limited useable data in these studies, it is not possible to arrive at definitive conclusions. The preliminary pattern of evidence suggests that people with early episode schizophrenia treated with typical antipsychotic medications are less likely to leave the study early, but more likely to experience medication-related side effects. Data are too sparse to assess the effects of antipsychotic medication on outcomes in early episode schizophrenia. PMID:21678355

  2. Evaluation of an antipsychotic information sheet for patients.

    PubMed

    Whiskey, Eromona; Taylor, David

    2005-01-01

    Introduction. The objective of this study was to develop a decision aid that patients and clinicians might use to help the patient in the process of selecting an antipsychotic medication. In addition, we aimed to determine the antipsychotic that patients would choose given the information contained in the leaflet. Method. We designed a questionnaire for patients to appraise the contents of the leaflet, their understanding of the leaflet and the potential impact of the leaflet on compliance and therapeutic relationship between patient and doctor. Results. We recruited 30 stable patients with a diagnosis of a psychotic illness to evaluate the leaflet and to determine patient choice. Over 90% of patients felt that the leaflet improved their knowledge of antipsychotic medication. Seventy-six percent of patients agreed that the leaflet contained the right type and amount of information. Seventy percent of respondents believed the leaflet would improve the trust between them and their doctors, and almost half (47%) stated they were more likely to take their medicine after reading the leaflet. Forty percent of patients would prefer to switch antipsychotic medication, with quetiapine being the most frequently preferred option. Conclusion. The results indicate that, for patients in the stable phase of their illness, the leaflet is a useful tool in selecting an antipsychotic medication and may represent a way forward in improving outcomes in patients with psychotic disorders. A larger study examining outcomes using this tool would establish its clinical utility.

  3. Evaluation of an antipsychotic information sheet for patients.

    PubMed

    Whiskey, Eromona; Taylor, David

    2005-01-01

    Introduction. The objective of this study was to develop a decision aid that patients and clinicians might use to help the patient in the process of selecting an antipsychotic medication. In addition, we aimed to determine the antipsychotic that patients would choose given the information contained in the leaflet. Method. We designed a questionnaire for patients to appraise the contents of the leaflet, their understanding of the leaflet and the potential impact of the leaflet on compliance and therapeutic relationship between patient and doctor. Results. We recruited 30 stable patients with a diagnosis of a psychotic illness to evaluate the leaflet and to determine patient choice. Over 90% of patients felt that the leaflet improved their knowledge of antipsychotic medication. Seventy-six percent of patients agreed that the leaflet contained the right type and amount of information. Seventy percent of respondents believed the leaflet would improve the trust between them and their doctors, and almost half (47%) stated they were more likely to take their medicine after reading the leaflet. Forty percent of patients would prefer to switch antipsychotic medication, with quetiapine being the most frequently preferred option. Conclusion. The results indicate that, for patients in the stable phase of their illness, the leaflet is a useful tool in selecting an antipsychotic medication and may represent a way forward in improving outcomes in patients with psychotic disorders. A larger study examining outcomes using this tool would establish its clinical utility. PMID:24930924

  4. Clinical predictors of therapeutic response to antipsychotics in schizophrenia.

    PubMed

    Carbon, Maren; Correll, Christoph U

    2014-12-01

    The search for clinical outcome predictors for schizophrenia is as old as the field of psychiatry. However, despite a wealth of large, longitudinal studies into prognostic factors, only very few clinically useful outcome predictors have been identified. The goal of future treatment is to either affect modifiable risk factors, or use nonmodifiable factors to parse patients into therapeutically meaningful subgroups. Most clinical outcome predictors are nonspecific and/or nonmodifiable. Nonmodifiable predictors for poor odds of remission include male sex, younger age at disease onset, poor premorbid adjustment, and severe baseline psychopathology. Modifiable risk factors for poor therapeutic outcomes that clinicians can act upon include longer duration of untreated illness, nonadherence to antipsychotics, comorbidities (especially substance-use disorders), lack of early antipsychotic response, and lack of improvement with non-clozapine antipsychotics, predicting clozapine response. It is hoped that this limited capacity for prediction will improve as pathophysiological understanding increases and/or new treatments for specific aspects of schizophrenia become available.

  5. [The comparative study on the efficacy of the combination of serotonin reuptake inhibitor antidepressants and antipsychotics in the treatment of recurrent depressive disorders].

    PubMed

    D'iakonov, A L; Lobanova, I V

    2012-01-01

    A combination of serotonin reuptake inhibitor antidepressants (prozac and stimulaton) with atypical antipsychotics (zyprexa and solian) reduced depression in patients with recurrent depressive disorders during 10 days. The effect was evenly distributed between 10, 20 and 40 days of treatment. Other symptoms had a peculiar dynamics depending on the therapy. By the end of the study, similar effects were achieved for all groups. The addition of antipsychotics to antidepressant treatment insignificantly increased the number of adverse events.

  6. Recent clinical aspects of hyperprolactinemia induced by antipsychotics.

    PubMed

    Milano, Walter; D'Acunto, Cosimo Walter; De Rosa, Michele; Festa, Michela; Milano, Luca; Petrella, Claudio; Capasso, Anna

    2011-01-01

    This review will address the current understanding of the relationship between hyperprolactinemia and antipsychotic drugs. Hyperprolactinemia is a frequent but often neglected side effect of typical, but also of many atypical antipsychotics. Release of PRL from lactotrope cells is influenced by several factors, such as stress, physical and sexual activity and food assumption. PRL secretion is regulated by hypothalamic-pituitary portal system and its homeostasis is the result of a complex balance between stimulating and inhibitory factors, both endogeneous and esogeneous. The main physiological control mechanism of secretion is played by the inhibitory action of dopamine. Conversely, among stimulation factors, serotonin is probably the main modulator of PRL release. An high number of drugs may cause PRL increase too, such as drugs that reduce dopaminergic functions at SNC level, or drugs with an antagonistic action towards dopaminergic receptors and those increasing serotonergic neurotransmission. Hyperprolactinemia is one of the most frequent endocrine pathologies of the hypothalamic-pituitary axis. Antipsychotics (AP) are the most common cause of druginduced hyperprolactinemia. Not all AP have the same impact on inducing hyperprolactinemia. In this review we will focus on the subdivision of AP in 'PRL-raising' (stimulators) and 'PRL-sparing' (sparers) and on their differences in inducing hyperprolactinemia. Finally we evaluated different complications in patients with antipsychotics induced hyperprolactinemia that may cause not only short-term side effects but also important systemic long-term effects. At the end of the review we finally report the possible options of treatment considering however that at present there are no ideal therapies or evaluations, and decisions have to be made on a case by case basis. PMID:20868350

  7. Prevalence and trends in the use of antipsychotic medications during pregnancy in the U.S., 2001–2007: A population-based study of 585,615 deliveries

    PubMed Central

    Toh, Sengwee; Li, Qian; Cheetham, T. Craig; Cooper, William O.; Davis, Robert L.; Dublin, Sascha; Hammad, Tarek A.; Li, De-Kun; Pawloski, Pamala A.; Pinheiro, Simone P.; Raebel, Marsha A.; Scott, Pamela E.; Smith, David H.; Bobo, William V.; Lawrence, Jean M.; Dashevsky, Inna; Haffenreffer, Katherine; Avalos, Lyndsay A.; Andrade, Susan E.

    2013-01-01

    Purpose To estimate the prevalence of and temporal trends in prenatal antipsychotic medication use within a cohort of pregnant women in the U.S. Methods We identified live born deliveries to women aged 15–45 years in 2001–2007 from 11 U.S. health plans participating in the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP). We ascertained prenatal exposure to antipsychotics from health plan pharmacy dispensing files, gestational age from linked infant birth certificate files, and ICD-9-CM diagnosis codes from health plan claims files. We calculated the prevalence of prenatal use of atypical and typical antipsychotics according to year of delivery, trimester of pregnancy, and mental health diagnosis. Results Among 585,615 qualifying deliveries, 4,223 (0.72%) were to women who received an atypical antipsychotic and 548 (0.09%) were to women receiving a typical antipsychotic any time from 60 days before pregnancy through delivery. There was a 2.5-fold increase in atypical antipsychotic use during the study period, from 0.33% (95% confidence interval: 0.29%, 0.37%) in 2001 to 0.82% (0.76%, 0.88%) in 2007, while the use of typical antipsychotics remained stable. Depression was the most common mental health diagnosis among deliveries to women with atypical antipsychotic use (63%), followed by bipolar disorder (43%) and schizophrenia (13%). Conclusions The number and proportion of pregnancies exposed to atypical antipsychotics has increased dramatically in recent years. Studies are needed to examine the comparative safety and effectiveness of these medications relative to other therapeutic options in pregnancy. PMID:23389622

  8. Prevalence and trends in the use of antipsychotic medications during pregnancy in the U.S., 2001-2007: a population-based study of 585,615 deliveries.

    PubMed

    Toh, Sengwee; Li, Qian; Cheetham, T Craig; Cooper, William O; Davis, Robert L; Dublin, Sascha; Hammad, Tarek A; Li, De-Kun; Pawloski, Pamala A; Pinheiro, Simone P; Raebel, Marsha A; Scott, Pamela E; Smith, David H; Bobo, William V; Lawrence, Jean M; Dashevsky, Inna; Haffenreffer, Katherine; Avalos, Lyndsay A; Andrade, Susan E

    2013-04-01

    This study aims to estimate the prevalence of and temporal trends in prenatal antipsychotic medication use within a cohort of pregnant women in the U.S. We identified live born deliveries to women aged 15-45 years in 2001-2007 from 11 U.S. health plans participating in the Medication Exposure in Pregnancy Risk Evaluation Program. We ascertained prenatal exposure to antipsychotics from health plan pharmacy dispensing files, gestational age from linked infant birth certificate files, and ICD-9-CM diagnosis codes from health plan claims files. We calculated the prevalence of prenatal use of atypical and typical antipsychotics according to year of delivery, trimester of pregnancy, and mental health diagnosis. Among 585,615 qualifying deliveries, 4,223 (0.72%) were to women who received an atypical antipsychotic and 548 (0.09%) were to women receiving a typical antipsychotic any time from 60 days before pregnancy through delivery. There was a 2.5-fold increase in atypical antipsychotic use during the study period, from 0.33% (95% confidence interval: 0.29%, 0.37%) in 2001 to 0.82% (0.76%, 0.88%) in 2007, while the use of typical antipsychotics remained stable. Depression was the most common mental health diagnosis among deliveries to women with atypical antipsychotic use (63%), followed by bipolar disorder (43%) and schizophrenia (13%). The number and proportion of pregnancies exposed to atypical antipsychotics has increased dramatically in recent years. Studies are needed to examine the comparative safety and effectiveness of these medications relative to other therapeutic options in pregnancy.

  9. Impact of antipsychotic medication on transcranial direct current stimulation (tDCS) effects in schizophrenia patients.

    PubMed

    Agarwal, Sri Mahavir; Bose, Anushree; Shivakumar, Venkataram; Narayanaswamy, Janardhanan C; Chhabra, Harleen; Kalmady, Sunil V; Varambally, Shivarama; Nitsche, Michael A; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N

    2016-01-30

    Transcranial direct current stimulation (tDCS) has generated interest as a treatment modality for schizophrenia. Dopamine, a critical pathogenetic link in schizophrenia, is also known to influence tDCS effects. We evaluated the influence of antipsychotic drug type (as defined by dopamine D2 receptor affinity) on the impact of tDCS in schizophrenia. DSM-IV-TR-diagnosed schizophrenia patients [N=36] with persistent auditory hallucinations despite adequate antipsychotic treatment were administered add-on tDCS. Patients were divided into three groups based on the antipsychotic's affinity to D2 receptors. An auditory hallucinations score (AHS) was measured using the auditory hallucinations subscale of the Psychotic Symptom Rating Scales (PSYRATS). Add-on tDCS resulted in a significant reduction inAHS. Antipsychotic drug type had a significant effect on AHS reduction. Patients treated with high affinity antipsychotics showed significantly lesser improvement compared to patients on low affinity antipsychotics or a mixture of the two. Furthermore, a significant sex-by-group interaction occurred; type of medication had an impact on tDCS effects only in women. Improvement differences could be due to the larger availability of the dopamine receptor system in patients taking antipsychotics with low D2 affinity. Sex-specific differences suggest potential estrogen-mediated effects. This study reports a first-time observation on the clinical utility of antipsychotic drug type in predicting tDCS effects in schizophrenia.

  10. Antipsychotic Trials in Schizophrenia from India: A Systematic Review and Meta-analysis

    PubMed Central

    Grover, S.; Sarkar, S.

    2015-01-01

    Ethnic and regional variations have been found in the pharmacological treatment response. Though many efficacy studies have been conducted in India for antipsychotic treatment modalities of schizophrenia, there is a lack meta-analytic data of the existing literature from India. This study aimed to conduct a systematic review and meta-analysis of the antipsychotic treatment trials of schizophrenia in the Indian context. All controlled trials from India evaluating the clinical efficacy of antipsychotics in patients with schizophrenia were evaluated and 28 trials were included in the metanalysis. Effect sizes were computed using Cohen's ‘d’ and risk of bias was evaluated. Meta analysis revealed superiority of first generation antipsychotics over placebo (mean effect size of 1.387, confidence interval of 1.127 to 1.648). Second generation antipsychotics were marginally better than first generation antipsychotics (effect size 0.106, confidence intervals 0.009 to 0.204). There was improvement in the methodology of the trials over time (Kendall tau=0.289, P=0.049), though no statistically significant increase in trial duration and sample size was noted. There is lack of data on long term efficacy of antipsychotic in schizophrenia from India. First generation antipsychotics have demonstrated benefits over placebo in patients with schizophrenia in the Indian context, though marginally lesser than second generation ones. PMID:26997707

  11. Amisulpride Switching in Schizophrenic Patients Who Showed Suboptimal Effect and/or Tolerability to Current Antipsychotics in a Naturalistic Setting: An Explorative Study

    PubMed Central

    Kim, Yongmin; Wang, Sheng-Min; Kwak, Kyung-Phil; Yoon, Ho-Kyoung; Pae, Chi-Un; Kim, Jung-Jin; Bahk, Won-Myong

    2016-01-01

    Objective Despite numerous atypical antipsychotics (AAP) available, many patients with schizophrenia still experience lack of efficacy and persistent side-effects. Switching from one AAP to another with a different side-effect profile has become a common clinical strategy. We aimed to investigate effect of switching to amisulpride in patients who showed suboptimal effect and/or tolerability to current antipsychotics treatment. Methods This was a 6-week, prospective, multicenter, open-label, flexible-dose study in patients with schizophrenia. Switching to amisulpride was achieved using cross-titration within 7 days (day 1: 300 mg on day 1 then flexibly dosed 400–800 mg/day). The primary end-point measure was proportion of patients achieving improvement in clinical benefit at week 6 based on Clinical Global Impressions-Clinical Benefit (CGI-CB). Secondary endpoints included change in scores in CGI-CB, CGI-Severity (CGI-S), Subjective Satisfaction Scores (SSS), Brief Psychiatric Rating Scale (BPRS), and Simpson and Angus Rating Scale. Results Among 37 patients switched to amisulpride, 76% completed study and 56.8% had clinical benefit measure by CGI-CB. CGI-CB and CGI-S scores showed significant improvement at week 6 compared to baseline (mean changes of CGI-CB and CGI-S scores: −1.7+1.0, p<0.0001 and −0.6±0.0, p=0.001, respectively). SSS scores also improved significantly (mean change: 2.1±2.6, p<0.0001). Mean weight of patients significantly lowered compared to baseline (mean change: −1.2±2.0, p<0.0001). Conclusion Patients with schizophrenia who showed suboptimal efficacy or tolerability with their current antipsychotics and thereby switched to amisulpride resulted in clinical benefit in terms of both improved efficacy and tolerability. The small sample size limits generalizability of the study results. PMID:27776390

  12. Recognizing and Managing Antipsychotic Drug Treatment Side Effects in the Elderly

    PubMed Central

    Saltz, Bruce L.; Robinson, Delbert G.; Woerner, Margaret G.

    2004-01-01

    Although atypical antipsychotics differ from conventional antipsychotics in their decreased ability to cause reversible drug-induced movement disorders/motor side effects such as dystonia, drug-induced parkinsonism, and akathisia and potentially persistent drug-induced movement disorders/motor side effects such as tardive dyskinesia, no antipsychotic agent completely eradicates this risk. Antipsychotic agents are frequently used in facilities for the elderly and in general hospitals to treat older patients with behavioral problems. Drug-induced movement disorders are more common and more persistent in elderly patients than in younger patients, and this problem is exacerbated by the fact that antipsychotic medications are often misused by practitioners lacking adequate psychopharmacologic training. Movement disorders can be detrimental to an elderly patient's quality of life and may transform what were otherwise routine activities into difficult tasks. Educational programs are needed to teach primary care physicians, specialists, and patients and their families how to identify and manage drug-induced movement disorders in order to achieve safer and more efficacious care for elderly patients. PMID:16001096

  13. Decreased glial reactivity could be involved in the antipsychotic-like effect of cannabidiol.

    PubMed

    Gomes, Felipe V; Llorente, Ricardo; Del Bel, Elaine A; Viveros, Maria-Paz; López-Gallardo, Meritxell; Guimarães, Francisco S

    2015-05-01

    NMDA receptor hypofunction could be involved, in addition to the positive, also to the negative symptoms and cognitive deficits found in schizophrenia patients. An increasing number of data has linked schizophrenia with neuroinflammatory conditions and glial cells, such as microglia and astrocytes, have been related to the pathogenesis of schizophrenia. Cannabidiol (CBD), a major non-psychotomimetic constituent of Cannabis sativa with anti-inflammatory and neuroprotective properties induces antipsychotic-like effects. The present study evaluated if repeated treatment with CBD (30 and 60 mg/kg) would attenuate the behavioral and glial changes observed in an animal model of schizophrenia based on the NMDA receptor hypofunction (chronic administration of MK-801, an NMDA receptor antagonist, for 28 days). The behavioral alterations were evaluated in the social interaction and novel object recognition (NOR) tests. These tests have been widely used to study changes related to negative symptoms and cognitive deficits of schizophrenia, respectively. We also evaluated changes in NeuN (a neuronal marker), Iba-1 (a microglia marker) and GFAP (an astrocyte marker) expression in the medial prefrontal cortex (mPFC), dorsal striatum, nucleus accumbens core and shell, and dorsal hippocampus by immunohistochemistry. CBD effects were compared to those induced by the atypical antipsychotic clozapine. Repeated MK-801 administration impaired performance in the social interaction and NOR tests. It also increased the number of GFAP-positive astrocytes in the mPFC and the percentage of Iba-1-positive microglia cells with a reactive phenotype in the mPFC and dorsal hippocampus without changing the number of Iba-1-positive cells. No change in the number of NeuN-positive cells was observed. Both the behavioral disruptions and the changes in expression of glial markers induced by MK-801 treatment were attenuated by repeated treatment with CBD or clozapine. These data reinforces the proposal

  14. Methods of cost-effectiveness analysis in the evaluation of new antipsychotics: implications for schizophrenia treatment.

    PubMed

    Neumann, P J

    1999-01-01

    Because health care payers are increasingly interested in learning whether new treatments offer value for money, there has been an abundance of research into the cost-effectiveness of pharmacologic therapies in the United States. In the past few years, a number of studies comparing the cost-effectiveness of the conventional neuroleptics with that of the atypical antipsychotics have been published. Cost-effectiveness analyses show the relationship between the resources used (costs) and the health benefits achieved (effects) for a health or medical intervention compared with an alternative strategy. Ideally, the analyses can help decision makers improve the health of the population by better allocating society's limited health care resources. However, the extent to which cost-effectiveness data are actually used in decision making is unclear. The analyses are sometimes viewed with skepticism, in part because studies differ in their methodological approaches. Recently, the U.S. Panel on Cost-Effectiveness in Health and Medicine offered recommendations for standard methodological practices, which may help improve the quality of studies and the acceptability of the approach in the future. The issue is particularly important in light of new legislation governing how the Food and Drug Administration will regulate promotional claims made by drug companies regarding health economic information. PMID:10073371

  15. [Metabolic disorders under antipsychotic treatment].

    PubMed

    Steffenhagen, N; Rummel-Kluge, C; Himmerich, H

    2012-03-01

    Patients with severe mental illness, such as schizophrenia, depression or bipolar disorder, are more likely to be overweight and to suffer from dyslipidaemia, diabetes or cardiovascular disease. Unhealthy lifestyles, including poor diet and sedentary behaviour, but also pharmacotherapy contribute to the adverse risk profile. This article reviews the epidemiology and pharmacodynamics of metabolic abnormalities in psychiatric patients treated with antipsychotics, focusing on substance-specific differences. PMID:21206997

  16. Antipsychotic Induced Gene Regulation in Multiple Brain Regions

    PubMed Central

    Girgenti, Matthew James; Nisenbaum, Laura K.; Bymaster, Franklin; Terwilliger, Rosemarie; Duman, Ronald S; Newton, Samuel Sathyanesan

    2010-01-01

    The molecular mechanism of action of antipsychotic drugs is not well understood. Their complex receptor affinity profiles indicate that their action could extend beyond dopamine receptor blockade. Single gene expression studies and high-throughput gene profiling have shown the induction of genes from several molecular classes and functional categories. Using a focused microarray approach we investigated gene regulation in rat striatum, frontal cortex and hippocampus after chronic administration of haloperidol or olanzapine. Regulated genes were validated by in-situ hybridization, realtime PCR and immunohistochemistry. Only limited overlap was observed in genes regulated by haloperidol and olanzapine. Both drugs elicited maximal gene regulation in the striatum and least in the hippocampus. Striatal gene induction by haloperidol was predominantly in neurotransmitter signaling, G-protein coupled receptors and transcription factors. Olanzapine prominently induced retinoic acid and trophic factor signaling genes in the frontal cortex. The data also revealed the induction of several genes that could be targeted in future drug development efforts. The study uncovered the induction of several novel genes, including somatostatin receptors and metabotropic glutamate receptors. The results demonstrating the regulation of multiple receptors and transcription factors suggests that both typical and atypical antipsychotics could possess a complex molecular mechanism of action. PMID:20070867

  17. [Towards better evaluation of antipsychotic drugs].

    PubMed

    Falissard, Bruno

    2010-03-01

    The methodology for evaluating medicinal products is now well established. It is based partly on scientific studies provided in support of marketing application, and also on less rigorous "real-life" studies conducted in a specific healthcare system. The gap between these two methodological perspectives needs to be reduced. In the case of antipsychotic drugs, what is needed most is a better definition of endpoints for efficacy. Recent studies show that symptomatic improvements may enhance patients' insight and, in turn, increase their expectations, with a resulting stagnation of their perceived quality of life. The results of randomized trials are difficult to extrapolate to everyday clinical practice. Epidemiological studies with strict methodologies and conducted by independent bodies should be encouraged. PMID:21171252

  18. Pharmacogenetics of antipsychotic treatment in schizophrenia.

    PubMed

    Pouget, Jennie G; Müller, Daniel J

    2014-01-01

    Antipsychotics are the mainstay treatment for schizophrenia. There is large variability between individuals in their response to antipsychotics, both in efficacy and adverse effects of treatment. While the source of interindividual variability in antipsychotic response is not completely understood, genetics is a major contributing factor. The identification of pharmacogenetic markers that predict antipsychotic efficacy and adverse reactions is a growing area of research, and holds the potential to replace the current trial-and-error approach to treatment selection in schizophrenia with a personalized medicine approach.In this chapter, we provide an overview of the current state of pharmacogenetics in schizophrenia treatment. The most promising pharmacogenetic findings are presented for both antipsychotic response and commonly studied adverse reactions. The application of pharmacogenetics to schizophrenia treatment is discussed, with an emphasis on the clinical utility of pharmacogenetic testing and directions for future research.

  19. Principles of antipsychotic prescribing for policy makers, circa 2008. Translating knowledge to promote individualized treatment.

    PubMed

    Parks, Joseph; Radke, Alan; Parker, George; Foti, May-Ellen; Eilers, Robert; Diamond, Mary; Svendsen, Dale; Tandon, Rajiv

    2009-09-01

    Findings from 2 pivotal government-funded studies of comparative antipsychotic effectiveness undermine assumptions about the marked superiority of the more expensive second-generation "atypical" medications in comparison to the less expensive first-generation "typical" drugs. Because this assumption was the basis for the almost universal recommendation that these newer antipsychotics be used preferentially resulting in a 10-fold increase in state governmental expenditures on this class of medications over the past decade, a reassessment of policy is called for. To address the issue, the Medical Directors Council of the National Association of State Mental Health Program Directors critically reviewed findings of these studies in the context of other data and considered policy implications in the light of the obligations of state government to make available best possible and individually optimized treatment that is cost-effective. The Medical Directors Council unanimously adopted a set of recommendations to promote appropriate access, efficient utilization, and best practice use. We present our policy statement, in which we provide a succinct background, articulate general principles, and describe a set of 4 broad recommendations. We then summarize our understanding of the current state of knowledge about comparative antipsychotic effectiveness, best antipsychotic practice, and considerations for state policy that represent the basis of our position statement.

  20. Benzodiazepines, benzodiazepine-like drugs, and typical antipsychotics impair manual dexterity in patients with schizophrenia.

    PubMed

    Sasayama, Daimei; Hori, Hiroaki; Teraishi, Toshiya; Hattori, Kotaro; Ota, Miho; Matsuo, Junko; Kinoshita, Yukiko; Okazaki, Mitsutoshi; Arima, Kunimasa; Amano, Naoji; Higuchi, Teruhiko; Kunugi, Hiroshi

    2014-02-01

    Impaired dexterity is a major psychomotor deficit reported in patients with schizophrenia. In the present study, the Purdue pegboard test was used to compare the manual dexterity in patients with schizophrenia and healthy controls. We also examined the influence of antipsychotics, benzodiazepines, and benzodiazepine-like drugs on manual dexterity. Subjects were 93 patients with schizophrenia and 93 healthy controls, matched for sex and age distributions. Control subjects scored significantly higher on all scores of Purdue pegboard than patients with schizophrenia. Age, PANSS negative symptom scale, typical antipsychotic dose, and use of benzodiazepines and/or benzodiazepine-like drugs were negatively correlated with the pegboard scores in patients with schizophrenia. The present results indicate that patients with schizophrenia have impaired gross and fine fingertip dexterity compared to healthy controls. The use of typical antipsychotics and benzodiazepines and/or benzodiazepine-like drugs, but not atypical antipsychotics, had significant negative impact on dexterity in patients with schizophrenia. Psychiatrists should be aware that some psychotropic medications may enhance the disability caused by the impairment of dexterity in patients with schizophrenia.

  1. Basal ganglia volume in unmedicated patients with schizophrenia is associated with treatment response to antipsychotic medication.

    PubMed

    Hutcheson, Nathan L; Clark, David G; Bolding, Mark S; White, David M; Lahti, Adrienne C

    2014-01-30

    We investigated the relationship between basal ganglia volume and treatment response to the atypical antipsychotic medication risperidone in unmedicated patients with schizophrenia. Basal ganglia volumes included the bilateral caudate, putamen, and pallidum and were measured using the Freesurfer automated segmentation pipeline in 23 subjects. Also, baseline symptom severity, duration of illness, age, gender, time off medication, and exposure to previous antipsychotic were measured. Treatment response was significantly correlated with all three regions of the bilateral basal ganglia (caudate, putamen, and pallidum), baseline symptom severity, duration of illness, and age but not gender, time off antipsychotic medication, or exposure to previous antipsychotic medication. The caudate volume was the basal ganglia region that demonstrated the strongest correlation with treatment response and was significantly negatively correlated with patient age. Caudate volume was not significantly correlated with any other measure. We demonstrated a novel finding that the caudate volume explains a significant amount of the variance in treatment response over the course of 6 weeks of risperidone pharmacotherapy even when controlling for baseline symptom severity and duration of illness.

  2. Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine.

    PubMed

    Kim, Il Hwan; Rossi, Mark A; Aryal, Dipendra K; Racz, Bence; Kim, Namsoo; Uezu, Akiyoshi; Wang, Fan; Wetsel, William C; Weinberg, Richard J; Yin, Henry; Soderling, Scott H

    2015-06-01

    Psychiatric and neurodevelopmental disorders may arise from anomalies in long-range neuronal connectivity downstream of pathologies in dendritic spines. However, the mechanisms that may link spine pathology to circuit abnormalities relevant to atypical behavior remain unknown. Using a mouse model to conditionally disrupt a critical regulator of the dendritic spine cytoskeleton, the actin-related protein 2/3 complex (Arp2/3), we report here a molecular mechanism that unexpectedly reveals the inter-relationship of progressive spine pruning, elevated frontal cortical excitation of pyramidal neurons and striatal hyperdopaminergia in a cortical-to-midbrain circuit abnormality. The main symptomatic manifestations of this circuit abnormality are psychomotor agitation and stereotypical behaviors, which are relieved by antipsychotics. Moreover, this antipsychotic-responsive locomotion can be mimicked in wild-type mice by optogenetic activation of this circuit. Collectively these results reveal molecular and neural-circuit mechanisms, illustrating how diverse pathologies may converge to drive behaviors relevant to psychiatric disorders.

  3. Dopamine receptor signaling and current and future antipsychotic drugs

    PubMed Central

    Boyd, Kevin N.; Mailman, Richard B.

    2015-01-01

    All currently efficacious antipsychotic drugs have as part of their mechanism the ability to attenuate some or all of their signaling through the dopamine D2 receptor. More recently, the dopamine D1 receptor has been hypothesized to be a promising target for the treatment of negative and/or cognitive aspects of schizophrenia that are not improved by current antipsychotics. Although cAMP has been presumed to be the primary messenger for signaling through the dopamine receptors, the last decade has unveiled a complexity that has provided exciting avenues for the future discovery of antipsychotic drugs (APDs). We review the signaling mechanisms of currently approved APDs at dopamine D2 receptors, and note that aripiprazole is a compound that is clearly differentiated from other approved drugs. Although aripiprazole has been postulated to cause dopamine stabilization due to its partial D2 agonist properties, a body of literature suggests that an alternate mechanism, functional selectivity, is of primary importance. Finally, we review the signaling at dopamine D1 receptors, and the idea that drugs that activate D1 receptors may have use as APDs for improving negative and cognitive symptoms. We address the current state of drug discovery in the D1 area, and its relationship to novel signaling mechanisms. Our conclusion is that although the first APD targeting dopamine receptors was discovered more than a half-century ago, recent research advances offer the possibility that novel and/or improved drugs will emerge in the next decade. PMID:23129328

  4. Improved Correlation of the Neuropathologic Classification According to Adapted World Health Organization Classification and Outcome After Radiotherapy in Patients With Atypical and Anaplastic Meningiomas

    SciTech Connect

    Combs, Stephanie E.; Schulz-Ertner, Daniela; Debus, Juergen; Deimling, Andreas von; Hartmann, Christian

    2011-12-01

    Purpose: To evaluate the correlation between the 1993 and 2000/2007 World Health Organization (WHO) classification with the outcome in patients with high-grade meningiomas. Patients and Methods: Between 1985 and 2004, 73 patients diagnosed with atypical or anaplastic meningiomas were treated with radiotherapy. Sections from the paraffin-embedded tumor material from 66 patients (90%) from 13 different pathology departments were re-evaluated according to the first revised WHO classification from 1993 and the revised classifications from 2000/2007. In 4 cases, the initial diagnosis meningioma was not reproducible (5%). Therefore, 62 patients with meningiomas were analyzed. Results: All 62 tumors were reclassified according to the 1993 and 2000/2007 WHO classification systems. Using the 1993 system, 7 patients were diagnosed with WHO grade I meningioma (11%), 23 with WHO grade II (37%), and 32 with WHO grade III meningioma (52%). After scoring using the 2000/2007 system, we found 17 WHO grade I meningiomas (27%), 32 WHO grade II meningiomas (52%), and 13 WHO grade III meningiomas (21%). According to the 1993 classification, the difference in overall survival was not statistically significant among the histologic subgroups (p = .96). Using the 2000/2007 WHO classifications, the difference in overall survival became significant (p = .02). Of the 62 reclassified patients 29 developed tumor progression (47%). No difference in progression-free survival was observed among the histologic subgroups (p = .44). After grading according to the 2000/2007 WHO classifications, significant differences in progression-free survival were observed among the three histologic groups (p = .005). Conclusion: The new 2000/2007 WHO classification for meningiomas showed an improved correlation between the histologic grade and outcome. This classification therefore provides a useful basis to determine the postoperative indication for radiotherapy. According to our results, a comparison of the

  5. Pharmacogenetic tests for antipsychotic medications: clinical implications and considerations

    PubMed Central

    Eum, Seenae; Lee, Adam M.; Bishop, Jeffrey R.

    2016-01-01

    Optimizing antipsychotic pharmacotherapy is often challenging due to significant variability in effectiveness and tolerability. Genetic factors influencing pharmacokinetics and pharmacodynamics may contribute to some of this variability. Research studies have characterized these pharmacogenetic relationships, and some genetic markers are now available as clinical tests. These advances in pharmacogenetics research and test availability have great potential to improve clinical outcomes and quality of life in psychiatric patients. For clinicians considering using pharmacogenetics, it is important to understand the clinical implications and also the limitations of markers included in currently available tests. This review focuses on pharmacokinetic and pharmacodynamic gene variants that are currently available in commercial genetic testing panels. Associations of these variants with clinical efficacy and adverse effects, as well as other clinical implications, in antipsychotic pharmacotherapy are discussed. PMID:27757066

  6. Experimental treatment of antipsychotic-induced movement disorders

    PubMed Central

    Shireen, Erum

    2016-01-01

    Antipsychotic drugs are extensively prescribed for the treatment of schizophrenia and other related psychiatric disorders. These drugs produced their action by blocking dopamine (DA) receptors, and these receptors are widely present throughout the brain. Therefore, extended antipsychotic use also leads to severe extrapyramidal side effects. The short-term effects include parkinsonism and the later appearing tardive dyskinesia. Currently available treatments for these disorders are mostly symptomatic and insufficient, and are often linked with a number of detrimental side effects. Antipsychotic-drug-induced tardive dyskinesia prompted researchers to explore novel drugs with fewer undesirable extrapyramidal side effects. Preclinical studies suggest a role of 5-hydroxytryptamine (serotonin)-1A and 2A/2C receptors in the modulation of dopaminergic neurotransmission and motivating a search for better therapeutic strategies for schizophrenia and related disorders. In addition, adjunctive treatment with antioxidants such as vitamin E, red rice bran oil, and curcumin in the early phases of illness may prevent additional oxidative injury, and thus improve and prevent further possible worsening of related neurological and behavioral deficits in schizophrenia. This review explains the role of serotonergic receptors and oxidative stress, with the aim of providing principles for prospect development of compounds to improve therapeutic effects of antischizophrenic drugs. PMID:27540314

  7. Experimental treatment of antipsychotic-induced movement disorders.

    PubMed

    Shireen, Erum

    2016-01-01

    Antipsychotic drugs are extensively prescribed for the treatment of schizophrenia and other related psychiatric disorders. These drugs produced their action by blocking dopamine (DA) receptors, and these receptors are widely present throughout the brain. Therefore, extended antipsychotic use also leads to severe extrapyramidal side effects. The short-term effects include parkinsonism and the later appearing tardive dyskinesia. Currently available treatments for these disorders are mostly symptomatic and insufficient, and are often linked with a number of detrimental side effects. Antipsychotic-drug-induced tardive dyskinesia prompted researchers to explore novel drugs with fewer undesirable extrapyramidal side effects. Preclinical studies suggest a role of 5-hydroxytryptamine (serotonin)-1A and 2A/2C receptors in the modulation of dopaminergic neurotransmission and motivating a search for better therapeutic strategies for schizophrenia and related disorders. In addition, adjunctive treatment with antioxidants such as vitamin E, red rice bran oil, and curcumin in the early phases of illness may prevent additional oxidative injury, and thus improve and prevent further possible worsening of related neurological and behavioral deficits in schizophrenia. This review explains the role of serotonergic receptors and oxidative stress, with the aim of providing principles for prospect development of compounds to improve therapeutic effects of antischizophrenic drugs. PMID:27540314

  8. Antipsychotics for delirium in the general hospital setting in consecutive 2453 inpatients: a prospective observational study

    PubMed Central

    Hatta, Kotaro; Kishi, Yasuhiro; Wada, Ken; Odawara, Toshinari; Takeuchi, Takashi; Shiganami, Takafumi; Tsuchida, Kazuo; Oshima, Yoshio; Uchimura, Naohisa; Akaho, Rie; Watanabe, Akira; Taira, Toshihiro; Nishimura, Katsuji; Hashimoto, Naoko; Usui, Chie; Nakamura, Hiroyuki

    2014-01-01

    Objective Attention to risk of antipsychotics for older patients with delirium has been paid. A clinical question was whether risk of antipsychotics for older patients with delirium would exceed efficacy of those even in the general hospital setting. Methods A prospective observational study proceeded over a 1-year period at 33 general hospitals, where at least one psychiatrist worked full time. Subjects were patients who developed delirium during their admission due to acute somatic diseases or surgery, and who received antipsychotics for delirium. The primary outcome was rates and kinds of serious adverse events. Results Among 2834 patients who developed delirium, 2453 patients received antipsychotics, such as risperidone (34%), quetiapine (32%), and parenteral haloperidol (20%), for delirium. Out of 2453 patients, 22 serious adverse events (0.9%) were reported. Aspiration pneumonia was the most frequent (17 patients, 0.7%), followed by cardiovascular events (4 patients, 0.2%) and venous thromboembolism (1 patient, 0.0%). There was no patient with a fracture or intracranial injury due to a fall. No one died because of antipsychotic side effects. The mean Clinical Global Impressions—Improvement Scale score was 2.02 (SD 1.09). Delirium was resolved within 1 week in more than half of the patients (54%). Conclusions In the general hospital setting under management including fine dosage adjustment and early detection of side effects, risk of antipsychotics for older patients with delirium might be low, in contrast to antipsychotics for dementia in the nursing home or outpatient settings. A point may be not how to avoid using antipsychotics but how to monitor their risk. PMID:23801358

  9. Antipsychotic Medicines for Schizophrenia and Bipolar Disorder: What You Should Know

    MedlinePlus

    Antipsychotic Drugs for Schizophrenia and Bipolar Disorder: What You Should Know What are antipsychotic drugs? Antipsychotics are prescription drugs used to treat schizophrenia. They can also be used— ...

  10. ACNP White Paper: Update on Use of Antipsychotic Drugs in Elderly Persons with Dementia

    PubMed Central

    Jeste, Dilip V.; Blazer, Dan; Casey, Daniel; Meeks, Thomas; Salzman, Carl; Schneider, Lon; Tariot, Pierre; Yaffe, Kristine

    2008-01-01

    In elderly persons, antipsychotic drugs are clinically prescribed off-label for a number of disorders outside of their Food and Drug Administration (FDA)-approved indications (schizophrenia and bipolar disorder). The largest number of antipsychotic prescriptions in older adults is for behavioral disturbances associated with dementia. In April 2005, the FDA, based on a meta-analysis of 17 double-blind randomized placebo-controlled trials among elderly people with dementia, determined that atypical antipsychotics were associated with a significantly (1.6−1.7 times) greater mortality risk compared with placebo, and asked that drug manufacturers add a ‘black box’ warning to prescribing information for these drugs. Most deaths were due to either cardiac or infectious causes, the two most common immediate causes of death in dementia in general. Clinicians, patients, and caregivers are left with unclear choices of treatment for dementia patients with psychosis and/or severe agitation. Not only are psychosis and agitation common in persons with dementia but they also frequently cause considerable caregiver distress and hasten institutionalization of patients. At the same time, there is a paucity of evidence-based treatment alternatives to antipsychotics for this population. Thus, there is insufficient evidence to suggest that psychotropics other than antipsychotics represent an overall effective and safe, let alone better, treatment choice for psychosis or agitation in dementia; currently no such treatment has been approved by the FDA for these symptoms. Similarly, the data on the efficacy of specific psychosocial treatments in patients with dementia are limited and inconclusive. The goal of this White Paper is to review relevant issues and make clinical and research recommendations regarding the treatment of elderly dementia patients with psychosis and/or agitation. The role of shared decision making and caution in using pharmacotherapy for these patients is

  11. The role of antipsychotics in the management of fibromyalgia.

    PubMed

    Calandre, Elena P; Rico-Villademoros, Fernando

    2012-02-01

    amisulpride, have demonstrated antidepressant activity, with quetiapine approved for the treatment of bipolar depression and refractory major depression, and aripiprazole approved as an adjunctive treatment for major depressive disorder. Finally, several old and new antipsychotics, including promethazine, levopromazine, olanzapine, quetiapine and ziprasidone, have been shown to improve sleep parameters in healthy subjects. Each of these properties suggests that antipsychotics could represent a new potential alternative for the treatment of fibromyalgia syndrome. To date, most of the published studies on the use of antipsychotics in the treatment of fibromyalgia syndrome have been uncontrolled, either case reports or case series, dealing with olanzapine, quetiapine, ziprasidone, levopromazine and amisulpride. The studies on olanzapine and quetiapine have suggested therapeutic efficacy although, in the case of olanzapine, hampered by tolerability problems. A double-blind controlled trial, published in 1980, showed that chlorpromazine increased slow-wave sleep and improved pain and mood disturbances. More recently, four double-blind controlled studies have explored the efficacy of quetiapine, either alone or as an add-on treatment, in fibromyalgia management. None of these trials has yet been published, although two of them have been presented as congress communications, both of them suggesting that quetiapine could be a potential alternative treatment for fibromyalgia. In summary, the current available evidence suggests that at least some antipsychotics, specifically quetiapine, could be useful for the treatment of fibromyalgia and that further studies on the efficacy of these compounds are worth pursuing. PMID:22296316

  12. Atypical autoerotic deaths

    SciTech Connect

    Gowitt, G.T.; Hanzlick, R.L. )

    1992-06-01

    So-called typical' autoerotic fatalities are the result of asphyxia due to mechanical compression of the neck, chest, or abdomen, whereas atypical' autoeroticism involves sexual self-stimulation by other means. The authors present five atypical autoerotic fatalities that involved the use of dichlorodifluoromethane, nitrous oxide, isobutyl nitrite, cocaine, or compounds containing 1-1-1-trichloroethane. Mechanisms of death are discussed in each case and the pertinent literature is reviewed.

  13. Phencyclidine-induced disruption of oscillatory activity in prefrontal cortex: Effects of antipsychotic drugs and receptor ligands.

    PubMed

    Lladó-Pelfort, L; Troyano-Rodriguez, E; van den Munkhof, H E; Cervera-Ferri, A; Jurado, N; Núñez-Calvet, M; Artigas, F; Celada, P

    2016-03-01

    The non-competitive NMDA receptor (NMDA-R) antagonist phencyclidine (PCP) markedly disrupts thalamocortical activity, increasing excitatory neuron discharge and reducing low frequency oscillations (LFO, <4Hz) that temporarily group neuronal discharge. These actions are mainly driven by PCP interaction with NMDA-R in GABAergic neurons of the thalamic reticular nucleus and likely underlie PCP psychotomimetic activity. Here we report that classical (haloperidol, chlorpromazine, perphenazine) and atypical (clozapine, olanzapine, quetiapine, risperidone, ziprasidone, aripripazole) antipsychotic drugs--but not the antidepressant citalopram--countered PCP-evoked fall of LFO in the medial prefrontal cortex (mPFC) of anesthetized rats. PCP reduces LFO by breaking the physiological balance between excitatory and inhibitory transmission. Next, we examined the role of different neurotransmitter receptors to reverse PCP actions. D2-R and D1-R blockade may account for classical antipsychotic action since raclopride and SCH-23390 partially reversed PCP effects. Atypical antipsychotic reversal may additionally involve 5-HT1A-R activation (but not 5-HT2A-R blockade) since 8-OH-DPAT and BAYx3702 (but not M100907) fully countered PCP effects. Blockade of histamine H1-R (pyrilamine) and α1-adrenoceptors (prazosin) was without effect. However, the enhancement of GABAA-R-mediated neurotransmission (using muscimol, diazepam or valproate) and the reduction of excitatory neurotransmission (using the mGluR2/3 agonist LY379268 and the preferential kainite/AMPA antagonist CNQX--but not the preferential AMPA/kainate antagonist NBQX) partially or totally countered PCP effects. Overall, these results shed new light on the neurobiological mechanisms used by antipsychotic drugs to reverse NMDA-R antagonist actions and suggest that agents restoring the physiological excitatory/inhibitory balance altered by PCP may be new targets in antipsychotic drug development.

  14. Atypical presentation of atypical mycobacteria in atypical diabetes

    PubMed Central

    Biswas, Sugata Narayan; Chakraborty, Partha Pratim; Satpathi, Partha Sarathi; Patra, Shinjan

    2016-01-01

    A 45-year-old, non-obese male presented with low-grade, remittent fever and a fluctuant swelling over the posterior aspect of his lower left flank. Laboratory tests revealed leukocytosis, raised ESR, hyperglycemia and raised HbA1C levels. Light microscopy of Ziehl–Neelsen-stained pus sample revealed numerous acid-fast bacilli. After 72 h of incubating aspirated pus in Löwenstein–Jensen media, non-pigmented, cream-colored colonies were observed, suggestive of rapid-growing atypical forms of mycobacteria. Polymerase chain reaction of isolated bacteria identified Mycobacterium chelonae as causative organism. Abdominal skiagram revealed extensive pancreatic intraductal calcifications suggestive of fibrocalculous pancreatic diabetes and lumbar vertebral body destruction with evidence of paravertebral abscess. The patient was prescribed a split-mixed insulin regimen, clarithromycin and ciprofloxacin with complete resolution of the subcutaneous abscess at 6 months. Diabetic patients are prone to infections. Mycobacteria, especially atypical ones, involving the spine and subcutaneous tissues have rarely been reported. PMID:27127641

  15. Is the Superior Efficacy of New Generation Antipsychotics an Artifact of LOCF?

    PubMed Central

    Leucht, Stefan; Engel, Rolf R.; Bäuml, Josef; Davis, John M.

    2007-01-01

    It has been argued that the efficacy superiority found in meta-analyses for some of the atypical antipsychotics is an artifact of higher dropout rates due to side effects in the haloperidol group combined with last-observation-carried-forward (LOCF) analyses. We therefore reanalyzed a number of pivotal studies comparing new generation antipsychotics (NGAs) and conventional antipsychotics (CAs). A total of 5 studies (n = 1271) comparing amisulpride and 3 studies (n = 2454) comparing olanzapine with CAs were reanalyzed using original patient data. We applied 4 different models: LOCF, completer analysis, LOCF but excluding dropouts due to adverse events, and LOCF but excluding all dropouts with the exception of dropouts related to efficacy. Effect sizes expressed as standardized mean differences between NGAs and CAs based on the 4 different analysis models were compared. The overall results were not different irrespective of the model used. Single studies, however, showed higher effect sizes when LOCF instead of other models was used. Overall, it does not seem that higher dropout rates due to side effects in the haloperidol groups together with LOCF analyses consistently biased the results in favor of amisulpride and olanzapine. Because the results of the single studies, however, showed that this may occasionally be the case, future studies should look at the data from different angles applying sensitivity analyses, and they may use alternative statistics such as mixed models, which need to be developed further. Ultimately, strategies to reduce dropout rates are needed. PMID:16905632

  16. Magic bullets for mental disorders: the emergence of the concept of an "antipsychotic" drug.

    PubMed

    Moncrieff, Joanna

    2013-01-01

    When "antipsychotic" drugs were introduced into psychiatry in the 1950s, they were thought to work by inducing a state of neurological suppression, which reduced behavioral disturbance as well as psychotic symptoms. This view was reflected in the name "neuroleptic." Within a few years, however, the idea that the drugs were a disease-specific treatment for schizophrenia or psychosis, and that they worked by modifying the underlying pathology of the condition, replaced this earlier view, and they became known as "antipsychotics." This transformation of views about the drugs' mode of action occurred with little debate or empirical evaluation in the psychiatric literature and obscured earlier evidence about the nature of these drugs. Drug advertisements in the British Journal of Psychiatry reflect the same changes, although the nondisease-specific view persisted for longer. It is suggested that professional interests rather than scientific merit facilitated the rise of the disease-specific view of drug action. The increasing popularity of atypical antipsychotics makes it important to examine the origins of the assumptions on which modern drug treatment is based. PMID:23323530

  17. Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs

    SciTech Connect

    Farde, L.; Wiesel, F.A.; Halldin, C.; Sedvall, G.

    1988-01-01

    Using positron emission tomography and the carbon 11-labeled ligand raclopride, central D2-dopamine receptor occupancy in the putamen was determined in psychiatric patients treated with clinical doses of psychoactive drugs. Receptor occupancy in drug-treated patients was defined as the percent reduction of specific carbon 11-raclopride binding in relation to the expected binding in the absence of drug treatment. Clinical treatment of schizophrenic patients with 11 chemically distinct antipsychotic drugs (including both classic and atypical neuroleptics such as clozapine) resulted in a 65% to 85% occupancy of D2-dopamine receptors. In a depressed patient treated with the tricyclic antidepressant nortriptyline, no occupancy was found. The time course for receptor occupancy and drug levels was followed after withdrawal of sulpiride or haloperidol. D2-dopamine receptor occupancy remained above 65% for many hours despite a substantial reduction of serum drug concentrations. In a sulpiride-treated patient, the dosage was reduced in four steps over a nine-week period and a curvilinear relationship was demonstrated between central D2-dopamine receptor occupancy and serum drug concentrations. The results demonstrate that clinical doses of all the currently used classes of antipsychotic drugs cause a substantial blockade of central D2-dopamine receptors in humans. This effect appears to be selective for the antipsychotics, since it was not induced by the antidepressant nortriptyline.

  18. Group II Metabotropic Glutamate Receptors as Targets for Novel Antipsychotic Drugs

    PubMed Central

    Muguruza, Carolina; Meana, J. Javier; Callado, Luis F.

    2016-01-01

    Schizophrenia is a chronic psychiatric disorder which substantially impairs patients’ quality of life. Despite the extensive research in this field, the pathophysiology and etiology of schizophrenia remain unknown. Different neurotransmitter systems and functional networks have been found to be affected in the brain of patients with schizophrenia. In this context, postmortem brain studies as well as genetic assays have suggested alterations in Group II metabotropic glutamate receptors (mGluRs) in schizophrenia. Despite many years of drug research, several needs in the treatment of schizophrenia have not been addressed sufficiently. In fact, only 5–10% of patients with schizophrenia successfully achieve a full recovery after treatment. In recent years mGluRs have turned up as novel targets for the design of new antipsychotic medications for schizophrenia. Concretely, Group II mGluRs are of particular interest due to their regulatory role in neurotransmission modulating glutamatergic activity in brain synapses. Preclinical studies have demonstrated that orthosteric Group II mGluR agonists exhibit antipsychotic-like properties in animal models of schizophrenia. However, when these compounds have been tested in human clinical studies with schizophrenic patients results have been inconclusive. Nevertheless, it has been recently suggested that this apparent lack of efficacy in schizophrenic patients may be related to previous exposure to atypical antipsychotics. Moreover, the role of the functional heterocomplex formed by 5-HT2A and mGlu2 receptors in the clinical response to Group II mGluR agonists is currently under study. PMID:27242534

  19. Rapid Growth Of Antipsychotic Prescriptions For Children Who Are Publicly Insured Has Ceased, But Concerns Remain.

    PubMed

    Crystal, Stephen; Mackie, Thomas; Fenton, Miriam C; Amin, Shahla; Neese-Todd, Sheree; Olfson, Mark; Bilder, Scott

    2016-06-01

    The rapid growth of antipsychotic medication use among publicly insured children in the early and mid-2000s spurred new state efforts to monitor and improve prescription behavior. A starting point for many oversight initiatives was the foster care system, where most of the children are insured publicly through Medicaid. To understand the context and the effects of these initiatives, we analyzed patterns and trends in antipsychotic treatment of Medicaid-insured children in foster care and those in Medicaid but not in foster care. We found that the trend of rapidly increasing use of antipsychotics appears to have ceased since 2008. Children in foster care treated with antipsychotic medications are now more likely than other Medicaid-insured children to receive psychosocial interventions and metabolic monitoring for the side effects of the medications. However, challenges persist in increasing safety monitoring and access to psychosocial treatment. Development of specialized managed care plans for children in foster care represents a promising policy opportunity. New national quality measures for safe and judicious antipsychotic medication use are also now available to guide improvement. Oversight policies developed for foster care appear to have potential for adaptation to the broader population of Medicaid-covered children. PMID:27269012

  20. LASSBio-579, a prototype antipsychotic drug, and clozapine are effective in novel object recognition task, a recognition memory model.

    PubMed

    Antonio, Camila B; Betti, Andresa H; Herzfeldt, Vivian; Barreiro, Eliezer J; Fraga, Carlos A M; Rates, Stela M K

    2016-06-01

    Previous studies on the N-phenylpiperazine derivative LASSBio-579 have suggested that LASSBio-579 has an atypical antipsychotic profile. It binds to D2, D4 and 5-HT1A receptors and is effective in animal models of schizophrenia symptoms (prepulse inhibition disruption, apomorphine-induced climbing and amphetamine-induced stereotypy). In the current study, we evaluated the effect of LASSBio-579, clozapine (atypical antipsychotic) and haloperidol (typical antipsychotic) in the novel object recognition task, a recognition memory model with translational value. Haloperidol (0.01 mg/kg, orally) impaired the ability of the animals (CF1 mice) to recognize the novel object on short-term and long-term memory tasks, whereas LASSBio-579 (5 mg/kg, orally) and clozapine (1 mg/kg, orally) did not. In another set of experiments, animals previously treated with ketamine (10 mg/kg, intraperitoneally) or vehicle (saline 1 ml/100 g, intraperitoneally) received LASSBio-579, clozapine or haloperidol at different time-points: 1 h before training (encoding/consolidation); immediately after training (consolidation); or 1 h before long-term memory testing (retrieval). LASSBio-579 and clozapine protected against the long-term memory impairment induced by ketamine when administered at the stages of encoding, consolidation and retrieval of memory. These findings point to the potential of LASSBio-579 for treating cognitive symptoms of schizophrenia and other disorders.

  1. The Effects of Antipsychotic Quality Reporting on Antipsychotic and Psychoactive Medication Use

    PubMed Central

    Bowblis, John R; Lucas, Judith A; Brunt, Christopher S

    2015-01-01

    Objective The objective of this study is to examine how nursing homes changed their use of antipsychotic and other psychoactive medications in response to Nursing Home Compare’s initiation of publicly reporting antipsychotic use in July 2012. Research Design and Subjects The study includes all state recertification surveys (n = 40,415) for facilities six quarters prior and post the initiation of public reporting. Using a difference-in-difference framework, the change in use of antipsychotics and other psychoactive medications is compared for facilities subject to public reporting and facilities not subject to reporting. Principal Findings The percentage of residents using antipsychotics, hypnotics, or any psychoactive medication is found to decline after public reporting. Facilities subject to reporting experienced an additional decline in antipsychotic use (−1.94 vs. −1.40 percentage points) but did not decline as much for hypnotics (−0.60 vs. −1.21 percentage points). Any psychoactive use did not vary with reporting status, and the use of antidepressants and anxiolytics did not change. Conclusion Public reporting of an antipsychotic quality measure can be an effective policy tool for reducing the use of antipsychotic medications—though the effect many only exist in the short run. PMID:25600861

  2. Atypical Hemolytic Uremic Syndrome

    PubMed Central

    Kavanagh, David; Goodship, Tim H.; Richards, Anna

    2013-01-01

    Summary Hemolytic uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. The atypical form of HUS is a disease characterized by complement overactivation. Inherited defects in complement genes and acquired autoantibodies against complement regulatory proteins have been described. Incomplete penetrance of mutations in all predisposing genes is reported, suggesting that a precipitating event or trigger is required to unmask the complement regulatory deficiency. The underlying genetic defect predicts the prognosis both in native kidneys and after renal transplantation. The successful trials of the complement inhibitor eculizumab in the treatment of atypical HUS will revolutionize disease management. PMID:24161037

  3. Atypical pityriasis rosea.

    PubMed

    Imamura, S; Ozaki, M; Oguchi, M; Okamoto, H; Horiguchi, Y

    1985-01-01

    Six cases of pityriasis rosea with atypical morphology and distribution of the eruption are reported. The eruption did not show a typical 'Christmas-tree' arrangement, confined to the trunk and proximal parts of the extremities. However, the histology of the eruption revealed dyskeratotic cells in the epidermis and extravasated erythrocytes in the dermis, which were recently reported as rather characteristic findings of this disease. Prodromal symptoms, course and response to therapy were compatible with pityriasis rosea. Histological examination is important and helpful for the diagnosis of atypical cases.

  4. Osteoporosis Associated with Antipsychotic Treatment in Schizophrenia

    PubMed Central

    Wu, Haishan; Deng, Lu; Zhao, Lipin; Zhao, Jingping; Li, Lehua; Chen, Jindong

    2013-01-01

    Schizophrenia is one of the most common global mental diseases, with prevalence of 1%. Patients with schizophrenia are predisposed to diabetes, coronary heart disease, hypertension, and osteoporosis, than the normal. In comparison with the metabolic syndrome, for instance, there are little reports about osteoporosis which occurs secondary to antipsychotic-induced hyperprolactinaemia. There are extensive recent works of literature indicating that osteoporosis is associated with schizophrenia particularly in patients under psychotropic medication therapy. As osteoporotic fractures cause significantly increased morbidity and mortality, it is quite necessary to raise the awareness and understanding of the impact of antipsychotic-induced hyperprolactinaemia on physical health in schizophrenia. In this paper, we will review the relationship between schizophrenia, antipsychotic medication, hyperprolactinaemia, and osteoporosis. PMID:23690768

  5. Antipsychotics for the management of psychosis in Parkinson's disease: systematic review and meta-analysis

    PubMed Central

    Onalaja, Oluwademilade A.

    2015-01-01

    Background Antipsychotics can exacerbate motor symptoms in Parkinson's disease psychosis. Aims To systematically review the literature on the efficacy and acceptability of antipsychotics for Parkinson's disease psychosis. Method Randomised controlled trials comparing an antipsychotic with placebo were systematically reviewed. Results The final selection list included nine studies using quetiapine (3), clozapine (2), olanzapine (3) and pimavanserin (1). A narrative synthesis and meta-analyses (where appropriate) were presented for each antipsychotic. Clozapine demonstrated superiority over placebo in reducing psychotic symptoms. Quetiapine and olanzapine did not significantly improve psychotic symptoms. All three antipsychotics may exacerbate motor symptoms. Quetiapine studies were associated with high drop-out rates due to adverse events. Pimavanserin is a novel treatment that warrants further investigation. Conclusions Further research is needed. Clozapine and pimavanserin appear to be a promising treatment for Parkinson's disease psychosis. Declaration of interest None. 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.

  6. [Venous thromboembolism as an adverse effect of antipsychotic treatment].

    PubMed

    Bałkowiec-Iskra, Ewa; Cessak, Grzegorz; Kryńska, Łucja; Łoza, Bartosz; Wojnar, Marcin

    2014-01-01

    Many studies, suggest an association between the use of antipsychotics (APs) and occurrence of venous thromboembolism (VTE). Thromboembolism is often related to a significant r'iisk of disability or death. Despite many years of investigating the interrelationsbetween use of APs and VTE, they have not been specified yet. This paper aims to summarize reports on the VTE risk factors in patients using APs. Based on the analyzed clinical studies, meta-analyses and.data published by European Medicines Agency, it has been determined, that the main risk factors for VTE are duration of treatment and patient-related factors, such as gender, age, body mass, and physical activity. Current data do not allow to identify the prothrombotic potential for individual APs or indicate a higher risk for developing VTE in patients treated ' with newer atypical APs. Due to the complex pathogenesis of VTE it would benecessaryto perform large, comparative studies, allowing to identify precisely differences in prothrombotic potential of individual APs. It is necessary to specify products with the lowest VTE risk, what would be useful in the treatment of high-risk patients. All patients treated with APs should be assessed with the risk ofVTE and, if needed, appropriate prevention methods (including most of all the elimination of modifiable risk factors) should be implemented. Moreover, patients should be educated in scope of VTE prodromal symptoms. All patients with the higher VTE risk should be diagnosed as soon as possible and adequate treatment should be implemented.

  7. Prevention of antipsychotic-induced hyperglycaemia by vitamin D: a data mining prediction followed by experimental exploration of the molecular mechanism

    PubMed Central

    Nagashima, Takuya; Shirakawa, Hisashi; Nakagawa, Takayuki; Kaneko, Shuji

    2016-01-01

    Atypical antipsychotics are associated with an increased risk of hyperglycaemia, thus limiting their clinical use. This study focused on finding the molecular mechanism underlying antipsychotic-induced hyperglycaemia. First, we searched for drug combinations in the FDA Adverse Event Reporting System (FAERS) database wherein a coexisting drug reduced the hyperglycaemia risk of atypical antipsychotics, and found that a combination with vitamin D analogues significantly decreased the occurrence of quetiapine–induced adverse events relating diabetes mellitus in FAERS. Experimental validation using mice revealed that quetiapine acutely caused insulin resistance, which was mitigated by dietary supplementation with cholecalciferol. Further database analysis of the relevant signalling pathway and gene expression predicted quetiapine-induced downregulation of Pik3r1, a critical gene acting downstream of insulin receptor. Focusing on the phosphatidylinositol 3-kinase (PI3K) signalling pathway, we found that the reduced expression of Pik3r1 mRNA was reversed by cholecalciferol supplementation in skeletal muscle, and that insulin-stimulated glucose uptake into C2C12 myotube was inhibited in the presence of quetiapine, which was reversed by concomitant calcitriol in a PI3K-dependent manner. Taken together, these results suggest that vitamin D coadministration prevents antipsychotic-induced hyperglycaemia and insulin resistance by upregulation of PI3K function. PMID:27199286

  8. Prevention of antipsychotic-induced hyperglycaemia by vitamin D: a data mining prediction followed by experimental exploration of the molecular mechanism.

    PubMed

    Nagashima, Takuya; Shirakawa, Hisashi; Nakagawa, Takayuki; Kaneko, Shuji

    2016-01-01

    Atypical antipsychotics are associated with an increased risk of hyperglycaemia, thus limiting their clinical use. This study focused on finding the molecular mechanism underlying antipsychotic-induced hyperglycaemia. First, we searched for drug combinations in the FDA Adverse Event Reporting System (FAERS) database wherein a coexisting drug reduced the hyperglycaemia risk of atypical antipsychotics, and found that a combination with vitamin D analogues significantly decreased the occurrence of quetiapine-induced adverse events relating diabetes mellitus in FAERS. Experimental validation using mice revealed that quetiapine acutely caused insulin resistance, which was mitigated by dietary supplementation with cholecalciferol. Further database analysis of the relevant signalling pathway and gene expression predicted quetiapine-induced downregulation of Pik3r1, a critical gene acting downstream of insulin receptor. Focusing on the phosphatidylinositol 3-kinase (PI3K) signalling pathway, we found that the reduced expression of Pik3r1 mRNA was reversed by cholecalciferol supplementation in skeletal muscle, and that insulin-stimulated glucose uptake into C2C12 myotube was inhibited in the presence of quetiapine, which was reversed by concomitant calcitriol in a PI3K-dependent manner. Taken together, these results suggest that vitamin D coadministration prevents antipsychotic-induced hyperglycaemia and insulin resistance by upregulation of PI3K function. PMID:27199286

  9. Costs and effects of long-acting risperidone compared with oral atypical and conventional depot formulations in Germany.

    PubMed

    Laux, Gerd; Heeg, Bart; van Hout, Ben A; Mehnert, Angelika

    2005-01-01

    Schizophrenia is one of the most expensive psychiatric conditions because of high direct and indirect costs associated with the nature of the illness, its resistance to treatment and the consequences of relapse. Long-acting risperidone is a new formulation of an atypical antipsychotic drug that also offers the improvements in compliance associated with haloperidol depot. The aim of this simulation study was to compare the benefits and costs of three pharmacological treatment strategies comprising first-line treatment with long-acting risperidone injection, a haloperidol depot or an oral atypical antipsychotic agent, over a 5-year period in Germany. A discrete event simulation model was developed to compare three treatment scenarios from the perspective of major third-party payers (sickness funds and social security 'Sozialversicherung'). The scenarios comprised first-line treatment with haloperidol depot (scenario 1), long-acting risperidone (scenario 2) and oral olanzapine (scenario 3). Switches to second or third-line options were allowed when side-effects occurred or a patient suffered more than a fixed number of relapses. The model accounted for fixed patient characteristics, and on the basis of these, simulated patient histories according to several time-dependent variables. The time horizon for this model was limited to 5 years, and in accordance with German guidelines, costs and effects were discounted by between 3 and 10%. Direct costs included medication, type of physician visits and treatment location. Indirect costs were not included. Information on treatment alternatives, transition probabilities, model structure and healthcare utilization were derived from the literature and an expert panel. Outcomes were expressed in terms of the number and duration of psychotic episodes, cumulative symptom scores, costs, and quality-adjusted life-years (QALY). Univariate sensitivity analyses were carried out, as were subgroup analyses based on disease severity and

  10. Sleep disturbances in patients with schizophrenia : impact and effect of antipsychotics.

    PubMed

    Cohrs, Stefan

    2008-01-01

    Difficulties initiating or maintaining sleep are frequently encountered in patients with schizophrenia. Disturbed sleep can be found in 30-80% of schizophrenic patients, depending on the degree of psychotic symptomatology. Measured by polysomnography, reduced sleep efficiency and total sleep time, as well as increased sleep latency, are found in most patients with schizophrenia and appear to be an important part of the pathophysiology of this disorder. Some studies also reported alterations of stage 2 sleep, slow-wave sleep (SWS) and rapid eye movement (REM) sleep variables, i.e. reduced REM latency and REM density. A number of sleep parameters, such as the amount of SWS and the REM latency, are significantly correlated to clinical variables, including severity of illness, positive symptoms, negative symptoms, outcome, neurocognitive impairment and brain structure.Concerning specific sleep disorders, there is some evidence that schizophrenic patients carry a higher risk of experiencing a sleep-related breathing disorder, especially those demonstrating the known risk factors, including being overweight but also long-term use of antipsychotics. However, it is still unclear whether periodic leg movements in sleep or restless legs syndrome (RLS) are found with a higher or lower prevalence in schizophrenic patients than in healthy controls.There are no consistent effects of first-generation antipsychotics on measures of sleep continuity and sleep structure, including the percentage of sleep stages or sleep and REM latency in healthy controls. In contrast to first-generation antipsychotics, the studied atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone, ziprasidone and paliperidone) demonstrate a relatively consistent effect on measures of sleep continuity, with an increase in either total sleep time (TST) or sleep efficiency, and individually varying effects on other sleep parameters, such as an increase in REM latency observed for olanzapine

  11. Sleep disturbances in patients with schizophrenia : impact and effect of antipsychotics.

    PubMed

    Cohrs, Stefan

    2008-01-01

    Difficulties initiating or maintaining sleep are frequently encountered in patients with schizophrenia. Disturbed sleep can be found in 30-80% of schizophrenic patients, depending on the degree of psychotic symptomatology. Measured by polysomnography, reduced sleep efficiency and total sleep time, as well as increased sleep latency, are found in most patients with schizophrenia and appear to be an important part of the pathophysiology of this disorder. Some studies also reported alterations of stage 2 sleep, slow-wave sleep (SWS) and rapid eye movement (REM) sleep variables, i.e. reduced REM latency and REM density. A number of sleep parameters, such as the amount of SWS and the REM latency, are significantly correlated to clinical variables, including severity of illness, positive symptoms, negative symptoms, outcome, neurocognitive impairment and brain structure.Concerning specific sleep disorders, there is some evidence that schizophrenic patients carry a higher risk of experiencing a sleep-related breathing disorder, especially those demonstrating the known risk factors, including being overweight but also long-term use of antipsychotics. However, it is still unclear whether periodic leg movements in sleep or restless legs syndrome (RLS) are found with a higher or lower prevalence in schizophrenic patients than in healthy controls.There are no consistent effects of first-generation antipsychotics on measures of sleep continuity and sleep structure, including the percentage of sleep stages or sleep and REM latency in healthy controls. In contrast to first-generation antipsychotics, the studied atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone, ziprasidone and paliperidone) demonstrate a relatively consistent effect on measures of sleep continuity, with an increase in either total sleep time (TST) or sleep efficiency, and individually varying effects on other sleep parameters, such as an increase in REM latency observed for olanzapine

  12. [Therapy of dementia with antipsychotics and antidepressives].

    PubMed

    Frölich, L; Hausner, L

    2015-04-01

    In dementia depressive symptoms, anxiety, hallucinations and delusions often occur and are accompanied by unspecific behavioral changes. A targeted pharmacotherapy is complicated by the underlying cognitive impairment and physical comorbidities. The current review focusses on recent evidence on the use of antidepressives and antipsychotics for psychotic disturbances, agitation and depression in dementia and analyzes currently published randomized controlled clinical trials and meta-analyses. The evidence on the use of antipsychotics for different indications favors risperidone, with lower evidence levels for quetiapine and aripiprazole, whereas haloperidol should be avoided. Increased mortality and the risk of cerebrovascular events due to antipsychotics are of major concern. With respect to antidepressives, the benefit of antidepressive pharmacotherapy in dementia is critically discussed because of limited efficacy and increased side effects; however, selective serotonin reuptake inhibitors (SSRI), such as citalopram and sertraline have demonstrated efficacy on neuropsychiatric behavioral symptoms in general. These conclusions on the risk-benefit ratio of antidepressives and antipsychotics in dementia are in accordance with the recommendations of the German Society of Neurology and German Association for Psychiatry, Psychotherapy and Psychosomatics (DGN/DGPPN) S3 guidelines on the treatment of dementia. PMID:25787724

  13. Patient, Physician and Organizational Influences on Variation in Antipsychotic Prescribing Behavior

    PubMed Central

    Tang, Yan; Chang, Chung-Chou H.; Lave, Judith R.; Gellad, Walid F.; Huskamp, Haiden A.; Donohue, Julie M.

    2016-01-01

    Background Physicians face the choice of multiple ingredients when prescribing drugs in many therapeutic categories. For conditions with considerable patient heterogeneity in treatment response, customizing treatment to individual patient needs and preferences may improve outcomes. Aims of the Study To assess variation in the diversity of antipsychotic prescribing for mental health conditions, a necessary although not sufficient condition for personalizing treatment. To identify patient caseload, physician, and organizational factors associated with the diversity of antipsychotic prescribing. Methods Using 2011 data from Pennsylvania’s Medicaid program, IMS Health’s HCOS™ database, and the AMA Masterfile, we identified 764 psychiatrists who prescribed antipsychotics to ≥10 patients. We constructed three physician-level measures of diversity/concentration of antipsychotic prescribing: number of ingredients prescribed, share of prescriptions for most preferred ingredient, and Herfindahl-Hirschman index (HHI). We used multiple membership linear mixed models to examine patient caseload, physician, and healthcare organizational predictors of physician concentration of antipsychotic prescribing. Results There was substantial variability in antipsychotic prescribing concentration among psychiatrists, with number of ingredients ranging from 2-17, share for most preferred ingredient from 16%-85%, and HHI from 1,088-7,270. On average, psychiatrist prescribing behavior was relatively diversified; however, 11% of psychiatrists wrote an average of 55% of their prescriptions for their most preferred ingredient. Female prescribers and those with smaller shares of disabled or serious mental illness patients had more concentrated prescribing behavior on average. Discussion Antipsychotic prescribing by individual psychiatrists in a large state Medicaid program varied substantially across psychiatrists. Our findings illustrate the importance of understanding physicians

  14. Risk of Ischemic Stroke Associated with the Use of Antipsychotic Drugs in Elderly Patients: A Retrospective Cohort Study in Korea

    PubMed Central

    Shin, Ju-Young; Choi, Nam-Kyong; Lee, Joongyub; Seong, Jong-Mi; Park, Mi-Ju; Lee, Shin Haeng; Park, Byung-Joo

    2015-01-01

    Objective Strong concerns have been raised about whether the risk of ischemic stroke differs between conventional antipsychotics (CAPs) and atypical antipsychotics (AAPs). This study compared the risk of ischemic stroke in elderly patients taking CAPs and AAPs. Method We conducted a retrospective cohort study of 71,584 elderly patients who were newly prescribed the CAPs (haloperidol or chlorpromazine) and those prescribed the AAPs (risperidone, quetiapine, or olanzapine). We used the National Claims Database from the Health Insurance Review and Assessment Service (HIRA) from January 1, 2006 to December 31, 2009. Incident cases for ischemic stroke (ICD-10, I63) were identified. The hazard ratios (HR) for AAPs, CAPs, and for each antipsychotic were calculated using multivariable Cox regression models, with risperidone as a reference. Results Among a total of 71,584 patients, 24,668 patients were on risperidone, 15,860 patients on quetiapine, 3,888 patients on olanzapine, 19,564 patients on haloperidol, and 7,604 patients on chlorpromazine. A substantially higher risk was observed with chlorpromazine (HR = 3.47, 95% CI, 1.97–5.38), which was followed by haloperidol (HR = 2.43, 95% CI, 1.18–3.14), quetiapine (HR = 1.23, 95% CI, 0.78–2.12), and olanzapine (HR = 1.12, 95% CI, 0.59–2.75). Patients who were prescribed chlorpromazine for longer than 150 days showed a higher risk (HR = 3.60, 95% CI, 1.83–6.02) than those who took it for a shorter period of time. Conclusions A much greater risk of ischemic stroke was observed in patients who used chlorpromazine and haloperidol compared to risperidone. The evidence suggested that there is a strong need to exercise caution while prescribing these agents to the elderly in light of severe adverse events with atypical antipsychotics. PMID:25790285

  15. Effectiveness of long-acting antipsychotics in clinical practice: 2. Effects of antipsychotic polypharmacy on risperidone long-acting injection and zuclopenthixol decanoate

    PubMed Central

    Cordiner, Matthew; Shajahan, Polash; McAvoy, Sarah; Bashir, Muhammad; Taylor, Mark

    2016-01-01

    Objectives: Antipsychotic polypharmacy (APP) is common clinical practice. Theoretically, APP runs the risk of additional side effects, drug interactions, adherence and cost. A limited evidence base is emerging to support the effectiveness of APP in clinical practice. Our companion paper highlighted the extent of APP alongside commonly prescribed long-acting antipsychotic injections (LAIs). We aimed to examine the effects of APP on discontinuation rates and Clinical Global Impression (CGI) outcomes in patients commenced on risperidone long-acting injection (RLAI) and zuclopenthixol decanoate. Method: LAI-naïve patients commenced on RLAI (n = 102) and zuclopenthixol decanoate(n = 105) were identified using our electronic patient record (running from 2002) within NHS Lanarkshire, Scotland, UK. This was a retrospective, electronic case note review with an 18-month follow up. Patient groups were divided into those receiving the LAI as the sole antipsychotic and those who were receiving additional oral antipsychotic polypharmacy (APP) for at least 50% of the duration of the treatment with their LAI. Kaplan–Meier statistics were calculated for discontinuation rates. CGI severity and improvement scores were retrospectively assigned by the investigating team. Results: Antipsychotic polypharmacy occurred with RLAI (37%) and zuclopenthixol decanoate (46%) and was associated with lower discontinuation rates (statistical significant with zuclopenthixol for any cause and adverse effects discontinuation). APP had no adverse outcomes on hospital admissions or CGI ratings. Patients on APP did not have more severe, chronic or treatment resistant illnesses. Conclusions: For RLAI and zuclopenthixol decanoate, APP had some favourable outcomes when examining discontinuation rates for any cause, and adverse effects. This was unexpected as we had considered APP would signal illness chronicity and severity and be associated with increased adverse effects resulting in early

  16. Olanzapine improves social dysfunction in cluster B personality disorder.

    PubMed

    Zullino, Daniele F; Quinche, Philippe; Häfliger, Thomas; Stigler, Michael

    2002-07-01

    Treatment with antipsychotics is a common approach for personality disorder. Conventional antipsychotics may be efficacious particularly against psychoticism, but less against other symptoms in these patients. They are, furthermore, associated with adverse drug reactions poorly tolerated by patients with personality disorder. Atypical antipsychotics have a more convenient pharmacological profile with a lower risk for extrapyramidal symptoms and a broader therapeutic profile, showing some efficacy against impulsivity, aggressivity and affective symptoms. The medical records of ten patients with a DSM-IV diagnosis of a cluster B personality disorder who had received olanzapine treatment were reviewed. A mirror-image design anchored to the start date of olanzapine treatment and extending 8 weeks in either direction was used. The assessment consisted of a qualitative chart review and a retrospective completion of the GCI-C and an adapted French version of the SDAS, using the observer-rated items. The olanzapine dose range was 2.5-20 mg during the 8 weeks of observation. The mean SDAS score (items 1-15) was 28.8+/-8.4 for the 8 weeks preceding olanzapine prescription and was improved to 13.6+/-5.8 after 8 weeks of treatment.

  17. Paranoid personality masking an atypical case of frontotemporal dementia.

    PubMed

    Iroka, Nneka; Jehangir, Waqas; Ii, Jay Littlefield; Pattan, Vishwanath; Yousif, Abdalla; Mishra, Arunesh K

    2015-05-01

    Frontotemporal dementia (FTD) is a debilitating disease that is well described in the "Diagnostic and statistical manual of mental disorders, fifth edition (DSM-5)", and typically presents with memory impairment, progressive decline in cortical functioning, and behavioral changes. Age of onset is generally in the late fifties, and usually the first presentation involves a change in behavior and emotional blunting. Treatment of FTD involves management of any neurobehavioral symptoms while trials of atypical antipsychotics are ongoing but suggest some efficacy. We present a case of a patient who first presented with severe paranoid personality traits and frank persecutory delusions. This atypical presentation of our patient first led to her incorrect diagnosis of a psychotic disorder and paranoid personality disorder. As a result of this diagnosis, she was treated unsuccessfully. A subsequent magnetic resonance imaging (MRI) then showed atrophy of frontal and temporal lobes bilaterally (left more prominent than right) which confirmed the diagnosis of FTD. The importance of this case involves the atypical presentation of paranoia and delusions, and our patient's incorrect diagnosis based on her clinical presentation led to a trial of unsuccessful treatment. Only after performing an MRI, which showed atrophy, was the patient appropriately treated and deemed medically stable. This case report illustrates the importance of considering a rare presentation of frontotemporal lobe dementia with patients who are in the typical age range and present with paranoia and delusions.

  18. Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia

    PubMed Central

    Honey, Garry D.; Bullmore, Edward T.; Soni, William; Varatheesan, Malini; Williams, Steve C. R.; Sharma, Tonmoy

    1999-01-01

    Antipsychotic drug treatment of schizophrenia may be complicated by side effects of widespread dopaminergic antagonism, including exacerbation of negative and cognitive symptoms due to frontal cortical hypodopaminergia. Atypical antipsychotics have been shown to enhance frontal dopaminergic activity in animal models. We predicted that substitution of risperidone for typical antipsychotic drugs in the treatment of schizophrenia would be associated with enhanced functional activation of frontal cortex. We measured cerebral blood oxygenation changes during periodic performance of a verbal working memory task, using functional MRI, on two occasions (baseline and 6 weeks later) in two cohorts of schizophrenic patients. One cohort (n = 10) was treated with typical antipsychotic drugs throughout the study. Risperidone was substituted for typical antipsychotics after baseline assessment in the second cohort (n = 10). A matched group of healthy volunteers (n = 10) was also studied on a single occasion. A network comprising bilateral dorsolateral prefrontal and lateral premotor cortex, the supplementary motor area, and posterior parietal cortex was activated by working memory task performance in both the patients and comparison subjects. A two-way analysis of covariance was used to estimate the effect of substituting risperidone for typical antipsychotics on power of functional response in the patient group. Substitution of risperidone increased functional activation in right prefrontal cortex, supplementary motor area, and posterior parietal cortex at both voxel and regional levels of analysis. This study provides direct evidence for significantly enhanced frontal function in schizophrenic patients after substitution of risperidone for typical antipsychotic drugs, and it indicates the potential value of functional MRI as a tool for longitudinal assessment of psychopharmacological effects on cerebral physiology. PMID:10557338

  19. Genetics of Common Antipsychotic-Induced Adverse Effects.

    PubMed

    MacNeil, Raymond R; Müller, Daniel J

    2016-07-01

    The effectiveness of antipsychotic drugs is limited due to accompanying adverse effects which can pose considerable health risks and lead to patient noncompliance. Pharmacogenetics (PGx) offers a means to identify genetic biomarkers that can predict individual susceptibility to antipsychotic-induced adverse effects (AAEs), thereby improving clinical outcomes. We reviewed the literature on the PGx of common AAEs from 2010 to 2015, placing emphasis on findings that have been independently replicated and which have additionally been listed to be of interest by PGx expert panels. Gene-drug associations meeting these criteria primarily pertain to metabolic dysregulation, extrapyramidal symptoms (EPS), and tardive dyskinesia (TD). Regarding metabolic dysregulation, results have reaffirmed HTR2C as a strong candidate with potential clinical utility, while MC4R and OGFR1 gene loci have emerged as new and promising biomarkers for the prediction of weight gain. As for EPS and TD, additional evidence has accumulated in support of an association with CYP2D6 metabolizer status. Furthermore, HSPG2 and DPP6 have been identified as candidate genes with the potential to predict differential susceptibility to TD. Overall, considerable progress has been made within the field of psychiatric PGx, with inroads toward the development of clinical tools that can mitigate AAEs. Going forward, studies placing a greater emphasis on multilocus effects will need to be conducted. PMID:27606321

  20. Metformin treatment of antipsychotic-induced dyslipidemia: an analysis of two randomized, placebo-controlled trials

    PubMed Central

    Wu, R-R; Zhang, F-Y; Gao, K-M; Ou, J-J; Shao, P; Jin, H; Guo, W-B; Chan, P K; Zhao, J-P

    2016-01-01

    Dyslipidemia is one of the most common adverse effects in schizophrenia patients treated with antipsychotics. However, there are no established effective treatments. In this study, data were pooled from two randomized, placebo-controlled trials, which were originally designed to examine the efficacy of metformin in treating antipsychotic-induced weight gain and other metabolic abnormalities. In total, 201 schizophrenia patients with dyslipidemia after being treated with an antipsychotic were assigned to take 1000 mg day–1 metformin (n=103) or placebo (n=98) for 24 weeks, with evaluation at baseline, week 12 and week 24. The primary outcome was the low-density lipoprotein cholesterol (LDL-C) levels. After metformin treatment, the mean difference in the LDL-C value between metformin treatment and placebo was from 0.16 mmol l–1 at baseline to –0.86 mmol l–1 at the end of week 24, decreased by 1.02 mmol l–1 (P<0.0001); and 25.3% of patients in the metformin group had LDL-C ≥3.37 mmol l–1, which is significantly <64.8% in the placebo group (P<0.001) at week 24. Compared with the placebo, metformin treatment also have a significant effect on reducing weight, body mass index, insulin, insulin resistance index, total cholesterol and triglyceride, and increasing high-density lipoprotein cholesterol. The treatment effects on weight and insulin resistance appeared at week 12 and further improved at week 24, but the effects on improving dyslipidemia only significantly occurred at the end of week 24. We found that metformin treatment was effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effects improving antipsychotic-induced insulin resistance appeared earlier than the reducing dyslipidemia. PMID:26809842

  1. Managing atypical hemolytic uremic syndrome: chapter 2.

    PubMed

    Nester, Carla M

    2015-05-01

    Licht et al. present the 2-year follow-up data of the landmark trials studying the efficacy of eculizumab in the treatment of atypical hemolytic uremic syndrome (aHUS). They report sustained improvements in hematologic parameters, continued safety, and additional improvements in kidney function with extended treatment. This report adds a layer of comfort to our care of patients with this rare disease; however, it is unlikely to be the final chapter in the treatment of aHUS.

  2. Pharmacogenetics and outcome with antipsychotic drugs

    PubMed Central

    Pouget, Jennie G.; Shams, Tahireh A.; Tiwari, Arun K.; Müller, Daniel J.

    2014-01-01

    Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h2~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future. PMID:25733959

  3. Pharmacogenetics and outcome with antipsychotic drugs.

    PubMed

    Pouget, Jennie G; Shams, Tahireh A; Tiwari, Arun K; Müller, Daniel J

    2014-12-01

    Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h(2)~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future.

  4. Safety and Tolerability of Antipsychotic Polypharmacy

    PubMed Central

    Gallego, Juan A.; Nielsen, Jimmi; De Hert, Marc; Kane, John M.; Correll, Christoph U.

    2012-01-01

    Introduction Antipsychotic polypharmacy (APP), the concomitant use of ≥2antipsychotics, is common in clinical practice. Prior reviews have focused on the efficacy of APP, but no systematic review exists regarding the safety and tolerability of this practice. Areas covered in this review We conducted a systematic review of adverse effects associated with APP. Case series with ≥2 patients, chart reviews, naturalistic, data base, cohort and randomized studies that reported on the association between APP in general or specific APP combinations and global or specific adverse effect were included. We discuss methodological limitations of available studies and provide recommendations for clinicians and future research. Expert Opinion Across mostly small and uncontrolled studies, APP has been associated with increased global side effect burden, rates of Parkinsonian side effects, anticholinergic use, hyperprolactinemia, sexual dysfunction, hypersalivation, sedation/somnolence, cognitive impairment, and diabetes. Effects on akathisia and mortality were inconclusive. Although some combinations, particularly aripiprazole augmentation of an agent with greater side effect burden, may reduce weight gain, dyslipidemia, hyperprolactinemia and sexual dysfunction, APP should remain a last resort treatment option after monotherapy, switching and non-antipsychotic combinations have failed. More and high quality data are needed to further inform the individualized risk-benefit evaluation of APP. PMID:22563628

  5. Physician and patient benefit–risk preferences from two randomized long-acting injectable antipsychotic trials

    PubMed Central

    Katz, Eva G; Hauber, Brett; Gopal, Srihari; Fairchild, Angie; Pugh, Amy; Weinstein, Rachel B; Levitan, Bennett S

    2016-01-01

    Purpose To quantify clinical trial participants’ and investigators’ judgments with respect to the relative importance of efficacy and safety attributes of antipsychotic treatments for schizophrenia, and to assess the impact of formulation and adherence. Methods Discrete-choice experiment surveys were completed by patients with schizophrenia and physician investigators participating in two phase-3 clinical trials of paliperidone palmitate 3-month long-acting injectable (LAI) antipsychotic. Respondents were asked to choose between hypothetical antipsychotic profiles defined by efficacy, safety, and mode of administration. Data were analyzed using random-parameters logit and probit models. Results Patients (N=214) and physicians (N=438) preferred complete improvement in positive symptoms (severe to none) as the most important attribute, compared with improvement in any other attribute studied. Both respondents preferred 3-month and 1-month injectables to oral formulation (P<0.05), irrespective of prior adherence to oral antipsychotic treatment, with physicians showing greater preference for a 3-month over a 1-month LAI for nonadherent patients. Physicians were willing to accept treatments with reduced efficacy for patients with prior poor adherence. The maximum decrease in efficacy (95% confidence interval [CI]) that physicians would accept for switching a patient from daily oral to 3-month injectable was as follows: adherent: 9.8% (95% CI: 7.2–12.4), 20% nonadherent: 25.4% (95% CI: 21.0–29.9), and 50% nonadherent: >30%. For patients, adherent: 10.1% (95% CI: 6.1–14.1), nonadherent: the change in efficacy studied was regarded as unimportant. Conclusion Improvement in positive symptoms was the most important attribute. Patients and physicians preferred LAIs over oral antipsychotics, with physicians showing a greater preference for 3-month over 1-month LAI. Physicians and patients were willing to accept reduced efficacy in exchange for switching a patient from

  6. [Atypical presentation of preeclampsia].

    PubMed

    Ditisheim, A; Boulvain, M; Irion, O; Pechère-Bertschi, A

    2015-09-01

    Preeclampsia is a pregnancy-related syndrome, which still represents one of the major causes of maternal-fetal mortality and morbidity. Diagnosis can be made difficult due to the complexity of the disorder and its wide spectrum of clinical manifestations. In order to provide an efficient diagnostic tool to the clinician, medical societies regularly rethink the definition criteria. However, there are still clinical presentations of preeclampsia that escape the frame of the definition. The present review will address atypical forms of preeclampsia, such as preeclampsia without proteinuria, normotensive preeclampsia, preeclampsia before 20 weeks of gestation and post-partum preeclampsia.

  7. Antipsychotic Drug-Induced Somnolence: Incidence, Mechanisms, and Management.

    PubMed

    Fang, Fang; Sun, Hongwei; Wang, Zuowei; Ren, Ming; Calabrese, Joseph R; Gao, Keming

    2016-09-01

    Somnolence is a common side effect of antipsychotics. To assess the incidence of this side effect, we performed a MEDLINE search for randomized, double-blinded, placebo- or active-controlled studies of adult patients treated with antipsychotics for schizophrenia, mania, bipolar depression, or bipolar disorder. We extracted rates of somnolence from original publications and pooled them based on the dose of each antipsychotic in the same psychiatric condition, then estimated the absolute risk increase (ARI) and the number needed to harm (NNH) of an antipsychotic relative to placebo or an active comparator in the same psychiatric condition. According to the ARI in acute schizophrenia, bipolar mania, and bipolar depression, antipsychotics can be classified as high somnolence (clozapine), moderate somnolence (olanzapine, perphenazine, quetiapine, risperidone, ziprasidone), and low somnolence (aripiprazole, asenapine, haloperidol, lurasidone, paliperidone, cariprazine). The risk of somnolence with blonanserin, brexpiprazole, chlorpromazine, iloperidone, sertindole, and zotepine needs further investigation. The rates of somnolence were positively correlated to dose and duration for some antipsychotics, but not for others. Many factors, including antipsychotic per se, the method used to measure somnolence, patient population, study design, and dosing schedule, might affect the incidence of antipsychotic-induced somnolence. The mechanisms of antipsychotic-induced somnolence are likely multifactorial, although the blockade of histamine 1 receptors and α1 receptors may play a major role. The management of antipsychotic-induced somnolence should include sleep hygiene education, choosing an antipsychotic with a lower risk for somnolence, starting at a lower dose with a slower titration based on psychiatric diagnoses, adjusting doses when necessary, and minimizing concurrent somnolence-prone agents. Since most cases of somnolence were mild to moderate, allowing tolerance to

  8. Comparing the safety and efficacy of atypical antipsychotics in psychiatric patients with comorbid medical illnesses.

    PubMed

    Newcomer, John W

    2009-01-01

    Patients with severe mental illnesses have a higher risk of premature mortality than the general US population. Illnesses such as schizophrenia and bipolar disorder are frequently complicated by physical comorbidities such as diabetes and cardiovascular disease, including both coronary heart disease and cerebrovascular disease, which are associated with increased mortality and morbidity. Coronary heart disease is the leading cause of death among individuals with severe mental illnesses. Modifiable risk factors such as dyslipidemia, hyperglycemia, hypertension, smoking, and obesity are common in this population and contribute to risk for both diabetes and coronary heart disease. While many psychotropic medications used in the treatment of schizophrenia or bipolar disorder have similar efficacy, some medications are associated with more metabolic side effects than others, and clinicians should consider these risks when choosing among these medications. Patients with severe mental illnesses tend to have reduced access to health care and treatment for medical comorbidities compared with the general population. Therefore, clinicians involved in the care of this patient population should screen and monitor carefully for cardiometabolic side effects and risk factors. PMID:19570499

  9. Mental health pharmacists views on shared decision-making for antipsychotics in serious mental illness.

    PubMed

    Younas, Mediha; Bradley, Eleanor; Holmes, Nikki; Sud, Dolly; Maidment, Ian D

    2016-10-01

    Background People diagnosed with serious mental illnesses (SMIs) such as schizophrenia and bipolar affective disorder are frequently treated with antipsychotics. National guidance advises the use of shared decision-making (SDM) in antipsychotic prescribing. There is currently little data on the opinions of health professionals on the role of SDM. Objective To explore the views and experiences of UK mental health pharmacists regarding the use of SDM in antipsychotic prescribing in people diagnosed with SMI. Setting The study was conducted by interviewing secondary care mental health pharmacists in the UK to obtain qualitative data. Methods Semi-structured interviews were recorded. An inductive thematic analysis was conducted using the method of constant comparison. Main outcome measure Themes evolving from mental health pharmacists on SDM in relation to antipsychotic prescribing in people with SMI. Results Thirteen mental health pharmacists were interviewed. SDM was perceived to be linked to positive clinical outcomes including adherence, service user satisfaction and improved therapeutic relations. Despite more prescribers and service users supporting SDM, it was not seen as being practised as widely as it could be; this was attributed to a number of barriers, most predominantly issues surrounding service user's lacking capacity to engage in SDM and time pressures on clinical staff. The need for greater effort to work around the issues, engage service users and adopt a more inter-professional approach was conveyed. Conclusion The mental health pharmacists support SDM for antipsychotic prescribing, believing that it improves outcomes. However, barriers are seen to limit implementation. More research is needed into overcoming the barriers and measuring the benefits of SDM, along with exploring a more inter-professional approach to SDM. PMID:27450504

  10. Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney.

    PubMed

    Nikolić-Kokić, Aleksandra; Mijušković, Ana; Tatalović, Nikola; Nestorov, Jelena; Miler, Marko; Oreščanin-Dušić, Zorana; Nikolić, Milan; Milošević, Verica; Blagojević, Duško; Spasić, Mihajlo; Miljević, Čedo

    2016-01-01

    The use of atypical antipsychotic drugs (APD) was reported to be associated with adverse effects on the kidneys. Thus, the aim of this study was to examine whether APD exerted their adverse effects by interfering with the renal antioxidant defense system. Male 3-mo-old Wistar rats were treated for 28 d with ziprasidone (ZIP), clozapine (CLO), or sertindole (SER) using a daily dose recommended for antipsychotic drug therapy. The expression and activities of antioxidant enzymes superoxide dismutase (SOD) type 1 and type 2, catalase (CAT), glutathione reductase (GR), and glutathione S-transferases (GSTs) activity were measured in the kidneys. Changes in the kidneys were also evaluated histologically. Ziprasidone, CLO, and SER reduced renal SOD type 1 and type 2 activities. Decreased CAT activity was observed only in SER-treated rats. An inhibition in GR activity and increased activity of GST was found only after treatment with CLO. Histological analysis showed dilatation of proximal tubules in kidneys with all three drugs. In conclusion, data indicate that redox disturbances may contribute to renal morphologic alterations in proximal tubules in rats treated with all APD. PMID:27644343

  11. Adjunctive treatment with mianserin enhances effects of raclopride on cortical dopamine output and, in parallel, its antipsychotic-like effect

    PubMed Central

    Wiker, Charlotte; Linnér, Love; Wadenberg, Marie-Louise; Svensson, Torgny H

    2005-01-01

    Clinical studies indicate that adjunctive treatment with the antidepressant drug mianserin, a 5-hydroxytryptamine (5-HT)2A/C receptor antagonist and an α2- and α1-adrenoceptor antagonist, may enhance the effect of conventional antipsychotic drugs in schizophrenia, in particular on negative symptoms such as withdrawal retardation, akathisia, and some aspects of cognitive impairment. Here, we have examined the effect of mianserin in combination with the selective dopamine (DA) D2/3 receptor antagonist raclopride on conditioned avoidance response (CAR), a preclinical test of antipsychotic efficacy with high predictive validity; catalepsy, a preclinical test of extrapyramidal side effect liability; and DA output in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAC), respectively. Mianserin (5 mg/kg intraperitoneal) significantly enhanced the suppressant effect of a low dose of raclopride (0.1 mg/kg subcutaneous) on CAR without any increase in catalepsy. Administration of raclopride to rats pretreated with mianserin resulted in a large enhancement of DA output in the mPFC and, at the same time, a small but significant reduction in the raclopride-induced DA output in the NAC. These experimental results indicate that adjunctive treatment with mianserin to a typical D2 antagonist generates an atypical antipsychotic profile. PMID:18568103

  12. Adjunctive treatment with mianserin enhances effects of raclopride on cortical dopamine output and, in parallel, its antipsychotic-like effect

    PubMed Central

    Wiker, Charlotte; Linnér, Love; Wadenberg, Marie-Louise; Svensson, Torgny H

    2005-01-01

    Clinical studies indicate that adjunctive treatment with the antidepressant drug mianserin, a 5-hydroxytryptamine (5-HT)2A/C receptor antagonist and an α2- and α1-adrenoceptor antagonist, may enhance the effect of conventional antipsychotic drugs in schizophrenia, in particular on negative symptoms such as withdrawal retardation, akathisia, and some aspects of cognitive impairment. Here, we have examined the effect of mianserin in combination with the selective dopamine (DA) D2/3 receptor antagonist raclopride on conditioned avoidance response (CAR), a preclinical test of antipsychotic efficacy with high predictive validity; catalepsy, a preclinical test of extrapyramidal side effect liability; and DA output in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAC), respectively. Mianserin (5 mg/kg intraperitoneal) significantly enhanced the suppressant effect of a low dose of raclopride (0.1 mg/kg subcutaneous) on CAR without any increase in catalepsy. Administration of raclopride to rats pretreated with mianserin resulted in a large enhancement of DA output in the mPFC and, at the same time, a small but significant reduction in the raclopride-induced DA output in the NAC. These experimental results indicate that adjunctive treatment with mianserin to a typical D2 antagonist generates an atypical antipsychotic profile. PMID:18568117

  13. Successful treatment of a prolactinoma with the antipsychotic drug aripiprazole

    PubMed Central

    Bakker, Ilse C A; Schubart, Chris D

    2016-01-01

    Summary In this report, we describe a female patient with both prolactinoma and psychotic disorder who was successfully treated with aripiprazole, a partial dopamine 2 receptor agonist. During the follow-up of more than 10 years, her psychotic symptoms improved considerably, prolactin levels normalised and the size of the prolactinoma decreased. This observation may be of clinical relevance in similar patients who often are difficult to treat with the regular dopaminergic drugs. Learning points Prolactinoma coinciding with psychosis can represent a therapeutic challenge. In contrast to many other antipsychotic drugs, aripiprazole is associated with a decrease in prolactin levels. Aripiprazole can be a valuable pharmaceutical tool to treat both prolactinoma and psychosis. PMID:27284453

  14. Atypical presentation of macrophagic myofasciitis 10 years post vaccination.

    PubMed

    Ryan, Aisling M; Bermingham, Niamh; Harrington, Hugh J; Keohane, Catherine

    2006-12-01

    Macrophagic myofasciitis (MMF) is an uncommon inflammatory disorder of muscle believed to be due to persistence of vaccine-derived aluminium hydroxide at the site of injection. The condition is characterised by diffuse myalgias, arthralgia and fatigue. We describe a patient with histologically confirmed MMF whose presentation was atypical with left chest and upper limb pain beginning more than 10 years post vaccination. Treatment with steroids led to symptomatic improvement. Although rare, clinicians should consider MMF in cases of atypical myalgia.

  15. Atypical causes of cholestasis

    PubMed Central

    Nguyen, Ken D; Sundaram, Vinay; Ayoub, Walid S

    2014-01-01

    Cholestatic liver disease consists of a variety of disorders. Primary sclerosing cholangitis and primary biliary cirrhosis are the most commonly recognized cholestatic liver disease in the adult population, while biliary atresia and Alagille syndrome are commonly recognized in the pediatric population. In infants, the causes are usually congenital or inherited. Even though jaundice is a hallmark of cholestasis, it is not always seen in adult patients with chronic liver disease. Patients can have “silent” progressive cholestatic liver disease for years prior to development of symptoms such as jaundice and pruritus. In this review, we will discuss some of the atypical causes of cholestatic liver disease such as benign recurrent intrahepatic cholestasis, progressive familial intrahepatic cholestasis, Alagille Syndrome, biliary atresia, total parenteral nutrition induced cholestasis and cholestasis secondary to drug induced liver injury. PMID:25071336

  16. Unusual atypical language lateralization.

    PubMed

    Khan, Muhammad T; Oghlakian, Roger; Koubeissi, Mohamad Z

    2016-01-01

    Determining the language-dominant hemisphere is essential for planning epilepsy surgery. A 60-year-old right-handed woman with epilepsy since age 16 failed a partial right anterior lobectomy at age 21. Later, a brain MRI found extensive right-sided cortical dysplasia and periventricular heterotopia. Subsequently, prolonged video-EEG monitoring localized her seizures to the right temporoparietal region. Functional MRI was inconclusive in lateralizing her language, prompting a Wada test, which strongly lateralized language to the right. This unique case of atypical language representation in a right-handed individual with an extensive right-hemispheric congenital malformation and seizure focus illustrates the important thorough presurgical language assessment. PMID:27668182

  17. Dermatofibroma: Atypical Presentations.

    PubMed

    Bandyopadhyay, Mousumi Roy; Besra, Mrinal; Dutta, Somasree; Sarkar, Somnath

    2016-01-01

    Dermatofibroma is a common benign fibrohistiocytic tumor and its diagnosis is easy when it presents classical clinicopathological features. However, a dermatofibroma may show a wide variety of clinicopathological variants and, therefore, the diagnosis may be difficult. The typical dermatofibroma generally occurs as a single or multiple firm reddish-brown nodules. We report here two atypical presentations of dermatofibroma - Atrophic dermatofibroma and keloidal presentation of dermatofibroma. Clinical dermal atrophy is a common phenomenon in dermatofibromas as demonstrated by the dimpling on lateral pressure. However, this feature is exaggerated in the atrophic variant of dermatofibroma. Atrophic dermatofibroma is defined by dermal atrophy of more than 50% of the lesion apart from the usual features of common dermatofibroma. The keloidal variant of dermatofibroma should not be overlooked as a simple keloid. The findings of keloidal change in dermatofibromas may support that trauma is a possible cause of dermatofibroma. PMID:26955137

  18. Nonadherence with antipsychotic medication in schizophrenia: challenges and management strategies.

    PubMed

    Haddad, Peter M; Brain, Cecilia; Scott, Jan

    2014-01-01

    Nonadherence with medication occurs in all chronic medical disorders. It is a particular challenge in schizophrenia due to the illness's association with social isolation, stigma, and comorbid substance misuse, plus the effect of symptom domains on adherence, including positive and negative symptoms, lack of insight, depression, and cognitive impairment. Nonadherence lies on a spectrum, is often covert, and is underestimated by clinicians, but affects more than one third of patients with schizophrenia per annum. It increases the risk of relapse, rehospitalization, and self-harm, increases inpatient costs, and lowers quality of life. It results from multiple patient, clinician, illness, medication, and service factors, but a useful distinction is between intentional and unintentional nonadherence. There is no gold standard approach to the measurement of adherence as all methods have pros and cons. Interventions to improve adherence include psychoeducation and other psychosocial interventions, antipsychotic long-acting injections, electronic reminders, service-based interventions, and financial incentives. These overlap, all have some evidence of effectiveness, and the intervention adopted should be tailored to the individual. Psychosocial interventions that utilize combined approaches seem more effective than unidimensional approaches. There is increasing interest in electronic reminders and monitoring systems to enhance adherence, eg, Short Message Service text messaging and real-time medication monitoring linked to smart pill containers or an electronic ingestible event marker. Financial incentives to enhance antipsychotic adherence raise ethical issues, and their place in practice remains unclear. Simple pragmatic strategies to improve medication adherence include shared decision-making, regular assessment of adherence, simplification of the medication regimen, ensuring that treatment is effective and that side effects are managed, and promoting a positive

  19. A preliminary analysis of microRNA-21 expression alteration after antipsychotic treatment in patients with schizophrenia.

    PubMed

    Chen, Sheng-Dong; Sun, Xin-Yang; Niu, Wei; Kong, Ling-Ming; He, Ming-Jun; Fan, Hui-Min; Li, Wan-Shuai; Zhong, Ai-Fang; Zhang, Li-Yi; Lu, Jim

    2016-10-30

    Schizophrenia is a severe and debilitating psychiatric disorder of unknown etiology, and its diagnosis is essentially based on clinical symptoms. Despite growing evidence on the relation of altered expression of miRNAs and schizophrenia, most patients with schizophrenia usually had an extensive antipsychotic treatment history before miRNA expression profile analysis, and the pharmacological effects on miRNA expression are largely unknown. To overcome these impediments, miRNA microarray analysis was performed in peripheral blood mononuclear cells (PBMCs) obtained from patients with schizophrenia who were not on antipsychotic medication and healthy controls. Then, using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), we verified the top 10 miRNAs with the highest fold-change values from microarray analysis in 82 patients with schizophrenia and 43 healthy controls, and nine miRNAs demonstrated significant differences in expression levels. Finally, we compared these nine miRNA profiles before and after antipsychotic treatment. Our results revealed that serum miR-21 expression decreased strikingly in patients after antipsychotic treatment. The change of miR-21 expression was negatively correlated with improvement of positive, general psychopathology, and aggressiveness symptoms. This study preliminarily analyzed the possible changes in circulating miRNAs expression in response to antipsychotic medication for schizophrenia, and the molecular mechanisms of this needs to be further explored. PMID:27512922

  20. Modulation of midbrain dopamine neurotransmission by serotonin, a versatile interaction between neurotransmitters and significance for antipsychotic drug action.

    PubMed

    Olijslagers, J E; Werkman, T R; McCreary, A C; Kruse, C G; Wadman, W J

    2006-01-01

    Schizophrenia has been associated with a dysfunction of brain dopamine (DA). This, so called, DA hypothesis has been refined as new insights into the pathophysiology of schizophrenia have emerged. Currently, dysfunction of prefrontocortical glutamatergic and GABAergic projections and dysfunction of serotonin (5-HT) systems are also thought to play a role in the pathophysiology of schizophrenia. Refinements of the DA hypothesis have lead to the emergence of new pharmacological targets for antipsychotic drug development. It was shown that effective antipsychotic drugs with a low liability for inducing extra-pyramidal side-effects have affinities for a range of neurotransmitter receptors in addition to DA receptors, suggesting that a combination of neurotransmitter receptor affinities may be favorable for treatment outcome.This review focuses on the interaction between DA and 5-HT, as most antipsychotics display affinity for 5-HT receptors. We will discuss DA/5-HT interactions at the level of receptors and G protein-coupled potassium channels and consequences for induction of depolarization blockade with specific attention to DA neurons in the ventral tegmental area (VTA) and the substantia nigra zona compacta (SN), neurons implicated in treatment efficacy and the side-effects of schizophrenia, respectively. Moreover, it has been reported that electrophysiological interactions between DA and 5-HT show subtle, but important, differences between the SN and the VTA which could explain (in part) the effectiveness and lower propensity to induce side-effects of the newer atypical antipsychotic drugs. In that respect the functional implications of DA/5-HT interactions for schizophrenia will be discussed.

  1. Atypical Cutaneous Manifestations in Syphilis.

    PubMed

    Ivars Lleó, M; Clavo Escribano, P; Menéndez Prieto, B

    2016-05-01

    Although the diversity of the clinical manifestations of syphilis is well-known, atypical presentations can also occur. Such atypical presentations are associated with a high risk of transmission as a result of diagnostic confusion and treatment delays owing to the disease's ability to mimic other common skin diseases, deviate from classic clinical presentations, and adopt unique forms. Cases of atypical syphilis have been described most frequently in patients with concomitant human immunodeficiency virus (HIV) infection. Because the incidence of syphilis has been growing over recent years -particularly in patients with HIV co-infection- dermatologists need to be familiar with the less well-known clinical presentations of this venereal disease.

  2. Antipsychotic Polypharmacy and Corrected QT Interval: A Systematic Review

    PubMed Central

    Takeuchi, Hiroyoshi; Suzuki, Takefumi; Remington, Gary; Uchida, Hiroyuki

    2015-01-01

    Objective: It remains unclear whether antipsychotic polypharmacy, a common clinical practice, is related to an increased risk of corrected time between start of Q wave and end of T wave (QTc) interval prolongation. We conducted a systematic review of the literature to address this important issue. Method: A systematic literature search was conducted in October 2014, using MEDLINE, Embase, and PsycINFO. Studies and case reports were included if they reported QTc intervals or QTc interval changes before and after antipsychotic polypharmacy or QTc intervals in both antipsychotic polypharmacy and monotherapy groups. Results: A total of 21 articles (10 clinical trials, 4 observational studies, and 7 case reports) met inclusion criteria. The clinical trials have shown that a combination treatment with risperidone or pimozide is not obviously related to an increase in QTc interval, whereas ziprasidone or sertindole combined with clozapine may prolong QTc interval. Among the 4 observational studies, antipsychotic polypharmacy was not clearly associated with QTc prolongation in 3 studies, each cross-sectional. In contrast, one prospective study showed a significant increase in QTc interval following antipsychotic coadministration. The case reports indicated an increased risk of QTc prolongation in at least some patients receiving antipsychotic polypharmacy. Conclusions: Currently available evidence fails to confirm that antipsychotic polypharmacy worsens QTc prolongation in general, although the evidence is scarce and inconsistent. Clinicians are advised to remain conservative in resorting to antipsychotic polypharmacy, as a combination of some QTc-prolongation liable antipsychotics may further prolong QTc interval, and efficacy supporting the clinical benefits of antipsychotic polypharmacy is equivocal, at best. PMID:26174525

  3. [Antipsychotic medication change and reduction of rehospitalization in clients of ACT-J].

    PubMed

    Satake, Naoko

    2011-01-01

    Polypharmacy and high-dose treatment of antipsychotics have been major problems in Japanese mental health. Although importance of simplifying prescription has been recognized, polypharmacy and high-dose medication especially for Schizophrenia remains prevalent. It's considered that psycho-social approach; for example, improvement of coping skills and social support such as care management can make reform of treatment efficiently and also improve patient's QOL. In ACT service, Medication, rehabilitation and social support work closely together and it could make prescription change even for SMI patients. Low-dose medication leads improvement of cognitive function and furthermore social activity. Considering the higher dose of antipsychotics prescribed concurrency in Japan, it's important to evaluate the change in medication for patients of ACT in Japan. We did one year follow up study about prescription change for 52 patients who have used ACT program at ACT-J team for more than one year at the end of December 2009. It was found that the dosage antipsychotics significantly decreased from 1131.3 mg converted to the relative potency equivalent of 100 mg of Chlorpromazine (CPZ eq), to 731.3 mg (CPZ eq) over the course of the 12 months. But there was no significant change about polyphamacy. Also it could be possible to reduce rehospitalization under the ACT program. Because recovery model could make improve not only drop out from psychiatric service, but user's dependency for hospitalization. PMID:21815472

  4. Invasive atypical thymic carcinoid: three case reports and literature review

    PubMed Central

    Zhu, Shan; Wang, Zhong-Tang; Liu, Wen-Zhi; Zong, Shi-Xiang; Li, Bao-Sheng

    2016-01-01

    Atypical thymic carcinoid is an extremely rare thymic neuroendocrine tumor derived from the neuroendocrine system. The aims of this paper were to investigate the clinical features of atypical thymic carcinoid and collate information and experience to improve the diagnosis and treatment of this disease. We describe three cases of atypical carcinoid of the thymus; clinical features, pathological data, treatment modalities, and short-term patient outcomes were summarized and analyzed. The initial clinical symptoms and signs of all three patients were nonspecific and an anterior mediastinal mass was found in each patient on chest computed tomography scan. All three patients underwent surgical resection (total thymectomy and complete excision of the tumor), followed by postoperative radiotherapy, with or without chemotherapy. The diagnoses of three patients were confirmed by pathological and immunohistochemical evaluation. We also present a review of the literature to collate as much information as possible and provide a reference for proper diagnosis and treatment of atypical thyroid carcinoid. PMID:27785065

  5. Pharmacogenetics of second-generation antipsychotics.

    PubMed

    Brennan, Mark D

    2014-04-01

    This review considers pharmacogenetics of the so called 'second-generation' antipsychotics. Findings for polymorphisms replicating in more than one study are emphasized and compared and contrasted with larger-scale candidate gene studies and genome-wide association study analyses. Variants in three types of genes are discussed: pharmacokinetic genes associated with drug metabolism and disposition, pharmacodynamic genes encoding drug targets, and pharmacotypic genes impacting disease presentation and subtype. Among pharmacokinetic markers, CYP2D6 metabolizer phenotype has clear clinical significance, as it impacts dosing considerations for aripiprazole, iloperidone and risperidone, and variants of the ABCB1 gene hold promise as biomarkers for dosing for olanzapine and clozapine. Among pharmacodynamic variants, the TaqIA1 allele of the DRD2 gene, the DRD3 (Ser9Gly) polymorphism, and the HTR2C -759C/T polymorphism have emerged as potential biomarkers for response and/or side effects. However, large-scale candidate gene studies and genome-wide association studies indicate that pharmacotypic genes may ultimately prove to be the richest source of biomarkers for response and side effect profiles for second-generation antipsychotics.

  6. Atypical vertebral Paget's disease.

    PubMed

    Beaudouin, Constance; Dohan, Anthony; Nasrallah, Toufic; Parlier, Caroline; Touraine, Sébastien; Ea, Korng; Kaci, Rachid; Laredo, Jean-Denis

    2014-07-01

    A 40-year-old Mauritanian man consulted for back pain. A computed tomography of the spine showed patchy sclerosis of the fifth and seventh thoracic vertebral bodies with normal neural arch of T5 and sclerosis and hypertrophy of the neural arch of T7, as well as diffuse sclerosis of the T11 vertebral body with a normal neural arch. At MRI, low signal-intensity on T1-weighted images and high signal-intensity on T2-weighted images involved the whole T5 and T7 vertebrae and the vertebral body of T11. Working diagnoses included metastatic disease and lymphoma, and a biopsy of T7 and then T11 was carried out. Both showed pathological findings very suggestive of Paget's disease. Since CT is usually the more specific radiological examination in vertebral Paget's disease, we thought it could be useful to report this atypical CT presentation (patchy sclerosis of the vertebral body without diffuse bone texture changes and isolated involvement of the vertebral body) of vertebral Paget's disease. PMID:24445956

  7. [Atypical hemolytic uremic syndrome].

    PubMed

    Blasco Pelicano, Miquel; Rodríguez de Córdoba, Santiago; Campistol Plana, Josep M

    2015-11-20

    The hemolytic uremic syndrome (HUS) is a clinical entity characterized by thrombocytopenia, non-immune hemolytic anemia and renal impairment. Kidney pathology shows thrombotic microangiopathy (TMA) with endothelial cell injury leading to thrombotic occlusion of arterioles and capillaries. Traditionally, HUS was classified in 2 forms: Typical HUS, most frequently occurring in children and caused by Shiga-toxin-producing bacteria, and atypical HUS (aHUS). aHUS is associated with mutations in complement genes in 50-60% of patients and has worse prognosis, with the majority of patients developing end stage renal disease. After kidney transplantation HUS may develop as a recurrence of aHUS or as de novo disease. Over the last years, many studies have demonstrated that complement dysregulation underlies the endothelial damage that triggers the development of TMA in most of these patients. Advances in our understanding of the pathogenic mechanisms of aHUS, together with the availability of novel therapeutic options, will enable better strategies for the early diagnosis and etiological treatment, which are changing the natural history of aHUS. This review summarizes the aHUS clinical entity and describes the role of complement dysregulation in the pathogenesis of aHUS. Finally, we review the differential diagnosis and the therapeutic options available to patients with aHUS.

  8. Imaging brain gene expression profiles by antipsychotics: region-specific action of amisulpride on postsynaptic density transcripts compared to haloperidol.

    PubMed

    de Bartolomeis, Andrea; Marmo, Federica; Buonaguro, Elisabetta Filomena; Rossi, Rodolfo; Tomasetti, Carmine; Iasevoli, Felice

    2013-11-01

    Induction of motor disorders is considered the clinical landmark differentiating typical from atypical antipsychotics, and has been mainly correlated to dopamine D2 receptors blockade in striatum. This view is challenged by benzamides, such as amisulpride, which display low liability for motor side effects despite being D2/D3 receptors high-affinity blocking agents. These effects have been explained with the prominent presynaptic action of amisulpride or with the fast dissociation at D2 receptors, but there is scarce information on the effects of amisulpride on postsynaptic signaling. We carried out a molecular imaging study of gene expression after acute administration of haloperidol (0.8 mg/kg), amisulpride (10 or 35 mg/kg), or vehicle, focusing on postsynaptic genes that are key regulators of synaptic plasticity, such as Arc, c-fos, Zif-268, Norbin, Homer. The last one has been associated to schizophrenia both in clinical and preclinical studies, and is differentially induced by antipsychotics with different D2 receptors affinity. Topography of gene expression revealed that amisulpride, unlike haloperidol, triggers transcripts expression peak in medial striatal regions. Correlation analysis of gene expression revealed a prevalent correlated gene induction within motor corticostriatal regions by haloperidol and a more balanced gene induction within limbic and motor corticostriatal regions by amisulpride. Despite the selective dopaminergic profile of both compounds, our results demonstrated a differential modulation of postsynaptic molecules by amisulpride and haloperidol, the former impacting preferentially medial regions of striatum whereas the latter inducing strong gene expression in lateral regions. Thus, we provided a possible molecular profile of amisulpride, putatively explaining its "atypical atypicality".

  9. Atypical manifestations of dengue fever.

    PubMed

    Pawaria, Arti; Mishra, Devendra; Juneja, Monica; Meena, Jagdish

    2014-06-01

    We reviewed case records of 40 in-patients (22 boys) with serologically confirmed dengue fever between 1st October and 30th November, 2013. Severe dengue was seen in 30, out of which 12 (30%) had compensated shock. Splenomegaly (6,15%) and encephalopathy (4,10%) were the commonest atypical features. Atypical manifestations of dengue fever were more common than that reported in the past.

  10. KINOMIC ALTERATIONS IN ATYPICAL MENINGIOMA

    PubMed Central

    Anderson, Joshua C.; Taylor, Robert B.; Fiveash, John B.; de Wijn, Rik; Gillespie, G. Yancey; Willey, Christopher D.

    2015-01-01

    Background We sought to profile Atypical Meningioma in a high-throughput manner to better understand the altered signaling within these tumors and specifically the kinases altered in recurrent atypical meningioma. Kinomic Profiles could be used to identify prognostic biomarkers for responders/non-responders to classify future patients that are unlikely to benefit from current therapies. Directly these results could be used to identify drug-actionable kinase targets as well. Methods Peptide-substrate microarray kinase activity analysis was conducted with a PamStation®12 analyzing the tyrosine kinome in each tumor kinetically against ~144 target peptides. These data were then analyzed relative to clinical outcome (e.g., tumor recurrence). Results 3 major clusters of atypical meningiomas were identified with highly variant peptides primarily being targets of EGFR family, ABL, BRK and BMX kinases. Kinomic analysis of recurrent atypical meningiomas indicated patterns of increased phosphorylation of BMX, TYRO3 and FAK substrates as compared to non-recurrent tumors. Conclusion The atypical meningiomas profiled here exhibited molecular sub-clustering that may have phenotypic corollaries predictive of outcome. Recurrent tumors had increases in kinase activity that may predict resistance to current therapies, and may guide selection of directed therapies. Taken together these data further the understanding of kinomic alteration in atypical meningioma, and the processes that may not only mediate recurrence, but additionally may identify kinase targets for intervention. PMID:27158663

  11. Pharmacogenetics of antipsychotic treatment response and side effects

    PubMed Central

    Mackenzie, B; Souza, RP; Likhodi, O; Tiwari, AK; Zai, CC; Sturgess, J

    2011-01-01

    Antipsychotic drugs are particularly interesting in pharmacogenetic studies as they are associated with a large interindividual variability in terms of response and side effects and, therefore, frequently need to be discontinued, requiring switches to other antipsychotics. Any information that allows the prediction of outcome to a given antipsychotic in a particular patient will, therefore, be of great help for the clinician to minimize time and find the right drug for the right patient, thus optimizing response and minimizing side effects. This will also have a substantial impact on compliance and doctor–patient relationships. Moreover, antipsychotic drug treatments are often required for life-long treatment and are also frequently prescribed to the more ‘vulnerable’ populations: children, adolescents and the elderly. This article focuses on some important studies performed with candidate gene variants associated with antipsychotic response. In addition, important findings in pharmacogenetic studies of antipsychotic-induced side effects will be briefly summarized, such as antipsychotic treatment induced tardive dyskinesia and weight gain. PMID:22287936

  12. Interventional trials in atypical parkinsonism.

    PubMed

    Eschlböck, S; Krismer, F; Wenning, G K

    2016-01-01

    Atypical parkinson disorders (APD) are rapidly progressive neurodegenerative diseases with a variable clinical presentation that may even mimic Parkinson's disease. Multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are commonly summarized under this umbrella term. Significant developments in research have expanded knowledge and have broadened available symptomatic treatments, particularly for the treatment of neurogenic orthostatic hypotension. Nonetheless, symptomatic support still remains limited in all of these disorders. Currently, there exists no effective treatment to delay disease progression and disease-modifying trials have failed to provide coherent and convincing results. Recent trials of rasagiline (in MSA), rifampicin (in MSA), tideglusib (in PSP) and davunetide (in PSP) reported negative results. Nevertheless, large cohorts of patients were recruited for interventional studies in the last few years which improved our understanding of trial methodology in APDs immensely. In addition, remarkable progress in basic research has been reported recently and will provide a solid foundation for future therapeutic trials. In this review, we will summarize published randomized, placebo-controlled clinical trials (RCTs) in APDs. Additionally, the design of ongoing and unpublished interventions will be presented.

  13. Nonlinear parameters of surface EMG in schizophrenia patients depend on kind of antipsychotic therapy

    PubMed Central

    Meigal, Alexander Yu.; Miroshnichenko, German G.; Kuzmina, Anna P.; Rissanen, Saara M.; Georgiadis, Stefanos D.; Karjalainen, Pasi A.

    2015-01-01

    We compared a set of surface EMG (sEMG) parameters in several groups of schizophrenia (SZ, n = 74) patients and healthy controls (n = 11) and coupled them with the clinical data. sEMG records were quantified with spectral, mutual information (MI) based and recurrence quantification analysis (RQA) parameters, and with approximate and sample entropies (ApEn and SampEn). Psychotic deterioration was estimated with Positive and Negative Syndrome Scale (PANSS) and with the positive subscale of PANSS. Neuroleptic-induced parkinsonism (NIP) motor symptoms were estimated with Simpson-Angus Scale (SAS). Dyskinesia was measured with Abnormal Involuntary Movement Scale (AIMS). We found that there was no difference in values of sEMG parameters between healthy controls and drug-naïve SZ patients. The most specific group was formed of SZ patients who were administered both typical and atypical antipsychotics (AP). Their sEMG parameters were significantly different from those of SZ patients taking either typical or atypical AP or taking no AP. This may represent a kind of synergistic effect of these two classes of AP. For the clinical data we found that PANSS, SAS, and AIMS were not correlated to any of the sEMG parameters. Conclusion: with nonlinear parameters of sEMG it is possible to reveal NIP in SZ patients, and it may help to discriminate between different clinical groups of SZ patients. Combined typical and atypical AP therapy has stronger effect on sEMG than a therapy with AP of only one class. PMID:26217236

  14. Atypical hemolytic uremic syndrome

    PubMed Central

    2011-01-01

    Hemolytic uremic syndrome (HUS) is defined by the triad of mechanical hemolytic anemia, thrombocytopenia and renal impairment. Atypical HUS (aHUS) defines non Shiga-toxin-HUS and even if some authors include secondary aHUS due to Streptococcus pneumoniae or other causes, aHUS designates a primary disease due to a disorder in complement alternative pathway regulation. Atypical HUS represents 5 -10% of HUS in children, but the majority of HUS in adults. The incidence of complement-aHUS is not known precisely. However, more than 1000 aHUS patients investigated for complement abnormalities have been reported. Onset is from the neonatal period to the adult age. Most patients present with hemolytic anemia, thrombocytopenia and renal failure and 20% have extra renal manifestations. Two to 10% die and one third progress to end-stage renal failure at first episode. Half of patients have relapses. Mutations in the genes encoding complement regulatory proteins factor H, membrane cofactor protein (MCP), factor I or thrombomodulin have been demonstrated in 20-30%, 5-15%, 4-10% and 3-5% of patients respectively, and mutations in the genes of C3 convertase proteins, C3 and factor B, in 2-10% and 1-4%. In addition, 6-10% of patients have anti-factor H antibodies. Diagnosis of aHUS relies on 1) No associated disease 2) No criteria for Shigatoxin-HUS (stool culture and PCR for Shiga-toxins; serology for anti-lipopolysaccharides antibodies) 3) No criteria for thrombotic thrombocytopenic purpura (serum ADAMTS 13 activity > 10%). Investigation of the complement system is required (C3, C4, factor H and factor I plasma concentration, MCP expression on leukocytes and anti-factor H antibodies; genetic screening to identify risk factors). The disease is familial in approximately 20% of pedigrees, with an autosomal recessive or dominant mode of transmission. As penetrance of the disease is 50%, genetic counseling is difficult. Plasmatherapy has been first line treatment until presently

  15. Pharmacology of new antipsychotic drugs: are they stabilizers of schizophrenic psychosis?

    PubMed

    Jolliet, P; Bourin, M

    1998-12-01

    Antipsychotic drugs with greater efficacy and tolerance have been sought and studied in recent years. Some of them could be used in new treatment strategies to replace the D(2) receptor antagonism induced by classic neuroleptics such as haloperidol. The development strategies in this field are not only focused on discovering specific antagonists of one subtype of dopaminergic receptor, but on the synthesis of molecules having different effects on different brain areas. Drugs with limbic and frontal cortex specificity are associated with improved tolerance, increased efficacy against negative symptoms and a higher quality of life for patients. Furthermore, some investigation is being made into the possibility of alternatives to the dopaminergic system as a target for antipsychotics. Serotonergic antagonists and alpha-adrenoceptor antagonists, for example, are also being considered as potential options in the treatment of mental diseases such as schizophrenia.

  16. Transpupillary thermotherapy for atypical central serous chorioretinopathy

    PubMed Central

    Kawamura, Ryosuke; Ideta, Hidenao; Hori, Hideyuki; Yuki, Kenya; Uno, Tsuyoshi; Tanabe, Tatsurou; Tsubota, Kazuo; Kawasaki, Tsutomu

    2012-01-01

    Background Central serous chorioretinopathy (CSC) has been traditionally treated with laser photocoagulation. We thought that transpupillary thermotherapy (TTT) utilizing a lower temperature than that of conventional laser photocoagulation might minimize permanent retinal and choroidal damage. Studies suggest that undesirable effects on vision due to TTT are minimal even if it is applied to foveal and/or parafoveal lesions when TTT requires a larger irradiation spot. The aim of this study was to evaluate the efficacy of TTT in the management of atypical CSC. Methods We defined atypical CSC as bullous retinal detachment with diffuse or several leakages, severe leakage with fibrin formation under serous retinal detachment, or leakage within a pigment epithelium detachment. Eight consecutive patients with atypical CSC underwent visual acuity testing, ophthalmic examination, color photography, fluorescein angiography, and optical coherence tomography to evaluate the results of transpupillary thermotherapy. Retreatment of atypical CSC was based on ophthalmic examination, optical coherence tomography, and fluorescein angiography. TTT was performed on the leaking spots shown in fluorescein angiography, with a power of 50–250 mW, spot size of 500–1200 μm, and exposure time of 13–60 seconds to minimize retinal damage. Results In five of eight affected eyes, serous detachments completely resolved within 1 month after the initial TTT. One eye had persistent subretinal fluid and required a second TTT treatment. Two eyes showed no resolution of CSC and were treated by conventional photocoagulation. Initial best-corrected visual acuity (BCVA) ranged from 20/600 to 20/20 (mean, 20/40; median, 20/30). Final BCVA ranged from 20/200 to 20/20 (mean, 20/25; median, 20/20). BCVA improved in all cases. Only two eyes with persistent subretinal fibrin and existing retinal pigment epithelial alternations in macular area showed limited improvement of BCVA despite the absence of

  17. The Potential Role of Long-acting Injectable Antipsychotics in People with Schizophrenia and Comorbid Substance Use

    PubMed Central

    Koola, Maju Mathew; Wehring, Heidi J.; Kelly, Deanna L.

    2012-01-01

    Objective Treatment of schizophrenia in patients with comorbid substance use (alcohol/illicit drug use, abuse or dependence) presents challenges for public health systems. Substance use in people with schizophrenia is up to four times greater than the general population and is associated with medication nonadherence and poor outcomes. Therefore, continuous antipsychotic treatment in this population may pose more of a challenge than for those with schizophrenia alone. Many clinical trials and treatment recommendations in schizophrenia do not take into consideration substance use as people with comorbid substance use have typically been excluded from most antipsychotic trials. Nonetheless, antipsychotic treatment appears to be as efficacious in this population, although treatment discontinuation remains high. The objective of this review was to highlight the importance and utility of considering long-acting injectable antipsychotics for patients with schizophrenia and comorbid substance use. Methods We did a literature search using PubMed with key words schizophrenia and substance use/abuse/dependence, nonadherence, antipsychotics, long acting injectables, relapse, and psychosocial interventions. We limited our search to human studies published in English and 4,971 articles were identified. We focused on clinical trials, case reports, case series, reviews and meta-analyses resulting in 125 articles from 1975-2011. Results Our review suggests the potential role of long-acting injectables for people with comorbid substance use and schizophrenia in leading to improvements in psychopathology, relapse prevention, fewer rehospitalizations, and better outcomes. Conclusions While more research is needed, long-acting antipsychotics should be considered an important option in the management of people with schizophrenia and comorbid substance use. PMID:22754405

  18. Antidepressants but not antipsychotics have antiepileptogenic effects with limited effects on comorbid depressive-like behaviour in the WAG/Rij rat model of absence epilepsy

    PubMed Central

    Citraro, Rita; Leo, Antonio; De Fazio, Pasquale; De Sarro, Giovambattista; Russo, Emilio

    2015-01-01

    Background and Purpose Two of the most relevant unmet needs in epilepsy are represented by the development of disease-modifying drugs able to affect epileptogenesis and/or the study of related neuropsychiatric comorbidities. No systematic study has investigated the effects of chronic treatment with antipsychotics or antidepressants on epileptogenesis. However, such drugs are known to influence seizure threshold. Experimental Approach We evaluated the effects of an early long-term treatment (ELTT; 17 weeks), started before seizure onset (P45), with fluoxetine (selective 5-HT-reuptake inhibitor), duloxetine (dual-acting 5-HT-noradrenaline reuptake inhibitor), haloperidol (typical antipsychotic drug), risperidone and quetiapine (atypical antipsychotic drugs) on the development of absence seizures and comorbid depressive-like behaviour in the WAG/Rij rat model. Furthermore, we studied the effects of these drugs on established absence seizures in adult (6-month-old) rats after a chronic 7 weeks treatment. Key Results ELTT with all antipsychotics did not affect the development of seizures, whereas, both ELTT haloperidol (1 mg·kg−1 day−1) and risperidone (0.5 mg·kg−1 day−1) increased immobility time in the forced swimming test and increased absence seizures only in adult rats (7 weeks treatment). In contrast, both fluoxetine (30 mg·kg−1 day−1) and duloxetine (10–30 mg·kg−1 day−1) exhibited clear antiepileptogenic effects. Duloxetine decreased and fluoxetine increased absence seizures in adult rats. Duloxetine did not affect immobility time; fluoxetine 30 mg·kg−1 day−1 reduced immobility time while at 10 mg·kg−1 day−1 an increase was observed. Conclusions and Implications In this animal model, antipsychotics had no antiepileptogenic effects and might worsen depressive-like comorbidity, while antidepressants have potential antiepileptogenic effects even though they have limited effects on comorbid depressive-like behaviour. PMID

  19. The Mentally Restored Client on Antipsychotic Medication: Counselor Considerations.

    ERIC Educational Resources Information Center

    Schlenoff, David

    1979-01-01

    The article addresses the role of the rehabilitation counselor in assisting the discharged psychiatric patient on maintenance doses of antipsychotic medication. Suggestions are offered to the counselor to help maintain the client outside the hospital setting. (Author/PHR)

  20. Sudden cardiac death secondary to antidepressant and antipsychotic drugs

    PubMed Central

    Sicouri, Serge; Antzelevitch, Charles

    2008-01-01

    A number of antipsychotic and antidepressant drugs are known to increase the risk of ventricular arrhythmias and sudden cardiac death. Based largely on a concern over QT prolongation and the development of life-threatening arrhythmias, a number of antipsychotic drugs have been temporarily or permanently withdrawn from the market or their use restricted. Some antidepressants and antipsychotics have been linked to QT prolongation and the development of Torsade de pointes arrhythmias, whereas others have been associated with a Brugada syndrome phenotype and the development of polymorphic ventricular arrhythmias. This review examines the mechanisms and predisposing factors underlying the development of cardiac arrhythmias, and sudden cardiac death, associated with antidepressant and antipsychotic drugs in clinical use. PMID:18324881

  1. Mirtazapine improves visual hallucinations in Parkinson's disease: a case report.

    PubMed

    Tagai, Kenji; Nagata, Tomoyuki; Shinagawa, Shunichiro; Tsuno, Norifumi; Ozone, Motohiro; Nakayama, Kazuhiko

    2013-06-01

    Psychotic symptoms often occur as a complication in Parkinson's disease patients, and a set of criteria for Parkinson's disease with psychosis (PDPsy) has been established. Among these criteria, hallucinations are one of the specific symptoms, with visual hallucinations being the most common. While atypical antipsychotic agents are often used for the treatment of PDPsy, adverse effects, including extrapyramidal symptoms, often hinder its continuation or tolerance. There have been some reports and reviews indicating that antidepressants may be effective for PDPsy and other forms of dementia with psychosis. In this report, we present a patient with PDPsy who was treated with one of the new-generation antidepressants, mirtazapine. Mirtazapine improved the patient's refractory psychotic symptoms, especially her visual hallucinations, without worsening her motor symptoms.

  2. Antipsychotic Induced Symptomatic Hyperprolactinemia: Are Dopamine Agonists Safe?

    PubMed Central

    Lertxundi, Unax; Domingo-Echaburu, Saioa; Peral, Javier; García, Montserrat

    2011-01-01

    Published literature shows that dopamine agonists can reverse antipsychotic-induced hyperprolactinemia without worsening psychotic symptoms in the majority of schizophrenic patients. However, psychiatrists have been reluctant to use drugs with dopaminergic properties for fear of exacerbating psychiatric symptoms. There are reported cases of psychosis worsening published for both cabergoline and bromocriptine. Cabergoline has proven to be more effective and safe when used to treat hyperprolactinemia, but whether cabergoline is also safer than bromocriptine in antipsychotic induced hyperprolactinemia remains unproven.

  3. Behavioral Weight Loss Treatment in Antipsychotic Treated Youth

    PubMed Central

    Nicol, Ginger E.; Kolko, Rachel P.; Mills, Monica; Gunnarsdottir, Thrudur; Yingling, Michael D.; Schweiger, Julia A.; Lenze, Eric J.; Newcomer, John W.; Wilfley, Denise

    2016-01-01

    Background Antipsychotic-treated youth have increased risk for the development of obesity and type 2 diabetes. Behavioral weight loss treatments show promise in reducing obesity and diabetes risk in antipsychotic treated adults, but have received no study in antipsychotic treated youth. Objective We describe a rationale for behavioral weight loss interventions in high-weight antipsychotic treated youth, and report behavioral, anthropomorphic, and metabolic findings from a case series of obese antipsychotic-treated adolescents participating in a short-term, family-based behavioral weight loss intervention. Methods We adapted the Traffic Light Plan, a 16-week family-based weight loss intervention that promotes healthy energy balance using the colors of the traffic light to categorize the nutritional value of foods and intensity of physical activity, adapting a social ecological framework to address health behavior change in multiple social contexts. The intervention was administered to three obese adolescents with long-term antipsychotic medication exposure. Efficacy of the intervention was evaluated with a battery of anthropomorphic and metabolic assessments including weight, body mass index percentile, whole body adiposity, liver fat content, and fasting plasma glucose and lipids. Participants and their parents also filled out a treatment satisfaction questionnaire upon study completion. Results Two males and 1 female (all aged 14 years) participated. All 3 participants attended all 16 sessions, and experienced beneficial changes in adiposity, fasting lipids and liver fat content associated with weight stabilization or weight loss. Adolescents and their parents all reported a high level of satisfaction with the treatment. Conclusions Family-based behavioral weight loss treatment can be feasibly delivered and is acceptable to antipsychotic-treated youth and their families. Randomized controlled trials are needed to fully evaluate the effectiveness and acceptability

  4. Update on the right to refuse antipsychotic medication.

    PubMed

    Williams, Karl G

    1991-01-01

    The legal history and current developments in the right to refuse antipsychotic medication are reviewed. In Washington v. Harper the US Supreme Court analyzed the right to refuse antipsychotic medication under the due process clause of the Fourteenth Amendment to the US Constitution. A narrow issue was clarified but substantial uncertainty remains. As a result, law and policy problems at both state and institutional levels have become evident and may need to be addressed by drug policy decision makers. PMID:11659419

  5. Atypical Cutaneous Manifestations in Syphilis.

    PubMed

    Ivars Lleó, M; Clavo Escribano, P; Menéndez Prieto, B

    2016-05-01

    Although the diversity of the clinical manifestations of syphilis is well-known, atypical presentations can also occur. Such atypical presentations are associated with a high risk of transmission as a result of diagnostic confusion and treatment delays owing to the disease's ability to mimic other common skin diseases, deviate from classic clinical presentations, and adopt unique forms. Cases of atypical syphilis have been described most frequently in patients with concomitant human immunodeficiency virus (HIV) infection. Because the incidence of syphilis has been growing over recent years -particularly in patients with HIV co-infection- dermatologists need to be familiar with the less well-known clinical presentations of this venereal disease. PMID:26708562

  6. Secondary Effects of Antipsychotics: Women at Greater Risk Than Men

    PubMed Central

    Seeman, Mary V.

    2009-01-01

    Context: The health burden of antipsychotic medication is well known, but the disproportionate effect on women as compared with men is underappreciated. Objective: The goal of this article is preventive—to better inform clinicians so that the risks to women and to their offspring can be diminished. Method: All PubMed sources in which the search term gender (or sex) was linked to a side effect of antipsychotic medication were reviewed. Result: There is general agreement in the literature on women's increased susceptibility to weight gain, diabetes, and specific cardiovascular risks of antipsychotics, with less consensus on malignancy risks and risks to the fetus. Cardiovascular death, to which men are more susceptible than women, is disproportionately increased in women by the use of antipsychotics. Sedating antipsychotics raise the risk of embolic phenomena during pregnancy, and postpartum. Prolactin-elevating drugs suppress gonadal hormone secretion and may enhance autoimmune proclivity. Conclusions: Clinicians need to be aware of the differential harm that women (and their offspring) can incur from the side effects of antipsychotics. PMID:18400811

  7. Designing naturalistic prospective studies of economic and effectiveness outcomes associated with novel antipsychotic therapies.

    PubMed

    Tunis, S L; Johnstone, B M; Kinon, B J; Barber, B L; Browne, R A

    2000-01-01

    The cornerstone of recent pharmacoeconomic work in schizophrenia is the hypothesis that the improved efficacy of novel antipsychotic medications will lead to a reduction in medical services utilization, thereby reducing direct medical costs associated with treatment. Creating the most valid design to prospectively examine the effectiveness and costs of competing pharmacotherapies requires a dialectic of opposing research paradigms. The final protocol must represent a series of decisions that strike a careful balance between being scientifically sound (internal validity) and generalizable to the real world of clinical treatment (external validity). The results must be useful to decision-makers in determining to what extent reductions in healthcare expenditures can offset higher drug acquisition costs within their type of treatment environment. This article is a review of several methodological challenges in the design of medical effectiveness trials, including whether to blind the study, definition of the patient population, degree of physician discretion in treatment, and how to collect and analyze data for patients who discontinue their originally assigned medication. The article also provides a discussion of how clinical practices can inform decisions made to meet these challenges. The issues are illustrated through a prospective study designed to evaluate the cost-effectiveness of the newer antipsychotics in general and olanzapine in particular. Cost-effectiveness studies of novel antipsychotic medications, particularly those with naturalistic designs, will increase in importance as the use of these second-generation agents continues to expand.

  8. Weight Maintenance Following the STRIDE Weight Loss and Lifestyle Intervention for Individuals taking Antipsychotic Medications

    PubMed Central

    Green, Carla A.; Yarborough, Bobbi Jo H.; Leo, Michael C.; Stumbo, Scott P.; Perrin, Nancy A.; Nichols, Gregory A.; Stevens, Victor J.

    2015-01-01

    Objective Individuals taking antipsychotic medications have increased risk of obesity-related early morbidity/mortality. This report presents weight maintenance results from a successful weight loss and behavioral lifestyle change program developed for people taking antipsychotic medications. Design and Methods STRIDE was a 2-arm, randomized controlled trial. Intervention participants attended weekly group meetings for 6 months, then monthly group meetings for 6 months. Assessments were completed at baseline, 6, 12, and 24 months. Results At 24-months, intervention participants lost 3.7% of baseline weight and control participants 2.1%, a non-significant difference. Fasting glucose results followed a similar pattern. There was a statistically significant difference, however, for fasting insulin—the intervention group’s levels decreased between the end of the intensive intervention (at 6 months) and 24 months (10.1 to 7.91μU/mL); control participants’ levels increased (11.66 to 12.92μU/mL) during this period. There were also fewer medical hospitalizations among intervention participants (5.7%) than controls (21.1%; Χ2=8.47, p=0.004) during the 12 to 24-month post-intervention maintenance period. Conclusions Weight-change differences between arms diminished following the intervention period, though fasting insulin levels continued to improve. Reduced hospitalizations suggest that weight loss, even with regain, may have long-term positive benefits for people taking antipsychotic medications and may reduce costs. PMID:26334929

  9. Metacognitive therapy (MCT+) in patients with psychosis not receiving antipsychotic medication: A case study

    PubMed Central

    Balzan, Ryan P.; Galletly, Cherrie

    2015-01-01

    Background: Psychotherapies for psychosis typically aim to develop an awareness of the implausible content of a delusion or target the underlying cognitive biases (i.e., problematic thinking styles, such as hasty decisions and illusory control) that foster and maintain delusional beliefs. A recently designed individual-based treatment entitled metacognitive therapy (MCT+) combines these two approaches. Emerging evidence suggests individualized MCT+, when used concurrently with antipsychotic medication, may be an effective psychological treatment for reducing delusional symptoms. However, it remains to be tested whether MCT+ can be effective in patients with active delusions who are not currently receiving psychotropic drugs. Method: We present two cases (one patient with schizophrenia and the other with delusional disorder) experiencing active delusions who underwent 4-weeks of intensive MCT+, without concurrent antipsychotic medication (minimum 6-months unmedicated). Baseline and 6-week follow-up data are presented on a variety of measures assessing delusion symptom severity (i.e., PANSS, PSYRATS, SAPS), clinical insight, and cognitive bias propensity. Results: After 4-weeks of MCT+, both patients showed substantial reduction in delusional symptoms, reported improved clinical insight, and were less prone to making illusory correlations. Conclusions: The presented case studies provide preliminary evidence for the feasibility of MCT+ in treating patients not taking, or resistant to, antipsychotic medication. PMID:26217283

  10. A systematic review of factors influencing adherence to antipsychotic medication in schizophrenia-spectrum disorders.

    PubMed

    Sendt, Kyra-Verena; Tracy, Derek Kenneth; Bhattacharyya, Sagnik

    2015-01-30

    Adherence to antipsychotics improves outcome in schizophrenia. There is a lack of consensus on which factors most influence adherence behaviour and methodological issues hinder interpretation of existing evidence. A rigorous systematic search designed to identify robustly implicated factors emerging from methodologically rigorous studies narrowed our search to 13 observational studies (total N=6235) relating to adherence, antipsychotics and schizophrenia. Studies varied significantly, with reported adherence rates ranging from 47.2% to 95%. Positive attitude to medication and illness insight were the only factors consistently associated with better adherence, while contradictory results were found for socio-demographic characteristics, symptom severity and side effects. Only distinct aspects of the therapeutic relationship and social support in younger patients were related to good adherence. Antipsychotic type or formulation and neurocognitive functioning did not appear to impact medication adherence. Despite greater methodological rigour in determining studies to include in the present systematic review, it remains difficult to guide clinicians in this vital area and most of the work discussed contained small sample sizes. Future research in this field should therefore prioritise prospective study designs over longer periods and larger samples in naturalistic settings, providing a more appropriate and clinically meaningful framework than widely used cross-sectional designs.

  11. [Pathogenesis of atypical femoral fracture].

    PubMed

    Iwata, Ken; Mashiba, Tasuku

    2016-01-01

    We demonstrated microdamage accumulation in the fracture sites in the patients of subtrochanteric atypical femoral fracture with long term bisphosphonate therapy and of incomplete shaft fracture of lateral femoral bowing without bisphosphonate therapy. Based on these findings, pathogenesis of atypical femoral fracture is revealed stress fracture caused by accumulation of microdamages between distal to the lesser trochanter and proximal to the supracondylar flare in the femur in association with severely suppressed bone turnover and/or abnormal lower limb alignment, that causes stress concentration on the lateral side cortex of the femur. PMID:26728533

  12. Mobile phone text message reminders of antipsychotic medication: is it time and who should receive them? A cross-sectional trust-wide survey of psychiatric inpatients

    PubMed Central

    2014-01-01

    Background Poor adherence to antipsychotic medication is a widespread problem, and the largest predictor of relapse in patients with psychosis. Electronic reminders are increasingly used to improve medication adherence for a variety of medical conditions, but have received little attention in the context of psychotic disorders. We aimed to explore the feasibility and acceptability of including short message service (SMS) medication reminders in the aftercare plan of service users discharged from inpatient care on maintenance antipsychotic medication. Methods We conducted a cross-sectional, trust-wide survey in the inpatient units of the Oxleas National Health Service (NHS) Foundation Trust in the UK between June 29 and August 3, 2012. Using a self-report questionnaire and the Drug Attitude Inventory, we examined inpatient attitudes towards antipsychotic drugs, past adherence to antipsychotic medication, frequency of mobile phone ownership, and interest in receiving SMS medication reminders upon discharge from the ward. Predictors of a patient’s interest in receiving electronic reminders were examined using simple logistic regression models. Results Of 273 inpatients, 85 met eligibility criteria for the survey, showed decisional capacity, and agreed to participate. Of the 85 respondents, over a third (31-35%) admitted to have forgotten to take/collect their antipsychotic medication in the past, and approximately half (49%) to have intentionally skipped their antipsychotics or taken a smaller dose than prescribed. Male patients (55%), those with negative attitudes towards antipsychotics (40%), and those unsatisfied with the information they received on medication (35%) were approximately 3 to 4 times more likely to report past intentional poor adherence. The large majority of respondents (80-82%) reported having a mobile phone and knowing how to use SMS, and a smaller majority (59%) expressed an interest in receiving SMS medication reminders after discharge. No

  13. Development of a Web-Based Clinical Decision Support System for Drug Prescription: Non-Interventional Naturalistic Description of the Antipsychotic Prescription Patterns in 4345 Outpatients and Future Applications

    PubMed Central

    Berrouiguet, Sofian; Barrigón, Maria Luisa; Brandt, Sara A.; Ovejero-García, Santiago; Álvarez-García, Raquel; Carballo, Juan Jose; Lenca, Philippe; Courtet, Philippe; Baca-García, Enrique

    2016-01-01

    Purpose The emergence of electronic prescribing devices with clinical decision support systems (CDSS) is able to significantly improve management pharmacological treatments. We developed a web application available on smartphones in order to help clinicians monitor prescription and further propose CDSS. Method A web application (www.MEmind.net) was developed to assess patients and collect data regarding gender, age, diagnosis and treatment. We analyzed antipsychotic prescriptions in 4345 patients attended in five Psychiatric Community Mental Health Centers from June 2014 to October 2014. The web-application reported average daily dose prescribed for antipsychotics, prescribed daily dose (PDD), and the PDD to defined daily dose (DDD) ratio. Results The MEmind web-application reported that antipsychotics were used in 1116 patients out of the total sample, mostly in 486 (44%) patients with schizophrenia related disorders but also in other diagnoses. Second generation antipsychotics (quetiapine, aripiprazole and long-acting paliperidone) were preferably employed. Low doses were more frequently used than high doses. Long acting paliperidone and ziprasidone however, were the only two antipsychotics used at excessive dosing. Antipsychotic polypharmacy was used in 287 (26%) patients with classic depot drugs, clotiapine, amisulpride and clozapine. Conclusions In this study we describe the first step of the development of a web application that is able to make polypharmacy, high dose usage and off label usage of antipsychotics visible to clinicians. Current development of the MEmind web application may help to improve prescription security via momentary feedback of prescription and clinical decision support system. PMID:27764107

  14. Antipsychotics differ in their ability to internalise human dopamine D2S and human serotonin 5-HT1A receptors in HEK293 cells.

    PubMed

    Heusler, Peter; Newman-Tancredi, Adrian; Loock, Timothé; Cussac, Didier

    2008-02-26

    Antipsychotic drugs act preferentially via dopamine D(2) receptor blockade, but interaction with serotonin 5-HT(1A) receptors has attracted interest as additional target for antipsychotic treatment. As receptor internalisation is considered crucial for drug action, we tested the propensity of antipsychotics to internalise human (h)D(2S) receptors and h5-HT(1A) receptors. Agonist-induced internalisation of hemaglutinin (HA)-tagged hD(2S) and HA-h5-HT(1A) receptors expressed in HEK293 cells was increased by coexpression of G-protein coupled receptor kinase 2 and beta-arrestin2. At the HA-hD(2S) receptor, dopamine, quinpirole and bromocriptine behaved as full agonists, while S(-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine [(-)-3PPP] and sarizotan were partial agonists. The typical antipsychotic, haloperidol, and the atypical compounds, olanzapine, nemonapride, ziprasidone and clozapine did not internalise HA-hD(2S) receptors, whereas aripiprazole potently internalised these receptors (>50% relative efficacy). Among antipsychotics with combined D(2)/5-HT(1A) properties, bifeprunox and (3-exo)-8-benzoyl-N-[[(2S)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl]methyl]-8-azabicyclo-[3.2.1]octane-3-methanamine (SSR181507) partially internalised HA-hD(2S) receptors, piperazine, 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-[[5-(4-fluorophenyl)-3-pyridinyl]methyl (SLV313) and N-[(2,2-dimethyl-2,3-dihydro-benzofuran-7-yloxy)ethyl]-3-(cyclopent-1-enyl)-benzylamine (F15063) were inactive. At the HA-h5-HT(1A) receptor, serotonin, (+)-8-hydroxy-2-(di-n-propylamino)tetralin [(+)-8-OH-DPAT] and sarizotan were full agonists, buspirone acted as partial agonist. (-)-Pindolol showed little activity and no internalising properties were manifested for the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY100635). Most antipsychotics induced HA-h5-HT(1A) receptor internalisation, with an efficacy rank order: nemonapride>F15063>SSR181507

  15. Effect of antipsychotic medication on overall life satisfaction among individuals with chronic schizophrenia: findings from the NIMH CATIE study.

    PubMed

    Fervaha, Gagan; Agid, Ofer; Takeuchi, Hiroyoshi; Foussias, George; Remington, Gary

    2014-07-01

    The field of schizophrenia is redefining optimal outcome, moving beyond clinical remission to a more comprehensive model including functional recovery and improved subjective well-being. Although numerous studies have evaluated subjective outcomes within the domain of subjective quality of life in patients with schizophrenia, less is known about global evaluations of subjective well-being. This study examined the effects of antipsychotic medication on overall life satisfaction in patients with chronic schizophrenia. Data were drawn from the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) study, where participants with a DSM-IV diagnosis of schizophrenia were randomized to receive olanzapine, perphenazine, quetiapine, risperidone or ziprasidone under double-blind conditions (N=753). The primary outcome measure was prospective change in subjectively evaluated overall life satisfaction scores following 12 months of antipsychotic treatment. Psychopathology, medication side effects and functional status were also evaluated, among other variables. Patients experienced modest improvements in overall life satisfaction (d=0.22, p<0.001), with no differences between antipsychotic medications (all tests, p>0.05). Change in severity of positive, negative, and depressive symptoms as well as functional status each demonstrated a small, albeit statistically significant, association with change in life satisfaction (r=0.10-0.21, p׳s<0.01). In a multivariate regression model, change in clinical symptoms and functional status had limited independent predictive value for change in life satisfaction scores (explained variance <3%). These data suggest that despite antipsychotic medications being effective for symptom-based psychopathology, such clinical effectiveness does not necessarily translate to improved general satisfaction with life. Clinicians should be aware that these two domains are not inextricably linked.

  16. Atypical moles: diagnosis and management.

    PubMed

    Perkins, Allen; Duffy, R Lamar

    2015-06-01

    Atypical moles are benign pigmented lesions. Although they are benign, they exhibit some of the clinical and histologic features of malignant melanoma. They are more common in fair-skinned individuals and in those with high sun exposure. Atypical moles are characterized by size of 6 mm or more at the greatest dimension, color variegation, border irregularity, and pebbled texture. They are associated with an increased risk of melanoma, warranting enhanced surveillance, especially in patients with more than 50 moles and a family history of melanoma. Because an individual lesion is unlikely to display malignant transformation, biopsy of all atypical moles is neither clinically beneficial nor cost-effective. The ABCDE (asymmetry, border irregularity, color unevenness, diameter of 6 mm or more, evolution) mnemonic is a valuable tool for clinicians and patients to identify lesions that could be melanoma. Also, according to the "ugly duckling" concept, benign moles tend to have a similar appearance, whereas an outlier with a different appearance is more likely to be undergoing malignant change. Atypical moles with changes suggestive of malignant melanoma should be biopsied, using an excisional method, if possible.

  17. Atypical SARS in Geriatric Patient

    PubMed Central

    Oh, Helen M.L.; Hui, K.P.; Lien, Christopher T.C.; Narendran, K.; Heng, B.H.; Ling, A.E.

    2004-01-01

    We describe an atypical presentation of severe acute respiratory syndrome (SARS) in a geriatric patient with multiple coexisting conditions. Interpretation of radiographic changes was confounded by cardiac failure, with resolution of fever causing delayed diagnosis and a cluster of cases. SARS should be considered even if a contact history is unavailable, during an ongoing outbreak. PMID:15030694

  18. Cholecystokinin appears to have antipsychotic properties.

    PubMed

    Nair, N P; Bloom, D M; Nestoros, J N

    1982-01-01

    1. According to a currently popular biological hypothesis schizophrenic symptoms are caused by a hyperactivity in dopaminergic neurotransmission. Since cholecystokinin (CCK) is a neuromodulator of dopaminergic neurotransmission, the effects of CCK (0.3 microgram/kg; given in a single dose intravenously) were studied in six chronic paranoid schizophrenic patients. 2. Following 3 baseline assessments on separate days, the effects of CCK treatment were assessed immediately after the injection, daily for one week and weekly thereafter for 5 weeks by the Brief Psychiatric Rating Scale (BPRS) and by the Schizophrenia Subscale of the Present State Examination (SS-PSE). 3. One way analysis of variance revealed statistically significant changes in all BPRS factors as well as in the nuclear syndrome and in the total score of the SS-PSE. Dunnett's tests revealed that the time at which the changes from baseline became statistically significant was as follows: anxiety-depression factor of the BPRS, immediately after the injection; anergia factor of the BPRS, by day 2; thought disturbance factor of the BPRS, immediately after; activation factor of the BPRS, immediately after; hostile-suspiciousness factor of the BPRS, by day 1; total BPRS score, immediately after; nuclear syndrome of the SS-PSE, by day 1; and total score of the SS-PSE, by day 1. 4. It is concluded that further controlled studies of the antipsychotic properties of CCK are warranted. PMID:6891817

  19. Pharmacogenetics of antipsychotic-induced side effects

    PubMed Central

    Lencz, Todd; Malhotra, Anil K.

    2009-01-01

    Currently available antipsychotic drugs (APDs) carry significant, though highly variable, liability to neurologic and metabolic side effects. Pharmacogenetics approaches offer the possibility of identifying patient-specific biomarkers for predicting risk of these side effects. To date, a few single nucleotide polymorphisms (SNPs) in a handful of genes have received convergent support across multiple studies. The primary focus has been on SNPs in dopamine and serotonin receptor genes: persuasive meta-analytic evidence exists for an effect of the dopamine D2 and D3 receptor genes (DRD2 and DRD3) in risk for tardr inesia (TD) and for an effect of variation at the receptor gene (HTR2C) for liability to APD-inducec gain. However, effect sizes appear to be modest, and pharmacoeconomic considerations have not been sufficiently studied, thereby limiting clinical applicability at this time. Effects of these genes and others on risk for TD, extrapyramidal side effects, hyperprolactinemia, and weight gain are revieved in this article. PMID:20135898

  20. Emergency Department Visits Involving Misuse and Abuse of the Antipsychotic Quetiapine: Results from the Drug Abuse Warning Network (DAWN).

    PubMed

    Mattson, Margaret E; Albright, Victoria A; Yoon, Joanna; Council, Carol L

    2015-01-01

    Case reports in medical literature suggest that the atypical antipsychotic quetiapine, a medication not previously considered to have abuse potential, is now being subject to misuse and abuse (MUA; ie, taken when not prescribed for them or used in a way other than instructed by their health professional). Here we present systematic, nationally representative data from the 2005 to 2011 Drug Abuse Warning Network (DAWN) for prevalence of emergency department (ED) visits among the U.S. general population involving quetiapine and related to MUA, suicide attempts, and adverse reactions. Nationally, quetiapine-related ED visits increased 90% between 2005 and 2011, from 35,581 ED visits to 67,497. DAWN data indicate that when used without medical supervision for recreational/self-medication purposes, quetiapine poses health risks for its users, especially among polydrug users and women. These findings suggest that the medical and public health communities should increase vigilance concerning this drug and its potential for MUA. PMID:26056465

  1. Emergency Department Visits Involving Misuse and Abuse of the Antipsychotic Quetiapine: Results from the Drug Abuse Warning Network (DAWN)

    PubMed Central

    Mattson, Margaret E; Albright, Victoria A; Yoon, Joanna; Council, Carol L

    2015-01-01

    Case reports in medical literature suggest that the atypical antipsychotic quetiapine, a medication not previously considered to have abuse potential, is now being subject to misuse and abuse (MUA; ie, taken when not prescribed for them or used in a way other than instructed by their health professional). Here we present systematic, nationally representative data from the 2005 to 2011 Drug Abuse Warning Network (DAWN) for prevalence of emergency department (ED) visits among the U.S. general population involving quetiapine and related to MUA, suicide attempts, and adverse reactions. Nationally, quetiapine-related ED visits increased 90% between 2005 and 2011, from 35,581 ED visits to 67,497. DAWN data indicate that when used without medical supervision for recreational/self-medication purposes, quetiapine poses health risks for its users, especially among polydrug users and women. These findings suggest that the medical and public health communities should increase vigilance concerning this drug and its potential for MUA. PMID:26056465

  2. Role of community pharmacists in the use of antipsychotics for behavioural and psychological symptoms of dementia (BPSD): a qualitative study

    PubMed Central

    Aston, Lydia; Hilton, Andrea; Iqbal, Naveed; Child, Anne; Shaw, Rachel

    2016-01-01

    Objective This study aimed to use qualitative methodology to understand the current role of community pharmacists in limiting the use of antipsychotics prescribed inappropriately for behavioural and psychological symptoms of dementia. Design A qualitative study employing focus groups was conducted. Data were analysed using thematic analysis. Setting 3 different geographical locations in the England. Participants Community pharmacists (n=22). Results The focus groups identified an array of factors and constraints, which affect the ability of community pharmacists to contribute to initiatives to limit the use of antipsychotics. 3 key themes were revealed: (1) politics and the medical hierarchy, which created communication barriers; (2) how resources and remit impact the effectiveness of community pharmacy; and (3) understanding the nature of the treatment of dementia. Conclusions Our findings suggest that an improvement in communication between community pharmacists and healthcare professionals, especially general practitioners (GPs) must occur in order for community pharmacists to assist in limiting the use of antipsychotics in people with dementia. Additionally, extra training in working with people with dementia is required. Thus, an intervention which involves appropriately trained pharmacists working in collaboration with GPs and other caregivers is required. Overall, within the current environment, community pharmacists question the extent to which they can contribute in helping to reduce the prescription of antipsychotics. PMID:26983947

  3. Changes in Physician Antipsychotic Prescribing Preferences, 2002–2007

    PubMed Central

    Donohue, Julie; O'Malley, A. James; Horvitz-Lennon, Marcela; Taub, Anna Levine; Berndt, Ernest; Huskamp, Haiden

    2014-01-01

    Objective Evidence on antipsychotic comparative effectiveness, regulatory warnings, and formulary and other restrictions on antipsychotics may have influenced physician prescribing behavior. This study measured changes in the degree to which physicians customize treatment choices to individual patients and changes in physician preferences for specific agents following these events. Methods The study used 2002-2007 data from IMS Health Xponent™ and the AMA on the prescribing and characteristics of a longitudinal cohort of 7,399 physicians. Descriptive and multivariable regression analyses of the concentration of prescribing (physician-level Herfindahl index), and preferences for and likelihood of prescribing 2 first-generation antipsychotics and 6 second-generation antipsychotics adjusting for prescribing volume, specialty, demographics, practice setting and education were conducted. Results Antipsychotic prescribing was highly concentrated at the physician-level, with a mean unadjusted Herfindahl index of .33 in 2002 and .29 in 2007. Psychiatrists reduced the concentration of their prescribing more over time than did other physicians. High volume psychiatrists had a Herfindahl that was half that of low-volume physicians in other specialties (.18 vs. .36), a difference that remained significant (p<.001) after adjusting for physician characteristics. The share of physicians preferring olanzapine dropped from 29.9% in 2002 to 10.3% in 2007 (p<.001) while the share favoring quetiapine increased (from 9.4% to 44.5%, p<.001). Few physicians (<5%) preferred a first-generation antipsychotic in 2002 or 2007. Conclusions Preferences for specific antipsychotics changed dramatically during this period. While physician prescribing remained heavily concentrated, it did decrease over time, particularly among psychiatrists. PMID:24337224

  4. Adherence to Antipsychotic Medication in Bipolar Disorder and Schizophrenic Patients

    PubMed Central

    García, Saínza; Martínez-Cengotitabengoa, Mónica; López-Zurbano, Saioa; Zorrilla, Iñaki; López, Purificación; Vieta, Eduard; González-Pinto, Ana

    2016-01-01

    Abstract Antipsychotics are the drugs prescribed to treat psychotic disorders; however, patients often fail to adhere to their treatment, and this has a severe negative effect on prognosis in these kinds of illnesses. Among the wide range of risk factors for treatment nonadherence, this systematic review covers those that are most important from the point of view of clinicians and patients and proposes guidelines for addressing them. Analyzing 38 studies conducted in a total of 51,796 patients, including patients with schizophrenia spectrum disorders and bipolar disorder, we found that younger age, substance abuse, poor insight, cognitive impairments, low level of education, minority ethnicity, poor therapeutic alliance, experience of barriers to care, high intensity of delusional symptoms and suspiciousness, and low socioeconomic status are the main risk factors for medication nonadherence in both types of disorder. In the future, prospective studies should be conducted on the use of personalized patient-tailored treatments, taking into account risk factors that may affect each individual, to assess the ability of such approaches to improve adherence and hence prognosis in these patients. PMID:27307187

  5. [Antipsychotics for schizophrenia: the paradigm of psychiatric drugs].

    PubMed

    Pol Yanguas, Emilio

    2015-03-01

    Antipsychotic drugs do not appear to reverse the causes of schizophrenia, and although they can relieve symptoms in the short to medium term, in the long term they may not be beneficial and could even be counterproductive. Their use should be limited to acute situations in which agitation and tension is disabling. The drugs have significant adverse effects, and given the refusal of a person to continue taking them, a harm reduction strategy to support and monitor the withdrawal may be preferable to coercion. There are alternatives to neuroleptics. Prescribers should be more vigilant and consider the assessments of users regarding the drugs' effects. Adherence to treatment guidelines is low, probably because the guidelines are based on clinical trials of deficient quality which consequently should be improved and extended over a greater period of time. The root of the problem is likely the tautology on the etiology and biological nature of what is known as schizophrenia, which in fact does not seem to be more than a commercial and ideological construct.

  6. Effects of prenatal exposure to antipsychotic risperidone on developmental neurotoxicity, apoptotic neurodegeneration and neurobehavioral sequelae in rat offspring.

    PubMed

    Singh, K P; Singh, Manoj Kr; Singh, Manish

    2016-08-01

    A tremendous increase has been documented in the recent past in prescribing second generation atypical antipsychotic drugs (AAPDs) to the pregnant women with psychosis, considering their reproductive and teratogenic safety. Among AAPDs, risperidone (RIS) ranked third after olanzapine (OLZ) and quetiapine (QUE) used during pregnancy, as OLZ is associated to substantial weight gain in adults and offspring. Although teratogenic safety of RIS has been established, its potential role in developmental neurotoxicity and related neurobehavioral impairments in adolescents has not been documented so far. Therefore, present study has been undertaken to elucidate the effect of prenatal exposure to risperidone (RIS) on developmental neurotoxicity and apoptotic neurodegeneration in neocortical region of fetal brain; and related functional sequelae in young rat offspring. The pregnant Wistar rats were exposed to RIS at 0.8, 1.0 and 2.0mg/kg, at equivalent therapeutic doses, orally from GD 6 to 21. Half of the pregnant rats were sacrificed and their brains were collected, weighed, and processed for neurohistopathological and apoptotic neurodegenerative evaluation. The remaining dams were allowed to deliver naturally, and their offspring were reared up to 10 weeks for neurobehavioral study. Prenatal exposure to RIS induced significant stunting of fetal body and brain weight, substantial reduction in the thickness of neocortical layers and apoptotic neurodegeneration in fetal brains, and delayed postnatal development and growth of the offspring; as well as long- lasting impact on anxiety like impaired behavioral responses on explorative mazes. Therefore, health care providers should be careful in prescribing atypical antipsychotics in general and RIS in particular, to the pregnant psychotic population. PMID:27184437

  7. [Obstructive sleep apnoea syndrome as the cause of atypical depression].

    PubMed

    Lang, F U; Hösch, H; Seibert, H; Klug, R; Köppler, D; Jäger, M

    2011-09-01

    Sleep apnoea is a common disorder presenting with somatic comorbidities and psychiatric symptoms. This case report describes a 43-year-old man with an organic depressive disorder due to obstructive sleep apnoea. Initially, an atypical depressive episode or schizophrenic residual syndrome had been considered likely diagnoses; subsequent polysomnography results, however, suggested obstructive sleep apnoea instead. Upon nasal continuous positive airway pressure (nCPAP), the respiratory distress symptoms improved. The case report highlights the association between sleep disturbances and depressive symptoms. In patients presenting with symptoms of atypical depression and excess body weight sleep apnoea should be considered.

  8. Effects of antipsychotic drugs on the expression of synapse-associated proteins in the frontal cortex of rats subjected to immobilization stress.

    PubMed

    Seo, Mi Kyoung; Lee, Chan Hong; Cho, Hye Yeon; You, Young Sun; Lee, Bong Ju; Lee, Jung Goo; Park, Sung Woo; Kim, Young Hoon

    2015-10-30

    The present study examined the effects of antipsychotic drugs on the expression of synapse-associated proteins in the frontal cortex of rats with and without immobilization stress. Rats were subjected to immobilization stress 6h/day for 3 weeks. The effects of atypical antipsychotic drugs, olanzapine and aripiprazole, on expression of serine(9)-phosphorylated GSK-3β, β-catenin, BDNF, PSD-95, and synaptophysin were determined by Western blotting. A typical antipsychotic drug, haloperidol, was used for comparison. Immobilization stress significantly decreased the expression of these proteins in the frontal cortex. Chronic administration of olanzapine and aripiprazole significantly attenuated the immobilization stress-induced decrease in the levels of these proteins, whereas haloperidol had no such effect. Additionally, olanzapine and aripiprazole significantly increased levels of phosphorylated GSK-3β under normal conditions without stress, and aripiprazole also increased BDNF levels under this condition. These results indicate that olanzapine and aripiprazole, and, haloperidol, differentially regulate the levels of synapse-associated proteins in the rat frontal cortex. These findings may contribute to explain the neurobiological basis of how olanzapine and aripiprazole up-regulated synapse-associated proteins. PMID:26254796

  9. Antipsychotic induced weight gain in schizophrenia:mechanisms and management.

    PubMed

    Rege, Sanil

    2008-05-01

    The aim of the present paper was to describe the mechanisms and management of antipsychotic-induced weight gain in schizophrenia patients. A comprehensive literature review of all available articles on the mechanisms and management of antipsychotic-induced weight gain was done by searching databases PsychINFO and PubMed. A summary of the available guidelines for monitoring of antipsychotic-induced weight gain and metabolic syndrome is also provided. There has been a substantial increase in the number of studies investigating the mechanisms and management of antipsychotic-induced weight gain after 2002. These include advances in the understanding of pharmacogenomics of weight gain and several randomized controlled trials (RCTs) evaluating pharmacological and psychological treatments to promote weight loss. The most effective strategy for prevention of weight gain is the choice of antipsychotic medication with low weight gain potential. In individuals with established weight gain and metabolic issues, switching to an antipsychotic agent with lower weight gain potential and/or lifestyle modifications with physical activity are most effective in promoting weight loss. Pharmacological agents such as orlistat and sibutramine are effective in general obesity but have not been sufficiently evaluated in antipsychotic-induced weight gain. The case to prescribe routine pharmacological treatment to promote weight loss is weak. Long-term, pragmatic studies are required to inform clinical practice. Weight gain in schizophrenia is associated with significant physical and psychological morbidity. Achieving an optimal trade-off between effectiveness and side-effects of antipsychotic agents, although difficult, is achievable. This should be based on three main principles: (i) a shared decision-making model between the patient, clinician and carer(s) when choosing an antipsychotic; (ii) a commitment to baseline and follow-up monitoring with explicit identification of the responsible

  10. [Clinical stakes when switching from one antipsychotic to another].

    PubMed

    Constant, É

    2013-12-01

    Switching antipsychotics is more and more common in our clinical practice. Several reasons can explain this observation. We have more and more antipsychotics available on the market with different receptor binding profiles and also different tolerability issues. Usually, the reasons of the switch are the following: insufficient efficacy or problems of tolerance (weight gain, metabolic disorders, extrapyramidal symptoms, hyperprolactinemia, sedation, sexual dysfunction). So that the switch takes place without complications, it is essential for the clinician to have full knowledge of both the receptor binding profiles of the antipsychotics in question and their half-life. The clinician has to expect a dopaminergic rebound when the introduced antipsychotic has a lesser affinity for the dopaminergic D2 receptor than that which is withdrawn or if it is a partial agonist with a particularly long half-life. On the other hand, a histaminergic or cholinergic rebound can be expected if the new antipsychotic has a lesser affinity for these two receptors. In all these scenarios, a "plateau" switch will often be recommended. Now, if a faster switch is imperative, various medication strategies exist to try to decrease the impact of the rebound effects.

  11. Hyperprolactinemia during antipsychotics treatment increases the level of coagulation markers

    PubMed Central

    Ishioka, Masamichi; Yasui-Furukori, Norio; Sugawara, Norio; Furukori, Hanako; Kudo, Shuhei; Nakamura, Kazuhiko

    2015-01-01

    Objective The strong association between psychiatric patients who receive antipsychotics and the incidence of venous thromboembolism (VTE) is known. Although previous reports suggest that hyperprolactinemia often increases markers of activated coagulation, few studies have examined the direct relationship between the prolactin level elevated by antipsychotics and activated markers of activated coagulation. Method The participants included 182 patients with schizophrenia (male =89, female =93) who received antipsychotic treatments for at least 3 months. Markers of VTE (D-dimer, fibrin/fibrinogen degradation products, and thrombin–antithrombin complex) and serum prolactin concentrations were measured. Results Prolactin levels were significantly correlated with the logarithmic transformation of the D-dimer (r=0.320, P=0.002) and fibrin/fibrinogen degradation product levels (r=0.236, P=0.026) but not of the thrombin–antithrombin complex level (r=0.117, ns) among men. However, no correlations were found between the VTE markers and prolactin levels among women. These results were confirmed using multiple regression analyses that included demographic factors and antipsychotic dosages. Conclusion The current study indicates that hyperprolactinemia is associated with an increase in markers of activated coagulation among men receiving antipsychotics. This finding clinically implies that monitoring and modulating prolactin levels among men are important to decrease the risk of VTE. PMID:25750528

  12. Pharmacogenetics of Antipsychotics: Recent Progress and Methodological Issues

    PubMed Central

    Zhang, Jian-Ping; Malhotra, Anil K.

    2012-01-01

    Importance of the field Antipsychotic drug is the mainstay of treatment for schizophrenia, and there are large inter-individual differences in clinical response and side effects. Pharmacogenetics provides a valuable tool to fulfill the promise of personalized medicine by tailoring treatment based on one’s genetic markers. Areas covered in this review This article reviews the recent progress in pharmacogenetic research of antipsychotic drugs since 2010, focusing on two areas: antipsychotic-induced weight gain and clozapine-induced agranulocytosis. Important methodological issues in this area of research are discussed. What the reader will gain Readers are expected to learn the up-to-date evidence in pharmacogenetic research, and to gain familiarity to the issues and challenges facing the field. Take home message Pharmacogenetic studies of antipsychotic drugs are promising despite of many challenges. Recent advances as reviewed in this article push the field closer to routine clinical utilization of pharmacogenetic testing. Progress in genomic technology and bioinformatics, larger sample sizes, better phenotype characterization, and careful consideration of study design issues will help to elevate antipsychotic pharmacogenetics to its next level. PMID:23199282

  13. Monitoring of physical health parameters for inpatients on a child and adolescent mental health unit receiving regular antipsychotic therapy.

    PubMed

    Pasha, Nida; Saeed, Shoaib; Drewek, Katherine

    2015-01-01

    Physical health monitoring of patients receiving antipsychotics is vital. Overall it is estimated that individuals suffering with conditions like schizophrenia have a 20% shorter life expectancy than the average population, moreover antipsychotic use has been linked to a number of conditions including diabetes, obesity, and cardiovascular disease.[1-4] The severity of possible adverse effects to antipsychotics in adults has raised awareness of the importance of monitoring physical health in this population. However, there is little literature available as to the adverse effects of these medications in the child and adolescent community, which make physical health monitoring in this predominantly antipsychotic naïve population even more important. An expert group meeting in the UK has laid down recommendations in regards to screening and management of adult patients receiving antipsychotics, however no specific guidelines have been put in place for the child and adolescent age group.[5] The aim of this audit was to establish whether in-patients receiving antipsychotics had the following investigations pre-treatment and 12 weeks after treatment initiation: body mass index, hip-waist circumference, blood pressure, ECG, urea and electrolytes, full blood count, lipid profile, random glucose level, liver function test, and prolactin. This is in addition to a pre-treatment VTE risk assessment. These standards were derived from local trust guidelines, NICE guidelines on schizophrenia [6] and The Maudsley Prescribing Guidelines.[7] We retrospectively reviewed 39 electronic case notes in total, of which 24 cases were post intervention. Intervention included the use of a prompting tool. This tool was filed in the physical health files of all patients receiving antipsychotics which was intended as a reminder to doctors regarding their patient's need for physical health monitoring. Professionals involved in the monitoring of such parameters were educated in the importance and

  14. Impact of Second-Generation Antipsychotics and Perphenazine on Depressive Symptoms in a Randomized Trial of Treatment for Chronic Schizophrenia

    PubMed Central

    Addington, Donald E.; Mohamed, Somaia; Rosenheck, Robert A.; Davis, Sonia M.; Stroup, Thomas Scott; McEvoy, Joseph P.; Swartz, Marvin S.; Lieberman, Jeffrey A.

    2016-01-01

    Background According to the American Psychiatric Association Clinical Practice Guidelines for schizophrenia, second-generation antipsychotics may be specifically indicated for the treatment of depression in schizophrenia. We examined the impact of these medications on symptoms of depression using the data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), conducted between January 2001 and December 2004. Method Patients with DSM-IV–defined schizophrenia (N = 1,460) were assigned to treatment with a first-generation antipsychotic (perphenazine) or one of 4 second-generation drugs (olanzapine, quetiapine, risperidone, or ziprasidone) and followed for up to 18 months (phase 1). Patients with tardive dyskinesia were excluded from the randomization that included perphenazine. Depression was assessed with the Calgary Depression Scale for Schizophrenia (CDSS). Mixed models were used to evaluate group differences during treatment with the initially assigned drug. An interaction analysis evaluated differences in drug response by whether patients had a baseline score on the CDSS of ≥ 6, indicative of a current major depressive episode (MDE). Results There were no significant differences between treatment groups on phase 1 analysis, although there was a significant improvement in depression across all treatments. A significant interaction was found between treatment and experiencing an MDE at baseline (P = .05), and further paired comparisons suggested that quetiapine was superior to risperidone among patients who were in an MDE at baseline (P = .0056). Conclusions We found no differences between any second-generation antipsychotic and the first-generation antipsychotic perphenazine and no support for clinical practice recommendations, but we did detect a signal indicating a small potential difference favoring quetiapine over risperidone only in patients with an MDE at baseline. PMID:20868641

  15. 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. PMID:27285996

  16. Antipsychotic Medication Prescribing Practices Among Adult Patients Discharged From State Psychiatric Inpatient Hospitals

    PubMed Central

    HOLLEN, VERA; SCHACHT, LUCILLE

    2016-01-01

    Objectives: The goal of this study was to explore antipsychotic medication prescribing practices in a sample of 86,034 patients discharged from state psychiatric inpatient hospitals and to find the prevalence of patients discharged with no antipsychotic medications, on antipsychotic monotherapy, and on antipsychotic polypharmacy. For patients discharged on antipsychotic polypharmacy, the study explored the adjusted rates of antipsychotic polypharmacy, the reasons patients were discharged on antipsychotic polypharmacy, the proportion of antipsychotic polypharmacy by mental health disorder, and the characteristics associated with being discharged on antipsychotic polypharmacy. Methods: This cross-sectional study analyzed all discharges for adult patients (18 to 64 y of age) from state psychiatric inpatient hospitals between January 1 and December 31, 2011. The relationship among variables was explored using χ2, t test, and analysis of variance. Logistic regression was used to determine predictors of antipsychotic polypharmacy. Results: The prevalence of antipsychotic polypharmacy was 12%. Of the discharged patients receiving at least 1 antipsychotic medication (adjusted rate), 18% were on antipsychotic polypharmacy. The strongest predictors of antipsychotic polypharmacy being prescribed were having a diagnosis of schizophrenia and a length of stay of 90 days or more. Patients were prescribed antipsychotic polypharmacy primarily to reduce their symptoms. Conclusions: Antipsychotic polypharmacy continues at a high enough rate to affect nearly 10,000 patients with a diagnosis of schizophrenia each year in state psychiatric inpatient hospitals. Further analysis of the clinical presentation of these patients may highlight particular aspects of the illness and its previous treatment that are contributing to practices outside the best-practice guideline. An increased understanding of trend data, patient characteristics, and national benchmarks provides an opportunity for

  17. Dissociable effects of antipsychotics on ketamine-induced changes in regional oxygenation and inter-regional coherence of low frequency oxygen fluctuations in the rat.

    PubMed

    Li, Jennifer; Ishiwari, Keita; Conway, Michael W; Francois, Jennifer; Huxter, John; Lowry, John P; Schwarz, Adam J; Tricklebank, Mark; Gilmour, Gary

    2014-06-01

    Typical and atypical antipsychotics have been shown to alleviate N-methyl-D-aspartate (NMDA) receptor antagonist-induced BOLD signals in healthy humans and animals to differing degrees; factors that might relate to their different molecular mechanisms and clinical profiles. Recent studies have also extended these investigations to the analysis of resting state functional connectivity measures of BOLD signals in different brain regions. Using constant potential amperometry, we examined the effects of the NMDA receptor antagonist S-(+)-ketamine on tissue oxygen levels in medial prefrontal cortex (mPFC) and medial ventral striatum (mVS), and temporal coherence of low-frequency oxygen fluctuations between these regions in freely moving rats. Furthermore, we assessed the extent to which the atypical antipsychotic clozapine and the typical antipsychotic haloperidol could modulate the effects of S-(+)-ketamine on these measures. Acute S-(+)-ketamine (5-25 mg/kg) produced dose-dependent increases in both tissue O2 levels and coherence. Although effects of clozapine and haloperidol alone were relatively minor, their effects on ketamine-induced signals were markedly more distinct. Clozapine dose-dependently attenuated the absolute S-(+)-ketamine (25 mg/kg) O2 signal in both regions, and also attenuated ketamine-induced increases in regional coherence. Haloperidol had no effect on the absolute ketamine O2 signal yet potentiated increases in regional coherence. The dissociable effects of haloperidol and clozapine on ketamine-induced hyperoxygenation and mPFC-mVS coherence elucidate potentially important mechanistic differences between these classes of pharmacology. This study demonstrates for the first time that in vivo amperometry can measure both regional brain tissue O2 levels and inter-regional coherence, advancing BOLD-like measurements of functional connectivity into awake, unconstrained animals.

  18. Atypical fractures, a biased perspective.

    PubMed

    Aspenberg, Per

    2016-01-01

    When stress fractures started to show up in the femurs of elderly ladies, it was soon evident that bisphosphonate use lay behind, and the absolute risk increase due to bisphosphonate use was reasonably well estimated already in 2008. Thereafter followed a period of confusion: the term atypical fracture was introduced, with a definition so vague that the true stress fractures tended to disappear in a cloud of ambiguity. This cast doubt on the association with bisphosphonates. The association was then re-established by large epidemiological studies based on radiographic adjudication. Atypical fractures are largely caused by bisphosphonates. With a correct indication, bisphosphonates prevent many more fractures than they cause, at least during the first years of use. With an incorrect indication they are likely to cause more harm than good. PMID:26768286

  19. Repurposing antipsychotics as glioblastoma therapeutics: Potentials and challenges

    PubMed Central

    LEE, JIN-KU; NAM, DO-HYUN; LEE, JEONGWU

    2016-01-01

    Glioblastoma multiforme (GBM) is the most common and most lethal primary brain tumor, with tragically little therapeutic progress over the last 30 years. Surgery provides a modest benefit, and GBM cells are resistant to radiation and chemotherapy. Despite significant development of the molecularly targeting strategies, the clinical outcome of GBM patients remains dismal. The challenges inherent in developing effective GBM treatments have become increasingly clear, and include resistance to standard treatments, the blood-brain barrier, resistance of GBM stem-like cells, and the genetic complexity and molecular adaptability of GBM. Recent studies have collectively suggested that certain antipsychotics harbor antitumor effects and have potential utilities as anti-GBM therapeutics. In the present review, the anti-tumorigenic effects and putative mechanisms of antipsychotics, and the challenges for the potential use of antipsychotic drugs as anti-GBM therapeutics are reviewed. PMID:26893731

  20. Atypical neuroimaging in Wilson's disease.

    PubMed

    Patell, Rushad; Dosi, Rupal; Joshi, Harshal K; Storz, Dennis

    2014-06-06

    Wilson's disease is a rare metabolic disease involving copper metabolism. Neuroimaging plays an important part in evaluation of patients with a neuropsychiatric presentation. We present a case of a 14-year-old girl with atypical confluent white matter disease and cystic degeneration on MRI, with a rapidly progressive course, who succumbed to complications despite treatment with trientine. Wilson's disease should be considered as a differential for leucoencephalopathy in young patients with progressive neurological disease for its early recognition and optimum outcome.

  1. Atypical centrioles during sexual reproduction

    PubMed Central

    Avidor-Reiss, Tomer; Khire, Atul; Fishman, Emily L.; Jo, Kyoung H.

    2015-01-01

    Centrioles are conserved, self-replicating, microtubule-based, 9-fold symmetric subcellular organelles that are essential for proper cell division and function. Most cells have two centrioles and maintaining this number of centrioles is important for animal development and physiology. However, how animals gain their first two centrioles during reproduction is only partially understood. It is well established that in most animals, the centrioles are contributed to the zygote by the sperm. However, in humans and many animals, the sperm centrioles are modified in their structure and protein composition, or they appear to be missing altogether. In these animals, the origin of the first centrioles is not clear. Here, we review various hypotheses on how centrioles are gained during reproduction and describe specialized functions of the zygotic centrioles. In particular, we discuss a new and atypical centriole found in sperm and zygote, called the proximal centriole-like structure (PCL). We also discuss another type of atypical centriole, the “zombie” centriole, which is degenerated but functional. Together, the presence of centrioles, PCL, and zombie centrioles suggests a universal mechanism of centriole inheritance among animals and new causes of infertility. Since the atypical centrioles of sperm and zygote share similar functions with typical centrioles in somatic cells, they can provide unmatched insight into centriole biology. PMID:25883936

  2. Atypical centrioles during sexual reproduction.

    PubMed

    Avidor-Reiss, Tomer; Khire, Atul; Fishman, Emily L; Jo, Kyoung H

    2015-01-01

    Centrioles are conserved, self-replicating, microtubule-based, 9-fold symmetric subcellular organelles that are essential for proper cell division and function. Most cells have two centrioles and maintaining this number of centrioles is important for animal development and physiology. However, how animals gain their first two centrioles during reproduction is only partially understood. It is well established that in most animals, the centrioles are contributed to the zygote by the sperm. However, in humans and many animals, the sperm centrioles are modified in their structure and protein composition, or they appear to be missing altogether. In these animals, the origin of the first centrioles is not clear. Here, we review various hypotheses on how centrioles are gained during reproduction and describe specialized functions of the zygotic centrioles. In particular, we discuss a new and atypical centriole found in sperm and zygote, called the proximal centriole-like structure (PCL). We also discuss another type of atypical centriole, the "zombie" centriole, which is degenerated but functional. Together, the presence of centrioles, PCL, and zombie centrioles suggests a universal mechanism of centriole inheritance among animals and new causes of infertility. Since the atypical centrioles of sperm and zygote share similar functions with typical centrioles in somatic cells, they can provide unmatched insight into centriole biology.

  3. Atypical centrioles during sexual reproduction.

    PubMed

    Avidor-Reiss, Tomer; Khire, Atul; Fishman, Emily L; Jo, Kyoung H

    2015-01-01

    Centrioles are conserved, self-replicating, microtubule-based, 9-fold symmetric subcellular organelles that are essential for proper cell division and function. Most cells have two centrioles and maintaining this number of centrioles is important for animal development and physiology. However, how animals gain their first two centrioles during reproduction is only partially understood. It is well established that in most animals, the centrioles are contributed to the zygote by the sperm. However, in humans and many animals, the sperm centrioles are modified in their structure and protein composition, or they appear to be missing altogether. In these animals, the origin of the first centrioles is not clear. Here, we review various hypotheses on how centrioles are gained during reproduction and describe specialized functions of the zygotic centrioles. In particular, we discuss a new and atypical centriole found in sperm and zygote, called the proximal centriole-like structure (PCL). We also discuss another type of atypical centriole, the "zombie" centriole, which is degenerated but functional. Together, the presence of centrioles, PCL, and zombie centrioles suggests a universal mechanism of centriole inheritance among animals and new causes of infertility. Since the atypical centrioles of sperm and zygote share similar functions with typical centrioles in somatic cells, they can provide unmatched insight into centriole biology. PMID:25883936

  4. Antipsychotic Medication Prescription Patterns in Adults with Developmental Disabilities Who Have Experienced Psychiatric Crisis

    ERIC Educational Resources Information Center

    Lunsky, Yona; Elserafi, Jonny

    2012-01-01

    Antipsychotic medication rates are high in adults with developmental disability. This study considered rates of antipsychotic use in 743 adults with developmental disability who had experienced a psychiatric crisis. Nearly half (49%) of these adults were prescribed antipsychotics. Polypharmacy was common with 22% of those prescribed antipsychotics…

  5. Antipsychotic-induced insulin resistance and postprandial hormonal dysregulation independent of weight gain or psychiatric disease.

    PubMed

    Teff, Karen L; Rickels, Michael R; Grudziak, Joanna; Fuller, Carissa; Nguyen, Huong-Lan; Rickels, Karl

    2013-09-01

    Atypical antipsychotic (AAP) medications that have revolutionized the treatment of mental illness have become stigmatized by metabolic side effects, including obesity and diabetes. It remains controversial whether the defects are treatment induced or disease related. Although the mechanisms underlying these metabolic defects are not understood, it is assumed that the initiating pathophysiology is weight gain, secondary to centrally mediated increases in appetite. To determine if the AAPs have detrimental metabolic effects independent of weight gain or psychiatric disease, we administered olanzapine, aripiprazole, or placebo for 9 days to healthy subjects (n = 10, each group) under controlled in-patient conditions while maintaining activity levels. Prior to and after the interventions, we conducted a meal challenge and a euglycemic-hyperinsulinemic clamp to evaluate insulin sensitivity and glucose disposal. We found that olanzapine, an AAP highly associated with weight gain, causes significant elevations in postprandial insulin, glucagon-like peptide 1 (GLP-1), and glucagon coincident with insulin resistance compared with placebo. Aripiprazole, an AAP considered metabolically sparing, induces insulin resistance but has no effect on postprandial hormones. Importantly, the metabolic changes occur in the absence of weight gain, increases in food intake and hunger, or psychiatric disease, suggesting that AAPs exert direct effects on tissues independent of mechanisms regulating eating behavior.

  6. Neural changes induced by antipsychotic administration in adolescence: A review of studies in laboratory rodents.

    PubMed

    Moe, Aung Aung Kywe; Scott, James G; Burne, Thomas Hj; Eyles, Darryl W

    2016-08-01

    Adolescence is characterized by major remodelling processes in the brain. Use of antipsychotic drugs (APDs) in adolescents has increased dramatically in the last 20 years; however, our understanding of the neurobiological consequences of APD treatment on the adolescent brain has not kept the same pace and significant concerns have been raised. In this review, we examined currently available preclinical studies of the effects of APDs on the adolescent brain. In animal models of neuropsychiatric disorders, adolescent APD treatment appears to be protective against selected structural, behavioural and neurochemical phenotypes. In "neurodevelopmentally normal" adolescent animals, a range of short- and long-term alterations in behaviour and neurochemistry have been reported. In particular, the adolescent brain appears to be sensitive to long-term locomotor/reward effects of chronic atypical APDs in contrast with the outcomes in adults. Long-lasting changes in dopaminergic, glutamatergic and gamma-amino butyric acid-ergic systems induced by adolescent APD administration have been observed in the nucleus accumbens. A detailed examination of other potential target regions such as striatum, prefrontal cortex and ventral tegmental area is still required. Through identification of specific neural pathways targeted by adolescent APD treatment, future studies will expand the current knowledge on long-term neural outcomes which are of translational value. PMID:27413140

  7. Antipsychotic pathway genes with expression altered in opposite direction by antipsychotics and amphetamine.

    PubMed

    Ko, Françoise; Tallerico, Teresa; Seeman, Philip

    2006-08-01

    To develop a new strategy for identifying possible psychotic- or antipsychotic-related pathway genes, rats were treated with clinical doses of haloperidol and clozapine for 4 days, and the altered expression of genes was compared with the genes altered in expression after amphetamine sensitization. The objective was to identify genes with expression altered in the same direction by haloperidol and clozapine but in the opposite direction in the amphetamine-sensitized rat striatum. These criteria were met by 21 genes, consisting of 15 genes upregulated by amphetamine, and 6 genes downregulated by amphetamine. Of the 21 genes, 15 are not presently identified, and only 3 genes (cathepsin K, GRK6, and a gene with accession number AI177589) are located in chromosome regions known to be associated with schizophrenia.

  8. Antipsychotic Cardiometabolic Side Effect Monitoring in a State Community Mental Health System.

    PubMed

    Cotes, Robert O; de Nesnera, Alex; Kelly, Michael; Orsini, Karen; Xie, Haiyi; McHugo, Greg; Bartels, Stephen; Brunette, Mary F

    2015-08-01

    Antipsychotic medications can cause serious cardiometabolic side effects. No recent research has broadly evaluated monitoring and strategies to improve monitoring in U.S. public mental health systems. To address this knowledge gap, we evaluated education with audit and feedback to leaders to improve cardiometabolic monitoring in a state mental health system. We used Chi square statistics and logistic regressions to explore changes in monitoring recorded in randomly sampled records over 2 years. In 2009, assessment of patients on antipsychotics was 29.6 % for cholesterol, 40.4 % for glucose, 29.1 % for triglycerides, 54.3 % for weight, 33.6 % for blood pressure, and 5.7 % for abdominal girth. In 2010, four of ten mental health centers improved their rate of adult laboratory monitoring. Overall monitoring in the state did not increase. Education for prescribers with audit and feedback to leaders can improve monitoring in some settings, but more intensive and/or prolonged interventions may be required.

  9. Antipsychotic Cardiometabolic Side Effect Monitoring in a State Community Mental Health System.

    PubMed

    Cotes, Robert O; de Nesnera, Alex; Kelly, Michael; Orsini, Karen; Xie, Haiyi; McHugo, Greg; Bartels, Stephen; Brunette, Mary F

    2015-08-01

    Antipsychotic medications can cause serious cardiometabolic side effects. No recent research has broadly evaluated monitoring and strategies to improve monitoring in U.S. public mental health systems. To address this knowledge gap, we evaluated education with audit and feedback to leaders to improve cardiometabolic monitoring in a state mental health system. We used Chi square statistics and logistic regressions to explore changes in monitoring recorded in randomly sampled records over 2 years. In 2009, assessment of patients on antipsychotics was 29.6 % for cholesterol, 40.4 % for glucose, 29.1 % for triglycerides, 54.3 % for weight, 33.6 % for blood pressure, and 5.7 % for abdominal girth. In 2010, four of ten mental health centers improved their rate of adult laboratory monitoring. Overall monitoring in the state did not increase. Education for prescribers with audit and feedback to leaders can improve monitoring in some settings, but more intensive and/or prolonged interventions may be required. PMID:25645893

  10. Olanzapine-induced cerebral metabolic changes related to symptom improvement in schizophrenia.

    PubMed

    Molina, Vicente; Gispert, Juan D; Reig, Santiago; Pascau, Javier; Martínez, Raúl; Sanz, Javier; Palomo, Tomás; Desco, Manuel

    2005-01-01

    The pattern of brain metabolic changes produced by olanzapine has yet to be described, despite the theoretical and clinical interest of this new antipsychotic. We studied a group of 17 schizophrenic patients who underwent two fluoro-deoxyglucose-positron emission tomography (FDG-PET) studies under two different conditions: a baseline scan during treatment with either conventional antipsychotics (n=15) or risperidone (n=2) and a second scan performed 17-24 weeks after switching to olanzapine. PET scans were obtained while performing a standard cognitive paradigm (Continuous Performance Test) and analysed by means of Statistical Parametric Mapping. No significant metabolic changes were found in the comparison between pre- and post-olanzapine conditions. A brain map of the statistical power of our design showed that changes up to 3% in the frontal and up to 8% in the occipital region were not likely to exist (1-beta=0.8). The degree of improvement in positive symptoms was related to the amount of activity decrease in the right orbital region and to the amount of activity increase in the primary visual area. Improvement in negative symptoms was associated with an activity increase in the dorsal prefrontal cortex, and a higher baseline activity in both temporal poles. These correlation patterns suggest that the functional mechanism of action of olanzapine may share traits from both typical and atypical neuroleptics.

  11. Current Trends on Antipsychotics: Focus on Asenapine.

    PubMed

    Marazziti, Donatella; Piccinni, Armando; Baroni, Stefano; Mungai, Francesco; Presta, Silvio; Mucci, Federico; Dell'Osso, Liliana

    2016-01-01

    Over the years, both first- (FGAs) and second-generation antipsychotics (SGAs), continue to gain increasing evidence of being effective in the treatment of psychotic symptoms. Currently, they represent the first-line treatment of schizophrenia and bipolar disorder, although they are widely used in psychotic depression and other clinical conditions, such as agitation and/or behavioural disturbances. Despite representing an indispensable tool for the treatment of severe psychotic disorders, they are widely known to have a number of unwanted side effects that the clinician must be aware of, and handle carefully to provide the patient the best available treatment in the short and long-term. However, even with respect to the long-term use of some of the most effective SGAs, it is imperative for clinicians not to overlook the risk linked to the onset of potentially severe metabolic side effects such as weight gain, dyslipidaemia, insulinresistance and type II diabetes. Asenapine is one of the newest SGAs licenced in Europe for the treatment of manic episodes and in the US for schizophrenia. It belongs to the same class of clozapine, olanzapine and quetiapine, sharing with them a rather complex pharmacological binding profile. In fact, asenapine shows a high affinity for the serotonin (5HT) receptor of the type 2A (5HT2A) and to a lesser extent for the dopamine receptor of the type 2 (D2), similar to other SGAs. Asenapine behaves also as an antagonist at the level of 5HT2C, H1 and α2-receptors. Asenapine has been reported to be effective either in monotherapy or in combination with mood stabilers (lithium and valproate) in the treatment of manic or mixed episodes, with a lower propensity to induce, or being followed by, depressive symptoms, when compared to other SGAs. These unique properties may explain the increasing interest towards the use of this drug in mixed states, besides schizophrenia and acute mania. The aim of this paper was at reviewing current data on

  12. Early Freezing of Gait: Atypical versus Typical Parkinson Disorders.

    PubMed

    Lieberman, Abraham; Deep, Aman; Dhall, Rohit; Tran, An; Liu, Ming-Jai

    2015-01-01

    In 18 months, 850 patients were referred to Muhammad Ali Parkinson Center (MAPC). Among them, 810 patients had typical Parkinson disease (PD) and 212 had PD for ≤5 years. Among the 212 patients with early PD, 27 (12.7%) had freezing of gait (FOG). Forty of the 850 had atypical parkinsonism. Among these 40 patients, all of whom had symptoms for ≤5 years, 12 (30.0%) had FOG. FOG improved with levodopa in 21/27 patients with typical PD but did not improve in the 12 patients with atypical parkinsonism. FOG was associated with falls in both groups of patients. We believe that FOG unresponsive to levodopa in typical PD resembles FOG in atypical parkinsonism. We thus compared the 6 typical PD patients with FOG unresponsive to levodopa plus the 12 patients with atypical parkinsonism with the 21 patients with typical PD responsive to levodopa. We compared them by tests of locomotion and postural stability. Among the patients with FOG unresponsive to levodopa, postural stability was more impaired than locomotion. This finding leads us to believe that, in these patients, postural stability, not locomotion, is the principal problem underlying FOG.

  13. Atypical presentation of oral tuberculosis ulcer.

    PubMed

    Mahajan, Sumita; Srikant, Natarajan; George, Thomas

    2007-11-01

    Tuberculosis is a chronic infectious disease that can affect any part of the body, including the mouth. An upsurge in the number of tuberculosis cases, with a strong association with HIV infection, has been noted. We present a case of tuberculosis that clinically resembles a malignant chronic ulcer in the retromolar trigone-an uncommon site of occurrence. Histologically, the case demonstrated an atypical epitheloid granuloma with reduced lymphocyte count. The diagnosis of tuberculosis was confirmed following sputum culture of M tuberculosis. Antitubercular therapy improved the patient's condition. Although rare, tuberculosis must be considered as a differential diagnosis in chronic ulcers in the oral region; and its association with HIV must not be overlooked.

  14. Mycobacterium chelonae Is an Ubiquitous Atypical Mycobacterium

    PubMed Central

    Pinto-Gouveia, Miguel; Gameiro, Ana; Ramos, Leonor; Cardoso, José Carlos; Brites, Maria Manuel; Tellechea, Óscar; Figueiredo, Américo

    2015-01-01

    The type of cutaneous infection varies mainly according to the patient's immune status, and the disseminated form is mostly found in the context of immunosuppression. We report the case of a 62-year-old male who was under long-term systemic corticosteroid therapy and presented with a 7-month history of multiple painless cutaneous lesions at various stages of development: papules, nodules, pustules and hemorrhagic crusts, as well as small erosions and ulcers distributed over the limbs and scalp. Cutaneous biopsy showed a suppurative granulomatous infiltrate with abscess formation. Fite stain revealed numerous extracellular bacilli, suggesting mycobacterial infection, particularly by atypical mycobacteria. Culture of a skin sample revealed Mycobacterium chelonae. The patient started multidrug therapy and showed clinical improvement despite of resistance to one of the antibiotics. This striking presentation underlines the role of immunosuppression with corticotherapy as a major risk factor for these infections. Multidrug therapy is advised and antibiogram is essential in directing treatment. PMID:26351432

  15. Information Display System for Atypical Flight Phase

    NASA Technical Reports Server (NTRS)

    Statler, Irving C. (Inventor); Ferryman, Thomas A. (Inventor); Amidan, Brett G. (Inventor); Whitney, Paul D. (Inventor); White, Amanda M. (Inventor); Willse, Alan R. (Inventor); Cooley, Scott K. (Inventor); Jay, Joseph Griffith (Inventor); Lawrence, Robert E. (Inventor); Mosbrucker, Chris J. (Inventor); Rosenthal, Loren J. (Inventor); Lynch, Robert E. (Inventor); Chidester, Thomas R. (Inventor); Prothero, Gary L. (Inventor); Andrei, Adi (Inventor); Romanowski, Timothy P. (Inventor); Robin, Daniel E. (Inventor); Prothero, Jason W. (Inventor)

    2007-01-01

    Method and system for displaying information on one or more aircraft flights, where at least one flight is determined to have at least one atypical flight phase according to specified criteria. A flight parameter trace for an atypical phase is displayed and compared graphically with a group of traces, for the corresponding flight phase and corresponding flight parameter, for flights that do not manifest atypicality in that phase.

  16. Addressing Cardiometabolic Risk During Treatment With Antipsychotic Medications

    PubMed Central

    Amiel, Jonathan M.; Mangurian, Christina V.; Ganguli, Rohan; Newcomer, John W.

    2009-01-01

    Purpose of Review To raise awareness of and inform evidence-based practice regarding medical and behavioral interventions for antipsychotic medication-induced metabolic abnormalities. Recent Findings The current literature indicates that individuals with severe and persistent mental illness have significantly worse health outcomes and premature mortality compared to the general population, due to a combination of under-recognition and treatment of medical risk factors, reduced access to care, sedentary lifestyle and poor diet, and the potential contribution of adverse metabolic side effects of antipsychotic medications like weight gain, hyperglycemia and dyslipidemia. A combination of administrative, behavioral and medical approaches to addressing these medical risks may be more effective than any one of these approaches alone. Summary Treatment with antipsychotic medications can induce significant weight gain and abnormalities in lipid and glucose metabolism that increase risk for cardiovascular disease and diabetes in a population already at risk from multiple other sources. Managing the side effects of antipsychotics and lowering risk in general is an important aspect of the management of chronic mental illness. There are a variety of effective medical and behavioral interventions that can be employed to achieve primary and secondary prevention aims. PMID:18852570

  17. Development of a Patient-Centered Antipsychotic Medication Adherence Intervention

    ERIC Educational Resources Information Center

    Pyne, Jeffrey M.; Fischer, Ellen P.; Gilmore, LaNissa; McSweeney, Jean C.; Stewart, Katharine E.; Mittal, Dinesh; Bost, James E.; Valenstein, Marcia

    2014-01-01

    Objective: A substantial gap exists between patients and their mental health providers about patient's perceived barriers, facilitators, and motivators (BFMs) for taking antipsychotic medications. This article describes how we used an intervention mapping (IM) framework coupled with qualitative and quantitative item-selection methods to…

  18. Antipsychotic Drug Side Effects for Persons with Intellectual Disability

    ERIC Educational Resources Information Center

    Matson, Johnny L.; Mahan, Sara

    2010-01-01

    Antipsychotic drugs are the most frequently prescribed of the psychotropic drugs among the intellectually disabled (ID) population. Given their widespread use, efforts to systematically assess and report side effects are warranted. Specific scaling methods such as the "Matson Evaluation of Side Effects" ("MEDS"), the "Abnormal Inventory Movement…

  19. Prescribing of antipsychotics in UK primary care: a cohort study

    PubMed Central

    Marston, Louise; Nazareth, Irwin; Petersen, Irene; Walters, Kate; Osborn, David P J

    2014-01-01

    Objective To examine the recorded indication for antipsychotic prescriptions in UK primary care. Design Cohort study. Setting Primary care. Participants Individuals prescribed antipsychotics between 2007 and 2011. Measures The proportion of individuals prescribed antipsychotics with a diagnosis of (1) psychosis and bipolar disorder, (2) other diagnoses including depression, anxiety and dementia and (3) none of these diagnoses. Results We identified 47 724 individuals prescribed antipsychotic agents. 13 941 received first-generation agents and 27 966 received second-generation agents. The rates of prescribing were higher in females (incidence rate ratio (IRR) 1.092 (95% CI 1.088 to 1.095), older people (80+ vs 40–49; IRR 2.234 (2.222 to 2.246)) and in those from the most deprived areas (most deprived vs least deprived IRR 3.487 (3.567 to 3.606). Of those receiving first-generation antipsychotics, less than 50% had a diagnosis of psychosis/bipolar disorder. For the second-generation agents, the numbers ranged from 4824 (36%) for quetiapine to 7094 (62%) for olanzapine. In patients without psychosis/bipolar disorder, common diagnoses included anxiety, depression, dementia, sleep and personality disorders. For example, in risperidone users, 14% had an anxiety code, 22% depression, 12% dementia, 11% sleep disorder and 4% personality disorder. The median daily doses and duration of treatment were greater in those with schizophrenia (eg, risperidone median daily dose 4 mg; IQR 2–6: median duration 1.2 years) than in those with non-psychotic/bipolar disorders such as depression or anxiety (eg, risperidone 1 mg; IQR 1–2: 0.6 years). A relatively large proportion (between 6% and 17%) of people receiving individual antipsychotics had none of the diagnoses stated above. Conclusions In UK primary care, a large proportion of people prescribed antipsychotics have no record of psychotic or bipolar disorder. They are often older people with conditions including

  20. Prenatal Antipsychotic Exposure and Neuromotor Performance During Infancy

    PubMed Central

    Johnson, Katrina C.; LaPrairie, Jamie L.; Brennan, Patricia A.; Stowe, Zachary N.; Newport, D. Jeffrey

    2016-01-01

    Context Despite the expanding clinical utility of antipsychotics beyond psychotic disorders to include depressive, bipolar, and anxiety disorders, reproductive safety data regarding the neurodevelopmental sequelae of fetal antipsychotic exposure are scarce. Objective To examine whether intrauterine antipsychotic exposure is associated with deficits in neuromotor performance and habituation in 6-month-old infants. Design, Setting, and Participants A prospective controlled study was conducted from December 1999 through June 2008 at the Infant Development Laboratory of the Emory Psychological Center examining maternal-infant dyads (N=309) at 6 months postpartum with pregnancy exposure to antipsychotics (n=22), antidepressants (n = 202), or no psychotropic agents (n = 85). Examiners masked to maternal-infant exposure status administered a standardized neuromotor examination (Infant Neurological International Battery [INFANIB]) that tests posture, tone, reflexes, and motor skills and a visual habituation paradigm using a neutral female face. Main Outcome Measures The INFANIB composite score; number of trials required to achieve a 50% decrease in infant fixation during a visual habituation task; and mean time looking at the stimulus across 10 trials. Results Infants prenatally exposed to antipsychotics (mean=64.71) showed significantly lower INFANIB scores than those with antidepressant (mean=68.57) or no psychotropic (mean=71.19) exposure, after controlling for significant covariates (F2,281=4.51; P =.01; partial η2=0.033). The INFANIB scores were also significantly associated with maternal psychiatric history, including depression, psychosis, and overall severity/chronicity (P’s<.05) and maternal depression during pregnancy was associated with less efficient habituation (r245=0.16; P <.02). There were no significant differences regarding habituation between medication exposure groups. Conclusions Among 6-month-old infants, a history of intrauterine antipsychotic

  1. A review of modafinil and armodafinil as add-on therapy in antipsychotic-treated patients with schizophrenia

    PubMed Central

    Arends, Johannes; Timmerman, Leo; Lancel, Marike

    2012-01-01

    Schizophrenia is characterized by reality distortion, psychomotor poverty and cognitive disturbances. These characteristics contribute to a lesser social functioning and lower quality of life in patients with schizophrenia. It has been suggested that modafinil and its isomer armodafinil as an add-on strategy to antipsychotic treatment in patients with schizophrenia may improve cognitive functioning, attenuate fatigue, inactiveness and other negative functions as well as weight gain. In this paper we review the literature relevant to the question of whether modafinil and armodafinil are beneficial as add-on therapy in antipsychotic-treated patients with schizophrenia. A total of 15 articles were included in this review; of the 15 articles, 10 were randomized controlled trials (RCTs). Evidence for the use of modafinil or armodafinil as add-on therapy to antipsychotic drugs to alleviate fatigue, sleepiness and inactivity is inconclusive. One cohort study and one out of two single-dose crossover RCTs in which modafinil addition was studied could demonstrate a positive effect. All five RCTs of modafinil (three RCTs) and armodafinil (two RCTs) addition with a longer study duration could not demonstrate a positive effect. With respect to cognitive disturbances, animal models of cognitive deficits show clear improvements with modafinil. In RCTs with a treatment duration of 4 weeks or more, however, no positive effect could be demonstrated on cognitive functioning with modafinil and armodafinil addition. Yet, four single-dose crossover RCTs of modafinil addition show significant positive effects on executive functioning, verbal memory span, visual memory, working memory, spatial planning, slowing in latency, impulse control and recognition of faces expressing sadness and sadness misattribution in the context of disgust recognition. The addition of modafinil or armodafinil to an antipsychotic regime, despite theoretical and preclinical considerations, has not been proved to

  2. A review of modafinil and armodafinil as add-on therapy in antipsychotic-treated patients with schizophrenia.

    PubMed

    Wittkampf, Laura Christina; Arends, Johannes; Timmerman, Leo; Lancel, Marike

    2012-06-01

    Schizophrenia is characterized by reality distortion, psychomotor poverty and cognitive disturbances. These characteristics contribute to a lesser social functioning and lower quality of life in patients with schizophrenia. It has been suggested that modafinil and its isomer armodafinil as an add-on strategy to antipsychotic treatment in patients with schizophrenia may improve cognitive functioning, attenuate fatigue, inactiveness and other negative functions as well as weight gain. In this paper we review the literature relevant to the question of whether modafinil and armodafinil are beneficial as add-on therapy in antipsychotic-treated patients with schizophrenia. A total of 15 articles were included in this review; of the 15 articles, 10 were randomized controlled trials (RCTs). Evidence for the use of modafinil or armodafinil as add-on therapy to antipsychotic drugs to alleviate fatigue, sleepiness and inactivity is inconclusive. One cohort study and one out of two single-dose crossover RCTs in which modafinil addition was studied could demonstrate a positive effect. All five RCTs of modafinil (three RCTs) and armodafinil (two RCTs) addition with a longer study duration could not demonstrate a positive effect. With respect to cognitive disturbances, animal models of cognitive deficits show clear improvements with modafinil. In RCTs with a treatment duration of 4 weeks or more, however, no positive effect could be demonstrated on cognitive functioning with modafinil and armodafinil addition. Yet, four single-dose crossover RCTs of modafinil addition show significant positive effects on executive functioning, verbal memory span, visual memory, working memory, spatial planning, slowing in latency, impulse control and recognition of faces expressing sadness and sadness misattribution in the context of disgust recognition. The addition of modafinil or armodafinil to an antipsychotic regime, despite theoretical and preclinical considerations, has not been proved to

  3. Second-generation long-acting injectable antipsychotics in schizophrenia: patient functioning and quality of life

    PubMed Central

    Montemagni, Cristiana; Frieri, Tiziana; Rocca, Paola

    2016-01-01

    Long-acting injectable antipsychotics (LAIs) were developed to make treatment easier, improve adherence, and/or signal the clinician when nonadherence occurs. Second-generation antipsychotic LAIs (SGA-LAIs) combine the advantages of SGA with a long-acting formulation. The purpose of this review is to evaluate the available literature concerning the impact of SGA-LAIs on patient functioning and quality of life (QOL). Although several studies regarding schizophrenia patients’ functioning and QOL have been performed, the quantity of available data still varies greatly depending on the SGA-LAI under investigation. After reviewing the literature, it seems that SGA-LAIs are effective in ameliorating patient functioning and/or QOL of patients with schizophrenia, as compared with placebo. However, while methodological design controversy exists regarding the superiority of risperidone LAI versus oral antipsychotics, the significant amount of evidence in recently published research demonstrates the beneficial influence of risperidone LAI on patient functioning and QOL in stable patients and no benefit over oral treatment in unstable patients. However, the status of the research on SGA-LAIs is lacking in several aspects that may help physicians in choosing the correct drug therapy. Meaningful differences have been observed between SGA-LAIs in the onset of their clinical efficacy and in the relationships between symptoms and functioning scores. Moreover, head-to-head studies comparing the effects of SGA-LAIs on classical measures of psychopathology and functioning are available mainly on risperidone LAI, while those comparing olanzapine LAI with other SGA-LAIs are still lacking. Lastly, some data on their use, especially in first-episode or recent-onset schizophrenia and in refractory or treatment-resistant schizophrenia, is available. PMID:27143893

  4. Factors associated with antipsychotic medication adherence in community-based patients with schizophrenia in Hong Kong: a cross sectional study.

    PubMed

    Bressington, Dan; Mui, Jolene; Gray, Richard

    2013-02-01

    The purpose of the present study was to examine the factors affecting adherence to antipsychotic medication in patients with schizophrenia registered with a community psychiatric nursing service in Hong Kong. The study was a cross-sectional observational survey; symptoms, drug attitudes, insight, side-effects, and sociodemographic characteristics were measured and explored in terms of their relationship with medication adherence. A total of 584 patients who were visited by community psychiatric nurses (CPN) participated, and 30% of these patients were non-adherent with their antipsychotic medication. Positive treatment attitudes, awareness of the need for treatment, being prescribed clozapine, receiving state benefits, lower levels of symptoms, and fewer side-effects were associated with adherence. The findings from this study suggest that the clinical efforts of CPN to improve adherence should aim to help patients amplify the personal relevance of treatment and modify patients' attitudes towards medication.

  5. Forging a Healthier Path: A Multidisciplinary Team Approach to Reducing Risk and Improving Child Outcomes

    ERIC Educational Resources Information Center

    Breidenstine, Angela S.; Couvillion, Joy; Many, Cecile

    2012-01-01

    At the age of 4 years, Joseph came to the Orleans Parish Early Childhood Supports and Services program (ECSS) for mental health services because of serious aggression and anger. His history included physical abuse before age 2, long-term maintenance on an atypical antipsychotic medication, and other biological, psychological, and…

  6. [Atypical case of bronchial carcinoid].

    PubMed

    Andrzejak, R; Mydłowski, R; Krajewski, E; Orłowski, T; Bochnia, M

    1997-01-01

    This article illustrates problems in diagnosis and treatment of an atypical form of bronchial carcinoid. We described the case of a 49-year old man, exposed to granite dust and noise for 25 years who had suffered from frequent bronchitis inflammations and pneumonias for 5 years prior to the diagnosis. He was admitted to our clinic because of supposed occupational nature of hearing deficiency. Although a pneumoconiosis was excluded before the admission, we found clinical and X-ray features of the right lung emphysema with medium restrictive ventilation disturbances. Bronchoscopy was performed because of "bright" right lung and ventilation disturbances and it showed presence of the carcinoid. Unusual in this case were tiny anamnestical findings (mild dyspnea attacks after physical effort or nervousness) plus increasing frequency of reported from the childhood bronchitis and pneumonias and uncharacteristic "bright" right lung in X-ray. Therapeutical difficulties resulted from atypical histological form of the tumor, its diameter, polypous-infiltrative character, and inconvenient localization. In spite of late diagnosis of carcinoid and significant acceleration of respiratory decompensation symptoms after the diagnosis the attempt of surgical therapy was appropriate but unsuccessful. After the operation the patient was suffering long lasting lowering of arterial pressure (what was corrected with catecholamine infusions) probably as a result of serotonin secretion. However it was not established because of technical reasons.

  7. Atypical Teratomas of the Pineal

    PubMed Central

    Lewis, I.; Baxter, D. W.; Stratford, J. G.

    1963-01-01

    Atypical teratomas of the pineal were studied pathologically and clinically, and five illustrative cases are described. The results of three postmortem examinations are available, while two of the patients are living, one leading a normal life. Pathological verification revealed that two had suprasellar “ectopic” pinealomas. One neoplasm was located in the pineal (collicular) region. The histology of the tumours was identical, consisting of small cells resembling lymphocytes and large cells with prominent nucleoli and mitoses. This feature plus the midline location led to adoption of the term “atypical teratoma”. Patients with collicular pinealomas presented with headache, vomiting, papilledema, Parinaud's syndrome and, rarely, nystagmus retractorius. Diabetes insipidus, visual difficulty and hypopituitarism were characteristic features in those with suprasellar neoplasms. Treatment of collicular pinealoma has consisted of the use of a palliative shunt followed by a course of radiation. Chiasmal decompression and radiation have produced favourable results in patients with suprasellar pinealoma. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12 PMID:20327617

  8. Pharmacogenetic associations of the type-3 metabotropic glutamate receptor (GRM3) gene with working memory and clinical symptom response to antipsychotics in first-episode schizophrenia

    PubMed Central

    Reilly, James L.; Harris, Margret S. H.; Patel, Shitalben R.; Kittles, Rick; Badner, Judith A.; Prasad, Konasale M.; Nimgaonkar, Vishwajit L.; Keshavan, Matcheri S.; Sweeney, John A.

    2014-01-01

    Rationale Type-3 metabotropic glutamate receptor gene (GRM3) single nucleotide polymorphisms (SNPs) have been associated with cognitive performance and prefrontal cortex brain activity in chronically treated schizophrenia patients. Whether these SNPs are associated with cognitive and symptom response to antipsychotic therapy has not been extensively evaluated. Objectives The aim of the study was to examine pharmacogenetic relationships between GRM3 and selected variants in relevant dopamine genes with changes in spatial working memory and clinical symptoms after treatment. Methods Sixty-one untreated first-episode schizophrenia patients were assessed before and after 6 weeks of antipsychotic pharmacotherapy, primarily consisting of risperidone. Patients’ level of cognitive performance on a spatial working memory task was assessed with a translational oculomotor paradigm. Changes after treatment in cognitive and clinical measures were examined in relationship to genetic polymorphisms in the GRM3, COMT, and DRD2/ANKK1 gene regions. Results Spatial working memory performance worsened after antipsychotic treatment. This worsening was associated with GRM3 rs1468412, with the genetic subgroup of patients known to have altered glutamate activity having greater adverse changes in working memory performance after antipsychotic treatment. Negative symptom improvement was associated with GRM3 rs6465084. There were no pharmacogenetic associations between DRD2/ANKK1 and COMT with working memory changes or symptom response to treatment. Conclusions These findings suggest important pharmacogenetic relationships between GRM3 variants and changes in cognition and symptom response with exposure to antipsychotics. This information may be useful in identifying patients susceptible to adverse cognitive outcomes associated with antipsychotic treatment and suggest that glutamatergic mechanisms contribute to such effects. PMID:25096017

  9. SSRI augmentation of antipsychotic alters expression of GABA(A) receptor and related genes in PMC of schizophrenia patients.

    PubMed

    Silver, Henry; Susser, Ehud; Danovich, Lena; Bilker, Warren; Youdim, Moussa; Goldin, Vladimir; Weinreb, Orly

    2011-06-01

    Clinical studies have shown that negative symptoms of schizophrenia unresponsive to antipsychotic given alone can improve after augmentation with SSRI antidepressant. Laboratory investigations into the mechanism of this synergism showed that co-administration of SSRI and antipsychotic produces changes in GABA(A) receptor and related systems, which differ from the effects of each drug alone. To examine the clinical relevance of these findings, the current study examined the effects of SSRI augmentation treatment on GABA(A) receptor and related systems in schizophrenia patients. Schizophrenia patients with high levels of negative symptoms unresponsive to antipsychotic treatment received add-on fluvoxamine (100 mg/d). Blood was taken before and 1, 3 and 6 wk after adding fluvoxamine and peripheral mononuclear cells (PMC) isolated. RNA encoding for GABA(A)β3, 5-HT2A, and 5-HT7 receptors, PKCβ2, and brain-derived neurotrophic factor (BDNF) was assayed with real-time RT-PCR. Plasma BDNF protein was assayed using ELISA. Clinical symptoms were assessed with validated rating scales. We found significant increase in mRNA encoding for GABA(A)β3 and 5-HT2A, 5-HT7 receptors and BDNF and a reduction in PKCβ2 mRNA. Plasma BDNF protein concentrations were increased. There were significant correlations among the genes. Clinical symptoms improved significantly. mRNA expression of PKCβ2, 5-HT2A and 5-HT7 showed significant associations with clinical symptoms. Combined SSRI+antipsychotic treatment is associated with changes in GABA(A) receptor and in related signalling systems in patients. These changes may be part of the mechanism of clinically effective drug action and may prove to be biomarkers of pharmacological response.

  10. Observing behavior and atypically restricted stimulus control.

    PubMed

    Dube, William V; Dickson, Chata A; Balsamo, Lyn M; O'Donnell, Kristin Lombard; Tomanari, Gerson Y; Farren, Kevin M; Wheeler, Emily E; McIlvane, William J

    2010-11-01

    Restricted stimulus control refers to discrimination learning with atypical limitations in the range of controlling stimuli or stimulus features. In the study reported here, 4 normally capable individuals and 10 individuals with intellectual disabilities (ID) performed two-sample delayed matching to sample. Sample-stimulus observing was recorded with an eye-tracking apparatus. High accuracy scores indicated stimulus control by both sample stimuli for the 4 nondisabled participants and 4 participants with ID, and eye tracking data showed reliable observing of all stimuli. Intermediate accuracy scores indicated restricted stimulus control for the remaining 6 participants. Their eye-tracking data showed that errors were related to failures to observe sample stimuli and relatively brief observing durations. Five of these participants were then given interventions designed to improve observing behavior. For 4 participants, the interventions resulted initially in elimination of observing failures, increased observing durations, and increased accuracy. For 2 of these participants, contingencies sufficient to maintain adequate observing were not always sufficient to maintain high accuracy; subsequent procedure modifications restored it, however. For the 5th participant, initial improvements in observing were not accompanied by improved accuracy, an apparent instance of observing without attending; accuracy improved only after an additional intervention that imposed contingencies on observing behavior. Thus, interventions that control observing behavior seem necessary but may not always be sufficient for the remediation of restricted stimulus control.

  11. Evidence for the role of metabotropic glutamate (mGlu)2 not mGlu3 receptors in the preclinical antipsychotic pharmacology of the mGlu2/3 receptor agonist (-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY404039).

    PubMed

    Fell, Matthew J; Svensson, Kjell A; Johnson, Bryan G; Schoepp, Darryle D

    2008-07-01

    (-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY404039) is a potent and selective group II metabotropic glutamate [(mGlu)2 and mGlu3] receptor agonist for which its prodrug LY2140023 [(1R,4S,5S,6S)-2-thiabicyclo[3.1.0]-hexane-4,6-dicarboxylic acid,4-[(2S)-2-amino-4-(methylthio)-1-oxobutyl]amino-, 2,2-dioxide monohydrate] has recently been shown to have efficacy in the treatment of the positive and negative symptoms of schizophrenia. In this article, we use mGlu receptor-deficient mice to investigate the relative contribution of mGlu2 and mGlu3 receptors in mediating the antipsychotic profile of LY404039 in the phencyclidine (PCP) and d-amphetamine (AMP) models of psychosis. To further explore the mechanism of action of LY404039, we compared the drugs' ability to block PCP-induced hyperlocomotion to that of atypical antipsychotics in wild-type and mice lacking mGlu2/3 receptors. In wild-type animals, LY404039 (3-30 mg/kg i.p.) significantly reversed AMP (5 mg/kg, i.p.)-induced increases in ambulations, distance traveled, and reduced time spent at rest. LY404039 reversed PCP (7.5 mg/kg i.p.)-evoked behaviors at 10 mg/kg. The antipsychotic-like effects of LY404039 (10 mg/kg i.p.) on PCP and AMP-evoked behavioral activation were absent in mGlu2 and mGlu2/3 but not in mGlu3 receptor-deficient mice, indicating that the activation of mGlu2 and not mGlu3 receptors is responsible for the antipsychotic-like effects of the mGlu2/3 receptor agonist LY404039. In contrast, the atypical antipsychotic drugs clozapine and risperidone inhibited PCP-evoked behaviors in both wild-type and mGlu2/3 receptor-deficient mice. These data demonstrate that the antipsychotic-like effects of the mGlu2/3 receptor agonist LY404039 in psychostimulant models of psychosis are mechanistically distinct from those of atypical antipsychotic drugs and are dependent on functional mGlu2 and not mGlu3 receptors. PMID:18424625

  12. Clozapine combined with different antipsychotic drugs for treatment resistant schizophrenia

    PubMed Central

    Cipriani, Andrea; Boso, Marianna; Barbui, Corrado

    2014-01-01

    Background Although clozapine has been shown to be the treatment of choice in people with schizophrenia that are resistant to treatment, one third to two thirds of people still have persistent positive symptoms despite clozapine monotherapy of adequate dosage and duration. The need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine is the most common reason for simultaneously prescribing a second antipsychotic drug in combination with clozapine. Objectives To determine the efficacy and tolerability of various clozapine combination strategies with antipsychotics in people with treatment resistant schizophrenia. Search methods We searched the Cochrane Schizophrenia Group Trials Register (March 2008) and MEDLINE (up to November 2008). We checked reference lists of all identified randomised controlled trials and requested pharmaceutical companies marketing investigational products to provide relevant published and unpublished data. Selection criteria We included only randomised controlled trials recruiting people of both sexes, aged 18 years or more, with a diagnosis of treatment-resistant schizophrenia (or related disorders) and comparing clozapine plus another antipsychotic drug with clozapine plus a different antipsychotic drug. Data collection and analysis Two review authors independently extracted data and resolved disagreement by discussion with third member of the team. When insufficient data were provided, we contacted the study authors. Main results Three small (range of number of participants 28 to 60) randomised controlled trials were included in the review. Even though results from individual studies did not find that one combination strategy is better than the others, the methodological quality of included studies was too low to allow authors to use the collected data to answer the research question correctly. Authors’ conclusions In this review we considered the risk of bias too high because of

  13. Antipsychotic Prescribing Patterns in First-episode Schizophrenia: A Five-year Comparison

    PubMed Central

    Roh, Daeyoung; Chang, Jhin-Goo; Yoon, Sol; Kim, Chan-Hyung

    2015-01-01

    Objective Early treatment choice is critical in first-episode schizophrenia-spectrum disorders. The purpose of this study was to describe prescribing trends of antipsychotics use in patients with first-episode schizophrenia in 2005 and 2010, respectively. Methods We reviewed the medical records of newly treated patients with schizophrenia from a university psychiatric hospital in 2005 (n=47) and 2010 (n=52). We defined patients as receiving a high antipsychotic dose if their ratio of prescribed daily dose (PDD) to defined daily dose (DDD) was greater than 1.5. Results The rates of high-dose antipsychotic prescription were 61.7% and 53.8% in 2005 and 2010, respectively. The rates of antipsychotic polypharmacy were 34.6% in 2005 and 34.0% in 2010. The most common first-prescribed antipsychotics were (in descending order of prescription frequency) olanzapine, risperidone, aripiprazole, and haloperidol in 2005 and risperidone, quetiapine, paliperidone, and olanzapine in 2010. High-dose antipsychotics were significantly associated with antipsychotic poly-pharmacy (odds ratio=23.97; p<0.01). More individuals were treated with mood stabilizers in 2010 than in 2005 (p=0.003). Conclusion The practice of prescribing high-dose antipsychotics and associated antipsychotic polypharmacy were common even for initial treatment of first-episode schizophrenia in 2005 and 2010. In 2010, the list of the most common first-prescribed antipsychotics changed, and the use of mood stabilizers increased in non-affective schizophrenia. PMID:26598586

  14. Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival

    PubMed Central

    Jansen, M.; Mohapatra, G.; Betensky, R.A.; Keohane, C.; Louis, D.N.

    2013-01-01

    Aims Atypical (WHO grade II) meningiomas have moderately high recurrence rates; even for completely resected tumours, approximately one-third will recur. Postoperative radiotherapy (RT) may aid local control and improve survival, but carries the risk of side effects. More accurate prediction of recurrence risk is therefore needed for patients with atypical meningioma. Previously, we used high-resolution array CGH to identify genetic variations in 47 primary atypical meningiomas and found that approximately 60% of tumors show gain of 1q at 1q25.1 and 1q25.3 to 1q32.1 and that 1q gain appeared to correlate with shorter progression-free survival. This study aimed to validate and extend these findings in an independent sample. Methods 86 completely resected atypical meningiomas (with 25 recurrences) from two neurosurgical centres in Ireland were identified and clinical follow up was obtained. Utilizing a dual-colour interphase FISH assay, 1q gain was assessed using BAC probes directed against 1q25.1 and 1q32.1. Results The results confirm the high prevalence of 1q gain at these loci in atypical meningiomas. We further show that gain at 1q32.1 and age each correlate with progression-free survival in patients who have undergone complete surgical resection of atypical meningiomas. Conclusions These independent findings suggest that assessment of 1q copy number status can add clinically useful information for the management of patients with atypical meningiomas. PMID:21988727

  15. Typical and atypical AIS. Pathogenesis.

    PubMed

    Dudin, M; Pinchuk, D

    2012-01-01

    AIS hypothesis has the right to recognition, if it explains the transition of "healthy" vertebra column into status of "scoliotic" one. AIS is the most investigated disease in the history of orthopedics, but up the present time there is no clear explanation of some its phenomena: vertebra column mono-form deformation along with its poly etiology character, interrelation of its origin and development and child's growth process etc. The key for authors' view at AIS was scoliosis with non-standard (concave side) rotation. On the bases of its' multifunctional instrumental investigation results (Rtg, EMG, EEG, optical topography, hormonal and neuropeptides trials, thermo-vision methods and other) in comparison with typical AIS was worked out the new hypothesis, part of it is suggested for discussion. In the work under observation is the sequence of appearance of typical and atypical scoliosis symptomatology beginning from the preclinical stage. PMID:22744477

  16. Atypical immunoglobulin light chain amyloidosis

    PubMed Central

    Wu, Xia; Feng, Jun; Cao, Xinxin; Zhang, Lu; Zhou, Daobin; Li, Jian

    2016-01-01

    Abstract Background: Primary immunoglobulin light chain amyloidosis (AL amyloidosis) is a plasma cell disorder which mainly affects heart, kidneys, liver, and peripheral nervous system. Cases of atypical AL amyloidosis presented as spontaneous vertebral compression fractures have been rarely reported, and data about the management and clinical outcomes of the patients are scarce. Methods: Herein, we present 3 new cases of AL amyloidosis with spontaneous vertebral compression fracture and review 13 cases retrieved from the literature. Results: Moreover, we observed overrepresentations of liver involvement and bone marrow involvement in AL amyloidosis with spontaneous vertebral compression fracture. Conclusion: We believe that better awareness of the rare clinical presentation as spontaneous vertebral compression fracture of AL amyloidosis can facilitate earlier diagnosis and earlier treatment. PMID:27603350

  17. Atypical parasitic ischiopagus conjoined twins.

    PubMed

    Corona-Rivera, J Román; Corona-Rivera, Enrique; Franco-Topete, Ramón; Acosta-León, Jorge; Aguila-Dueñas, Virginia; Corona-Rivera, Alfredo

    2003-02-01

    Occurrence of asymmetrical or parasitic conjoined twins (CT) is rare, and currently they are classified analogically to the common unions of symmetrical CT. The authors report on an infant with a parasitic third limb attached to the left lateral aspect of the autosite trunk, in whom male gonadal tissue was found histologically. Parasite parts included complete left lower limb, hemipelvis, lumbosacral vertebral column, spinal cord, and one kidney with ureter and adrenal gland. Autosite anomalies comprised a small left diaphragmatic defect, omphalocele, exstrophy of cloaca, and lumbar meningomyelocele. The authors considered this case to be a rare atypical parasitic ischiopagus CT. The differential diagnosis of the type of twining and other entities with caudal duplications is analyzed briefly. PMID:12596123

  18. Atypical parasitic ischiopagus conjoined twins.

    PubMed

    Corona-Rivera, J Román; Corona-Rivera, Enrique; Franco-Topete, Ramón; Acosta-León, Jorge; Aguila-Dueñas, Virginia; Corona-Rivera, Alfredo

    2003-02-01

    Occurrence of asymmetrical or parasitic conjoined twins (CT) is rare, and currently they are classified analogically to the common unions of symmetrical CT. The authors report on an infant with a parasitic third limb attached to the left lateral aspect of the autosite trunk, in whom male gonadal tissue was found histologically. Parasite parts included complete left lower limb, hemipelvis, lumbosacral vertebral column, spinal cord, and one kidney with ureter and adrenal gland. Autosite anomalies comprised a small left diaphragmatic defect, omphalocele, exstrophy of cloaca, and lumbar meningomyelocele. The authors considered this case to be a rare atypical parasitic ischiopagus CT. The differential diagnosis of the type of twining and other entities with caudal duplications is analyzed briefly.

  19. [Atypical trajectory of gunshot injury].

    PubMed

    Aygün, Mert; Tulay, Cumhur Murat

    2014-11-01

    Gunshot injuries are common medical-legal issues. Atypical tract lines resulting from this type of injuries cause difficulties in diagnosis and treatment. In this paper, a gunshot injury on the right anterior thigh extending to the right hemithorax was presented. A 67-year-old Syrian refugee patient was brought to the emergency service due to gunshot injury. Bullet entrance hole was determined on the right anterior thigh region; however, exit side could not be seen. Bullet was determined on the right thorax at tomography and the patient was taken to operation due to diaphragm rupture and lung parenchymal injury. Other body parts must be examined radiologically for the bullet which cannot be determined at gunshot injury side. PMID:25541926

  20. Randomized Trial of the Effect of Four Second-Generation Antipsychotics and One First-Generation Antipsychotic on Cigarette Smoking, Alcohol, and Drug Use in Chronic Schizophrenia.

    PubMed

    Mohamed, Somaia; Rosenheck, Robert A; Lin, Haiqun; Swartz, Marvin; McEvoy, Joseph; Stroup, Scott

    2015-07-01

    No large-scale randomized trial has compared the effect of different second-generation antipsychotic drugs and any first-generation drug on alcohol, drug and nicotine use in patients with schizophrenia. The Clinical Antipsychotic Trial of Intervention Effectiveness study randomly assigned 1432 patients formally diagnosed with schizophrenia to four second-generation antipsychotic drugs (olanzapine, risperidone quetiapine, and ziprasidone) and one first-generation antipsychotic (perphenazine) and followed them for up to 18 months. Secondary outcome data documented cigarettes smoked in the past week and alcohol and drug use severity ratings. At baseline, 61% of patients smoked, 35% used alcohol, and 23% used illicit drugs. Although there were significant effects of time showing reduction in substance use over the 18 months (all p < 0.0001), this study found no evidence that any antipsychotic was robustly superior to any other in a secondary analysis of data on substance use outcomes from a large 18-month randomized schizophrenia trial.

  1. An Epidemiological Study of Concomitant Use of Chinese Medicine and Antipsychotics in Schizophrenic Patients: Implication for Herb-Drug Interaction

    PubMed Central

    Zhang, Zhang-Jin; Tan, Qing-Rong; Tong, Yao; Wang, Xue-Yi; Wang, Huai-Hai; Ho, Lai-Ming; Wong, Hei Kiu; Feng, Yi-Bin; Wang, Di; Ng, Roger; McAlonan, Grainne M.; Wang, Chuan-Yue; Wong, Vivian Taam

    2011-01-01

    Background Herb-drug interactions are an important issue in drug safety and clinical practice. The aim of this epidemiological study was to characterize associations of clinical outcomes with concomitant herbal and antipsychotic use in patients with schizophrenia. Methods and Findings In this retrospective, cross-sectional study, 1795 patients with schizophrenia who were randomly selected from 17 psychiatric hospitals in China were interviewed face-to-face using a structured questionnaire. Association analyses were conducted to examine correlates between Chinese medicine (CM) use and demographic, clinical variables, antipsychotic medication mode, and clinical outcomes. The prevalence of concomitant CM and antipsychotic treatment was 36.4% [95% confidence interval (95% CI) 34.2%–38.6%]. Patients using concomitant CM had a significantly greater chance of improved outcomes than non-CM use (61.1% vs. 34.3%, OR = 3.44, 95% CI 2.80–4.24). However, a small but significant number of patients treated concomitantly with CM had a greater risk of developing worse outcomes (7.2% vs. 4.4%, OR = 2.06, 95% CI 2.06–4.83). Significant predictors for concomitant CM treatment-associated outcomes were residence in urban areas, paranoid psychosis, and exceeding 3 months of CM use. Herbal medicine regimens containing Radix Bupleuri, Fructus Gardenia, Fructus Schisandrae, Radix Rehmanniae, Akebia Caulis, and Semen Plantaginis in concomitant use with quetiapine, clozapine, and olanzepine were associated with nearly 60% of the risk of adverse outcomes. Conclusions Concomitant herbal and antipsychotic treatment could produce either beneficial or adverse clinical effects in schizophrenic population. Potential herb-drug pharmacokinetic interactions need to be further evaluated. PMID:21359185

  2. Effects of Shakuyaku-Kanzo-to on Extrapyramidal Symptoms During Antipsychotic Treatment: A Randomized, Open-Label Study.

    PubMed

    Ota, Takafumi; Miura, Itaru; Kanno-Nozaki, Keiko; Hoshino, Hiroshi; Horikoshi, Sho; Fujimori, Haruo; Kanno, Tomoyuki; Mashiko, Hirobumi; Yabe, Hirooki

    2015-06-01

    Extrapyramidal symptoms (EPS) are common adverse effects of antipsychotic treatment. This study examined the effects of the traditional Japanese herbal medicine (kampo) shakuyaku-kanzo-to on EPS during antipsychotic treatment. Twenty-two Japanese patients with psychiatric disorders who had developed EPS during antipsychotic treatment were randomly allocated to receive either shakuyaku-kanzo-to (7.5 g/d) or biperiden (3 mg/d) for 2 weeks. Extrapyramidal symptoms were evaluated using the Drug-Induced Extrapyramidal Symptom Scale (DIEPSS) and the Barnes Akathisia Rating Scale. Plasma levels of the monoamine metabolite homovanillic acid and serum prolactin levels were measured to investigate the mechanisms of action of shakuyaku-kanzo-to. Twenty of the 22 patients completed the study (10 patients in the shakuyaku-kanzo-to group and 10 patients in the biperiden group). There was a time effect on the Drug-Induced Extrapyramidal Symptom Scale total score (P < 0.01), suggesting that both shakuyaku-kanzo-to and biperiden decreased EPS. Notably, there was a time × drug interaction in dystonia, suggesting that shakuyaku-kanzo-to had a greater effect on dystonia compared with biperiden. No significant changes were observed in plasma homovanillic acid or serum prolactin levels after 2 weeks of treatment in either group. The effects of shakuyaku-kanzo-to on abnormal muscle tonus and dopamine D2 receptors may have contributed to improve EPS. These results suggest that shakuyaku-kanzo-to may be useful in decreasing EPS, especially dystonia, in patients undergoing treatment with antipsychotic agents.

  3. The effects of the atypical antipsychotic asenapine in a strain-specific battery of tests for mania-like behaviors.

    PubMed

    Ene, Hila M; Kara, Nirit Z; Einat, Haim

    2015-06-01

    Asenapine is indicated for the treatment of schizophrenia and manic episodes in bipolar disorder (BPD). There is a paucity of information on the effects of asenapine in animal models of BPD, but such work is essential to discover its scope of effects and its mechanisms of therapeutic action. This study evaluated the effects of asenapine in a validated test battery for manic-like behaviors in Black Swiss mice. Male Black Swiss mice received asenapine at 0.03, 0.1, and 0.3 mg/kg twice daily for 7 days and were tested for spontaneous activity, sweet solution preference, forced-swim test, social interaction, and amphetamine-induced hyperactivity. Asenapine treatment resulted in dose-dependent, clinically relevant plasma levels. Asenapine, at the 0.1 and 0.3 mg/kg doses, reduced activity, with the 0.3 mg/kg dose also resulting in increased time in the center of an open field, increased immobility in the forced-swim test, and reduced amphetamine-induced hyperactivity. Asenapine exerted no effects in the social interaction or sweet solution preference tests. The results suggest that asenapine exerts antimanic-like effects in some of the behavioral tests performed in Black Swiss mice. These data support the utilization of asenapine in the treatment of BPD.

  4. Menstrual disturbance and galactorrhea in people taking conventional antipsychotic medications.

    PubMed

    Thangavelu, Karthik; Geetanjali, S

    2006-11-01

    Endocrine disturbances are emerging as major side effects of antipsychotic medications. Of particular note is the profile of menstrual disturbance and galactorrhea as a consequence of hyperprolactinemia (A. Weick & P. M. Haddad, 2003), a sequela of antidopaminergic action at the hypothalamopituitary axis. Research into the clinical aspects of this sensitive issue is sparse. The authors completed a cross-sectional descriptive study of 50 patients on conventional antipsychotic medications. The prevalence of menstrual disturbance was 54%, and the prevalence of amenorrhea was 12%. Symptoms of galactorrhea were present in 32% of patients. A history of pregnancy and childbirth was noted to be significantly associated with the development of galactorrhea (p = .01). The authors hypothesized that pregnancy and lactation might sensitize the hypothalamopituitary axis for further development of hyperprolactinemia due to medications.

  5. When less is more: reducing the incidence of antipsychotic polypharmacy.

    PubMed

    Tucker, William M

    2007-05-01

    In 2003, the New York State Office of Mental Health initiated a program aimed at supporting patient recovery by simplifying antipsychotic regimens. A key component of the program, which has been essential in supporting physician autonomy, was the introduction of a software program, Psychiatric Clinical Knowledge Enhancement System, termed "PSYCKES." This software program enables physicians to visualize at a glance the medication history of each of their patients as well as of their colleagues' patients, as a way of making better-informed decisions. The fiscal impact, in the direction of a significant reduction in antipsychotic polypharmacy, was not lost on policy-makers, who have included $1.3 million in the current state budget for the dissemination of this program. PMID:17522566

  6. Sleepwalking, a possible side effect of antipsychotic medication.

    PubMed

    Seeman, Mary V

    2011-03-01

    Two case examples and a review of the sleep literature illustrate the potential of antipsychotic medication to trigger sleepwalking episodes in the context of schizophrenia. Causative hypotheses are briefly reviewed, as well as risk factors, differential diagnosis, and management. Sleepwalking may contribute to delusions, aggression, and accidental suicide. It is important to investigate sleep disorders in schizophrenia. They are not rare and may contribute to behavior that increases the stigma and isolation of individuals with schizophrenia. PMID:20734137

  7. Sleepwalking, a possible side effect of antipsychotic medication.

    PubMed

    Seeman, Mary V

    2011-03-01

    Two case examples and a review of the sleep literature illustrate the potential of antipsychotic medication to trigger sleepwalking episodes in the context of schizophrenia. Causative hypotheses are briefly reviewed, as well as risk factors, differential diagnosis, and management. Sleepwalking may contribute to delusions, aggression, and accidental suicide. It is important to investigate sleep disorders in schizophrenia. They are not rare and may contribute to behavior that increases the stigma and isolation of individuals with schizophrenia.

  8. Mood stabilizers and antipsychotics during breastfeeding: Focus on bipolar disorder.

    PubMed

    Pacchiarotti, Isabella; León-Caballero, Jordi; Murru, Andrea; Verdolini, Norma; Furio, Maria Antonietta; Pancheri, Corinna; Valentí, Marc; Samalin, Ludovic; Roigé, Eva Solé; González-Pinto, Ana; Montes, Jose Manuel; Benabarre, Antonio; Crespo, Jose Manuel; de Dios Perrino, Consuelo; Goikolea, Jose Manuel; Gutiérrez-Rojas, Luis; Carvalho, André F; Vieta, Eduard

    2016-10-01

    Breast milk is considered the best source of nutrients and provides much better protection than immune modified milk. However, the postpartum period is a phase of increased risk for all women to experience psychiatric symptoms and recurrences or new episodes of bipolar disorder (BD), especially in those who have discontinued treatment. This is a systematic review of the risks and benefits of mood stabilizers and antipsychotics during breastfeeding as they relate to the health and well-being of mothers and their infants. Evidence-based treatment advice for women with BD during lactation is also provided. This systematic review has been conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. We included studies examining the exposure and the effects of antipsychotics and mood stabilizers used to treat BD on infants during breastfeeding clearly reporting the estimated amount of drug or effects on infants. The final selection included 56 studies. The available data supports the use of lithium as a possible treatment option during breastfeeding. Carbamazepine and valproic acid are also considered relatively safe. Lamotrigine can be used but at the lowest doses and considered for individual cases. Among the antipsychotics, quetiapine and olanzapine should be considered as first-line treatment options. Risperidone may be compatible with breastfeeding under medical supervision. Clozapine and amisulpiride are currently contraindicated. Long-term outcome studies evaluating the infant׳s health and psychosocial and cognitive functioning are needed. PMID:27568278

  9. First-generation antipsychotics: not gone but forgotten

    PubMed Central

    Dibben, Claire R. M.; Khandaker, Golam M.; Underwood, Benjamin R.; O'Loughlin, Christopher; Keep, Catherine; Mann, Louisa; Jones, Peter B.

    2016-01-01

    Aims and method To identify training needs of the next generation of psychiatrists and barriers in prescribing first-generation antipsychotics (FGAs). We have surveyed psychiatry trainees in East Anglia with regard to their training experience, knowledge and attitudes to the use of oral FGAs as regular medication. Results Two-thirds of trainees were aware that first- and second-generation antipsychotics (SGAs) have similar efficacy, and a similar proportion perceived the older drugs to have more or ‘stronger’ side-effects. Lack of training experience was noted as the second leading concern for prescribing FGAs. A quarter of trainees received no training exposure to the older drugs and two-thirds had never initiated these drugs themselves. Although nearly 90% of trainees felt confident about initiating an oral SGA as a regular medication, only about 40% felt confident with FGAs (P<0.001). Clinical implications The survey highlights worrying gaps in training. FGAs can be used effectively, minimising side-effects, by careful dose titration, avoiding antipsychotic polypharmacy, high-dose, and high-potency drugs, thus ensuring they are not lost to future generations of psychiatrists. PMID:27087995

  10. Could cannabidiol be used as an alternative to antipsychotics?

    PubMed

    Fakhoury, Marc

    2016-09-01

    Schizophrenia is a mental disorder that affects close to 1% of the population. Individuals with this disorder often present signs such as hallucination, anxiety, reduced attention, and social withdrawal. Although antipsychotic drugs remain the cornerstone of schizophrenia treatment, they are associated with severe side effects. Recently, the endocannabinoid system (ECS) has emerged as a potential therapeutic target for pharmacotherapy that is involved in a wide range of disorders, including schizophrenia. Since its discovery, a lot of effort has been devoted to the study of compounds that can modulate its activity for therapeutic purposes. Among them, cannabidiol (CBD), a non-psychoactive component of cannabis, shows great promise for the treatment of psychosis, and is associated with fewer extrapyramidal side effects than conventional antipsychotic drugs. The overarching goal of this review is to provide current available knowledge on the role of the dopamine system and the ECS in schizophrenia, and to discuss key findings from animal studies and clinical trials investigating the antipsychotic potential of CBD. PMID:27267317

  11. Hyperprolactinemia in a patient with a pituitary adenoma receiving antipsychotic drug therapy.

    PubMed

    Carroll, Richard W; Christodoulou, Polyxeni; Baynes, Kevin C R; Kahn, David A

    2012-03-01

    Hyperprolactinemia is a common consequence of treatment with an antipsychotic medication. It can result in hypogonadism due to the inhibitory effect of elevated prolactin levels on the hypothalamic-pituitary-gonadal hormonal axis. We present a case of hypogonadism secondary to hyperprolactinemia in a patient taking antipsychotic medication, with radiological evidence of a pituitary microadenoma. The relevance and investigation of hyperprolactinemia in patients being treated with antipsychotic medications are discussed.

  12. The Impact of Antipsychotic Polytherapy Costs in the Public Health Care in Sao Paulo, Brazil

    PubMed Central

    Razzouk, Denise; Kayo, Monica; Sousa, Aglaé; Gregorio, Guilherme; Cogo-Moreira, Hugo; Cardoso, Andrea Alves; Mari, Jair de Jesus

    2015-01-01

    Introduction Guidelines for the treatment of psychoses recommend antipsychotic monotherapy. However, the rate of antipsychotic polytherapy has increased over the last decade, reaching up to 60% in some settings. Studies evaluating the costs and impact of antipsychotic polytherapy in the health system are scarce. Objective To estimate the costs of antipsychotic polytherapy and its impact on public health costs in a sample of subjects with psychotic disorders living in residential facilities in the city of Sao Paulo, Brazil. Method A cross-sectional study that used a bottom-up approach for collecting costs data in a public health provider´s perspective. Subjects with psychosis living in 20 fully-staffed residential facilities in the city of Sao Paulo were assessed for clinical and psychosocial profile, severity of symptoms, quality of life, use of health services and pharmacological treatment. The impact of polytherapy on total direct costs was evaluated. Results 147 subjects were included, 134 used antipsychotics regularly and 38% were in use of antipsychotic polytherapy. There were no significant differences in clinical and psychosocial characteristics between polytherapy and monotherapy groups. Four variables explained 30% of direct costs: the number of antipsychotics, location of the residential facility, time living in the facility and use of olanzapine. The costs of antipsychotics corresponded to 94.4% of the total psychotropic costs and to 49.5% of all health services use when excluding accommodation costs. Olanzapine costs corresponded to 51% of all psychotropic costs. Conclusion Antipsychotic polytherapy is a huge economic burden to public health service, despite the lack of evidence supporting this practice. Great variations on antipsychotic costs explicit the need of establishing protocols for rational antipsychotic prescriptions and consequently optimising resource allocation. Cost-effectiveness studies are necessary to estimate the best value for money

  13. Autophagy inhibition uncovers the neurotoxic action of the antipsychotic drug olanzapine

    PubMed Central

    Vucicevic, Ljubica; Misirkic-Marjanovic, Maja; Paunovic, Verica; Kravic-Stevovic, Tamara; Martinovic, Tamara; Ciric, Darko; Maric, Nadja; Petricevic, Sasa; Harhaji-Trajkovic, Ljubica; Bumbasirevic, Vladimir; Trajkovic, Vladimir

    2015-01-01

    We investigated the role of autophagy, a controlled cellular self-digestion process, in regulating survival of neurons exposed to atypical antipsychotic olanzapine. Olanzapine induced autophagy in human SH-SY5Y neuronal cell line, as confirmed by the increase in autophagic flux and presence of autophagic vesicles, fusion of autophagosomes with lysosomes, and increase in the expression of autophagy-related (ATG) genes ATG4B, ATG5, and ATG7. The production of reactive oxygen species, but not modulation of the main autophagy repressor MTOR or its upstream regulators AMP-activated protein kinase and AKT1, was responsible for olanzapine-triggered autophagy. Olanzapine-mediated oxidative stress also induced mitochondrial depolarization and damage, and the autophagic clearance of dysfunctional mitochondria was confirmed by electron microscopy, colocalization of autophagosome-associated MAP1LC3B (LC3B henceforth) and mitochondria, and mitochondrial association with the autophagic cargo receptor SQSTM1/p62. While olanzapine-triggered mitochondrial damage was not overtly toxic to SH-SY5Y cells, their death was readily initiated upon the inhibition of autophagy with pharmacological inhibitors, RNA interference knockdown of BECN1 and LC3B, or biological free radical nitric oxide. The treatment of mice with olanzapine for 14 d increased the brain levels of autophagosome-associated LC3B-II and mRNA encoding Atg4b, Atg5, Atg7, Atg12, Gabarap, and Becn1. The administration of the autophagy inhibitor chloroquine significantly increased the expression of proapoptotic genes (Trp53, Bax, Bak1, Pmaip1, Bcl2l11, Cdkn1a, and Cdkn1b) and DNA fragmentation in the frontal brain region of olanzapine-exposed animals. These data indicate that olanzapine-triggered autophagy protects neurons from otherwise fatal mitochondrial damage, and that inhibition of autophagy might unmask the neurotoxic action of the drug. PMID:25551567

  14. Use of the second-generation antipsychotic, risperidone, and secondary weight gain are associated with an altered gut microbiota in children

    PubMed Central

    Bahr, S M; Tyler, B C; Wooldridge, N; Butcher, B D; Burns, T L; Teesch, L M; Oltman, C L; Azcarate-Peril, M A; Kirby, J R; Calarge, C A

    2015-01-01

    The atypical antipsychotic risperidone (RSP) is often associated with weight gain and cardiometabolic side effects. The mechanisms for these adverse events are poorly understood and, undoubtedly, multifactorial in etiology. In light of growing evidence implicating the gut microbiome in the host's energy regulation and in xenobiotic metabolism, we hypothesized that RSP treatment would be associated with changes in the gut microbiome in children and adolescents. Thus, the impact of chronic (>12 months) and short-term use of RSP on the gut microbiome of pediatric psychiatrically ill male participants was examined in a cross-sectional and prospective (up to 10 months) design, respectively. Chronic treatment with RSP was associated with an increase in body mass index (BMI) and a significantly lower ratio of Bacteroidetes:Firmicutes as compared with antipsychotic-naïve psychiatric controls (ratio=0.15 vs 1.24, respectively; P<0.05). Furthermore, a longitudinal observation, beginning shortly after onset of RSP treatment, revealed a gradual decrease in the Bacteroidetes:Firmicutes ratio over the ensuing months of treatment, in association with BMI gain. Lastly, metagenomic analyses were performed based on extrapolation from 16S ribosomal RNA data using the software package, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Those data indicate that gut microbiota dominating the RSP-treated participants are enriched for pathways that have been implicated in weight gain, such as short-chain fatty acid production. PMID:26440540

  15. Saccular cyst with atypical presentation

    PubMed Central

    Zamfir-Chiru-Anton, A; Gheorghe, DC

    2016-01-01

    Respiratory obstruction and stridor in infants and children are not uncommon. A rare cause of these sometimes life-threatening symptoms is the congenital saccular cyst. Objectives: We present the case of a 5-year-old girl with a cervical tumor, which appeared after a laryngeal endoscopic surgery of a saccular cyst with two relapses and a particular local evolution of its recurrence through the cricothyroid membrane. Material and method: The patient data has been reviewed over the entire follow-up period and a thorough an analysis of her investigations and surgery was performed. Results: The unusual evolution of this case was marked by an atypical exteriorization – not found in the published literature. The surgical approach was external, by paramedian thyrotomy, with no further long-term recurrence. Conclusions: An accurate diagnosis of saccular cysts can be made with the help of medical history, by an endoscopic visualization of the lesion and by the CT-scan imaging of the cervical region. Sometimes, saccular cysts can extend beyond laryngeal limits, determining fluid-filled tumors in the cervical region. PMID:27453755

  16. Biopsychosocial Aspects of Atypical Odontalgia

    PubMed Central

    Ciaramella, A.; Paroli, M.; Lonia, L.; Bosco, M.; Poli, P.

    2013-01-01

    Background. A few studies have found somatosensory abnormalities in atypical odontalgia (AO) patients. The aim of the study is to explore the presence of specific abnormalities in facial pain patients that can be considered as psychophysical factors predisposing to AO. Materials and Methods. The AO subjects (n = 18) have been compared to pain-free (n = 14), trigeminal neuralgia (n = 16), migraine (n = 17), and temporomandibular disorder (n = 14). The neurometer current perception threshold (CPT) was used to investigate somatosensory perception. Structured clinical interviews based on the DSM-IV axis I and DSM III-R axis II criteria for psychiatric disorders and self-assessment questionnaires were used to evaluate psychopathology and aggressive behavior among subjects. Results. Subjects with AO showed a lower Aβ, Aδ, and C trigeminal fiber pain perception threshold when compared to a pain-free control group. Resentment was determined to be inversely related to Aβ (rho: 0.62, P < 0.05), Aδ (rho: 0.53, P < 0.05) and C fibers (rho: 0.54, P < 0.05), and depression was inversely related with C fiber (rho: 0.52, P < 0.05) perception threshold only in AO subjects. Conclusion. High levels of depression and resentment can be considered predictive psychophysical factors for the development of AO after dental extraction. PMID:24959561

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

    PubMed Central

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

    2016-01-01

    This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of the combination of electroconvulsive therapy (ECT) and antipsychotic medication (except for clozapine) versus the same antipsychotic monotherapy for treatment-resistant schizophrenia (TRS). Two independent investigators extracted data for a random effects meta-analysis and pre-specified subgroup and meta-regression analyses. Weighted and standard mean difference (WMD/SMD), risk ratio (RR) ±95% confidence intervals (CIs), number needed to treat (NNT), and number needed to harm (NNH) were calculated. Eleven studies (n = 818, duration = 10.2±5.5 weeks) were identified for meta-analysis. Adjunctive ECT was superior to antipsychotic monotherapy regarding (1) symptomatic improvement at last-observation endpoint with an SMD of -0.67 (p<0.00001; I2 = 62%), separating the two groups as early as weeks 1–2 with an SMD of -0.58 (p<0.00001; I2 = 0%); (2) study-defined response (RR = 1.48, p<0.0001) with an NNT of 6 (CI = 4–9) and remission rate (RR = 2.18, p = 0.0002) with an NNT of 8 (CI = 6–16); (3) PANSS positive and general symptom sub-scores at endpoint with a WMD between -3.48 to -1.32 (P = 0.01 to 0.009). Subgroup analyses were conducted comparing double blind/rater-masked vs. open RCTs, those with and without randomization details, and high quality (Jadad≥adadup analyses were Jadad<3) studies. The ECT-antipsychotic combination caused more headache (p = 0.02) with an NNH of 6 (CI = 4–11) and memory impairment (p = 0.001) with an NNH of 3 (CI = 2–5). The use of ECT to augment antipsychotic treatment (clozapine excepted) can be an effective treatment option for TRS, with increased frequency of self-reported memory impairment and headache. Trial registration CRD42014006689 (PROSPERO). PMID:27285996

  18. Antipsychotic polypharmacy in a regional health service: a population-based study

    PubMed Central

    2012-01-01

    Background To analyse the extent and profile of outpatient regular dispensation of antipsychotics, both in combination and monotherapy, in the Barcelona Health Region (Spain), focusing on the use of clozapine and long-acting injections (LAI). Methods Antipsychotic drugs dispensed for people older than 18 and processed by the Catalan Health Service during 2007 were retrospectively reviewed. First and second generation antipsychotic drugs (FGA and SGA) from the Anatomical Therapeutic Chemical classification (ATC) code N05A (except lithium) were included. A patient selection algorithm was designed to identify prescriptions regularly dispensed. Variables included were age, gender, antipsychotic type, route of administration and number of packages dispensed. Results A total of 117,811 patients were given any antipsychotic, of whom 71,004 regularly received such drugs. Among the latter, 9,855 (13.9%) corresponded to an antipsychotic combination, 47,386 (66.7%) to monotherapy and 13,763 (19.4%) to unspecified combinations. Of the patients given antipsychotics in association, 58% were men. Olanzapine (37.1%) and oral risperidone (36.4%) were the most common dispensations. Analysis of the patients dispensed two antipsychotics (57.8%) revealed 198 different combinations, the most frequent being the association of FGA and SGA (62.0%). Clozapine was dispensed to 2.3% of patients. Of those who were receiving antipsychotics in combination, 6.6% were given clozapine, being clozapine plus amisulpride the most frequent association (22.8%). A total of 3.800 patients (5.4%) were given LAI antipsychotics, and 2.662 of these (70.1%) were in combination. Risperidone was the most widely used LAI. Conclusions The scant evidence available regarding the efficacy of combining different antipsychotics contrasts with the high number and variety of combinations prescribed to outpatients, as well as with the limited use of clozapine. PMID:22587453

  19. Nocturnal manifestations of atypical parkinsonian disorders.

    PubMed

    Bhidayasiri, Roongroj; Jitkritsadakul, Onanong; Colosimo, Carlo

    2014-01-01

    Although nocturnal disturbances are increasingly recognized as an integral part of the continuum of daytime manifestations of Parkinson's disease (PD), there is still little evidence in the medical literature to support the occurrence of these complex phenomena in patients with atypical parkinsonian disorders (APDs). Based on the anatomical substrates in APDs, which are considered to be more extensive outside the basal ganglia than in PD, we might expect that patients with APDs encounter the whole range of nocturnal disturbances, including motor, sleep disorders, autonomic dysfunctions, and neuropsychiatric manifestations at a similar, or even greater, frequency than in PD. This article is a review of the current literature on the problems at nighttime of patients with progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, and dementia with Lewy bodies. MEDLINE, life science journals and online books were searched by querying appropriate key words. Reports were included if the studies were related to nocturnal manifestations in APDs. Forty articles fulfilled the selection criteria. Differences between these symptoms in APDs and PD are highlighted, given the evidence available about each manifestation. This analysis of nocturnal manifestations of APDs suggests the need for future studies to address these issues to improve the quality of life not only of patients with APDs but the caregivers who encounter the challenges of supporting these patients on a daily basis.

  20. Wnt pathway in atypical teratoid rhabdoid tumors

    PubMed Central

    Chakravadhanula, Madhavi; Hampton, Chris N.; Chodavadia, Parth; Ozols, Victor; Zhou, Li; Catchpoole, Daniel; Xu, Jingying; Erdreich-Epstein, Anat; Bhardwaj, Ratan D.

    2015-01-01

    Background Atypical teratoid rhabdoid tumor (ATRT) is an aggressive pediatric brain tumor with limited therapeutic options. The hypothesis for this study was that the Wnt pathway triggered by the Wnt5B ligand plays an important role in ATRT biology. To address this hypothesis, the role of WNT5B and other Wnt pathway genes was analyzed in ATRT tissues and ATRT primary cell lines. Methods Transcriptome-sequencing analyses were performed using nanoString platforms, immunohistochemistry, Western blotting, quantitative reverse transcriptase PCR, immunoprecipitation, short interference RNA studies, cell viability studies, and drug dose response (DDR) assays. Results Our transcriptome-sequencing results of Wnt pathway genes from ATRT tissues and cell lines indicated that the WNT5B gene is significantly upregulated in ATRT samples compared with nontumor brain samples. These results also indicated a differential expression of both canonical and noncanonical Wnt genes. Imunoprecipitation studies indicated that Wnt5B binds to Frizzled1 and Ryk receptors. Inhibition of WNT5B by short interference RNA decreased the expression of FRIZZLED1 and RYK. Cell viability studies a indicated significant decrease in cell viability by inhibiting Frizzled1 receptor. DDR assays showed promising results with some inhibitors. Conclusions These promising therapeutic options will be studied further before starting a translational clinical trial. The success of these options will improve care for these patients. PMID:25246426

  1. [The effects of antipsychotic treatment on the hypothalamo-pituitary-gonadal (HPG) axis in patients with schizophrenia].

    PubMed

    Wyszogrodzka-Kucharska, Anna; Rabe-Jabłońska, Jolanta; Kostulski, Adrian

    2003-01-01

    The functioning of Hypothalamic-Pituitary-Gonadal axis is commonly affected during a course of antipsychotic therapy. This paper presents epidemiology, possible cause and management of hormonal disturbances during antipsychotic treatment in patients with schizophrenia.

  2. Arterial Stiffness in Patients Taking Second-generation Antipsychotics

    PubMed Central

    Fındıklı, Ebru; Gökçe, Mustafa; Nacitarhan, Vedat; Camkurt, Mehmet Akif; Fındıklı, Hüseyin Avni; Kardaş, Selçuk; Şahin, Merve Coşgun; Karaaslan, Mehmet Fatih

    2016-01-01

    Objective That treatment with second-generation antipsychotics (SGAs) causes metabolic side effects and atherosclerosis in patients with schizophrenia and bipolar disorder (BD) is well-known. Increased arterial stiffness is an important marker of arteriosclerosis and has been identified as an independent risk factor for cardiovascular diseases. We measured pulse wave velocity (PWV) as a marker of arteriosclerosis in patients with schizophrenia and BD who use SGAs. Methods Patients and controls were collected from our psychiatry outpatient clinics or family medicine. Mental illness was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Mean age, gender, systolic and diastolic blood pressure, body mass index, Framingham risk score (FRS), etc. were determined. Simultaneous electrocardiography and pulse wave were recorded with an electromyography device. The photo-plethysmographic method was used to record the pulse wave. Inclusion criteria included use of SGAs for at least the last six months. Patients with diseases that are known to cause stiffness and the use of typical antipsychotics were excluded. Results Ninety-six subject (56 patients, 40 controls) were included in our study. There were 49 females, 47 males. Patients had schizophrenia (n=17) and BD (n=39). Their treatments were quetiapine (n=15), risperidone (n=13), olanzapine (n=15), and aripiprazole (n=13). Although differences in mean age, gender, and FRS in the patient and control groups were not statistically significant (p=1), PWV was greater in patients in the antipsychotic group (p=0.048). Conclusion This study supported the liability to stiffness in patients with schizophrenia and BD. Using SGAs may contribute to arterial stiffness in these patients. PMID:27776389

  3. A Systemic Review and Experts’ Consensus for Long-acting Injectable Antipsychotics in Bipolar Disorder

    PubMed Central

    Chou, Yuan Hwa; Chu, Po-Chung; Wu, Szu-Wei; Lee, Jen-Chin; Lee, Yi-Hsuan; Sun, I-Wen; Chang, Chen-Lin; Huang, Chien-Liang; Liu, I-Chao; Tsai, Chia-Fen; Yen, Yung-Chieh

    2015-01-01

    Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence, partial adherence, and in reducing relapse in BD. Various long-acting injectable (LAI) antipsychotics are available, including fluphenazine decanoate, haloperidol decanoate, olanzapine pamoate, risperidone microspheres, paliperidone palmitate, and aripiprazole monohydrate. Due to the increasing number of BD patients receiving LAI antipsychotics, treatment guidelines have been developed. However, the clinical applicability of LAI antipsychotics remains a global cause for concern, particularly in Asian countries. Expert physicians from Taiwan participated in a consensus meeting, which was held to review key areas based on both current literature and clinical practice. The purpose of this meeting was to generate a practical and implementable set of recommendations for LAI antipsychotic use to treat BD; target patient groups, dosage, administration, and adverse effects were considered. Experts recommended using LAI antipsychotics in patients with schizophrenia, rapid cycling BD, BD I, and bipolar-type schizoaffective disorder. LAI antipsychotic use was recommended in BD patients with the following characteristics: multiple episodes and low adherence; seldom yet serious episodes; low adherence potential per a physician’s clinical judgment; preference for injectable agents over oral agents; and multiple oral agent users still experiencing residual symptoms. PMID:26243837

  4. How antipsychotics impact the different dimensions of Schizophrenia: a test of competing hypotheses.

    PubMed

    Marques, Tiago Reis; Levine, Stephen Z; Reichenberg, Avi; Kahn, Rene; Derks, Eske M; Fleischhacker, Wolfgang W; Rabinowitz, Jonathan; Kapur, Shitij

    2014-08-01

    The clinical expression of schizophrenia is generally reported to be expressed by three to five different factors (i.e. positive, negative, disorganization, excitability, anxiety-depression symptoms). It is often claimed that antipsychotic medications are particularly helpful for positive symptoms, but not for the others, suggesting a differential efficacy for different aspects of the disorder. We formally tested this claim. Using Structural Equation Modeling in two large [1884 patients] clinical trials in schizophrenia, we compared the model of a common general effect of antipsychotics to models whereby the antipsychotics have multiple and differential effects on the different factors of the illness. We validated the generalizability of the model in further trials involving antipsychotics in chronic [1460 patients] and first-episode patients [1053 patients]. Across different populations, different trials and different antipsychotics - the best-fitting model suggests that symptom response in schizophrenia is underpinned by a single general effect with secondary and minor lower-order effects on specific symptom domains. This single-factor model explained nearly 80% of the variance, was superior to the assumption of unique efficacy for specific domains; and replicated across antipsychotics and illness stages. Despite theoretical and pharmacological claims the differential efficacy of antipsychotics on the various dimensions of schizophrenia is not supported in the prevailing data. The implication of this finding for the measurement of treatment response and our understanding of the neurobiology of antipsychotic action, for clinical practice and for future drug development are discussed.

  5. Antipsychotic Use and Metabolic Monitoring in Individuals with Developmental Disabilities Served in a Medicaid Medical Home

    ERIC Educational Resources Information Center

    Ruiz, Lisa M.; Damron, Mackenzie; Jones, Kyle B.; Weedon, Dean; Carbone, Paul S.; Bakian, Amanda V.; Bilder, Deborah A.

    2016-01-01

    This study describes antipsychotic use and metabolic monitoring rates among individuals with developmental disabilities enrolled in a subspecialty medical home (N = 826). Four hundred ninety-nine participants (60.4%) were taking antipsychotics, which was associated with male gender (p = 0.01), intellectual disability with and without autism…

  6. Trends in Antipsychotic Drug Use by Very Young, Privately Insured Children

    ERIC Educational Resources Information Center

    Olfson, Mark; Crystal, Stephen; Huang, Cecilia; Gerhard, Tobias

    2010-01-01

    Objective: This study describes recent trends and patterns in antipsychotic treatment of privately insured children aged 2 through 5 years. Method: A trend analysis is presented of antipsychotic medication use (1999-2001 versus 2007) stratified by patient characteristics. Data are analyzed from a large administrative database of privately insured…

  7. Nature and Quality of Antipsychotic Prescribing Practice in UK Psychiatry of Intellectual Disability Services

    ERIC Educational Resources Information Center

    Paton, C.; Flynn, A.; Shingleton-Smith, A.; McIntyre, S.; Bhaumik, S.; Rasmussen, J.; Hardy, S.; Barnes, T.

    2011-01-01

    Background: Antipsychotics are perceived to be over-used in the management of behavioural problems in people with an intellectual disability (ID). Published guidelines have set good practice standards for the use of these drugs for behavioural indications. We sought to identify the range of indications for which antipsychotic drugs are prescribed…

  8. Loxapine for Reversal of Antipsychotic-Induced Metabolic Disturbances: A Chart Review

    ERIC Educational Resources Information Center

    Jain, Seema; Andridge, Rebecca; Hellings, Jessica A.

    2016-01-01

    Loxapine substitution is a promising option for patients with autism spectrum disorder (ASD) who develop antipsychotic-induced metabolic illness. We performed a chart review of 15 adolescents and adults meeting DSM-IV-TR criteria for ASD, all with antipsychotic-associated weight gain, who received low dose loxapine in an attempt to taper or…

  9. Partnership to decrease antipsychotic medication use in nursing homes: impact at the state level.

    PubMed

    Mort, Jane R; Sailor, Ryan; Hintz, Lori

    2014-02-01

    In 2012, the Centers for Medicare & Medicaid Services (CMS) established a partnership among stakeholders to decrease the percentage of residents in nursing homes receiving an antipsychotic agent by 15 percent. This goal emanated from concerns including the large percentage of residents taking antipsychotic agents, the questionable use of antipsychotics (e.g., off-label use), the high cost of inappropriate antipsychotic use, and toxicity in patients with dementia (e.g., black box warning regarding mortality). The successful achievement of this goal is evaluated via quality measures, which are greatly influenced by changes in exclusion of residents from the population examined. The partnership is focused on optimizing use of antipsychotic agents by training clinicians on nonpharmacologic approaches, educating on the dangers of antipsychotic medication use and sharing data on antipsychotic medications. In South Dakota, these efforts have yielded a 12 percent relative reduction (21.3 percent to 18.7 percent) in the percent of residents prescribed antipsychotic agents from the second quarter of 2012 to the second quarter of 2013. Future efforts in South Dakota include a Nursing Home Quality Care Collaborative that involves the majority of facilities across the state learning from peers and national experts. The South Dakota Dementia Coalition includes 17 stakeholders who guide education activities and communicate these opportunities to their constituents. PMID:24624602

  10. Metabolic syndrome in schizophrenia: Differences between antipsychotic-naïve and treated patients

    PubMed Central

    Chadda, Rakesh K.; Ramshankar, Prashanth; Deb, Koushik S.; Sood, Mamta

    2013-01-01

    Metabolic syndrome (MetS) has been recognized as a risk factor for cardiovascular morbidity and mortality in general population and in patients with severe mental illnesses like schizophrenia. This paper reviews studies on MetS in schizophrenia and related psychotic disorders, and assesses the contribution of antipsychotics toward the development of MetS. Databases of Medline (PubMed), PsycINFO, and Scopus were searched for MetS, psychotic disorders, and antipsychotic drugs from inception till present. Prevalence of MetS in patients with schizophrenia was found to be ranging from 3.3% to 68.0%. Prevalence in antipsychotic-naïve and antipsychotic-treated patients ranged between 3.3-26.0% and 32.0-68.0% respectively, and was higher in younger patients, female gender and Hispanics, and lower in African-Americans and Orientals. Prevalence of metabolic abnormalities was higher in patients receiving second generation antipsychotics (SGAs), especially with clozapine, olanzapine, and risperidone, as compared to first generation antipsychotics (FGAs). Antipsychotic-induced changes on metabolic indices became evident after 2 weeks and reached maximum at 3 months of treatment. There is a need to sensitize the mental health professionals at all levels about the need of screening and monitoring for MetS in patients receiving antipsychotics. PMID:23960422

  11. Impact of antipsychotic medication on physical activity and physical fitness in adolescents: An exploratory study.

    PubMed

    Vancampfort, Davy; Probst, Michel; Daenen, Anne; Damme, Tine Van; De Hert, Marc; Rosenbaum, Simon; Bruyninckx, David

    2016-08-30

    Antipsychotics are used increasingly in adolescents for a range of psychiatric disorders. The aim of the current study was to investigate whether physical activity levels and physical fitness of adolescent inpatients treated with antipsychotic medication, differs from either (i) antipsychotic naïve adolescents with mental health problems and, (ii) healthy controls. All participants completed the Physical Activity Questionnaire for Adolescents, the Positive-and-Negative-Affect-Schedule and performed the Eurofit test battery. Adolescents with mental health problems (irrespective of antipsychotic medication) were significantly (P<0.05) less physically active and had an impaired whole body balance, running speed and cardiovascular endurance compared to healthy controls (n=15, 8♂, 15.9±1.3 years). Adolescents treated with antipsychotic medication (n=15, 8♂, 15.5±1.3 years) were less physically active and had an impaired whole body balance compared with antipsychotic naïve adolescents (n=15, 8♂, 15.7±1.4 years). Given the overwhelming deleterious impact of physical inactivity and low physical fitness on physical and mental health outcomes, interventions specifically targeting physical activity and physical fitness among adolescents experiencing mental illness, both treated with, and not treated with antipsychotic medication are warranted as a priority. Antipsychotic medication should be considered as a risk factor for physical inactivity and poor physical fitness. PMID:27288738

  12. Effectiveness of an Inpatient Movement Disorders Program for Patients with Atypical Parkinsonism

    PubMed Central

    Hohler, Anna D.; Tsao, Jyeming M.; Katz, Douglas I.; DiPiero, T. Joy; Hehl, Christina L.; Leonard, Alissa; Allen, Valerie; Gardner, Maura; Phenix, Heidi; Saint-Hilaire, Marie; Ellis, Terry

    2012-01-01

    This paper investigated the effectiveness of an inpatient movement disorders program for patients with atypical parkinsonism, who typically respond poorly to pharmacologic intervention and are challenging to rehabilitate as outpatients. Ninety-one patients with atypical parkinsonism participated in an inpatient movement disorders program. Patients received physical, occupational, and speech therapy for 3 hours/day, 5 to 7 days/week, and pharmacologic adjustments based on daily observation and data. Differences between admission and discharge scores were analyzed for the functional independence measure (FIM), timed up and go test (TUG), two-minute walk test (TMW), Berg balance scale (BBS) and finger tapping test (FT), and all showed significant improvement on discharge (P > .001). Clinically significant improvements in total FIM score were evident in 74% of the patients. Results were similar for ten patients whose medications were not adjusted. Patients with atypical parkinsonism benefit from an inpatient interdisciplinary movement disorders program to improve functional status. PMID:22135763

  13. Effectiveness of an inpatient movement disorders program for patients with atypical parkinsonism.

    PubMed

    Hohler, Anna D; Tsao, Jyeming M; Katz, Douglas I; Dipiero, T Joy; Hehl, Christina L; Leonard, Alissa; Allen, Valerie; Gardner, Maura; Phenix, Heidi; Saint-Hilaire, Marie; Ellis, Terry

    2012-01-01

    This paper investigated the effectiveness of an inpatient movement disorders program for patients with atypical parkinsonism, who typically respond poorly to pharmacologic intervention and are challenging to rehabilitate as outpatients. Ninety-one patients with atypical parkinsonism participated in an inpatient movement disorders program. Patients received physical, occupational, and speech therapy for 3 hours/day, 5 to 7 days/week, and pharmacologic adjustments based on daily observation and data. Differences between admission and discharge scores were analyzed for the functional independence measure (FIM), timed up and go test (TUG), two-minute walk test (TMW), Berg balance scale (BBS) and finger tapping test (FT), and all showed significant improvement on discharge (P > .001). Clinically significant improvements in total FIM score were evident in 74% of the patients. Results were similar for ten patients whose medications were not adjusted. Patients with atypical parkinsonism benefit from an inpatient interdisciplinary movement disorders program to improve functional status. PMID:22135763

  14. Prenatal exposure of a novel antipsychotic aripiprazole: impact on maternal, fetal and postnatal body weight modulation in rats.

    PubMed

    Singh, K P; Tripathi, Nidhi

    2014-03-01

    Nearly all atypical antipsychotic drugs (AAPDs) of second- generation are associated with body weight gain in adults with prolonged exposure; but reports on third-generation AAPDs like Aripiprazole (ARI) and weight gain are scanty and ambiguous. This may be attributed to some unknown mechanism of action, the study of which is essential to investigate gestational exposure of equivalent therapeutic doses of ARI on maternal and fetal weight gain and its longlasting impact on postnatal development and growth of offspring in rodent model. 30 pregnant Wistar rats were exposed to selected doses (2mg, 3mg and 5mg/kg BW) of ARI from GD3-21 orally, with control subjects. Half of the pregnant subjects of each group were sacrificed at GD22 and rest dams were allowed to deliver normally and pups were reared postnatally up to 10 weeks of age. In ARI treated groups, there was no substantial alteration of body weight gain and food intake in pregnant subjects while significant reduction was found in fetal and postnatal (pre-and post weaning) body weight gain. ARI was found neutral for substantial weight gain in pregnant rats but may induce significant weight loss in fetuses, creating long-lasting negative impact on offspring growth (in weight) till PND70. Therefore, ARI could be a good alternative of second- generation AAPDs for adult females but may not be safe for developing fetuses and offspring.

  15. Metabolic consequences of second-generation antipsychotics in youth: appropriate monitoring and clinical management

    PubMed Central

    Krill, Rebecca A; Kumra, Sanjiv

    2014-01-01

    Objective To review the metabolic consequences of second-generation antipsychotics in youth and current monitoring and intervention guidelines for optimal treatment. Background Second-generation antipsychotics have largely replaced the use of first-generation antipsychotics in treating psychotic disorders in youth. In addition, there has been a dramatic increase in using these medications to treat a variety of nonpsychotic disorders. These medications have significant metabolic side effects, including weight gain. This raises concern, given the problem of pediatric obesity. Materials and methods A review of current literature looking at prescribing practices and possible reasons for the increased use of second-generation antipsychotics in children and adolescents was conducted. Review of the mechanisms for why youth may be particularly vulnerable to the metabolic consequences (particularly weight gain) was similarly completed. In addition, data supporting the efficacy, rationale, and unique side-effect profile of each individual second-generation drug were evaluated to help inform providers on when and what to prescribe, along with current monitoring practices. The current evidence base for possible interventions regarding the management of antipsychotic-induced weight gain was also evaluated. Results and conclusion On the basis of the literature review, there are several speculated reasons for the increase in prescriptions of second-generation antipsychotics. The choice of antipsychotic for youth should be based upon the disorder being treated along with the unique side-effect profile for the most commonly used second-generation antipsychotics. Monitoring strategies are also individualized to each antipsychotic. The current interventions recommended for antipsychotic-induced weight gain include lifestyle management, switching medication to a drug with a lower propensity for weight gain, and pharmacologic (particularly metformin) treatment. PMID:25298741

  16. Antipsychotic-induced sensitization and tolerance: Behavioral characteristics, developmental impacts, and neurobiological mechanisms

    PubMed Central

    Li, Ming

    2016-01-01

    Antipsychotic sensitization and tolerance refer to the increased and decreased drug effects due to past drug use, respectively. Both effects reflect the long-term impacts of antipsychotic treatment on the brain and result from the brain’s adaptive response to the foreign property of the drug. In this review, clinical evidence of the behavioral aspect of antipsychotic sensitization and tolerance is selectively reviewed, followed by an overview of preclinical literature that examines these behavioral characteristics and the related pharmacological and nonpharmacological factors. Next, recent work on the developmental impacts of adolescent antipsychotic sensitization and tolerance is presented and recent research that delineates the neurobiological mechanisms of antipsychotic sensitization and tolerance is summarized. A theoretical framework based on “drug learning and memory” principles is proposed to account for the phenomena of antipsychotic sensitization and tolerance. It is maintained that antipsychotic sensitization and tolerance follow basic principles of learning or acquisition (“induction”) and memory (“expression”). The induction and expression of both effects reflect the consequences of associative and nonassociative processing and are strongly influenced by various pharmacological, environmental, and behavioral factors. Drug-induced neuroplasticity, such as functional changes of striatal dopamine D2 and prefrontal serotonin (5-HT)2A receptors and their mediated signaling pathways, in principle, is responsible for antipsychotic sensitization and tolerance. Understanding the behavioral characteristics and neurobiological underpinnings of antipsychotic sensitization and tolerance has greatly enhanced our understanding of mechanisms of antipsychotic action, and may have important implications for future drug discovery and clinical practice. PMID:27371498

  17. Impact of antipsychotics and anticholinergics on autonomic modulation in patients with schizophrenia.

    PubMed

    Huang, Wei-Lieh; Chang, Li-Ren; Kuo, Terry B J; Lin, Yu-Hsuan; Chen, Ying-Zai; Yang, Cheryl C H

    2013-04-01

    Antipsychotics are associated with cardiovascular risk, but the relationship between their anticholinergic properties and cardiac function is not clear. We hypothesize that antipsychotics with a high muscarinic affinity (HMA) may reduce parasympathetic modulation, which should be observable by means of heart rate variability (HRV) measurement. We also assume that anticholinergics, which are commonly used in patients with schizophrenia to treat drug-induced parkinsonism, interact with antipsychotics, and this may also affect HRV. Fifty-five patients with schizophrenia were recruited into this study. Twenty-eight subjects used antipsychotics with an HMA and 27 subjects used antipsychotics with a low muscarinic affinity (LMA). Heart rate variability values between the patients on antipsychotics with HMA and those on antipsychotics with LMA were compared. Correlation and regression analysis were then performed to clarify the relationship between HMA, LMA, and HRV. The influence of anticholinergics was also assessed by correlation analysis. The HMA group showed significantly reduced low-frequency (LF) power, high-frequency (HF) power, total power (TP), and normalized LF (LF%) than the LMA group. Regression analysis supported the hypothesis that muscarinic affinity was related to LF (β = -0.447; P < 0.001), HF (β = -0.390; P = 0.002), and TP (β = -0.399; P = 0.001). The interaction between LMA and anticholinergic use also influenced LF% (β = 0.326; P = 0.006). In the LMA group, the use of anticholinergics was positively correlated with LF% and LF/HF. In the HMA group, after exclusion of the patients using anticholinergics, the equivalent dose of antipsychotics showed a negative correlation with HF. Our results suggest that the muscarinic affinity of antipsychotics affects both sympathetic and parasympathetic modulation and that anticholinergics interact with antipsychotics to influence HRV.

  18. Early Response to Antipsychotic Drug Therapy as a Clinical Marker of Subsequent Response in the Treatment of Schizophrenia

    PubMed Central

    Kinon, Bruce J; Chen, Lei; Ascher-Svanum, Haya; Stauffer, Virginia L; Kollack-Walker, Sara; Zhou, Wei; Kapur, Shitij; Kane, John M

    2010-01-01

    Our objective was to prospectively assess whether early (ie, 2 weeks) response to an antipsychotic predicts later (12-week) response and whether ‘switching' early non-responders to another antipsychotic is a better strategy than ‘staying'. This randomized, double-blind, flexible-dosed, 12-week study enrolled 628 patients diagnosed with schizophrenia or schizoaffective disorder. All initiated treatment with risperidone. Early response was defined as ⩾20% improvement on the Positive and Negative Syndrome Scale (PANSS) total score following 2 weeks of treatment. Early responders (ERs) continued on risperidone, whereas early non-responders (ENRs) were randomized (1 : 1) to continue on risperidone 2–6 mg/day or switch to olanzapine 10–20 mg/day for 10 additional weeks. Compared with ENRs, risperidone ERs showed significantly greater reduction in PANSS total score (end point; p<001). Early response/non-response was highly predictive of subsequent clinical outcomes. Switching risperidone ENRs to olanzapine at week 2 resulted in a small but significantly greater reduction in PANSS total score (end point; p=0.020) and in depressive symptoms (end point; p=0.004); the reduction in PANSS was greater among those who were still moderately ill at 2 weeks. Switching risperidone ENRs to olanzapine also resulted in significantly greater increases in triglycerides, a significantly greater decrease in prolactin, and significantly less treatment-emergent dyskinesia. This is the first study to prospectively show that early response/non-response to an antipsychotic (risperidone) is a reliable clinical marker of subsequent clinical outcomes and that a ‘switching' strategy based on this information may lead to greater clinical improvement than staying on a drug for a longer period in some patients. PMID:19890258

  19. Fast Versus Slow Strategy of Switching Patients With Schizophrenia to Aripiprazole From Other Antipsychotics.

    PubMed

    Hwang, Tzung-Jeng; Lo, Wei-Ming; Chan, Hung-Yu; Lin, Ching-Feng; Hsieh, Ming H; Liu, Chen-Chun; Liu, Chih-Min; Hwu, Hai-Gwo; Kuo, Ching-Hua; Chen, Wei J

    2015-12-01

    This study aimed to compare strategies differing in the speed of switching schizophrenic patients to aripiprazole from other antipsychotic agents, with dual administration for 2 weeks and then tapering off the current antipsychotic in fast (within 1 week) versus slow (within 4 weeks) strategies. This 8-week, open-label, randomized, parallel study assigned patients with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of schizophrenia or schizoaffective disorder to either the fast-switching (n = 38) or slow-switching (n = 41) group. Efficacy assessments at 5 time points included Positive and Negative Syndrome Scale and Clinical Global Impression scale. Safety assessments included extrapyramidal symptoms, metabolic profile, serum prolactin level, QTc interval, and adverse events. Drug concentrations and cytochrome P450 CYP2D6 and CYP3A4 genotypes were also measured. The fast- and slow-switching groups were comparable in demographical and clinical features at baseline and dropout rate. In the intention-to-treat analysis using mixed-effects models, there were significant within-group decreases over time in the Positive and Negative Syndrome Scale total scores (P = 0.03) and its subscores except for positive subscores, whereas no between-group differences were found. A reduction in body weight (P = 0.01) and lower levels of total cholesterol (P = 0.03), triglycerides (P = 0.03), and prolactin (P = 0.01) were noted in both groups but no increase in extrapyramidal symptoms or prolongation of QTc. The blood concentrations of aripiprazole in all patients were in a therapeutic range at day 56, with CYP2D6*10 polymorphisms being associated with aripiprazole concentrations. In conclusion, there is no significant difference between the fast- and slow-switching strategy in terms of improvements in clinical symptoms and metabolic profile in this 8-week study.

  20. Fast Versus Slow Strategy of Switching Patients With Schizophrenia to Aripiprazole From Other Antipsychotics.

    PubMed

    Hwang, Tzung-Jeng; Lo, Wei-Ming; Chan, Hung-Yu; Lin, Ching-Feng; Hsieh, Ming H; Liu, Chen-Chun; Liu, Chih-Min; Hwu, Hai-Gwo; Kuo, Ching-Hua; Chen, Wei J

    2015-12-01

    This study aimed to compare strategies differing in the speed of switching schizophrenic patients to aripiprazole from other antipsychotic agents, with dual administration for 2 weeks and then tapering off the current antipsychotic in fast (within 1 week) versus slow (within 4 weeks) strategies. This 8-week, open-label, randomized, parallel study assigned patients with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of schizophrenia or schizoaffective disorder to either the fast-switching (n = 38) or slow-switching (n = 41) group. Efficacy assessments at 5 time points included Positive and Negative Syndrome Scale and Clinical Global Impression scale. Safety assessments included extrapyramidal symptoms, metabolic profile, serum prolactin level, QTc interval, and adverse events. Drug concentrations and cytochrome P450 CYP2D6 and CYP3A4 genotypes were also measured. The fast- and slow-switching groups were comparable in demographical and clinical features at baseline and dropout rate. In the intention-to-treat analysis using mixed-effects models, there were significant within-group decreases over time in the Positive and Negative Syndrome Scale total scores (P = 0.03) and its subscores except for positive subscores, whereas no between-group differences were found. A reduction in body weight (P = 0.01) and lower levels of total cholesterol (P = 0.03), triglycerides (P = 0.03), and prolactin (P = 0.01) were noted in both groups but no increase in extrapyramidal symptoms or prolongation of QTc. The blood concentrations of aripiprazole in all patients were in a therapeutic range at day 56, with CYP2D6*10 polymorphisms being associated with aripiprazole concentrations. In conclusion, there is no significant difference between the fast- and slow-switching strategy in terms of improvements in clinical symptoms and metabolic profile in this 8-week study. PMID:26488675

  1. Pharmacogenetics and Antipsychotics: Therapeutic Efficacy and Side Effects Prediction

    PubMed Central

    Zhang, Jian-Ping; Malhotra, Anil K.

    2010-01-01

    Importance of the field Antipsychotic drug is the mainstay of treatment for schizophrenia, and there are large inter-individual differences is clinical response and side effects. Pharmacogenetics provides a valuable tool to fulfill the promise of personalized medicine by tailoring treatment based on one's genetic markers. Areas covered in this review This article reviews the pharmacogenetic literature from early 1990s to 2010, focusing on two aspects of drug action: pharmacokinetics and pharmacodynamics. Genetic variants in the neurotransmitter receptors including dopamine and serotonin, and metabolic pathways of drugs including CYP2D6 and COMT, were discussed in association with clinical drug response and side effects. What the reader will gain Readers are expected to learn the up-to-date evidence in pharmacogenetic research, and to gain familiarity to the issues and challenges facing the field. Take home message Pharmacogenetic research of antipsychotic drugs is both promising and challenging. There is consistent evidence that some genetic variants can affect clinical response and side effects. However, more studies that are designed specifically to test pharmacogenetic hypotheses are clearly needed to advance the field. PMID:21162693

  2. Second-generation antipsychotics and bone turnover in schizophrenia.

    PubMed

    Okita, Kyoji; Kanahara, Nobuhisa; Nishimura, Motoi; Yoshida, Toshihiko; Yasui-Furukori, Norio; Niitsu, Tomihisa; Yoshida, Taisuke; Ishikawa, Masatomo; Kimura, Hiroshi; Nomura, Fumio; Iyo, Masaomi

    2014-08-01

    Accumulating evidence suggests that patients with schizophrenia are exposed to a high risk of osteoporosis/osteopenia caused by long-term antipsychotic treatment. The degree of bone mineral density (BMD) loss that a given antipsychotic may cause is not known. Examinations using a bone turnover marker may more accurately predict the ongoing bone states in psychiatric patients. We measured prolactin, estradiol, testosterone, and bone resorption marker (TRACP-5b) levels in 167 patients with schizophrenia and 60 normal controls. The patients showed significantly higher levels of prolactin and lower levels of TRACP-5b compared to the controls. Moreover, prolactin was negatively correlated with estradiol and testosterone in the group of all male subjects and the male patients. TRACP-5b was positively correlated with prolactin in the female patients and negatively correlated with estradiol in the group of all female subjects. The results show that the bone resorption rate was rather attenuated in the patients compared to the normal controls, suggesting a complicated etiology of BMD loss in schizophrenia patients. Several meaningful correlations between key factors in this study confirmed that hyperprolactinemia induced the suppression of sex hormones, and possibly led to the higher bone turnover. These results indicate that measurement of the resorption marker TRACP-5b might be useful to clarify the pathology of BMD loss. PMID:24888527

  3. Bipolar depression: Managing patients with second generation antipsychotics.

    PubMed

    Avery, Lindsay M; Drayton, Shannon J

    2016-01-01

    Bipolar affective disorder is a debilitating illness that manifests as cyclical episodes of mood elevation and depression, but the treatment of the depressive episodes (i.e., bipolar depression) differs considerably from the treatment of major depressive disorder. In bipolar affective disorder, it is well known that patients spend a significantly greater amount of time in depressive episodes than manic or hypomanic episodes, yet there are currently just three Food and Drug Administration-approved agents for the treatment of bipolar depression: (1) olanzapine/fluoxetine combination (2) quetiapine, both immediate- and extended-release, and (3) lurasidone. The literature review presented here focuses on the clinical trials that led to the Food and Drug Administration-approval of these second generation antipsychotics in the treatment of bipolar depression. The discussion highlights key considerations regarding overall treatment strategies to aid clinicians in the selection of pharmacologic agents. Recommended monitoring parameters, potential adverse effects, and pertinent counseling points for second generation antipsychotics used in bipolar depression are included. PMID:27079776

  4. Equine atypical myopathy: A metabolic study.

    PubMed

    Karlíková, R; Široká, J; Jahn, P; Friedecký, D; Gardlo, A; Janečková, H; Hrdinová, F; Drábková, Z; Adam, T

    2016-10-01

    Atypical myopathy (AM) is a potentially fatal disease of grazing horses. It is reportedly caused by the ingestion of sycamore seeds containing toxic hypoglycin A. In order to study metabolic changes, serum and urine samples from nine horses with atypical myopathy and 12 control samples from clinically healthy horses were collected and then analysed using a high-performance liquid chromatography coupled with tandem mass spectrometry; serum metabolic profiles as the disease progressed were also studied. Metabolic data were evaluated using unsupervised and supervised multivariate analyses. Significant differences were demonstrated in the concentrations of various glycine conjugates and acylcarnitines (C2-C26). Moreover, the concentrations of purine and pyrimidine metabolites, vitamins and their degradation products (riboflavin, trigonelline, pyridoxate, pantothenate), and selected organic and amino acids (aspartate, leucine, 2-oxoglutarate, etc.) were altered in horses with AM. These results represent a global view of altered metabolism in horses with atypical myopathy. PMID:27687939

  5. Atypical measles syndrome in adults: still around.

    PubMed

    Melenotte, Cléa; Cassir, Nadim; Tessonnier, Laurent; Brouqui, Philippe

    2015-09-23

    Measles, a vaccine-preventable disease, is currently responsible for worldwide outbreaks mainly due to the failure to maintain high coverage of childhood immunisation. Atypical measles syndrome was first described in the 1960s in association with the inactivated measles vaccine. We report a case of atypical measles syndrome in a 29-year-old man without previous measles immunisation. He presented with fever, shortness of breath and a purpuric rash. Radiological investigations allowed the diagnosis of severe nodular pneumonia. Positive PCR in nasal and pharyngeal samples, and positive serology for a primary infection confirmed measles diagnosis. Both clinical symptoms and pulmonary nodules regressed spontaneously, whereas mediastinal lymph nodes increased and persisted up to 3 months after the primary infection. Physicians should be aware of the atypical measles syndrome presentation in order to limit the delay of diagnosis, to avoid unnecessary investigations and to prevent the potential spread of this infectious disease.

  6. Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study

    PubMed Central

    Kroken, Rune A; Johnsen, Erik; Ruud, Torleif; Wentzel-Larsen, Tore; Jørgensen, Hugo A

    2009-01-01

    Background Surveys on prescription patterns for antipsychotics in the Scandinavian public health system are scarce despite the prevalent use of these drugs. The clinical differences between antipsychotic drugs are mainly in the areas of safety and tolerability, and international guidelines for the treatment of schizophrenia offer rational strategies to minimize the burden of side effects related to antipsychotic treatment. The implementation of treatment guidelines in clinical practice have proven difficult to achieve, as reflected by major variations in the prescription patterns of antipsychotics between different comparable regions and countries. The objective of this study was to evaluate the practice of treatment of schizophrenic patients with antipsychotics at discharge from acute inpatient settings at a national level. Methods Data from 486 discharges of patients from emergency inpatient treatment of schizophrenia were collected during a three-month period in 2005; the data were collected in a large national study that covered 75% of Norwegian hospitals receiving inpatients for acute treatment. Antipsychotic treatment, demographic variables, scores from the Global Assessment of Functioning and Health of the Nation Outcome Scales and information about comorbid conditions and prior treatment were analyzed to seek predictors for nonadherence to guidelines. Results In 7.6% of the discharges no antipsychotic treatment was given; of the remaining discharges, 35.6% were prescribed antipsychotic polypharmacy and 41.9% were prescribed at least one first-generation antipsychotic (FGA). The mean chlorpromazine equivalent dose was 450 (SD 347, range 25–2800). In the multivariate regression analyses, younger age, previous inpatient treatment in the previous 12 months before index hospitalization, and a comorbid diagnosis of personality disorder or mental retardation predicted antipsychotic polypharmacy, while previous inpatient treatment in the previous 12 months also

  7. A pharmacy led program to review anti-psychotic prescribing for people with dementia

    PubMed Central

    2012-01-01

    Background Anti-psychotics, prescribed to people with dementia, are associated with approximately 1,800 excess annual deaths in the UK. A key public health objective is to limit such prescribing of anti-psychotics. Methods This project was conducted within primary care in Medway Primary Care Trust (PCT) in the UK. There were 2 stages for the intervention. First, primary care information systems including the dementia register were searched by a pharmacy technician to identify people with dementia prescribed anti-psychotics. Second, a trained specialist pharmacist conducted targeted clinical medication reviews in people with dementia initiated on anti-psychotics by primary care, identified by the data search. Results Data were collected from 59 practices. One hundred and sixty-one (15.3%) of 1051 people on the dementia register were receiving low-dose anti-psychotics. People with dementia living in residential homes were nearly 3.5 times more likely to receive an anti-psychotic [25.5% of care home residents (118/462) vs. 7.3% of people living at home (43/589)] than people living in their own homes (p < 0.0001; Fisher’s exact test). In 26 practices there was no-one on the dementia register receiving low-dose anti-psychotics. Of the 161 people with dementia prescribed low-dose anti-psychotics, 91 were receiving on-going treatment from local secondary care mental health services or Learning Disability Teams. Of the remaining 70 patients the anti-psychotic was either withdrawn, or the dosage was reduced, in 43 instances (61.4%) following the pharmacy-led medication review. Conclusions In total 15.3% of people on the dementia register were receiving a low-dose anti-psychotic. However, such data, including the recent national audit may under-estimate the usage of anti-psychotics in people with dementia. Anti-psychotics were used more commonly within care home settings. The pharmacist-led medication review successfully limited the prescribing of anti-psychotics to

  8. Atypical solitary fibrous tumor of the vulva.

    PubMed

    Fukunaga, M

    2000-04-01

    An atypical solitary fibrous tumor (SFT) was encountered as a slow-growing, 15-cm, well-demarcated, vulvar tumor in a 70-year-old woman. The tumor was highly cellular and composed predominantly of hemangiopericytomatous and capillary hemangioma-like proliferations and short fascicular arrangements of spindled cells. Multinucleated giant cells and tumor necrosis also were present. The tumor cells were positive for vimentin, CD34, progesterone receptors, and bcl-2 and were diploid by flow cytometry. The patient was well without disease 9 months after surgery. Awareness of the occurrence of atypical SFT in the vulva is important so that confusion with other neoplasms can be avoided.

  9. Atypical RNAs in the coelacanth transcriptome.

    PubMed

    Nitsche, Anne; Doose, Gero; Tafer, Hakim; Robinson, Mark; Saha, Nil Ratan; Gerdol, Marco; Canapa, Adriana; Hoffmann, Steve; Amemiya, Chris T; Stadler, Peter F

    2014-09-01

    Circular and apparently trans-spliced RNAs have recently been reported as abundant types of transcripts in mammalian transcriptome data. Both types of non-colinear RNAs are also abundant in RNA-seq of different tissue from both the African and the Indonesian coelacanth. We observe more than 8,000 lincRNAs with normal gene structure and several thousands of circularized and trans-spliced products, showing that such atypical RNAs form a substantial contribution to the transcriptome. Surprisingly, the majority of the circularizing and trans-connecting splice junctions are unique to atypical forms, that is, are not used in normal isoforms.

  10. Effectiveness of antipsychotic drugs against hostility in patients with schizophrenia in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study

    PubMed Central

    Volavka, Jan; Czobor, Pál; Citrome, Leslie; Van Dorn, Richard A.

    2014-01-01

    Introduction Aggressive behavior can be a dangerous complication of schizophrenia. Hostility is related to aggression. This study aimed to compare the effects of olanzapine, perphenazine, risperidone, quetiapine, and ziprasidone on hostility in schizophrenia. Methods We used the data that were acquired in the 18-month Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. We analyzed the scores of the Positive and Negative Syndrome Scale (PANSS) hostility item in a subset of 614 patients who showed at least minimal hostility (a score ≥ 2) at baseline. Results The primary analysis of hostility indicated an effect of difference between treatments (F4,1487 = 7.78, P<0.0001). Olanzapine was significantly superior to perphenazine and quetiapine at months 1, 3, 6, and 9. It was also significantly superior to ziprasidone at months 1, 3, and 6, and to risperidone at months 3 and 6. Discussion Our results are consistent with those of a similar post-hoc analysis of hostility in first-episode subjects with schizophrenia enrolled in the European First-Episode Schizophrenia Trial (EUFEST) trial, where olanzapine demonstrated advantages compared with haloperidol, quetiapine, and amisulpride. Conclusion Olanzapine demonstrated advantages in terms of a specific antihostility effect over the other antipsychotics tested in Phase 1 of the CATIE trial. PMID:24284234

  11. Time to rehospitalization in patients with schizophrenia discharged on first generation antipsychotics, non-clozapine second generation antipsychotics, or clozapine.

    PubMed

    Werneck, Ana Paula; Hallak, Jaime Cecilio; Nakano, Eduardo; Elkis, Helio

    2011-08-15

    Rehospitalization is an important outcome of drug effectiveness in schizophrenia. In this study, the hypothesis that clozapine and some second generation antipsychotics (SGA) were superior to first generation antipsychotics (FGA) in preventing rehospitalization of patients with schizophrenia discharged from a university hospital in Brazil was tested. A retrospective observational study was conducted designed to evaluate time to rehospitalization of patients with schizophrenia discharged on a regimen of oral FGA, depot FGA, risperidone, olanzapine and amisulpride, other SGA, or clozapine, during a three-year follow-up period. Risk factors associated with rehospitalization were examined. Of the 464 patients with schizophrenia discharged from hospital, 242 met criteria for study entry. Higher rehospitalization rates were observed in patients treated with depot FGA (30%), risperidone (30%) and other SGA groups (28.5%), respectively. Clozapine was significantly associated with lower rehospitalization risk compared with risperidone. The risk of rehospitalization in patients on olanzapine and amisulpride, and oral FGA, was similar to that of patients in use of clozapine. These results however, are limited by the heterogeneity of illness severity across the groups. PMID:21596442

  12. Lost in the literature, but not the caseload: working with atypical disfluency from theory to practice.

    PubMed

    Sisskin, Vivian; Wasilus, Samantha

    2014-05-01

    Atypical disfluency is a frustrating but little addressed clinical problem. The purpose of this article and case study was to summarize what is known about atypical fluency profiles and to describe the presenting behaviors and successful treatment of an unusual fluency profile (numerous word-final syllable repetitions) in a school-aged child. To this end, we describe the speech fluency and associated communication characteristics of a young boy diagnosed with Asperger disorder who was between 7;2 and 8;0 when seen for evaluation and treatment. We describe a therapy protocol that was successful in nearly eliminating these atypical disfluencies. The protocol emphasized self-monitoring and was integrated with other goals to improve the child's communication, which had features consistent with mild autism spectrum disorder (ASD). Following an 8-week treatment, the child significantly reduced his percent stuttered syllables of atypical disfluencies (word-final repetition and phrase-final repetition), resulting in significant qualitative improvements to his speech. This case study demonstrates that traditional stuttering modification treatment can be successful in reducing atypical and typical disfluencies in a child with concomitant social language impairment consistent with ASD. The therapy approach reported here may be useful in treatment of other cases having symptoms similar to the child we treated. PMID:24782276

  13. Regional variation in physician adoption of antipsychotics: Impact on US Medicare expenditures

    PubMed Central

    Donohue, Julie M.; Normand, Sharon-Lise T.; Horvitz-Lennon, Marcela; Men, Aiju; Berndt, Ernst R.; Huskamp, Haiden A.

    2016-01-01

    Background Regional variation in US Medicare prescription drug spending is driven by higher prescribing of costly brand-name drugs in some regions. This variation likely arises from differences in the speed of diffusion of newly-approved medications. Second-generation antipsychotics were widely adopted for treatment of severe mental illness and for several off-label uses. Rapid diffusion of new psychiatric drugs likely increases drug spending but its relationship to non-drug spending is unclear. The impact of antipsychotic diffusion on drug and medical spending is of great interest to public payers like Medicare, which finance a majority of mental health spending in the U.S. Aims We examine the association between physician adoption of new antipsychotics and antipsychotic spending and non-drug medical spending among disabled and elderly Medicare enrollees. Methods We linked physician-level data on antipsychotic prescribing from an all-payer dataset (IMS Health's Xponent™) to patient-level data from Medicare. Our physician sample included 16,932 U.S. psychiatrists and primary care providers with ≥10 antipsychotic prescriptions per year from 1997-2011. We constructed a measure of physician adoption of 3 antipsychotics introduced during this period (quetiapine, ziprasidone and aripiprazole) by estimating a shared frailty model of the time to first prescription for each drug. We then assigned physicians to one of 306 U.S. hospital referral regions (HRRs) and measured the average propensity to adopt per region. Using 2010 data for a random sample of 1.6 million Medicare beneficiaries, we identified 138,680 antipsychotic users. A generalized linear model with gamma distribution and log link was used to estimate the effect of region-level adoption propensity on beneficiary-level antipsychotic spending and non-drug medical spending adjusting for patient demographic and socioeconomic characteristics, health status, eligibility category, and whether the antipsychotic was

  14. Antipsychotic Treatment Reduces Indices of Oxidative Stress in First-Episode Psychosis Patients

    PubMed Central

    Haring, Liina; Vasar, Eero; Vasar, Veiko; Zilmer, Mihkel

    2016-01-01

    38 first-episode psychosis (FEP) patients and 37 control subjects were recruited for the study of indices of oxidative stress (OxS). The main purpose of the study was to compare the OxS statuses (serum total antioxidant capacity (TAC), total level of peroxides (TPX), oxidative stress index (OSI), and ratio oxidized methionine (Met-SO) to methionine (Met)) between antipsychotic-naïve FEP patients and individuals without a history of psychiatric disorders. Subsequently, the impact of 7-month antipsychotic treatment was evaluated on the OxS status in FEP patients. An attempt was made to assess links between OxS signature and inflammation markers. The oxidative stress indices remained generally unchanged in antipsychotic-naïve FEP patients compared to control subjects. Despite that, there was a significant correlation between the levels of TPX and EGF (endothelial growth factor) in FEP patients. This correlation disappeared after antipsychotic treatment of FEP patients. Moreover, antipsychotic treatment was associated with a significant reduction in OxS indices, including TPX, OSI, and ratio between Met-SO and Met. By contrast, in chronic SCZ patients we established a significant high-grade OxS. In conclusion, the markers of total antioxidative capacity, lipid peroxidation, and protein oxidation revealed no high-grade OxS in FEP patients. Nevertheless, antipsychotic treatment induced a considerable anti-inflammatory effect. OxS levels were also significantly decreased if compared in FEP patients before and after antipsychotic treatment. PMID:27528889

  15. Antipsychotic dose modulates behavioral and neural responses to feedback during reinforcement learning in schizophrenia.

    PubMed

    Insel, Catherine; Reinen, Jenna; Weber, Jochen; Wager, Tor D; Jarskog, L Fredrik; Shohamy, Daphna; Smith, Edward E

    2014-03-01

    Schizophrenia is characterized by an abnormal dopamine system, and dopamine blockade is the primary mechanism of antipsychotic treatment. Consistent with the known role of dopamine in reward processing, prior research has demonstrated that patients with schizophrenia exhibit impairments in reward-based learning. However, it remains unknown how treatment with antipsychotic medication impacts the behavioral and neural signatures of reinforcement learning in schizophrenia. The goal of this study was to examine whether antipsychotic medication modulates behavioral and neural responses to prediction error coding during reinforcement learning. Patients with schizophrenia completed a reinforcement learning task while undergoing functional magnetic resonance imaging. The task consisted of two separate conditions in which participants accumulated monetary gain or avoided monetary loss. Behavioral results indicated that antipsychotic medication dose was associated with altered behavioral approaches to learning, such that patients taking higher doses of medication showed increased sensitivity to negative reinforcement. Higher doses of antipsychotic medication were also associated with higher learning rates (LRs), suggesting that medication enhanced sensitivity to trial-by-trial feedback. Neuroimaging data demonstrated that antipsychotic dose was related to differences in neural signatures of feedback prediction error during the loss condition. Specifically, patients taking higher doses of medication showed attenuated prediction error responses in the striatum and the medial prefrontal cortex. These findings indicate that antipsychotic medication treatment may influence motivational processes in patients with schizophrenia.

  16. Antipsychotic pharmacogenomics in first episode psychosis: a role for glutamate genes

    PubMed Central

    Stevenson, J M; Reilly, J L; Harris, M S H; Patel, S R; Weiden, P J; Prasad, K M; Badner, J A; Nimgaonkar, V L; Keshavan, M S; Sweeney, J A; Bishop, J R

    2016-01-01

    Genetic factors may underlie beneficial and adverse responses to antipsychotic treatment. These relationships may be easier to identify among patients early in the course of disease who have limited exposure to antipsychotic drugs. We examined 86 first episode patients (schizophrenia, psychotic bipolar disorder and major depressive disorder with psychotic features) who had minimal to no prior antipsychotic exposure in a 6-week pharmacogenomic study of antipsychotic treatment response. Response was measured by change in Brief Psychiatric Rating Scale total score. Risperidone monotherapy was the primary antipsychotic treatment. Pharmacogenomic association studies were completed to (1) examine candidate single-nucleotide polymorphisms (SNPs) in genes known to be involved with glutamate signaling, and (2) conduct an exploratory genome-wide association study of symptom response to identify potential novel associations for future investigation. Two SNPs in GRM7 (rs2069062 and rs2014195) were significantly associated with antipsychotic response in candidate gene analysis, as were two SNPs in the human glutamate receptor delta 2 (GRID2) gene (rs9307122 and rs1875705) in genome-wide association analysis. Further examination of these findings with those from a separate risperidone-treated study sample demonstrated that top SNPs in both studies were overrepresented in glutamate genes and that there were similarities in neurodevelopmental gene categories associated with drug response from both study samples. These associations indicate a role for gene variants related to glutamate signaling and antipsychotic response with more broad association patterns indicating the potential importance of genes involved in neuronal development. PMID:26905411

  17. Antipsychotic pharmacogenomics in first episode psychosis: a role for glutamate genes.

    PubMed

    Stevenson, J M; Reilly, J L; Harris, M S H; Patel, S R; Weiden, P J; Prasad, K M; Badner, J A; Nimgaonkar, V L; Keshavan, M S; Sweeney, J A; Bishop, J R

    2016-02-23

    Genetic factors may underlie beneficial and adverse responses to antipsychotic treatment. These relationships may be easier to identify among patients early in the course of disease who have limited exposure to antipsychotic drugs. We examined 86 first episode patients (schizophrenia, psychotic bipolar disorder and major depressive disorder with psychotic features) who had minimal to no prior antipsychotic exposure in a 6-week pharmacogenomic study of antipsychotic treatment response. Response was measured by change in Brief Psychiatric Rating Scale total score. Risperidone monotherapy was the primary antipsychotic treatment. Pharmacogenomic association studies were completed to (1) examine candidate single-nucleotide polymorphisms (SNPs) in genes known to be involved with glutamate signaling, and (2) conduct an exploratory genome-wide association study of symptom response to identify potential novel associations for future investigation. Two SNPs in GRM7 (rs2069062 and rs2014195) were significantly associated with antipsychotic response in candidate gene analysis, as were two SNPs in the human glutamate receptor delta 2 (GRID2) gene (rs9307122 and rs1875705) in genome-wide association analysis. Further examination of these findings with those from a separate risperidone-treated study sample demonstrated that top SNPs in both studies were overrepresented in glutamate genes and that there were similarities in neurodevelopmental gene categories associated with drug response from both study samples. These associations indicate a role for gene variants related to glutamate signaling and antipsychotic response with more broad association patterns indicating the potential importance of genes involved in neuronal development.

  18. Cost-effectiveness analysis of antipsychotics in reducing schizophrenia relapses

    PubMed Central

    2012-01-01

    Background Schizophrenia is a severe form of mental illness which is associated with significant and long-lasting health, social and financial burdens. The aim of this project is to assess the efficiency of the antipsychotics used in Spain in reducing schizophrenia relapses under the Spanish Health System perspective. Material and methods A decision-analytic model was developed to explore the relative cost-effectiveness of five antipsychotic medications, amisulpride, aripiprazole, olanzapine, paliperidone Extended-Release (ER) and risperidone, compared to haloperidol, over a 1-year treatment period among people living in Spain with schizophrenia. The transition probabilities for assessed therapies were obtained from the systemic review and meta-analysis performed by National Institute for Health and Clinical Excellence (NICE). Results Paliperidone ER was the option that yielded more quality-adjusted life years (QALYs) gained per patient (0.7573). In addition, paliperidone ER was the least costly strategy (€3,062), followed by risperidone (€3,194), haloperidol (€3,322), olanzapine (€3,893), amisulpride (€4,247) and aripiprazole (€4,712). In the incremental cost-effectiveness (ICE) analysis of the assessed antipsychotics compared to haloperidol, paliperidone ER and risperidone were dominant options. ICE ratios for other medications were €23,621/QALY gained, €91,584/QALY gained and €94,558/QALY gained for olanzapine, amisulpride and aripiprazole, respectively. Deterministic sensitivity analysis showed that risperidone is always dominant when compared to haloperidol. Paliperidone ER is also dominant apart from the exception of the scenario with a 20% decrease in the probability of relapses. Conclusions Our findings may be of interest to clinicians and others interested in outcomes and cost of mental health services among patients with schizophrenia. Paliperidone ER and risperidone were shown to be dominant therapies compared to haloperidol in Spain

  19. Does Insight Affect the Efficacy of Antipsychotics in Acute Mania?: An Individual Patient Data Regression Meta-Analysis.

    PubMed

    Welten, Carlijn C M; Koeter, Maarten W J; Wohlfarth, Tamar D; Storosum, Jitschak G; van den Brink, Wim; Gispen-de Wied, Christine C; Leufkens, Hubert G M; Denys, Damiaan A J P

    2016-02-01

    Patients having an acute manic episode of bipolar disorder often lack insight into their condition. Because little is known about the possible effect of insight on treatment efficacy, we examined whether insight at the start of treatment affects the efficacy of antipsychotic treatment in patients with acute mania. We used individual patient data from 7 randomized, double-blind, placebo-controlled registration studies of 4 antipsychotics in patients with acute mania (N = 1904). Insight was measured with item 11 of the Young Mania Rating Scale (YMRS) at baseline and study endpoint 3 weeks later. Treatment outcome was defined by (a) mean change score, (b) response defined as 50% or more improvement on YMRS, and (c) remission defined as YMRS score less than 8 at study endpoint. We used multilevel mixed effect linear (or logistic) regression analyses of individual patient data to assess the interaction between baseline insight and treatment outcomes. At treatment initiation, 1207 (63.5%) patients had impaired or no insight into their condition. Level of insight significantly modified the efficacy of treatment by mean change score (P = 0.039), response rate (P = 0.033), and remission rate (P = 0.043), with greater improvement in patients with more impaired insight. We therefore recommend that patients experiencing acute mania should be treated immediately and not be delayed until patients regain insight.

  20. Discontinuing financial incentives for adherence to antipsychotic depot medication: long-term outcomes of a cluster randomised controlled trial

    PubMed Central

    Priebe, Stefan; Bremner, Stephen A; Pavlickova, Hana

    2016-01-01

    Objectives In a cluster randomised controlled trial, offering financial incentives improved adherence to antipsychotic depot medication over a 1-year period. Yet, it is unknown whether this positive effect is sustained once the incentives stop. Methods and analyses Patients in the intervention and control group were followed up for 2 years after the intervention. Primary and secondary outcomes were assessed at 6 months and 24 months post intervention. Assessments were conducted between September 2011 and November 2014. Results After the intervention period, intervention and control groups did not show any statistically significant differences in adherence, neither in the first 6 months (71% and 77%, respectively) nor in the following 18 months (68%, 74%). There were no statistically significant differences in secondary outcomes, that is, adherence ≥95% and untoward incidents either. Conclusions It may be concluded that incentives to improve adherence to antipsychotic maintenance medication are effective only for as long as they are provided. Once they are stopped, adherence returns to approximately baseline level with no sustained benefit. Trial registration number ISRCTN77769281; Results. PMID:27655261

  1. Cohort study of atypical pressure ulcers development.

    PubMed

    Jaul, Efraim

    2014-12-01

    Atypical pressure ulcers (APU) are distinguished from common pressure ulcers (PU) with both unusual location and different aetiology. The occurrence and attempts to characterise APU remain unrecognised. The purpose of this cohort study was to analyse the occurrence of atypical location and the circumstances of the causation, and draw attention to the prevention and treatment by a multidisciplinary team. The cohort study spanned three and a half years totalling 174 patients. The unit incorporates two weekly combined staff meetings. One concentrates on wound assessment with treatment decisions made by the physician and nurse, and the other, a multidisciplinary team reviewing all patients and coordinating treatment. The main finding of this study identified APU occurrence rate of 21% within acquired PU over a three and a half year period. Severe spasticity constituted the largest group in this study and the most difficult to cure wounds, located in medial aspects of knees, elbows and palms. Medical devices caused the second largest occurrence of atypical wounds, located in the nape of the neck, penis and nostrils. Bony deformities were the third recognisable atypical wound group located in shoulder blades and upper spine. These three categories are definable and time observable. APU are important to be recognisable, and can be healed as well as being prevented. The prominent role of the multidisciplinary team is primary in identification, prevention and treatment. PMID:23374746

  2. [Atypical carcinoid of larynx: a case report].

    PubMed

    Gu, Wenjing; Wang, Xin; Shi, Jinfeng

    2015-09-01

    An 70-year-old male come for swallowing pain 5 years, turning worse 10 months. Laryngoscopy showed a tumor with rough surface at the laryngeal surface of epiglottic. Outpatient pathology: poorly differentiated carcinoma of the larynx. CT: the root of epiglottic is slightly thickened. He accepted the partial laryngectomy, tracheotomy, bilateral functional neck dissection. Pathology: atypical carcinoid of larynx.

  3. Cohort study of atypical pressure ulcers development.

    PubMed

    Jaul, Efraim

    2014-12-01

    Atypical pressure ulcers (APU) are distinguished from common pressure ulcers (PU) with both unusual location and different aetiology. The occurrence and attempts to characterise APU remain unrecognised. The purpose of this cohort study was to analyse the occurrence of atypical location and the circumstances of the causation, and draw attention to the prevention and treatment by a multidisciplinary team. The cohort study spanned three and a half years totalling 174 patients. The unit incorporates two weekly combined staff meetings. One concentrates on wound assessment with treatment decisions made by the physician and nurse, and the other, a multidisciplinary team reviewing all patients and coordinating treatment. The main finding of this study identified APU occurrence rate of 21% within acquired PU over a three and a half year period. Severe spasticity constituted the largest group in this study and the most difficult to cure wounds, located in medial aspects of knees, elbows and palms. Medical devices caused the second largest occurrence of atypical wounds, located in the nape of the neck, penis and nostrils. Bony deformities were the third recognisable atypical wound group located in shoulder blades and upper spine. These three categories are definable and time observable. APU are important to be recognisable, and can be healed as well as being prevented. The prominent role of the multidisciplinary team is primary in identification, prevention and treatment.

  4. Infant Perception of Atypical Speech Signals

    ERIC Educational Resources Information Center

    Vouloumanos, Athena; Gelfand, Hanna M.

    2013-01-01

    The ability to decode atypical and degraded speech signals as intelligible is a hallmark of speech perception. Human adults can perceive sounds as speech even when they are generated by a variety of nonhuman sources including computers and parrots. We examined how infants perceive the speech-like vocalizations of a parrot. Further, we examined how…

  5. Atypical Apocrine Adenosis: Diagnostic Challenges and Pitfalls.

    PubMed

    Asirvatham, Jaya Ruth; Falcone, Maria Monica Garcia; Kleer, Celina G

    2016-10-01

    Apocrine change in the breast is an extremely common finding. In most cases, the benign or malignant nature of the lesion is easily recognized. Apocrine adenosis is used to describe sclerosing adenosis with apocrine change. The term apocrine atypia is used when there is significant cytologic atypia in apocrine cells, characterized by a 3-fold nuclear enlargement, prominent/multiple nucleoli, and hyperchromasia. Atypical apocrine adenosis is diagnosed when apocrine adenosis and apocrine atypia are superimposed. However, there are no definite criteria to distinguish atypical apocrine adenosis from apocrine ductal carcinoma in situ. Immunohistochemical markers can be confounding and may lead to erroneous diagnoses. Atypical apocrine features in sclerosing lesions may be misinterpreted as invasive carcinoma if the underlying lesion is not recognized. In the absence of definite features of malignancy, the diagnosis of apocrine ductal carcinoma in situ may be extremely difficult. In the present article, we review atypical apocrine adenosis focusing on diagnostic challenges and their implications on clinical management. PMID:27684975

  6. Observing Behavior and Atypically Restricted Stimulus Control

    ERIC Educational Resources Information Center

    Dube, William V.; Dickson, Chata A.; Balsamo, Lyn M.; O'Donnell, Kristin Lombard; Tomanari, Gerson Y.; Farren, Kevin M.; Wheeler, Emily E.; McIlvane, William J.

    2010-01-01

    Restricted stimulus control refers to discrimination learning with atypical limitations in the range of controlling stimuli or stimulus features. In the study reported here, 4 normally capable individuals and 10 individuals with intellectual disabilities (ID) performed two-sample delayed matching to sample. Sample-stimulus observing was recorded…

  7. Atypical Visuomotor Performance in Children with PDD

    ERIC Educational Resources Information Center

    Schlooz, Wim A. J. M.; Hulstijn, Wouter

    2012-01-01

    Children with autism spectrum disorders (ASD) frequently encounter difficulties in visuomotor tasks, which are possibly caused by atypical visuoperceptual processing. This was tested in children (aged 9-12 years) with pervasive developmental disorder (PDD; including PDD-NOS and Asperger syndrome), and two same-age control groups (Tourette syndrome…

  8. Atypical Responding among Special Education Students.

    ERIC Educational Resources Information Center

    Berger, Mike

    1982-01-01

    Thirty special education high school students produced a significantly larger number of atypical responses to simple questions (name three colors, three common fruits, three major U.S. cities). Possible implications for classification as well as academic and emotional problems are noted. (CL)

  9. Atypical Alpha Asymmetry in Adults with ADHD

    ERIC Educational Resources Information Center

    Hale, T. Sigi; Smalley, Susan L.; Hanada, Grant; Macion, James; McCracken, James T.; McGough, James J.; Loo, Sandra K.

    2009-01-01

    Introduction: A growing body of literature suggests atypical cerebral asymmetry and interhemispheric interaction in ADHD. A common means of assessing lateralized brain function in clinical populations has been to examine the relative proportion of EEG alpha activity (8-12 Hz) in each hemisphere (i.e., alpha asymmetry). Increased rightward alpha…

  10. Identification of atypical scrapie in Canadian sheep

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Scrapie, a transmissible spongiform encephalopathy of sheep and goats, exists in most small ruminant producing countries of the world. An atypical form of this disease, originally termed Nor98, was discovered in large abattoir surveillance of clinically normal, predominantly older sheep and rarely ...

  11. Atypical Gifted Learners and Their Characteristics.

    ERIC Educational Resources Information Center

    Diket, Read M., Ed.; Abel, Trudy, Ed.

    This collection of 12 handouts focuses on different categories of atypical gifted learners and their characteristics. The handouts are generally two pages long and present a summary of the literature on the topic, some practical teaching suggestions, and references. The handouts include: (1) "Socioeconomically Disadvantaged Gifted Students" (Pam…

  12. Atypical Neural Self-Representation in Autism

    ERIC Educational Resources Information Center

    Lombardo, Michael V.; Chakrabarti, Bhismadev; Bullmore, Edward T.; Sadek, Susan A.; Pasco, Greg; Wheelwright, Sally J.; Suckling, John; Baron-Cohen, Simon

    2010-01-01

    The "self" is a complex multidimensional construct deeply embedded and in many ways defined by our relations with the social world. Individuals with autism are impaired in both self-referential and other-referential social cognitive processing. Atypical neural representation of the self may be a key to understanding the nature of such impairments.…

  13. Identifying metabolic risks with antipsychotics and monitoring and management strategies.

    PubMed

    Newcomer, John W; Sernyak, Michael J

    2007-07-01

    Mental health providers have an especially important responsibility to monitor the physical changes that patients have in response to medication. The current public health focus is on adiposity as a major risk factor for diabetes, coronary heart disease, insulin resistance syndrome, metabolic syndrome, and other diseases. Adiposity has an adverse effect on insulin action, which can lead to a cycle in which insulin loses its ability to stop the breakdown of fat. Because type 2 diabetes takes approximately 2 decades to develop, patients with increased BMI can be at risk for adverse effects to their physical health for many years. Because of the possibility that some antipsychotic treatments can lead to weight gain and metabolic changes and possibly to severe physical illness, regular physical checks should be made. PMID:17685728

  14. Antipsychotic polypharmacy: a Japanese survey of prescribers' attitudes and rationales.

    PubMed

    Kishimoto, Taishiro; Watanabe, Koichiro; Uchida, Hiroyuki; Mimura, Masaru; Kane, John M; Correll, Christoph U

    2013-10-30

    While combining antipsychotics is common in schizophrenia treatment, the literature on the reasons for antipsychotic polypharmacy (APP) is limited. We aimed to identify prescriber attitudes and rationales for APP in Japan where high APP utilization is reported. Two-hundred and seventeen psychiatrists participated in the survey, which assessed APP attitudes and behaviors. Prescribing APP to 47.7±24.7% (mean±S.D.) of their patients, psychiatrists reported that they were "moderately" concerned about APP. The most APP-justifiable factors were (1="not at all" to 5="extreme") cross titration (4.50±0.67), randomized controlled evidence (3.67±0.83), and treatment of comorbid conditions (3.31±0.83). Conversely, APP-discouraging factors were chronic side effects (4.14±0.64), difficulty determining cause and effect (4.07±0.74), and acute side effects (3.99±0.81). Comparing high to low APP prescribers (>50% vs. ≤50% of patients), no differences emerged regarding APP justification and concerns. In multivariate analyses, high APP use was associated with practice at a psychiatric hospital (OR: 2.70, 95% CI: 1.29-5.67, p=0.009), concern about potential drug-drug interactions (OR: 1.56, 95% CI: 1.04-2.35, p=0.031), and less reliance on case reports of APP showing efficacy (OR: 0.64, 95% CI: 0.44-0.92, p=0.017) (r(2)=0.111, p=0.001). High and low APP prescribers shared a comparable degree of justifications and concerns. Future research should examine the impact of cultural determinants on APP. PMID:23602697

  15. Therapeutic equivalence of antipsychotics and antidepressants - A systematic review.

    PubMed

    Cessak, Grzegorz; Rokita, Konrad; Dąbrowska, Marta; Sejbuk-Rozbicka, Katarzyna; Zaremba, Anna; Mirowska-Guzel, Dagmara; Bałkowiec-Iskra, Ewa

    2016-04-01

    The number of newly approved generic psychotropic drugs increases every year and, in many countries, their sales exceed the sales of brand-name counterparts. In order for any generic drug to receive an approval of regulatory authorities, its bioequivalence with the corresponding reference product must be demonstrated. Moreover, generic drugs must meet the same quality standards as reference drugs. However, many psychiatrists express concerns about use of generic drugs. We carried out a systematic analysis of the relevant literature indexed in PubMed and Cochrane databases. The MeSH term "generic" was combined with terms describing antipsychotic and antidepressive drugs, including their pharmaceutical names and relevant mental disorders. All 26 articles including either clinical studies or case reports have been qualified for a detailed analysis. No cases describing switches between two generics were found. Therapeutic equivalence studies evaluating antipsychotics included clozapine, olanzapine, and risperidone. The clinical status was judged to have worsened in 15.7% patients treated with clozapine. The number of relapses before and after the switch was not significantly different in patients treated with olanzapine. Two case reports showed clinical state deterioration after switch to generic risperidone. The clinical outcome after conversion to a generic antidepressant was evaluated only in one retrospective study. That study analyzed the outcomes of treatment with citalopram and revealed mental state deterioration in 11.6% of patients. Only single reports describe cases of impaired efficacy or adverse events after the switch to a generic antidepressant, including fluoxetine, mirtazapine, and venlafaxine. No cases of suicidal attempt after the switch were reported. Although the overall number of described cases is rather modest, health professionals should be aware of possible changes in the therapeutic effectiveness after changing to a generic medicine. PMID

  16. FITS into practice: translating research into practice in reducing the use of anti-psychotic medication for people with dementia living in care homes

    PubMed Central

    Brooker, Dawn J.; Latham, Isabelle; Evans, Simon C.; Jacobson, Nicola; Perry, Wendy; Bray, Jennifer; Ballard, Clive; Fossey, Jane; Pickett, James

    2016-01-01

    Objectives: This paper reports on the acceptability and effectiveness of the FITS (Focussed Intervention Training and Support) into Practice Programme. This intervention was scaled up from an earlier cluster randomised-controlled trial that had proven successful in significantly decreasing antipsychotic prescribing in care homes. Method: An in depth 10-day education course in person-centred care was delivered over a three-month period, followed by six supervision sessions. Participants were care-home staff designated as Dementia Care Coaches (DCCs) responsible for implementing interventions in 1 or 2 care homes. The course and supervision was provided by educators called Dementia Practice Development Coaches (DPDCs). Effectiveness data included monitoring antipsychotic prescriptions, goal attainment, knowledge, attitudes and implementation questionnaires. Qualitative data included case studies and reflective journals to elucidate issues of implementation. Results: Of the 100 DCCs recruited, 66 DCCs completed the programme. Pre-post questionnaires demonstrated increased knowledge and confidence and improved attitudes to dementia. Twenty per cent of residents were prescribed antipsychotics at baseline which reduced to 14% (31% reduction) with additional dose reductions being reported alongside improved personalised goal attainment. Crucial for FITS into Practice to succeed was the allocation and protection of time for the DCC to attend training and supervision and to carry out implementation tasks in addition to their existing job role. Evaluation data showed that this was a substantial barrier to implementation in a small number of homes. Discussion and conclusions: The FITS into practice programme was well evaluated and resulted in reduction in inappropriate anti-psychotic prescribing. Revisions to the intervention are suggested to maximise successful implementation. PMID:26167720

  17. Isolation of atypical enteropathogenic Escherichia coli from chicken and chicken-derived products.

    PubMed

    Alonso, M Z; Sanz, M E; Irino, K; Krüger, A; Lucchesi, P M A; Padola, N L

    2016-04-01

    Atypical enteropathogenic Escherichia coli (EPEC) strains from chicken and chicken-derived products were isolated and characterised. The strains presented a wide variety of serotypes, some have been reported in other animal species (O2:H40, O5:H40) and in children with diarrhoea (O8:H-). Most of the strains carried intimin β. The results indicate that chicken and chicken products are important sources of atypical EPEC strains that could be associated with human disease, and highlight the need to improve hygiene practices in chicken slaughtering and meat handling. PMID:26810335

  18. Unlocking the molecular mechanisms of antipsychotics - a new frontier for discovery.

    PubMed

    Bowling, Heather; Santini, Emanuela

    2016-01-01

    Despite the use of antipsychotics to treat schizophrenia for the last several decades, little was understood about their molecular mechanisms of action. In this review, we discuss recent studies that have helped elucidate mechanisms of action of antipsychotics and their potential interplay with genetic, metabolomic, proteomic, and other cellular process-related discoveries in schizophrenia pathology. We also highlight genes that have been identified in multiple studies in both schizophrenia patients and in antipsychotic action that are related to glucose and cellular metabolism, the cytoskeleton, protein synthesis, cell adhesion and synaptic activity. Though some questions of antipsychotic mechanisms of action, such as primary versus off-target effects, remain, the recent gains in understanding how to treat schizophrenia at the molecular level are promising. We propose that these recent insights provide a new and more complete landscape for drug discovery and patient biomarker development. PMID:27399321

  19. Use-dependent inhibition of synaptic transmission by the secretion of intravesicularly accumulated antipsychotic drugs.

    PubMed

    Tischbirek, Carsten H; Wenzel, Eva M; Zheng, Fang; Huth, Tobias; Amato, Davide; Trapp, Stefan; Denker, Annette; Welzel, Oliver; Lueke, Katharina; Svetlitchny, Alexei; Rauh, Manfred; Deusser, Janina; Schwab, Annemarie; Rizzoli, Silvio O; Henkel, Andreas W; Müller, Christian P; Alzheimer, Christian; Kornhuber, Johannes; Groemer, Teja W

    2012-06-01

    Antipsychotic drugs are effective for the treatment of schizophrenia. However, the functional consequences and subcellular sites of their accumulation in nervous tissue have remained elusive. Here, we investigated the role of the weak-base antipsychotics haloperidol, chlorpromazine, clozapine, and risperidone in synaptic vesicle recycling. Using multiple live-cell microscopic approaches and electron microscopy of rat hippocampal neurons as well as in vivo microdialysis experiments in chronically treated rats, we demonstrate the accumulation of the antipsychotic drugs in synaptic vesicles and their release upon neuronal activity, leading to a significant increase in extracellular drug concentrations. The secreted drugs exerted an autoinhibitory effect on vesicular exocytosis, which was promoted by the inhibition of voltage-gated sodium channels and depended on the stimulation intensity. Taken together, these results indicate that accumulated antipsychotic drugs recycle with synaptic vesicles and have a use-dependent, autoinhibitory effect on synaptic transmission. PMID:22681688

  20. Does subdivision of the "atypical" urine cytology increase predictive accuracy for urothelial carcinoma?

    PubMed

    Bostwick, David G; Hossain, Deloar

    2014-12-01

    Urine cytology is routinely used for early diagnosis and monitoring of patients with hematuria or a history of urothelial carcinoma, but its clinical utility is greatly diminished by a high frequency of "atypical" specimens, reportedly around 20% in the literature. We compared our results with double-stained urine cytology specimens (papanicolaou and acid hematoxylin stains) with published results with only a single or double papanicolaou stain. The acid hematoxylin stain enhanced nuclear chromatin staining, eliminated significant background debris, and improved visibility of diagnostic cells in the presence of obscuring blood. Medical records of all urine cytologies received between 2005 and 2012 in our laboratories were reviewed. The study group consisted of all cases with bladder biopsy follow-up within one year of cytology. Of 43,131 urine cytologies diagnosed in our laboratories, biopsy follow-up results were available within one year in 10,473 cases, including 852 for symptoms and 1,461 for follow-up of bladder cancer. An additional 6,427 cases had cystoscopy results in which no biopsy was obtained. Cases were classified as negative (81.6%), atypical, favor reactive (2.9%), atypical, favor neoplastic (7.3%), suspicious (5.7%), and malignant (2.5%), with subsequent frequencies for urothelial cancer on biopsy of 13.3%, 31.1%, 37.6%, 53.6%, and 74.3%, respectively. No significant difference was found if atypical was subdivided into two categories: favor reactive and favor neoplastic. Subdivision of the atypical category did not improve diagnostic accuracy. Addition of the acid hematoxylin stain decreased the incidence of atypical urine cytologies from about 20% to 10.2%. PMID:24838797

  1. Dose-dependent effect of antipsychotic drugs on autonomic nervous system activity in schizophrenia

    PubMed Central

    2012-01-01

    Background Antipsychotic drugs are considered a trigger factor for autonomic dysregulation, which has been shown to predict potentially fatal arrhythmias in schizophrenia. However, the dose-dependent effect of antipsychotic drugs and other psychotropic drugs on autonomic nervous system (ANS) activity remain unclear. The purpose of this study was to investigate the dose-dependent effect of antipsychotic drugs and other clinical factors on ANS activity in an adequate sample size of patients with schizophrenia. Methods A total of 211 Japanese patients with schizophrenia and 44 healthy subjects participated in this study. ANS activity was assessed by means of heart rate variability (HRV) power spectral analysis. Antipsychotic drug treatment and various clinical factors were investigated for each participant. The patient group was categorized into three subgroups according to daily dose of antipsychotic drug, and HRV was compared between groups. Results The results showed significantly decreased low-frequency and high-frequency components of HRV in the patient group compared to the control group. The high-dose group showed a significantly lower HRV than the medium-dose group and an even lower HRV than the low-dose group. In addition, a significant association between HRV and antipsychotic drug dose was identified by multiple regression analysis. HRV was not associated with age, sex, body mass index, duration of illness, or daily dose of other psychotropic drugs. Conclusion These results suggest that antipsychotic drugs exert a significant dose-dependent effect on the extent of decline in ANS activity, and that optimal antipsychotic medication is required to avoid possible cardiovascular adverse events in patients with schizophrenia. PMID:23151241

  2. Histamine H1 receptor involvement in prepulse inhibition and memory function: Relevance for the antipsychotic actions of clozapine

    PubMed Central

    Roegge, Cindy S.; Perraut, Charles; Hao, Xin; Levin, Edward D.

    2009-01-01

    Histamine H1 blockade is one of the more prominent actions of the multi-receptor acting antipsychotic clozapine. It is currently not known how much this H1 antagonism of clozapine contributes to the therapeutic or adverse side effects of clozapine. The current studies with Sprague-Dawley rats were conducted to determine the participation of histaminergic H1 receptor subtype in sensorimotor plasticity and memory function affected by clozapine using tests of prepulse inhibition (PPI) and radial-arm maze choice accuracy. The PPI impairment caused by the glutamate antagonist dizocilpine (MK-801) was significantly attenuated by clozapine. In the current project, we found that the selective H1 antagonist pyrilamine also reversed the dizocilpine-induced impairment in PPI of tactile startle with an auditory prepulse. In the radial-arm maze (RAM), pyrilamine, like clozapine, impaired working memory and caused a significant dose-related slowing of response. Pyrilamine, however, decreased the number of reference memory errors. We have previously shown that nicotine effectively attenuates the clozapine-induced working memory impairment, but in the current study, nicotine did not significantly alter the effects of pyrilamine on the RAM. In summary, the therapeutic effect of clozapine in reversing PPI impairment was mimicked by the H1 antagonist pyrilamine, while pyrilamine had a mixed effect on cognition. Pyrilamine impaired working memory but improved reference memory in rats. Thus, H1 antagonism seems to play a role in part of the beneficial actions of antipsychotics, such as clozapine. PMID:17382376

  3. Effects of Antipsychotics on Bone Mineral Density in Patients with Schizophrenia: Gender Differences

    PubMed Central

    Chen, Chien-Yu; Lane, Hsien-Yuan; Lin, Chieh-Hsin

    2016-01-01

    Low bone mineral density (BMD) and osteoporosis are common in patients with schizophrenia and detrimental to illness prognosis and life quality. Although the pathogenesis is not fully clear, series of studies have revealed factors related to low BMD such as life style, psychotic symptoms, medication use and the activity of bone absorption markers. It has been known that antipsychotic-induced hyperprolactinemia plays a critical role on decreased BMD. However, it remains uncertain whether the risk factors differ between men and women. According to the effect on prolactin, antipsychotics can be classified into two groups: prolactin-sparing (PS) and prolactin-raising (PR). Our previous study has demonstrated that clozapine which is among the PS antipsychotics is beneficial for BMD when compared with PR antipsychotics in women with chronic schizophrenia. We have also found that risks factors associated with low BMD are different between men and women, suggesting that gender-specific risk factors should be considered for intervention of bone loss in patients with schizophrenia. This article reviews the effects of antipsychotics use on BMD with particular discussion for the differences on gender and age, which implicate the alterations of sex and other related hormones. In addition, currently reported protective and risk factors, as well as the effects of medication use on BMD including the combination of antipsychotics and other psychotropic agents and other potential medications are also reviewed. PMID:27489377

  4. Youth, Caregiver, and Prescriber Experiences of Antipsychotic-Related Weight Gain

    PubMed Central

    Murphy, Andrea Lynn; Gardner, David Martin; Cooke, Charmaine; Kutcher, Stanley Paul; Hughes, Jean

    2013-01-01

    Objectives. To explore the lived experience of youth, caregivers, and prescribers with antipsychotic medications. Design. We conducted a qualitative interpretive phenomenology study. Youth aged 11 to 25 with recent experience taking antipsychotics, the caregivers of youth taking antipsychotics, and the prescribers of antipsychotics were recruited. Subjects. Eighteen youth, 10 caregivers (parents), and 11 prescribers participated. Results. Eleven of 18 youth, six of ten parents, and all prescribers discussed antipsychotic-related weight gain. Participants were attuned to the numeric weight changes usually measured in pounds. Significant discussions occurred around weight changes in the context of body image, adherence and persistence, managing weight increases, and metabolic effects. These concepts were often inextricably linked but maintained the significance as separate issues. Participants discussed tradeoffs regarding the perceived benefits and risks of weight gain, often with uncertainty and inadequate information regarding the short- and long-term consequences. Conclusion. Antipsychotic-related weight gain in youth influences body image and weight management strategies and impacts treatment courses with respect to adherence and persistence. In our study, the experience of monitoring for weight and metabolic changes was primarily reactive in nature. Participants expressed ambiguity regarding the short- and long-term consequences of weight and metabolic changes. PMID:24533223

  5. Brain Structural Effects of Antipsychotic Treatment in Schizophrenia: A Systematic Review.

    PubMed

    Roiz-Santiañez, Roberto; Suarez-Pinilla, Paula; Crespo-Facorro, Benedicto

    2015-01-01

    The findings about the progressive brain changes in schizophrenia are controversial, and the potential confounding effect of antipsychotics on brain structure is still under debate. The goal of the current article was to review the existing longitudinal neuroimaging studies addressing the impact of antipsychotic drug treatment on brain changes in schizophrenia. A comprehensive search of PubMed was performed using combinations of key terms distributed into four blocks: "MRI", "longitudinal", "schizophrenia" and "antipsychotic". Studies were considered to be eligible for the review if they were original articles. Studies that examined only changes in brain density were excluded. A total of 41 MRI studies were identified and reviewed. Longitudinal MRI studies did not provide a consistent notion of the effects of antipsychotic treatment on the pattern of brain changes over time in schizophrenia. Overall, most of the included articles did not find a linear relationship between the degree of exposure and progressive brain changes. Further short- and longterm studies are warranted to a better understanding of the influence of antipsychotics in brain structural changes in schizophrenia and also to verify whether first and second generation antipsychotics may differentially affect brain morphometry. PMID:26412062

  6. Effects of Antipsychotics on Bone Mineral Density in Patients with Schizophrenia: Gender Differences.

    PubMed

    Chen, Chien-Yu; Lane, Hsien-Yuan; Lin, Chieh-Hsin

    2016-08-31

    Low bone mineral density (BMD) and osteoporosis are common in patients with schizophrenia and detrimental to illness prognosis and life quality. Although the pathogenesis is not fully clear, series of studies have revealed factors related to low BMD such as life style, psychotic symptoms, medication use and the activity of bone absorption markers. It has been known that antipsychotic-induced hyperprolactinemia plays a critical role on decreased BMD. However, it remains uncertain whether the risk factors differ between men and women. According to the effect on prolactin, antipsychotics can be classified into two groups: prolactin-sparing (PS) and prolactin-raising (PR). Our previous study has demonstrated that clozapine which is among the PS antipsychotics is beneficial for BMD when compared with PR antipsychotics in women with chronic schizophrenia. We have also found that risks factors associated with low BMD are different between men and women, suggesting that gender-specific risk factors should be considered for intervention of bone loss in patients with schizophrenia. This article reviews the effects of antipsychotics use on BMD with particular discussion for the differences on gender and age, which implicate the alterations of sex and other related hormones. In addition, currently reported protective and risk factors, as well as the effects of medication use on BMD including the combination of antipsychotics and other psychotropic agents and other potential medications are also reviewed. PMID:27489377

  7. Effectiveness of long-acting injectable risperidone versus oral antipsychotics in the treatment of recent-onset schizophrenia: a case-control study.

    PubMed

    Barrio, Pablo; Batalla, Albert; Castellví, Pere; Hidalgo, Diego; García, Marta; Ortiz, Ana; Grande, Iria; Pons, Alexandre; Parellada, Eduard

    2013-07-01

    Long-acting injectable antipsychotics may offer a relevant improvement in treatment adherence in recent-onset psychosis, leading to a decreased rate of hospital readmission, a better rate of clinical remission and improved psychosocial adjustment. The aim of the study was to compare the clinical remission rates, number of hospital readmissions and personal and social functioning after 2 years between patients with recent-onset schizophrenia (<2 years) in treatment with risperidone long-acting injectable (RLAI) and patients with recent-onset schizophrenia receiving oral antipsychotics. This is a case-control study comparing patients with recent-onset schizophrenia who initiated RLAI treatment between 2004 and 2008 (n=26) with a control group matched for age and sex, diagnosed with recent-onset schizophrenia and treated with oral antipsychotics (n=26). Study assessments included sociodemographic variables, the Positive and Negative Syndrome Scale, the Personal and Social Functioning Scale, the number of hospital readmissions and the Andreasen remission criteria. To assess the effect of treatment on each dependent variable, separate generalized estimating equations models were constructed. After 2 years of treatment, and adjusting for educational level, the RLAI group showed a greater reduction in the Positive and Negative Syndrome Scale total scale [mean (SD)=47.7 (12.0) vs. 66.2 (18.5); mean difference =-17.56; 95% confidence interval (CI)=-27.11 to -8.00; P<0.001], as well as in the negative [mean (SD) 14.3 (6.1) vs. 19.4 (6.4); mean difference=-5.02; 95% CI=-8.28 to -1.77; P=0.002] and general psychopathology [mean (SD)=23.4 (6.3) vs. 32.7 (8.1); mean difference=-9.16; 95% CI=-13.3 to -5.03; P<0.001] subscales compared with the oral antipsychotic group. Personal and Social Functioning Scale scores were also higher in the RLAI group [mean (SD)=72.4 (14.8) vs. 59.7 (13.5); mean difference=13.41; 95% CI=5.65-21.18; P<0.001]. Although not statistically significant

  8. An atypical fracture in male patient with osteogenesis imperfecta

    PubMed Central

    Etxebarria-Foronda, Iñigo; Carpintero, Pedro

    2015-01-01

    Summary So-called atypical fractures have been related to prolonged treatment with bisphosphonates. Although there remain unanswered questions with respect to their etiology and physiopathology, it does appear to be a causal relationship. There are many references in the literature about this problem in patients in whom these drugs have been used to treat osteoporosis, but few reports in patients who have received this therapy for the management of osteogenesis imperfecta. The Authors describe a case of a young male patient with osteogenesis imperfecta with a number of historical fractures, and who received treatment with these drugs, initially parenterally and subsequently orally, presenting as a complication of the treatment, an atypical diaphyseal femoral fracture. The characteristics of the fracture are consistent with the updated diagnostic criteria of the American Society for Bone and Mineral Research. The clinical case, its treatment, both surgically and metabolically with teriparatide, and its development over a year, are analysed. The case is notable for, on the one hand, the significance of the presence of this type of fracture in a young patient with this disease, and on the other, because of the administration of teriparatide outside its established clinical indications, with twin objectives: to improve the bone structure of the patient’s underlying disease, and to counteract the harmful effects which bisphosphonates may have on this bone. PMID:26811713

  9. [Neuropathic pain due to herpes zoster infection with atypical localization].

    PubMed

    Sağır, Özlem; Özaslan, Sabri; Meriç, Yücel; Arslan, İsmail; Köroğlu, Ahmet

    2013-01-01

    Acute herpes zoster infection appears in the situation of depression of immune system and reactivation of varicella zoster virus which causes small pox. Pain and maculopapular lesion accompany clinical symptoms. Various pharmacological and invasive methods can be used for treatment. Efficient therapy is important for prevention of postherpetic neuralgia and cure of acute pain and dermatological lesions. A 55 years old, 160 cm height and 65 kg weight female patient with complaints of severe pain, sensation of burning, tingling at the right hand and forearm was admitted to our pain department. The patient who was diagnosed as cervical hernia at an other medical center had a normal physical servical spine examination. Patient history and physical examination findings with acute herpes zoster infection was considered. Right stellate ganglion blockade for diagnosis and treatment was performed because of regressed and atypically located lesions and a visual analog scale score of 10. VAS score decreased 50% at 9th min after block, VAS score at 2nd hour was 2. Antiviral, gabapentin, and tricyclic antidepressant treatment was started after stellat ganglion blockade and patient was discharged. After 3 months complaints dissapeared and drug doses were discreased and stopped. In conclusion we think that stellate ganglion blockade can be useful in diagnosis, acute pain control, improving patient comfort and compatibility to drug therapy in atypically located herpes zoster.

  10. Atypical Trigeminal Neuralgia Secondary to Meningioma

    PubMed Central

    Niwant, Premeshwar; Motwani, Mukta; Naik, Sushil

    2015-01-01

    Trigeminal neuralgia is a disorder of the fifth cranial nerve that causes episodes of intense, stabbing, electric shock-like pain that lasts from few seconds to few minutes in the areas of the face where the branches of the nerve are distributed. More than one nerve branch can be affected by the disorder. We report an unusual case of trigeminal neuralgia affecting right side of face presenting atypical features of neuralgia and not responding to the usual course of treatment. The magnetic resonance imaging study of brain revealed a large extra-axial mass involving right cerebellopontine angle region causing moderate pressure effect on trigeminal nerve and brain stem. The aim of this case report is to show a tumor of cerebellopontine angle, presenting clinically as atypical trigeminal neuralgia. PMID:26664753

  11. Atypical cases of Dowling–Degos disease

    PubMed Central

    Naveen, Kikkeri Narayanshetty; Athaniker, Sharatchandra B.; Hegde, Spandana P.; Shetty, Rahul; Radha, Hanumanthayya; Parinitha, Sadashivappa Sangam

    2016-01-01

    Dowling–Degos disease (DDD) is a rare autosomal dominant condition characterized by multiple, small, round pigmented macules usually arranged in reticular pattern, chiefly distributed in axillae and groins. Here we are reporting three atypical cases of DDD in a family. They had hypopigmented macules with typical features of DDD indicating generalized DDD. Histopathology confirmed the diagnosis. We present these three cases to stress the existence of generalized DDD phenotype in the Indian population. PMID:27057490

  12. Imaging pathological tau in atypical parkinsonian disorders

    PubMed Central

    Coakeley, Sarah; Strafella, Antonio P.

    2016-01-01

    Purpose of review This review examines the current literature on tau imaging in atypical parkinsonian disorders and other tauopathies. Recent findings There are a number of tau PET radiotracers that have demonstrated promising preliminary results in atypical parkinsonian disorders, such as progressive supranuclear palsy and corticobasal degeneration. These radiotracers were capable of selectively labeling tau in vitro and in vivo, with high affinity. Other radiotracers tested more extensively in patients with Alzheimer’s disease have also been able to successfully image tau deposition. Summary The development of tau radioligands for PET has led to the current testing of these tracers in clinical studies, many of which concentrate on patients with Alzheimer’s disease. Atypical parkinsonian disorders such as progressive supranuclear palsy and corticobasal degeneration are now being investigated as well. These disorders can be very difficult to diagnose, because of their clinical overlap with other parkinsonian disorders. Imaging tau using PET could serve as a diagnostic biomarker for these tauopathies and provide a means of assessing treatment that targets tau burden. PMID:26110795

  13. Aggressive papillary adenocarcinoma on atypical localization

    PubMed Central

    Balci, Mecdi Gurhan; Tayfur, Mahir; Deger, Ayse Nur; Cimen, Orhan; Eken, Huseyin

    2016-01-01

    Abstract Introduction: Aggressive digital papillary adenocarcinoma (ADPA) is a rare sweat gland tumor that is found on the fingers, toes, and the digits. To date, <100 cases have been reported in the literature. Apart from 1 case reported in the thigh, all of them were on digital or nondigital acral skin. Case presentation: A 67-year-old Caucasian woman was admitted to the hospital due to a mass on the scalp. This lesion was present for almost a year. It was a semimobile cyctic mass that elevated the scalp. There was no change in the skin color. Its dimensions were 1.5 × 1 × 0.6 cm. The laboratory, clinic, and radiologic findings (head x-ray) of the patient were normal. It was evaluated as a benign lesion such as lipoma or epidermal cyst by a surgeon due to a small semimobile mass and no erosion of the skull. It was excised by a local surgery excision. The result of the pathologic examination was aggressive papillary adenocarcinoma. This diagnosis is synonymous with ADPA. Conclusion: In our case, localization was scalp. This localization is the first for this tumor in the literature. In addition, another atypical localization of this tumor (ADPA) is thigh in the literature. This case was presented due to both the rare and atypical localizations. That is why, in our opinion, revision of “digital” term in ADPA is necessary due to seem in atypical localizations like thigh and scalp. PMID:27428196

  14. A hypothesis-driven association study of 28 nuclear-encoded mitochondrial genes with antipsychotic-induced weight gain in schizophrenia.

    PubMed

    Gonçalves, Vanessa F; Zai, Clement C; Tiwari, Arun K; Brandl, Eva J; Derkach, Andriy; Meltzer, Herbert Y; Lieberman, Jeffrey A; Müller, Daniel J; Sun, Lei; Kennedy, James L

    2014-05-01

    Mitochondria are the main source of energy for neurons and have a role in many vital neuronal functions. Mitochondrial dysfunction has been described in schizophrenia, and antipsychotics such as clozapine and olanzapine have been associated with differences in gene expression in mitochondria. We investigated the hypothesis that nuclear-encoded mitochondrial genes, particularly those involved in oxidative phosphorylation or involved in oxidative stress, mitochondrial biogenesis, inflammation, and apoptosis, would be associated with antipsychotic-induced weight gain (AIWG). In total, we selected 28 genes and analyzed 60 SNPs (50 are functional), in 283 schizophrenia subjects, treated with atypical medications for up to 14 weeks. Association between AIWG (as measured by the % of weight gain from baseline) and SNP genotypes were tested using linear regression with treatment duration, baseline body weight, and medication type as covariates. We observed a significant association between rs6435326 in the NDUFS1 gene and AIWG in the subset of European patients (N=150, Pcorrected=0.02). The haplotype carrying the risk alleles of rs6435326 and two other SNPs (rs1053517 and rs1801318) in NDUFS1 was also nominally associated with percentage of weight gain (T-C-G vs A-T-A, P=0.005). In addition, stepwise linear regression was performed to select important variables predictive of the outcome, and a gene-gene interaction analysis was carried out. We observed a significant interaction between the TT risk genotype of rs6435326 in NDUFS1 and AG genotype of rs3762883 in COX18 (Pcorrected=0.001). A permutation-based test of all 60 SNPs jointly showed significant association with weight gain (P=0.02). Finally, our replication study of rs6435326, rs1053517 and rs1801318 in NDUFS1 using samples from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) showed that rs1801318 was significantly associated with AIWG (N=200, Pcorrected=0.04), and the three SNPs were

  15. Detection of metabolic syndrome in schizophrenia and implications for antipsychotic therapy : is there a role for folate?

    PubMed

    Burghardt, Kyle J; Ellingrod, Vicki L

    2013-02-01

    In general, the presence of metabolic syndrome is associated with significant cardiovascular mortality and represents a growing public health concern in the USA. Patients with schizophrenia have a three times greater risk of death than the general population, with cardiovascular disease being the most common cause of this mortality. Use of atypical antipsychotics (AAPs) to treat schizophrenia contributes significantly to this cardiovascular risk. While several different clinical guidelines currently exist to monitor the metabolic consequences of AAP use, implementation is lacking. Because of under-monitoring of side effects and the lack of alternative treatment choices in schizophrenia, research has focused on identification of various biomarkers and pharmacogenomic targets to focus on the patients at greatest risk of metabolic syndrome, thus aiming to increase the efficacy and minimize the side effects of AAPs. This has led to several different lines of research. This review focuses on summarizing the differing metabolic syndrome criteria, monitoring guidelines for use of AAPs, and the role of folic acid as it relates to metabolic syndrome within the schizophrenia population. It concentrates not only on the pharmacogenomics of folic acid metabolism but also on its epigenetic interaction with the environment. From this work, genetic variation within both the methylenetetrahydrofolate reductase (MTHFR) gene and the catechol-O-methyltransferase (COMT) gene has been associated with an increased risk of metabolic syndrome in schizophrenia patients treated with AAPs. Furthermore, work on the combination of folate pharmacogenetics and epigenetics has uncovered relationships between methylation, schizophrenia disease, treatment type, and metabolic syndrome. Despite several areas of biomarker research into schizophrenia-related metabolic syndrome, translation into the clinical setting is still lacking, and further studies are needed to bridge this gap. In the future

  16. Detection of the Metabolic Syndrome in Schizophrenia and Implications for Antipsychotic Therapy: Is There a Role for Folate?

    PubMed Central

    Burghardt, Kyle J; Ellingrod, Vicki L

    2014-01-01

    In general, presence of the metabolic syndrome is associated with significant cardiovascular mortality and represents a growing public health concern in the United States. Patients with a schizophrenia have a three times greater risk of death compared to the general population, with cardiovascular disease being the most common cause of this mortality. Use of the atypical antipsychotics (AAPs) to treat schizophrenia contributes significantly to this cardiovascular disease risk. While currently several different clinical guidelines exist to monitor for the metabolic consequences of AAP use, implementation is lacking. Due to the under monitoring of side effects and the lack of alternative treatment choices in schizophrenia, research has focused on the identification of various biomarkers and pharmacogenomic targets to focus on those at greatest risk for metabolic syndrome, thus aiming to increase the efficacy and minimize the side effects of the AAPs. This has led to several different lines of research. This manuscript focuses on summarizing the differing metabolic syndrome criteria, monitoring guidelines for AAPs and the role of folic acid as it relates to metabolic syndrome within the schizophrenia population. It will concentrate not only on the pharmacogenomics of folic acid metabolism, but also its epigenetic interaction with the environment. From this work, genetic variation within both the methylenetetrahydrofolate reductase (MTHFR) and catechol-o-methyl transferase (COMT) genes has been associated with increased metabolic syndrome risk in schizophrenia patients treated with AAPs. Furthermore, the combination of folate pharmacogenetics and epigenetics has uncovered relationships between methylation, schizophrenia disease, treatment type and metabolic syndrome. Despite the several areas of biomarker research for schizophrenia related metabolic syndrome, translation to the clinical setting is still lacking and further studies are needed to bridge this gap. Future

  17. 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

  18. 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

  19. [Pharmacogenetic-based risk assessment of antipsychotic-induced extrapyramidal symptoms].

    PubMed

    Kirnichnaya, K A; Sosin, D N; Ivanov, M V; Mikhaylov, V A; Ivashchenko, D V; Ershov, E E; Taraskina, A E; Nasyrova, R F; Krupitsky, E M

    2015-01-01

    "Typical" antipsychotics remain the wide-prescribed drugs in modern psychiatry. But these drugs are associated with development of extrapyramidal symptoms (EPS). Preventive methods of EPS are actively developed and they concentrate on personalized approach. The method of taking into account genetic characteristics of patient for prescribing of treatment was proven as effective in cardiology, oncology, HIV-medicine. In this review the modern state of pharmacogenetic research of antipsychotic-induced EPS are considered. There are pharmacokinetic and pharmacodynamic factors which impact on adverse effects. Pharmacokinetic factors are the most well-studied to date, these include genetic polymorphisms of genes of cytochrome P450. However, evidence base while does not allow to do the significant prognosis of development of EPS based on genetic testing of CYP2D6 and CYP7A2 polymorphisms. Genes of pharmacodynamics factors, which realize the EPS during antipsychotic treatment, are the wide field for research. In separate part of review research of such systems as dopaminergic, serotonergic, adrenergic, glutamatergic, GABAergic, BDNF were analyzed. The role of oxidative stress factors in the pathogenesis of antipsychotic-induced EPS was enough detailed considered. The system of those factors may be used for personalized risk assessment of antipsychotics' safety in the future. Although there were numerous studies, the pharmacogenetic-based prevention of EPS before prescribing of antipsychotics was not introduced. However, it is possible to distinguish the most perspectives markers for further research. Furthermore, brief review of new candidate genes provides here, but only preliminary results were published. The main problem of the field is the lack of high- quality studies. Moreover, the several results were not replicated in repeat studies. The pharmacogenetic-based research must be standardized by ethnicity of patients. But there is the ethnical misbalance in world

  20. Do SSRI Antidepressants Increase The Risk of Extrapyramidal Side Effects In Patients Taking Antipsychotics?

    PubMed Central

    Allsbrook, Matthew; Fries, Brant E.; Szafara, Kristina L.; Regal, Randolph E.

    2016-01-01

    Purpose: Among antidepressants, selective serotonin reup-take inhibitors (SSRIs) have enjoyed great popularity among clinicians as well as generally wide acceptance and tolerance among patients. A potentially overlooked side effect of SSRIs is the occasional occurrence of extrapyramidal symptoms (EPS), which could be a concern when SSRIs are used with antipsychotics. This study was designed to explore the possible association between SSRI antidepressant use and the incidence of EPS side effects in patients who take concomitant antipsychotic medications. Methods: The University of Michigan conducted a study at the four Michigan state mental health hospitals between May 2010 and October 2010. The Michigan Public Health Institute collected data using the InterRAI Mental Health Assessment (InterRAI MH). The present study is a retrospective cohort analysis of the cross-sectional data that were collected. Within these institutions, 693 residents were using antipsychotics. We measured the observed frequency of seven EPS recorded in the InterRAI MH within three groups of patients: 1) those on antipsychotic drugs who were taking an SSRI antidepressant; 2) those on antipsychotic drugs who were not taking an antidepressant; and 3) those on antipsychotic drugs who were taking a non-SSRI antidepressant. Differences in the prevalence of EPS were tested using one-way analysis of variance. Results: There were no significant differences in the observed EPS frequencies among the three groups (F2,18 = 0.01; P < 0.9901). Conclusion: In this study, SSRIs did not appear to potentiate the occurrence of EPS in patients using antipsychotics. PMID:26909002