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Sample records for atypical antipsychotics improves

  1. Atypicality of Atypical Antipsychotics

    PubMed Central

    Farah, Andrew

    2005-01-01

    Objective: To review the current definition of atypicality, discuss the unique features of each atypical antipsychotic, and determine whether the available drugs in this class really meet the classical definition of atypicality. Data Sources: A PubMed search was conducted to identify literature on the subject of this review, supported by additional articles based on the author's clinical knowledge and experience. Study Selection and Data Extraction: Relevant references were extracted and summarized in order to meet the objective of the article. Data Synthesis: Atypical antipsychotics are considered a major advance over conventional antipsychotics, primarily because they offer effective treatment alternatives that are relatively free of extrapyramidal symptoms. In fact, the term atypicality was originally used to describe antipsychotic agents with a minimal risk of causing extrapyramidal symptoms. However, over the years the definition has been modified such that there is currently no consensus on a true definition of atypicality for these agents. Each of the atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole) commercially available in the United States is unique in terms of its pharmacologic profile, differing with respect to receptor-binding affinity, mechanism of action, and adverse events. Of the available atypical antipsychotics, clozapine and quetiapine have shown the lowest propensity to cause extrapyramidal symptoms. Although the risk of extra-pyramidal symptoms is lower with risperidone and olanzapine than with conventional antipsychotics, risk increases with dose escalation. Data for ziprasidone indicate that the risk of extrapyramidal symptoms may be similar to that of risperidone and olanzapine. There is a concern of akathisia with aripiprazole; however, more experience with this agent is needed before definitive conclusions are made. Conclusion: If the definition of “atypical” antipsychotic is

  2. [Atypical antipsychotics in the elderly].

    PubMed

    van Melick, E J M

    2004-12-01

    Central criteria for the definition of atypical antipsychotics are antipsychotic efficacy and minimal or none extrapyramidal symptoms (EPS). This last criterium is of importance in the differentiation with the traditional antipsychotics. Of the four atypical antipsychotics which are discussed here, clozapine is the most atypical. The best proof is its good efficacy in the treatment of Parkinson psychosis with minimal adverse effects on motor function. Clozapine is the best choice for this indication. At this moment there is not enough evidence available concerning quetiapine. Risperidon and olanzapine give more Dopamine2-occupancy with higher doses and can evoke EPS, but this is still less compared to the traditional antipsychotics. All four atypical drugs cause less tardive dyskinesia. Atypical antipsychotics are not well studied in the treatment of elderly patients with functional psychosis. However the available information and the literature on the treatment of young adults makes it probable that the atypical antipsychotics are at least as effective in the elderly as the traditional antipsychotics. The median daily doses are lower for elderly than for younger patients. Risperidon has been proven effective in the treatment of agressive behaviour in dementia. Atypical antipsychotics have their 'own' adverse effects. Those which have the most impact in the elderly are discussed. PMID:15704604

  3. [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. PMID:17915438

  4. 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

  5. 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.…

  6. 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…

  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. 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. PMID:26279176

  9. Pedal edema associated with atypical antipsychotics

    PubMed Central

    Munshi, Santanu; Mukherjee, Shatavisa; Saha, Indranil; Sen, Sukanta

    2016-01-01

    This study describes a patient diagnosed as a case of bipolar affective disorder complaining of bothersome incidence of pedal edema 1 month after the initiation of atypical antipsychotic regimen with risperidone and quetiapine. All hematological and biochemical profiles were found to be normal. On discontinuation of risperidone, the condition remained unresolved even after 2 weeks, and the edema progressed reaching her calves. On tapering the dose of quetiapine, she started showing gradual improvement in edematous condition. Quetiapine was slowly discontinued. No further recurrence of edema occurred, and hence, no further medication changes were implemented. Pedal edema was found to be resolved within weeks of dechallenge of the regimen. Naranjo adverse drug reaction probability scale gave a score of 7 which denotes “probable” adverse drug reaction with quetiapine. PMID:26997731

  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. Clozapine versus other atypical antipsychotics for schizophrenia

    PubMed Central

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

    2014-01-01

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

  12. 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

  13. Aripiprazole versus other atypical antipsychotics for schizophrenia

    PubMed Central

    Komossa, Katja; Rummel-Kluge, Christine; Schmid, Franziska; Hunger, Heike; Schwarz, Sandra; El-Sayeh, Hany George G; 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 aripiprazole differs from that of other second generation antipsychotics. Objectives To evaluate the effects of aripiprazole compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Group Trials Register (March 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. Selection criteria We included all randomised trials comparing oral aripiprazole with oral forms of amisulpride, 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 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 (MD) again based on a random-effects model. Main results The review currently includes four trials with 1404 participants on two out of eight possible comparisons - aripiprazole versus olanzapine and aripiprazole versus risperidone. The overall number of participants leaving the studies early was considerable (38.5%), limiting the validity of the findings, but with no significant differences between groups. Aripiprazole was less efficacious than olanzapine in terms of the general mental state (PANSS total score: n=794, 2 RCTs, MD 4.96 CI 1.85 to 8.06), but it was associated with fewer side

  14. 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

  15. Indications of atypical antipsychotics in the elderly.

    PubMed

    McKean, Andrew; Monasterio, Erik

    2015-01-01

    Atypical antipsychotics (AAP) have become some of the most commonly prescribed medications in primary and specialist care settings. Off-label prescribing accounts for much of the expanded use of AAPs. This has become common in the elderly. Marketing by pharmaceutical companies appears to have contributed to the off-label use of AAPs, in situations where their safety and efficacy is far from established. Although evidence provides varying degrees of support for their use for behavioural and psychological symptoms of dementia, augmentation of antidepressants in depression, anxiety, insomnia and in the management of psychosis in Parkinson's Disease, there are a number of potential problems with their expanded use in the elderly. These include weight gain, type two diabetes mellitus, sudden cardiac death and increased mortality rates in the elderly with dementia. It is recommended that whenever AAPs are used off-label, a review date is identified, informed consent is obtained and treatment and side-effects are closely monitored. PMID:25354148

  16. Sertindole versus other atypical antipsychotics for schizophrenia

    PubMed Central

    Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schwarz, Sandra; Schmid, Franziska; Lewis, Ruth; 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. Objectives To evaluate the effects of sertindole compared with other second generation antipsychotics for people with schizophrenia and schizophrenia-like psychosis. Search methods We searched the Cochrane Schizophrenia Group Trials Register (April 2007) and ClinicalTrials.gov (February 2009). Selection criteria We included all randomised trials comparing oral sertindole with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone or zotepine for 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. For continuous data, we calculated weighted mean differences (WMD) again based on a random-effects model. Main results The review currently includes two short-term low-quality randomised trials (total n=508) both comparing sertindole with risperidone. One third of participants left the studies early (2 RCTs, n=504, RR 1.23 CI 0.94 to 1.60). There was no difference in efficacy (2 RCTs, n=493, WMD PANSS total change from baseline 1.98 CI −8.24 to 12.20). Compared with relatively high doses of risperidone (between 4 and 12 mg/day), sertindole produced significantly less akathisia and parkinsonism (1 RCT, n=321, RR 0.24 CI 0.09 to 0.69, NNT 14, CI 8 to 100). Sertindole produced more cardiac effects (2 RCTs, n=508, RR QTc prolongation 4.86 CI 1.94 to 12.18), weight change (2 RCTs, n=328, WMD 0.99 CI 0.12 to 1.86) and male sexual dysfunction (2 RCTs, n=437, RR 2.90 CI 1.32 to 6.35, NNH 13 CI 8 to 33

  17. 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

  18. The use of atypical antipsychotics in Bipolar Spectrum disorders

    PubMed Central

    Grünze, H.; Möller, H.J.

    2003-01-01

    Viewed in the context of ever-expanding conceptual boundaries for the diagnosis of bipolar disorder including the spectrum concept of DSM-IV, or even beyond (Akiskal and Pinto, 1999), it becomes obvious that lithium is the treatment of choice in a minority′ of patients only (Bowden et al, 2000). This article reviews what additional benefit atypical antipsychotics may provide in patients with bipolar disorder. Due both to tradition and to the regulatory requirements in the USA (FDA) and European Union (EMEA), the main target of clinical trials with atypical antipsychotics has been typical manic disorder. More recently, a significant subgroup of atypical patients, e.g., with mixed states, marked psychosis, or rapid cycling, have participated in these studies to allow an estimation of the value of atypical antipsychotics in these conditions. For the purposes of filing applications for registration with the regulatory agencies, the existing evidence is probably weak, however; from a clinical perspective, it is important that most atypical antipsychotics have also been tested in combination treatments. Finally, first data are now available on long-term prophylactic efficacy of atypical antipsychotics. These combined efficacy data definitely support the use of atypical antipsychotics in bipolar disorder, and it is now the time to collect more experience with these substances in severely ill patients in clinical settings. PMID:21206806

  19. Atypical Antipsychotic Augmentation for Treatment-Resistant Depression: A Systematic Review and Network Meta-Analysis

    PubMed Central

    Zhou, Xinyu; Keitner, Gabor I; Qin, Bin; Ravindran, Arun V; Bauer, Michael; Del Giovane, Cinzia; Zhao, Jingping; Liu, Yiyun; Fang, Yiru; Zhang, Yuqing

    2015-01-01

    Background: Previous meta-analyses of atypical antipsychotics for depression were limited by few trials with direct comparisons between two treatments. We performed a network meta-analysis, which integrates direct and indirect evidence from randomized controlled trials (RCTs), to investigate the comparative efficacy and tolerability of adjunctive atypical antipsychotics for treatment-resistant depression (TRD). Methods: Systematic searches resulted in 18 RCTs (total n = 4422) of seven different types and different dosages of atypical antipsychotics and a placebo that were included in the review. Results: All standard-dose atypical antipsychotics were significantly more efficacious than placebo in the efficacy (standardized mean differences [SMDs] ranged from -0.27 to -0.43). There were no significant differences between these drugs. Low-dose atypical antipsychotics were not significantly more efficacious than the placebo. In terms of tolerability, all standard-dose atypical antipsychotics, apart from risperidone, had significantly more side-effect discontinuations than placebo (odds ratios [ORs] ranged from 2.72 to 6.40). In terms of acceptability, only quetiapine (mean 250–350mg daily) had significantly more all-cause discontinuation than placebo (OR = 1.89). In terms of quality of life/functioning, standard-dose risperidone and standard-dose aripiprazole were more beneficial than placebo (SMD = -0.38; SMD = -0.26, respectively), and standard-dose risperidone was superior to quetiapine (mean 250–350mg daily). Conclusions: All standard-dose atypical antipsychotics for the adjunctive treatment of TRD are efficacious in reducing depressive symptoms. Risperidone and aripiprazole also showed benefits in improving the quality of life of patients. Atypical antipsychotics should be prescribed with caution due to abundant evidence of side effects. PMID:26012350

  20. Repeated activation of mania by atypical antipsychotics in a patient

    PubMed Central

    Raghunath, Ashwati

    2012-01-01

    A 50-year-old, white female patient was diagnosed with schizophrenia in her teens. Her illness did not respond adequately to treatment until she was placed on a combination of fluoxetine and conventional antipsychotics. She discontinued the conventional antipsychotics on a number of occasions, which caused her to become psychotic, but not manic. On two separate occasions she was placed on atypical antipsychotics that were associated with the occurrence of manic symptoms. Once the patient was restarted on conventional antipsychotics, she remained stable. PMID:23188864

  1. 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

  2. Zotepine versus other atypical antipsychotics for schizophrenia

    PubMed Central

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

    2014-01-01

    Background In many parts of the world, particularly in industrialised countries, second generation (atypical) antipsychotic drugs have become first line treatment for people suffering from schizophrenia. The question as to whether the effects of various second generation antipsychotic drugs differ is a matter of debate. Objectives To evaluate the effects of zotepine compared with other second generation antipsychotic drugs for people suffering from schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Group Trials Register (November 2009), inspected references of all identified studies for further trials and contacted authors of trials for additional information. Selection criteria We included only randomised clinical controlled trials that compared zotepine with any forms of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, sertindole or ziprasidone in people suffering from only schizophrenia or schizophrenia-like psychoses. Data collection and analysis SS and KK 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. For continuous data, we calculated weighted mean differences (MD) again based on a random-effects model. Main results We included three studies (total n=289; 2 RCTs zotepine vs clozapine; 1 RCT zotepine vs clozapine vs risperidone (at 4 mg, 8 mg doses) vs remoxipride. All studies were of limited methodological quality. When zotepine was compared with clozapine, it was clozapine that was found to be more effective in terms of global state (n=59, 1 RCT, RR No clinically significant response 8.23 CI 1.14 to 59.17). Mental state scores also favoured clozapine (n=59, 1 RCT, MD average score (BPRS total, high = poor) 6.00 CI 2.17 to 9.83) and there was less use of antiparkinson medication in the clozapine group (n=116, 2 RCTs, RR 20.96 CI 2.89 to 151.90). In the

  3. 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

  4. 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. PMID:24983591

  5. Asenapine, blonanserin, iloperidone, lurasidone, and sertindole: distinctive clinical characteristics of 5 novel atypical antipsychotics.

    PubMed

    Wang, Sheng-Min; Han, Changsu; Lee, Soo-Jung; Patkar, Ashwin A; Masand, Prakash S; Pae, Chi-Un

    2013-01-01

    Schizophrenia is a serious, chronic, and devastating mental illness with a substantial impact on psychological, physical, social, and economical areas of an individual and society. To treat such critical mental illness, a number of first-generation (typical) and second-generation (atypical) antipsychotics are currently available in the market. Despite such treatment options, most of patients with schizophrenia have a poor treatment outcome and become treatment resistant, causing continual deterioration on positive, negative, and cognitive symptoms, resulting in impairment of socio-occupational functioning. Hence, additional novel antipsychotics with better efficacy, safety, and tolerability profiles are needed to enable clinicians to diversify treatment options to improve treatment of schizophrenia. Recently, the 3 antipsychotics, including iloperidone (2009), asenapine (2009), and lurasidone (2010), have been approved by the US Food and Drug Administration. Two other atypical antipsychotics, including sertindole and blonanserin, are approved and used outside the United States for treatment of schizophrenia. Sertindole, after it has been voluntarily suspended by the manufacturer in 1998 due to its potential risk in causing cardiovascular-related death, was relaunched to the European market in 2005. More recently, blonanserin was approved in Japan (2008) and in Korea (2009) for the management of schizophrenia. Individual antipsychotic may have differential pros and cons compared with other antipsychotic in terms of efficacy, safety, tolerability, restoration of functional capacity, and economic aspect reflecting relapse prevention. The purpose of this review was to provide distinctive clinical characteristics and up-to-date of clinical trial data of the 5 novel atypical antipsychotics for the management of schizophrenia, which may deliver clinicians better understanding in the use of such atypical antipsychotics for the treatment of schizophrenia in clinical

  6. 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

  7. Use of Atypical Antipsychotics in Nursing Homes and Pharmaceutical Marketing

    PubMed Central

    Pimentel, Camilla B.; Donovan, Jennifer L.; Field, Terry S.; Gurwitz, Jerry H.; Harrold, Leslie R.; Kanaan, Abir O.; Lemay, Celeste A.; Mazor, Kathleen M.; Tjia, Jennifer; Briesacher, Becky A.

    2014-01-01

    BACKGROUND Many nursing home (NH) residents are prescribed atypical antipsychotics despite US Food and Drug Administration warnings of increased risk of death in older adults with dementia. Aggressive pharmaceutical marketing has been cited as a potential cause, although data are scarce. The objectives of this study were to describe the current extent and type of pharmaceutical marketing in NHs in one state, and to provide preliminary evidence for the potential influence of pharmaceutical marketing on the use of atypical antipsychotics in NHs. DESIGN Nested mixed-methods, cross-sectional study of NHs in a cluster randomized trial. SETTING 41 NHs in Connecticut. PARTICIPANTS NH administrators, directors of nursing and medical directors (n = 93, response rate 75.6%). MEASUREMENTS Quantitative data, including prescription drug dispensing data (September 2009–August 2010) linked with Nursing Home Compare data (April 2011), were used to determine facility-level prevalence of atypical antipsychotic use, facility-level characteristics, NH staffing and NH quality. Qualitative data, including semi-structured interviews and surveys of NH leaders conducted in the first quarter of 2011, were used to determine encounters with pharmaceutical marketing. RESULTS Leadership at 46.3% of NHs (19/41) reported pharmaceutical marketing encounters, consisting of educational training, written/Internet-based materials and/or sponsored training. No association was detected between the level of atypical antipsychotic prescribing and reports of any pharmaceutical marketing by at least one NH leader. CONCLUSION NH leaders frequently encounter pharmaceutical marketing through a variety of ways, although the impact on atypical antipsychotic prescribing is unclear. PMID:25688605

  8. 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

  9. New atypical antipsychotics for schizophrenia: iloperidone

    PubMed Central

    Caccia, Silvio; Pasina, Luca; Nobili, Alessandro

    2010-01-01

    The optimal treatment of schizophrenia poses a challenge to develop more effective treatments and safer drugs, to overcome poor compliance, discontinuation and frequent switching with available antipsychotics. Iloperidone is a new dopamine type 2/serotonin type 2A (D2/5-HT2A) antagonist structurally related to risperidone, expected to give better efficacy with less extrapyramidal symptoms than D2 receptor antagonist antipsychotics. In double-blind phase III trials iloperidone reduced the symptoms of schizophrenia at oral doses from 12 to 24 mg. It was more effective than placebo in reducing positive and negative syndrome total score and Brief Psychiatric Rating scale scores; it was as effective as haloperidol and risperidone in post-hoc analysis. Its long-term efficacy was equivalent to that of haloperidol. The most common adverse events were dizziness, dry mouth, dyspepsia and somnolence, with few extrapyramidal symptoms and metabolic changes in short- and long-term studies in adults. Akathisia was rare, but prolongation of the corrected QT (QTc) interval was comparable to haloperidol and ziprasidone, which is of particular concern. Further comparative studies are needed to clarify the benefit/risk profile of iloperidone and its role in the treatment of schizophrenia. PMID:20368905

  10. Predictors of Effect of Atypical Antipsychotics on Speech

    PubMed Central

    Sinha, Preeti; Vandana, Valiya Parambath; Lewis, Nikita V; Jayaram, Mannaralukrishnaiah; Enderby, Pamela

    2015-01-01

    Background: Most of the studies have looked into the effect of typical antipsychotics on speech secondary to tardive dyskinesia. Aims: This study was aimed to explore the factors predicting the effect of atypical antipsychotic medications on the production of speech. Materials and Methods: One hundred and forty patients on stable regimen of three or more months on risperidone (92), olanzapine (28), aripiprazole (14), and clozapine (6) were recruited for the study. Speech was assessed by maximum phonation duration task, s/z ratio, diadochokinetic task, acoustic analysis and Frenchay Dysarthria Assessment (FDA). Extrapyramidal symptoms (EPS) were assessed by Simpson Angus scale. Statistical Analysis: Spearman correlation analysis was carried out to find the association between speech parameters and continuous variables. Effect of EPS, duration and dose of antipsychotic treatment on speech parameters was compared using Mann-Whitney test. Results: The risperidone group differ from other antipsychotics groups significantly in s/z ratio (0.07), FDA-total (0.23) and FDA-reflex (0.25). People who took antipsychotic for more than 2 years had lower score of FDA-palate (P = 0.042), and FDA-respiratory (P = 0.04) and higher values in noise-harmonic ratio (P = 0.011) and maximum /fundamental frequency (MFF) for males (P = 0.02). Effect of EPS was seen on MFF for males (spearman correlation coefficient = 0.34) and on almost all sections of FDA (spearman correlation coefficients = -0.2 to -0.33). Conclusion: Both duration of use and propensity of atypical antipsychotics to cause EPS can influence the speech performance of the patients. This information can be useful, particularly in people with the requirement of high quality speech. PMID:26702176

  11. The influence of atypical antipsychotic drugs on sexual function

    PubMed Central

    Just, Marek J

    2015-01-01

    Human sexuality is contingent upon many biological and psychological factors. Such factors include sexual drive (libido), physiological arousal (lubrication/erection), orgasm, and ejaculation, as well as maintaining normal menstrual cycle. The assessment of sexual dysfunction can be difficult due to the intimate nature of the problem and patients’ unwillingness to discuss it. Also, the problem of dysfunction is often overlooked by doctors. Atypical antipsychotic treatment is a key component of mental disorders’ treatment algorithms recommended by the National Institute of Health and Clinical Excellence, the American Psychiatric Association, and the British Society for Psychopharmacology. The relationship between atypical antipsychotic drugs and sexual dysfunction is mediated in part by antipsychotic blockade of pituitary dopamine D2 receptors increasing prolactin secretion, although direct correlations have not been established between raised prolactin levels and clinical symptoms. Variety of mechanisms are likely to contribute to antipsychotic-related sexual dysfunction, including hyperprolactinemia, sedation, and antagonism of a number of neurotransmitter receptors (α-adrenergic, dopaminergic, histaminic, and muscarinic). Maintaining normal sexual function in people treated for mental disorders can affect their quality of life, mood, self-esteem, attitude toward taking medication, and compliance during therapy. PMID:26185449

  12. Quetiapine versus other atypical antipsychotics for schizophrenia

    PubMed Central

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

    2014-01-01

    Background In many countries of the industrialised world second generation (’atypical’) antipsychotic drugs have become the first line drug treatment for people with schizophrenia. It is not clear how the effects of the various second generation antipsychotic drugs differ. Objectives To evaluate the effects of quetiapine compared with other second generation antipsychotic drugs for people with schizophrenia and schizophrenia-like psychosis. Search methods We searched the Cochrane Schizophrenia Group Trials Register (April 2007), inspected references of all identified studies, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. Selection criteria We included all randomised control trials comparing oral quetiapine with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, 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 21 randomised control trials (RCTs) with 4101 participants. These trials provided data on four comparisons - quetiapine versus clozapine, olanzapine, risperidone or ziprasidone. A major limitation to all findings is the high number of participants leaving studies prematurely (57.6%) and the substantial risk of biases in studies. Efficacy data favoured olanzapine and risperidone compared with quetiapine (PANSS total score versus olanzapine:10 RCTs, n=1449, WMD 3.66 CI 1.93 to 5.39; versus risperidone: 9 RCTs, n=1953, WMD 3.09 CI 1.01 to 5.16), but clinical meaning is unclear

  13. Deep venous thrombosis and atypical antipsychotics: three cases report

    PubMed Central

    2012-01-01

    Background Deep venous Thrombosis is a serious, possible life threatening event which is often ignored in psychiatric Settings. Purpose In this paper three cases of deep venous Thrombosis (DVT) following the use of olanzapine and risperidone are presented. Methods The data of Three patients was collected from hospital records. Results The patients were in good general physical health and had no personal or familial history of DVT. The patients were not overweight (BMI < 25) but they suffered from DVT after initiating risperidone and olanzapine. Conclusion Risk of DVT exists in patients under treatment with atypical antipsychotics in spite of no pre existing risk factor. PMID:23351722

  14. 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

  15. Cognitive Function and Depression in Symptom Resolution in Schizophrenia Patients Treated with an Atypical Antipsychotic

    ERIC Educational Resources Information Center

    Stip, Emmanuel; Mancini-Marie, Adham

    2004-01-01

    Objective: To investigate which cognitive and affective features contribute most to responder/non-responder group separation during a switching trial with atypical antipsychotic. Design: A prospective open trial with an atypical antipsychotic (olanzapine). Patients: One hundred and thirty-four patients meeting diagnostic criteria for…

  16. 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

  17. Restless leg syndrome associated with atypical antipsychotics: current status, pathophysiology, and clinical implications.

    PubMed

    Aggarwal, Shilpa; Dodd, Seetal; Berk, Michael

    2015-01-01

    Restless leg syndrome (RLS) is a common disorder, frequently of unclear origin, which is often associated with significant distress. There are a few case reports of atypical antipsychotic agents (AAP) causing RLS. The pathophysiological mechanisms resulting in emergence of these movements suggest central dopaminergic dysfunction. Dopamine agonists and L-dopa reduce the symptoms of RLS, and some agents that block the dopaminergic system aggravate RLS. Genetic influences are implicated in RLS and an association between gene polymorphisms and antipyschotic-associated onset of RLS has been postulated. Greater awareness of potential causes of RLS, and its differentiation from akathisia and illness related agitation might help in reducing the distress associated with it and improving patient compliance in patients using atypical antipsychotic agents. PMID:24861990

  18. 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

  19. Role of atypical antipsychotics in the treatment of generalized anxiety disorder.

    PubMed

    Hershenberg, Rachel; Gros, Daniel F; Brawman-Mintzer, Olga

    2014-06-01

    Evidence-based treatment approaches for generalized anxiety disorder (GAD) comprise psychotherapy, pharmacotherapy, or a combination of the two. First-line pharmacotherapy agents include selective serotonin reuptake inhibitors, selective serotonin-norepinephrine reuptake inhibitors, and, in certain European guidelines, pregabalin, which gained European Commission approval. Although short- and long-term efficacy have been established for these agents in controlled trials, response rates of 60-70 % are insufficient, remission rates are relatively modest, and relapse rates considerable. Moreover, questions increasingly arise regarding tolerability and side-effect profiles. As an alternative, antipsychotics have long been of interest for the treatment of anxiety disorders, but investigation had been tempered by their potential for irreversible side effects. With the improved side-effect profiles of atypical antipsychotics, these agents are increasingly being investigated across Axis I disorders. Atypical antipsychotics such as quetiapine, aripiprazole, olanzapine, and risperidone have been shown to be helpful in addressing a range of anxiety and depressive symptoms in individuals with schizophrenia and schizoaffective disorders, and have since been used in the treatment of a range of mood and anxiety disorders. In this article, we review the efficacy and tolerability of atypical antipsychotics as adjunctive therapy and/or monotherapy for individuals with GAD, a currently off-label indication. The most evidence has accumulated for quetiapine. Findings suggest that approximately 50 % of participants tolerate the side effects, most commonly sedation and fatigue. Among this subset, those who continue treatment demonstrate significant reductions in anxiety when used as adjunctive therapy or monotherapy. The appropriateness of the use of antipsychotics in the treatment of GAD is discussed. PMID:24794100

  20. 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. PMID:26084582

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

    PubMed Central

    Hrdlicka, Michal; Dudova, Iva

    2015-01-01

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

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26485545

  3. Association of Typical versus Atypical Antipsychotics with Symptoms and Quality of Life in Schizophrenia

    PubMed Central

    Fujimaki, Koichiro; Takahashi, Terumichi; Morinobu, Shigeru

    2012-01-01

    Background Several reports on patients with chronic schizophrenia suggest that atypical versus typical antipsychotics are expected to lead to better quality of life (QOL) and cognitive function. Our aim was to examine the association of chronic treatment with typical or atypical antipsychotics with cognitive function, psychiatric symptoms, QOL, and drug-induced extrapyramidal symptoms in long-hospitalized patients with schizophrenia. Methodology and Principal Findings The Hasegawa Dementia Scale-Revised (HDS-R), Brief Psychiatric Rating Scale (BPRS), the Schizophrenia Quality of Life Scale, translated into Japanese (JSQLS), and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) were used to evaluate cognitive function, psychiatric symptoms, QOL, and drug-induced extrapyramidal symptoms. We examined the correlation between the dose of antipsychotics and each measure derived from these psychometric tests. The student t-test was used to compare scores obtained from psychometric tests between patients receiving typical and atypical antipsychotics. Results showed significant correlations between chlorpromazine (CPZ)-equivalent doses of typical antipsychotics and atypical antipsychotics, and the total BPRS score and BPRS subscale scores for positive symptoms. CPZ-equivalent doses of typical antipsychotics were correlated with the JSQLS subscale score for dysfunction of psycho-social activity and DIEPSS score. Furthermore, the total BPRS scores, BPRS subscale score for positive symptoms, the JSQLS subscale score for dysfunction of psycho-social activity, and the DIEPSS score were significantly higher in patients receiving typical antipsychotics than atypical antipsychotics. Conclusion and Significance These findings suggest that long-term administration of typical antipsychotics has an unfavorable association with feelings of difficulties mixing in social situations in patients with chronic schizophrenia. PMID:22615901

  4. Use Pattern and Off-Label Use of Atypical Antipsychotics in Bipolar Disorder, 1998–2002

    PubMed Central

    Demland, Jeffery A.; Jing, Yonghua; Kelton, Christina M. L.; Guo, Jeff J.; Li, Hong; Wigle, Patricia R.

    2009-01-01

    Background Postmarketing surveillance that identifies patients at high risk for receiving off-label medications will help ensure that the benefits of such treatment outweigh the risks. Because many off-label uses have little scientific support, tracking the extent to which they occur as well as the particular circumstances under which they occur is important. Objective To describe the drug-use pattern for patients with bipolar disorder, and to identify demographic and clinical factors associated with off-label use of atypical antipsychotics before US Food and Drug Administration approval for this indication. Methods Using the PHARMetrics medical claims database, a total of 105,771 adult patients with a diagnosis of bipolar disorder were evaluated during the 5-year (1998–2002) study period. Study drugs included mood stabilizers, antipsychotics, and antidepressants. Off-label use of an atypical antipsychotic was defined as a patient taking olanzapine before March 2000 (when it received an indication for bipolar disorder) or any other atypical antipsychotic during the entire study period. Logistic regression analysis was used to determine the odds ratio of receiving a drug off-label. Results Utilization of and reimbursement for atypical antipsychotics increased during the 5-year period. Of the 10.5% of patients who took atypical antipsychotics, 7.1% took these drugs off-label. In addition, 11% of patients received lithium, 25% received other anticonvulsants, and 34% received antidepressants. Off-label use of atypical antipsychotics was associated with psychiatry specialist prescribers (odds ratio = 1.52; 95% CI, 1.44–1.59) and certain comorbidities, such as substance abuse (odds ratio = 1.51; 95% CI, 1.38–1.66), anxiety disorder (odds ratio = 1.20; 95% CI, 1.14–1.26), diabetes mellitus (odds ratio = 1.26; 95% CI, 1.16–1.37), cerebral vascular disease (odds ratio = 1.26; 95% CI, 1.10–1.45), and hypertension (odds ratio = 1.12; 95% CI, 1.05–1.20). Over

  5. [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

  6. 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

  7. Satisfaction of immediate or delayed switch to paliperidone palmitate in patients unsatisfied with current oral atypical antipsychotics.

    PubMed

    Kwon, Jun Soo; Kim, Sung Nyun; Han, Jaewook; Lee, Sang Ick; Chang, Jae Seung; Choi, Jung-Seok; Lee, Heon-Jeong; Cho, Seong Jin; Jun, Tae-Youn; Lee, Seung-Hwan; Han, Changsu; Lee, Kyoung-Uk; Lee, Kyung Kyu; Lee, EunJung

    2015-11-01

    Patient satisfaction with treatment is an important clinical index associated with the efficacy and adherence of treatment in schizophrenia. Although switching from oral antipsychotics to the long-acting injectable formulation may improve convenience, patient satisfaction has not been studied extensively. We carried out a 21-week, multicenter, randomized, open-label comparative study. A total of 154 patients with schizophrenia unsatisfied with current oral atypical antipsychotics were assigned randomly to either immediate or delayed switching to paliperidone palmitate, the long-acting injectable formulation of paliperidone. The Medication Satisfaction Questionnaire (MSQ) and the Treatment Satisfaction Questionnaire for Medication (TSQM) were used to evaluate patient satisfaction with treatment, whereas the Positive and Negative Syndrome Scale (PANSS) and the Personal and Social Performance (PSP) scale were used to evaluate efficacy. From baseline to the final assessment, the MSQ score increased significantly in both groups, and the increase was greatest after the first administration of paliperidone palmitate in the immediate switch group. The scores of TSQM effectiveness, convenience, and global satisfaction as well as the PSP total score increased significantly, whereas the PANSS total score decreased significantly in both groups. The immediate switch group showed a significant improvement in the TSQM convenience score compared with the delayed switch group on oral antipsychotics during the comparison period. Most adverse events were minor and tolerable. In short, switching from oral atypical antipsychotics to paliperidone palmitate because of poor satisfaction significantly improved patient satisfaction, with comparable efficacy and tolerability. PMID:26196188

  8. Satisfaction of immediate or delayed switch to paliperidone palmitate in patients unsatisfied with current oral atypical antipsychotics

    PubMed Central

    Kim, Sung Nyun; Han, Jaewook; Lee, Sang Ick; Chang, Jae Seung; Choi, Jung-Seok; Lee, Heon-Jeong; Cho, Seong Jin; Jun, Tae-Youn; Lee, Seung-Hwan; Han, Changsu; Lee, Kyoung-Uk; Lee, Kyung Kyu; Lee, EunJung

    2015-01-01

    Patient satisfaction with treatment is an important clinical index associated with the efficacy and adherence of treatment in schizophrenia. Although switching from oral antipsychotics to the long-acting injectable formulation may improve convenience, patient satisfaction has not been studied extensively. We carried out a 21-week, multicenter, randomized, open-label comparative study. A total of 154 patients with schizophrenia unsatisfied with current oral atypical antipsychotics were assigned randomly to either immediate or delayed switching to paliperidone palmitate, the long-acting injectable formulation of paliperidone. The Medication Satisfaction Questionnaire (MSQ) and the Treatment Satisfaction Questionnaire for Medication (TSQM) were used to evaluate patient satisfaction with treatment, whereas the Positive and Negative Syndrome Scale (PANSS) and the Personal and Social Performance (PSP) scale were used to evaluate efficacy. From baseline to the final assessment, the MSQ score increased significantly in both groups, and the increase was greatest after the first administration of paliperidone palmitate in the immediate switch group. The scores of TSQM effectiveness, convenience, and global satisfaction as well as the PSP total score increased significantly, whereas the PANSS total score decreased significantly in both groups. The immediate switch group showed a significant improvement in the TSQM convenience score compared with the delayed switch group on oral antipsychotics during the comparison period. Most adverse events were minor and tolerable. In short, switching from oral atypical antipsychotics to paliperidone palmitate because of poor satisfaction significantly improved patient satisfaction, with comparable efficacy and tolerability. PMID:26196188

  9. 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

  10. Auditing Clinical Outcomes after Introducing Off-Licence Prescribing of Atypical Antipsychotic Melperone for Patients with Treatment Refractory Schizophrenia

    PubMed Central

    Röhricht, Frank; Gadhia, Seema; Alam, Rinku; Willis, Melissa

    2012-01-01

    Aims and Method. To evaluate the practical utility of off-licence prescribing and clinical outcomes of treatment with atypical antipsychotic Melperone. Method: Prospective data collection on patient's clinical characteristics and outcomes. Results. 17 patients with a diagnosis of refractory schizophrenia were identified as suitable for off-license prescribing of Melperone and commenced treatment (13 were previously treated with Clozapine). Seven of those currently remain on Melperone (41%), and for six patents, the BPRS symptom scores reduced significantly over time (24–61%) additionally patients displayed improvements of their quality of life. Six patients were discontinued due to noncompliance and/or side effects. Melperone was ineffective in the other four patients. Clinical Implications. The example of a small group of patients responding well to a comparably safe and inexpensive atypical antipsychotic with favourable side effect profile should encourage clinicians to use this tool as third-line treatment and to conduct more systematic clinical research. PMID:22566771

  11. Analysis of Adverse Drug Reactions of Atypical Antipsychotic Drugs in Psychiatry OPD

    PubMed Central

    Piparva, Kiran G.; Buch, J. G.; Chandrani, Kalpesh V.

    2011-01-01

    Background: Novel atypical antipsychotics are superior to conventional antipsychotics as they significantly reduce both positive and negative symptoms of schizophrenia and have lower risk of extrapyramidal symptoms (EPS). However, these drugs have separate set of adverse drug reactions (ADRs). Therefore, this study was carried out to assess these ADRs, which can have impact on long-term compliance and achieving successful treatment. Materials and Methods: A prospective study of analysis of ADR of atypical antipsychotic drugs was carried out in the psychiatry outpatient department. Patients of psychotic disorder (any age, either sex), who were prescribed atypical antipsychotic drugs, were included. Those who were prescribed conventional antipsychotics or combinations of antipsychotics were excluded from the study. Apart from spontaneously reported ADRs, a questionnaire related to the likely ADR was used and patients’ responses were recorded in the case record form. Results: Totally 93 ADRs were recorded from 84 prescriptions. Majority of the ADRs (82 out of 93) were seen with risperidone and olanzepine, as they were the commonly prescribed drugs. Weight gain, dizziness, sleep disturbance and appetite disturbance accounted for nearly 78% of the total events. With risperidone (at 4–6 mg/day) and olanzepine (at 10–15 mg/day), gastrointestinal and sleep disturbance were observed in the initial (within 7 days to 2–3 months after treatment) course of treatment, while EPS, fatigue, seizure, increased frequency of micturition and dizziness were observed after long-term (3–9 months) use. Conclusion: The present study adds to the existing information on the prevalence of adverse effects of atypical antipsychotic drugs. Role of active surveillance in post-marketing phase is also emphasized. PMID:22345840

  12. Asenapine in the treatment of borderline personality disorder: an atypical antipsychotic alternative.

    PubMed

    Martín-Blanco, Ana; Patrizi, Barbara; Villalta, Laia; Gasol, Xero; Soler, Joaquim; Gasol, Miquel; Pascual, Juan C

    2014-03-01

    Many individuals with borderline personality disorder (BPD) receive medical treatment in clinical practice, although to date, there are no drugs specifically available for BPD. The recent Cochrane guideline suggests a benefit from using second-generation antipsychotics such as olanzapine or aripiprazole; nevertheless, side effects limit their use. Asenapine is a novel FDA-approved atypical antipsychotic for schizophrenia and bipolar disorder. However, it has not yet been tested for BPD. The goal of this observational open-label study was to assess the safety, tolerability and efficacy of asenapine in a series of cases of patients with BPD. Twelve individuals with BPD were recruited and treated with asenapine during an 8-week period. Eight individuals completed the study; a significant improvement was observed in the CGI-BPD (P<0.001) and BSL-23 (P<0.048) scales for BPD symptomatology. Besides, there was a significant improvement in the general psychopathology domains (BPRS, P<0.004), whereas no significant differences were observed in depressive symptoms. No serious adverse effects were reported and a significant weight reduction was observed (P=0.002). Asenapine appears to be a safe and effective agent in the treatment of patients with BPD, especially when other alternatives are not tolerated. These preliminary findings should be replicated in a controlled clinical trial. PMID:23962963

  13. 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…

  14. 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…

  15. Atypical antipsychotic properties of AD-6048, a primary metabolite of blonanserin.

    PubMed

    Tatara, Ayaka; Shimizu, Saki; Masui, Atsushi; Tamura, Miyuki; Minamimoto, Shoko; Mizuguchi, Yuto; Ochiai, Midori; Mizobe, Yusuke; Ohno, Yukihiro

    2015-11-01

    Blonanserin is a new atypical antipsychotic drug that shows high affinities to dopamine D2 and 5-HT2 receptors; however, the mechanisms underlying its atypicality are not fully understood. In this study, we evaluated the antipsychotic properties of AD-6048, a primary metabolite of blonanserin, to determine if it contributes to the atypicality of blonanserin. Subcutaneous administration of AD-6048 (0.3-1mg/kg) significantly inhibited apomorphine (APO)-induced climbing behavior with an ED50 value of 0.200mg/kg, the potency being 1/3-1/5 times that of haloperidol (HAL). AD-6048 did not cause extrapyramidal side effects (EPS) even at high doses (up to 10mg/kg, s.c.), whereas HAL at doses of 0.1-3mg/kg (s.c.) significantly induced bradykinesia and catalepsy in a dose-dependent manner. Thus, the therapeutic index (potency ratios of anti-APO action to that of EPS induction) of AD-6048 was much higher than that of haloperidol, illustrating that AD-6048 per se possesses atypical antipsychotic properties. In addition, immunohistochemical analysis of Fos protein expression revealed that both AD-6048 and HAL significantly increased Fos expression in the shell part of the nucleus accumbens and the striatum. However, in contrast to HAL which preferentially enhanced striatal Fos expression, AD-6048 showed a preferential action to the nucleus accumbens. These results indicate that AD-6048 acts as an atypical antipsychotic, which seems to at least partly contribute to the atypicality of blonanserin. PMID:26363311

  16. Atypical Antipsychotics Rapidly and Inappropriately Switch Peripheral Fuel Utilization to Lipids, Impairing Metabolic Flexibility in Rodents

    PubMed Central

    Albaugh, Vance L.; Vary, Thomas C.; Ilkayeva, Olga; Wenner, Brett R.; Maresca, Kevin P.; Joyal, John L.; Breazeale, Steven; Elich, Tedd D.; Lang, Charles H.; Lynch, Christopher J.

    2012-01-01

    Patients taking atypical antipsychotics are frequented by serious metabolic (eg, hyperglycemia, obesity, and diabetes) and cardiac effects. Surprisingly, chronic treatment also appears to lower free fatty acids (FFAs). This finding is paradoxical because insulin resistance is typically associated with elevated not lower FFAs. How atypical antipsychotics bring about these converse changes in plasma glucose and FFAs is unknown. Chronic treatment with olanzapine, a prototypical, side effect prone atypical antipsychotic, lowered FFA in Sprague–Dawley rats. Olanzapine also lowered plasma FFA acutely, concomitantly impairing in vivo lipolysis and robustly elevating whole-body lipid oxidation. Increased lipid oxidation was evident from accelerated losses of triglycerides after food deprivation or lipid challenge, elevated FFA uptake into most peripheral tissues (∼2-fold) except heart, rises in long-chain 3-hydroxylated acyl-carnitines observed in diabetes, and rapid suppression of the respiratory exchange ratio (RER) during the dark cycle. Normal rises in RER following refeeding, a sign of metabolic flexibility, were severely blunted by olanzapine. Increased lipid oxidation in muscle could be explained by ∼50% lower concentrations of the negative cytoplasmic regulator of carnitine palmitoyltransferase I, malonyl-CoA. This was associated with loss of anapleurotic metabolites and citric acid cycle precursors of malonyl-CoA synthesis rather than adenosine monophosphate-activated kinase activation or direct ACC1/2 inhibition. The ability of antipsychotics to lower dark cycle RER in mice corresponded to their propensities to cause metabolic side effects. Our studies indicate that lipocentric mechanisms or altered intermediary metabolism could underlie the FFA lowering and hyperglycemia (Randle cycle) as well as some of the other side effects of atypical antipsychotics, thereby suggesting strategies for alleviating them. PMID:20494946

  17. Valproic acid potentiates both typical and atypical antipsychotic-induced prefrontal cortical dopamine release.

    PubMed

    Ichikawa, Junji; Chung, Young-Chul; Dai, Jin; Meltzer, Herbert Y

    2005-08-01

    Antipsychotic drugs (APD)s and anticonvulsant mood-stabilizers are now frequently used in combination with one another in treating both schizophrenia and bipolar disorder. We have recently reported that the atypical APDs, e.g. clozapine and risperidone, as well as the anticonvulsant mood-stabilizers, valproic acid (VPA), zonisamide, and carbamazepine, but not the typical APD haloperidol, increase dopamine (DA) release in rat medial prefrontal cortex (mPFC). The increased DA release was partially (atypical APDs) or completely (mood-stabilizers) blocked by the serotonin (5-HT)1A receptor antagonist WAY100635. Diminished prefrontal cortical DA activity may contribute to cognitive impairment in virtually all the patients with schizophrenia and, perhaps, bipolar disorder. Thus, the enhanced release of cortical DA by these agents may be beneficial in this regard. It is, therefore, of considerable interest to determine whether combined administration of these agents augments prefrontal cortical DA release, and if so, whether the increase is dependent upon 5-HT1A receptor activation. VPA (50 mg/kg), which was insufficient by itself to increase prefrontal cortical DA release, potentiated the ability of clozapine (20 mg/kg) and risperidone (1 mg/kg) to increase DA release in the mPFC, but not in the nucleus accumbens (NAC). VPA (50 mg/kg) also potentiated haloperidol (0.5 mg/kg)-induced DA release in the mPFC; this increase was completely abolished by WAY100635 (0.2 mg/kg). These results suggest that, in combination with VPA, both typical and atypical APDs produce greater increases in prefrontal cortical DA release than either type of drug alone via a mechanism dependent upon 5-HT(1A) receptor activation. Furthermore, they provide a strong rationale for testing for possible clinical synergism of an APD and anticonvulsant mood-stabilizer in improving the cognitive deficits present in patients with schizophrenia and bipolar disorder. PMID:16061211

  18. Atypical antipsychotic drugs and pregnancy outcome: a prospective, cohort study.

    PubMed

    Habermann, Frank; Fritzsche, Juliane; Fuhlbrück, Frederike; Wacker, Evelin; Allignol, Arthur; Weber-Schoendorfer, Corinna; Meister, Reinhard; Schaefer, Christof

    2013-08-01

    Women of childbearing age are often affected with psychotic disorders, requiring the use of antipsychotic medication during pregnancy. In the present study, we prospectively followed the pregnancies of 561 women exposed to second-generation antipsychotic agents (SGAs; study cohort) and compared these to 284 pregnant women exposed to first-generation antipsychotic agents (FGAs; comparison cohort I) and to 1122 pregnant women using drugs known as not harmful to the unborn (comparison cohort II). Subjects were enrolled through the Institute's consultation service. Major malformation rates of SGA exposed were higher compared to comparison cohort II (adjusted odds ratio, 2.17; 95% confidence interval, 1.20-3.91), possibly reflecting a detection bias concerning atrial and ventricular septal defects. Postnatal disorders occurred significantly more often in infants prenatally exposed to SGAs (15.6%) and FGAs (21.6%) compared to 4.2% of comparison cohort II. Cumulative incidences of elective terminations of pregnancy were significantly higher in both the study cohort (17%) and comparison cohort I (21%) compared to comparison cohort II (3%), whereas the rates of spontaneous abortions did not differ. The numbers of stillbirths and neonatal deaths were within the reference range. Preterm birth and low birth weight were more common in infants exposed to FGAs. To conclude, our findings did not reveal a major teratogenic risk for SGAs, making the better studied drugs of this group a treatment option during pregnancy. Because neonates exposed to SGAs or FGAs in the last gestational week are at higher risk of postnatal disorders, delivery should be planned in clinics with neonatal intensive care units. PMID:23764684

  19. Diabetic ketoacidosis and severe hypertriglyceridaemia as a consequence of an atypical antipsychotic agent.

    PubMed

    Hepburn, Kirsten; Brzozowska, Malgorzata Monika

    2016-01-01

    The atypical antipsychotic agent clozapine, although an effective treatment for schizophrenia, is linked with metabolic adverse effects. We report a case of diabetic ketoacidosis and very severe hypertriglyceridaemia associated with clozapine use, in a patient with type 2 diabetes mellitus, who was successfully treated with continuous insulin infusion and fluids. As clozapine proved to be the most efficacious in controlling the patient's psychotic symptoms, the patient has been continued on clozapine despite its known metabolic side effects. Importantly the patient has achieved satisfactory long-term lipid and glycaemic control. The current recommendations related to the metabolic care for patients treated with atypical antipsychotic agents as well as the mechanisms behind abnormal glucose and lipid regulation with clozapine therapy are discussed. PMID:27507689

  20. [Guidelines on long-acting injectable atypical antipsychotics for first-episode schizophrenia].

    PubMed

    Azorin, J-M

    2013-09-01

    The current review raises the question of the place of long-acting injectable (LAI) atypical antipsychotics for the treatment of first-episode schizophrenia in current and future guidelines. After exposing the different points of view adopted in the former, the author presents the clinical trials conducted with LAI atypicals in this indication, as well as the surveys related to psychiatrists'opinion regarding the use of these drugs in early schizophrenia. Pros and cons of this therapeutic option are discussed and suggestions are made for further guidelines. PMID:24084422

  1. Prolactin and macroprolactin levels in psychiatric patients receiving atypical antipsychotics: A preliminary study.

    PubMed

    Park, Young-Min; Lee, Seung-Hwan; Lee, Bun-Hee; Lee, Kyu Young; Lee, Kye-Seong; Kang, Seung-Gul; Lee, Hwa-Young; Kim, Won

    2016-05-30

    The aims of this study were to clarify whether atypical antipsychotics can elevate serum levels of both macroprolactin and prolactin, and whether the macroprolactin levels differ according to the type of atypical antipsychotic being taken. In total, 245 subjects were enrolled consecutively in 6 hospitals. Serum prolactin and macroprolactin levels were measured at a single time point during maintenance antipsychotic monotherapy. The mean total serum prolactin levels including macroprolactin were 11.91, 20.73, 16.41, 50.83, 12.84, and 59.1ng/mL for patients taking aripiprazole, blonanserin, olanzapine, paliperidone, quetiapine, and risperidone, respectively, while those for macroprolactin were 1.71, 3.86, 3.73, 7.28, 2.77, and 8.0ng/mL. The total prolactin and macroprolactin levels were significantly higher among those taking paliperidone and risperidone than among those taking any of the other antipsychotics (p<0.01). Moreover, there was a strong positive correlation between serum levels of prolactin and macroprolactin. Sexual dysfunction was reported in 35.5% (87/245) of the total subjects. However, the total prolactin level did not differ significantly between subjects with and without sexual dysfunction except gynecomastia. These findings suggest that treatment with risperidone and paliperidone can induce hyperprolactinemia and macroprolactinemia in psychiatric patients. PMID:27010188

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. Tardive dyskinesia occurring in a young woman after withdrawal of an atypical antipsychotic drug

    PubMed Central

    Alblowi, Mohammed A.; Alosaimi, Fahad D.

    2015-01-01

    Tardive dyskinesia (TD) is one of the most serious and disturbing side-effects of dopamine receptor antagonists. It affects 20-50% of patients on long-term antipsychotic therapy. The pathophysiology of TD remains poorly understood, and treatment is often challenging. Here, we present a 32-year-old woman presenting with a 9-month history of TD occurring after risperidone withdrawal, and characterized almost exclusively by tongue protrusion. After being seen by different specialties and undergoing multiple investigations, she was eventually correctly diagnosed with TD by a specialist team and successfully treated with amantadine. Vigilance and awareness of this condition and its risk factors are required to make the correct diagnosis, especially in cases with unusual presentations caused by atypical antipsychotics, and treatment can be challenging. PMID:26492119

  9. Attenuation of MK-801-induced behavioral perseveration by typical and atypical antipsychotic pretreatment in rats.

    PubMed

    Tuplin, Erin W; Stocco, Marlaina R; Holahan, Matthew R

    2015-08-01

    The noncompetitive NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5-10-imine maleate (MK-801) has been shown to increase the probability of operant responding during extinction and reduce infralimbic prefrontal cortical activation, possibly modeling the cognitive dysfunction symptomology, and underlying cause, in patients with schizophrenia. The present study sought to determine if typical and/or atypical antipsychotics would attenuate the MK-801-induced behavioral perseveration and whether this would be associated with concomitant changes in phosphorylated ERK1/2 (pERK1/2) labeling in the infralimbic cortex (IL). Male, Long Evans rats were pretreated with the typical antipsychotic, Flupenthixol (0, 0.125, 0.25 or 0.5 mg/kg) or the atypical antipsychotic, aripiprazole (0, 0.3, 1.0, 3.0 mg/kg), then given 0.1 mg/kg MK-801 followed by a 60-min appetitive operant extinction session. Flupenthixol produced a dose-dependent decrease in MK-801-induced bar pressing behavior and locomotor activity and a dose-dependent increase in IL pERK1/2 labeling. Aripiprazole produced a U-shaped dose-response curve on MK-801-induced bar pressing behavior, a dose-dependent decrease in locomotor activity but no changes in IL pERK1/2 labeling. The attenuation of the MK-801-induced behavioral (bar pressing, locomotion) profile by Flupenthixol indicates a clear dopaminergic contribution to this behavior. The behavioral effect of aripiprazole may be due to its a) binding to presynaptic dopamine receptors at the midrange dose decreasing dopamine output and b) binding to postsynaptic dopamine receptors at the higher dose increasing dopamine tone. While both classes of antipsychotics can normalize perseverative behavioral symptoms, the underlying prefrontal cortical dysregulation seems to persist. PMID:26052791

  10. The potential role of atypical antipsychotics for the treatment of posttraumatic stress disorder.

    PubMed

    Han, Changsu; Pae, Chi-Un; Wang, Sheng-Min; Lee, Soo-Jung; Patkar, Ashwin A; Masand, Praksh S; Serretti, Alssandro

    2014-09-01

    Despite the fact that the majority of currently available treatment guidelines propose antidepressants as the first-line pharmacological therapy for posttraumatic stress disorder (PTSD), a substantial portion of patients fail to show an adequate response following this type of treatment. In this context, a number of small, open-label studies and randomized controlled clinical trials (RCTs) have found atypical antipsychotics (AAs) to be a beneficial treatment for patients with PTSD. Thus, the present meta-analysis was conducted to enhance the sample size power and further the current understanding of the role of AAs for the treatment of PTSD. An extensive search of several databases identified 12 appropriate RCTs and available data from 9 of these (n = 497) were included in the final meta-analysis. AAs may have potential benefits for the treatment of PTSD as indicated by changes from baseline of the total score on the Clinician Administered PTSD Scale (CAPS; standardized mean difference [SMD] = -0.289, 95% confidence intervals [CIs] = -0.471, -0.106), P = 0.002). Additionally, AAs were found to be significantly more effective (P < 0.0001) than a placebo in terms of change from baseline for the intrusion sub-score on the CAPS (SMD = -0.373, 95% CIs = -0.568, -0.178) but there were no significant reductions for the avoidance and hyperarousal sub-symptoms. The responder rate and rate of improvement of depressive symptoms were also significantly higher in the AA group than the placebo group (P = 0.004 and P < 0.0001, respectively). However, the present results should be interpreted carefully and be translated into clinical practice only with due consideration of the limited quality and quantity of existing RCTs included in this analysis. PMID:24882700

  11. Atypical Antipsychotics as Augmentation Therapy in Anorexia Nervosa

    PubMed Central

    Marzola, Enrica; Desedime, Nadia; Giovannone, Cristina; Amianto, Federico; Fassino, Secondo; Abbate-Daga, Giovanni

    2015-01-01

    Anorexia nervosa (AN) is a life-threatening and difficult to treat mental illness with the highest mortality rates of any psychiatric disorder. We aimed to garner preliminary data on the real-world use of olanzapine and aripiprazole as augmentation agents of Selective Serotonin Reuptake Inhibitors (SSRIs) in adult inpatients affected by AN. We retrospectively evaluated the clinical charts of patients who were hospitalized between 2012 and 2014. Patients were evaluated upon admission and discharge. We investigated eating symptomatology, and both general and eating psychopathology using: Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Yale-Brown-Cornell Eating Disorders Scale. The charts of 75 patients were included in this study. The sample resulted equally distributed among those receiving SSRIs and either aripiprazole or olanzapine in addition to SSRIs. Notwithstanding a few baseline clinical differences, upon discharge all groups were significantly improved on all measures. Interestingly, aripiprazole showed the greatest effectiveness in reducing eating-related preoccupations and rituals with a large effect size. The body of evidence on medication management in AN is in dismal condition. Augmentation therapy is a well-established approach to a variety of mental disorders and it is often used in every-day clinical practice with patients affected by AN as well. Nevertheless, to date very little data is available on this topic. Results from our sample yielded promising results on the effectiveness of aripiprazole augmentation in reducing eating-related obsessions and compulsions. Randomized controlled trials are warranted to confirm these encouraging findings. PMID:25922939

  12. Atypical antipsychotics as augmentation therapy in anorexia nervosa.

    PubMed

    Marzola, Enrica; Desedime, Nadia; Giovannone, Cristina; Amianto, Federico; Fassino, Secondo; Abbate-Daga, Giovanni

    2015-01-01

    Anorexia nervosa (AN) is a life-threatening and difficult to treat mental illness with the highest mortality rates of any psychiatric disorder. We aimed to garner preliminary data on the real-world use of olanzapine and aripiprazole as augmentation agents of Selective Serotonin Reuptake Inhibitors (SSRIs) in adult inpatients affected by AN. We retrospectively evaluated the clinical charts of patients who were hospitalized between 2012 and 2014. Patients were evaluated upon admission and discharge. We investigated eating symptomatology, and both general and eating psychopathology using: Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Yale-Brown-Cornell Eating Disorders Scale. The charts of 75 patients were included in this study. The sample resulted equally distributed among those receiving SSRIs and either aripiprazole or olanzapine in addition to SSRIs. Notwithstanding a few baseline clinical differences, upon discharge all groups were significantly improved on all measures. Interestingly, aripiprazole showed the greatest effectiveness in reducing eating-related preoccupations and rituals with a large effect size. The body of evidence on medication management in AN is in dismal condition. Augmentation therapy is a well-established approach to a variety of mental disorders and it is often used in every-day clinical practice with patients affected by AN as well. Nevertheless, to date very little data is available on this topic. Results from our sample yielded promising results on the effectiveness of aripiprazole augmentation in reducing eating-related obsessions and compulsions. Randomized controlled trials are warranted to confirm these encouraging findings. PMID:25922939

  13. The reproductive safety profile of mood stabilizers, atypical antipsychotics, and broad-spectrum psychotropics.

    PubMed

    Ernst, Carrie L; Goldberg, Joseph F

    2002-01-01

    There has been growing concern about the potential iatrogenic effects of several newer psychotropic drugs on reproductive health safety in women. Areas of particular concern in this regard include (1) controversies about a potential association between the use of valproate and development of polycystic ovary syndrome (PCOS), (2) the safety of use of newer psychotropic medications during pregnancy, and (3) safety issues with these medications in women while breastfeeding. This review summarizes current information about each of these areas. In particular, existing data suggest that (1) PCOS very likely represents a complex neuroendocrine disorder with multiple determinants; (2) menstrual irregularities may be a frequently seen phenomenon in women with bipolar illness, at least partially independent of psychotropic drug therapy; (3) potential central nervous system teratogenicity remains substantial during first-trimester exposure to valproate or carbamazepine; (4) with newer agents used for bipolar disorder and schizophrenia, safety data during pregnancy, while not definitive, are most abundant with olanzapine and with lamotrigine; relatively less is known about systematic pregnancy outcomes with other atypical antipsychotics or newer anticonvulsants; and (5) risks for neonatal safety during lactation continue to appear substantial with lithium, are of potential concern with lamotrigine and clozapine, are quite likely minimal with valproate or carbamazepine, and are indeterminate with most other new anticonvulsants or atypical antipsychotics. Recommendations are presented for clinical management in each of these instances. PMID:11913676

  14. 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

  15. 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.…

  16. Management of psychiatric disorders in children and adolescents with atypical antipsychotics: a systematic review of published clinical trials.

    PubMed

    Jensen, Peter S; Buitelaar, Jan; Pandina, Gahan J; Binder, Carin; Haas, Magali

    2007-03-01

    We aimed to provide a descriptive review of treatment studies of atypical antipsychotics in paediatric psychiatric disorders. A systematic review of the literature used Medline and EMBASE databases to identify clinical trials of atypical antipsychotics in children and adolescents between 1994 and 2006. Trials were limited to double-blind studies and open-label studies of > or = 8 weeks duration that included > or = 20 patients. Nineteen double-blind and 22 open-label studies were identified. Studies included use of clozapine, olanzapine, quetiapine, risperidone, and ziprasidone in the treatment of disruptive behavioural disorders (DBDs), pervasive developmental disorders (PDDs), tic disorder, psychotic disorders, and mania. These medications generally reduced the severity of a variety of psychiatric symptoms in children and adolescents. Less frequent adverse events included extrapyramidal symptoms, hyperglycaemia and diabetes, and endocrine effects. The review of published scientific data suggests that most of the atypical antipsychotics, excluding clozapine, have a favourable risk/benefit profile and effectively reduce disabling behaviours in paediatric psychiatric patients. While there is a body of evidence published of treatment of DBDs and PDDs, there is a lack of controlled data to guide clinical practice for the use of atypical antipsychotics for paediatric psychotic disorders and bipolar disorder. While there have been studies with duration up to 2 years, no definitive data are available that suggest long-term safety; additional studies are warranted. PMID:17075688

  17. 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…

  18. The range of therapeutic efficacy of atypical antipsychotics: a critical evaluation.

    PubMed

    Dimova, Aleksandra

    2003-08-01

    Atypical antipsychotics (AA) have revolutionized the treatment of schizophrenia, now being the treatment of choice for patients with this disorder. The positive therapeutic experience with the AA in the treatment of these disorders and their favourable adverse-effect profiles, has encouraged clinicians to extend their usage beyond their initial regulatory approval in several conditions and patient groups. It is noticeable that the positive results with AA in the treatment of aggression, depressive and manic syndromes tend to be overestimated and generalised, slowly creating the idea that these agents are omnipotent in the treatment of two big groups of psychiatric disorders: schizophrenia and affective disorders. The aim of this study is to summarize the clinical experiences in the treatment of these two groups of disorders, with the intention of taking the first step towards a clearer definition of their field of therapeutic usage and effectiveness. PMID:12888315

  19. Atypical antipsychotics are not all alike: side effects and risk assessment.

    PubMed

    Howland, Robert H

    2014-09-01

    Atypical antipsychotic drugs are not all alike with respect to their pharmacologies, therapeutic uses, and side eff ects, although many clinicians lump them together and do not distinguish among them. Risk assessment for the potential use of a drug, such as aripiprazole (Abilify), should not focus on any particular adverse effect, but rather should consider risk assessment in a broader context. Specifically, what are the alternatives, and what are their inherent risk profiles? What is the risk of no treatment? Side eff ects commonly associated with a particular drug or class of drugs can also occur with other drugs. For any drug prescribed for any reason, prescribers should document discussion about common and potentially serious adverse effects, as well as document clinical monitoring. Alternative treatments and their inherent risks, along with the risks of not taking medication for a particular condition, should also be discussed with patients and documented. PMID:25346958

  20. Vitamin D deficiency exacerbates atypical antipsychotic-induced metabolic side effects in rats: involvement of the INSIG/SREBP pathway.

    PubMed

    Dang, Ruili; Jiang, Pei; Cai, Hualin; Li, Huande; Guo, Ren; Wu, Yanqin; Zhang, Lihong; Zhu, Wenye; He, Xin; Liu, Yiping; Xu, Ping

    2015-08-01

    Metabolic syndrome is a major concern in psychotic patients receiving atypical antipsychotics. Recent evidence suggests that sterol regulatory element-binding proteins (SREBPs) and insulin-induced genes (INSIGs) are implicated in the antipsychotic-induced metabolic side-effects. Vitamin D (VD) deficiency, a highly prevalent phenomenon among patients with psychosis, might also predispose individuals to metabolic syndrome Considering that VD has modulating effects on the INSIG/SREBP pathway, it is possible that VD may have a role in the antipsychotic-induced metabolic disturbances involving its effects on the INSIG/SREBP system. Thus, the present study aimed to evaluate the effects of VD deficiency and VD supplementation on antipsychotic-induced metabolic changes in rats. After 4-week administration, clozapine (10mg/kg/d) and risperidone (1mg/kg/d) both caused glucose intolerance and insulin resistance in VD deficient rats, but not in rats with sufficient VD status. Antipsychotic treatments, especially clozapine, elevated serum lipid levels, which were most apparent in VD deficient rats, but alleviated in VD-supplemented rats. Additionally, antipsychotic treatments down-regulated INSIGs and up-regulated SREBPs expression in VD deficient rats, and these effects were attenuated when VD status was more sufficient. Collectively, this study disclose the novel findings that antipsychotic-induced metabolic disturbances is exacerbated by VD deficiency and can be alleviated by VD supplementation, providing new evidence for the promising role of VD in prevention and treatment of metabolic disorders caused by antipsychotic medications. Furthermore, our data also suggest the involvement of INSIG/SREBP pathway in the antipsychotic-induced hyperlipidemia and beneficial effects of VD on lipid profile. PMID:26003080

  1. Correlation of serum ghrelin levels with body mass index and carbohydrate metabolism in patients treated with atypical antipsychotics.

    PubMed

    Palik, E; Birkás, K D; Faludi, G; Karádi, I; Cseh, K

    2005-06-01

    The prevalence of diabetes mellitus and metabolic syndrome is higher in patients with schizophrenia than in the normal population. Atypical antipsychotic drugs are used in psychiatry since the beginning of 1990. These drugs differ from the "typical" antipsychotics used previously, as they have less extrapyramidal side effects, and because of this they are tolerated better, but are associated with weight-gain and disturbances in carbohydrate metabolism. Ghrelin is an orexigen hormone partaking in body weight regulation. It is produced in the enteroendocrine P/D1 cells of the gastric mucosa and secreted to the circulation. The aim of our study was to determine ghrelin levels of atypical antipsychotic-treated patients in relationship with their body mass index (BMI) and carbohydrate metabolism. We measured the fasting serum ghrelin levels in 56 patients (male/female: 16/40, age mean+/-S.D.: 50.6+/-5.6 years) treated with atypical antipsychotics (clozapine, olanzapine, risperidon and quetiapine), and in 75 healthy control subjects, age and gender matched (RIA Linco, USA) in relationship with their BMI and their fasting and 75 g OGTT 120 min blood glucose values. The serum ghrelin levels of the patient group were notably higher (1333+/-659 pg/ml) than in the control group (368+/-103, p<0.0001; Mann-Whitney). We found no difference among the four antipsychotics in weight-gain, diabetes prevalence and the serum ghrelin levels. The BMI of the patient group was significantly higher (29.3+/-7.2 kg/m2 versus 24.3+/-3.7 kg/m2, p<0.0001; Mann-Whitney); 32% of them had blood glucose abnormality (18/56). There was no difference between the ghrelin levels in diabetic and non-diabetic patients. We found a significant negative linear correlation between the serum ghrelin and BMI (r=-0.35, p=0.0078; Spearman), the ghrelin and fasting blood glucose (r=-0.32, p=0.015) and OGTT 75 g 120 min blood glucose levels (r=-0.27, p=0.036). The orexigen effect of elevated serum ghrelin levels can

  2. 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

  3. Adverse Effects and Toxicity of the Atypical Antipsychotics: What is Important for the Pediatric Emergency Medicine Practitioner

    PubMed Central

    Rasimas, J.J.; Liebelt, Erica L.

    2012-01-01

    Medications are being used with greater frequency to address pediatric mental health problems, and in recent years atypical antipsychotic (AAP) prescriptions have increased more than any other class. Acute care practitioners must be aware of the pharmacology of AAPs and the conditions, on- and off-label, for which they are prescribed. This involves identifying and managing side effects that manifest both mentally and physically. Although “atypicality” confers a lower risk of movement side effects compared to conventional agents, children are more sensitive than adults to extrapyramidal reactions. Like adults, they also may present with toxic sedation, confusion, cardiovascular dysfunction, and metabolic derangements. Evaluation and management of these toxicities requires an index of suspicion, a careful symptom and medication history, physical examination, and targeted interventions. This review is designed to orient the emergency practitioner to the challenging task of recognizing and treating adverse effects related to acute and chronic atypical antipsychotic exposure in children. PMID:23471213

  4. PSD-95 is Essential for Hallucinogen and Atypical Antipsychotic Drug Actions at Serotonin Receptors

    PubMed Central

    Abbas, Atheir I.; Yadav, Prem N.; Yao, Wei-Dong; Arbuckle, Margaret I.; Grant, Seth G.; Caron, Marc G.; Roth, Bryan L.

    2009-01-01

    Here we report that PSD-95, a postsynaptic density scaffolding protein classically conceptualized as being essential for the regulation of ionotropic glutamatergic signaling at the post-synaptic membrane, plays an unanticipated and essential role in mediating the actions of hallucinogens and atypical antipsychotic drugs at 5-HT2A and 5-HT2C serotonergic G protein-coupled receptors (GPCRs). We show that PSD-95 is crucial for normal 5-HT2A and 5- HT2C expression in vivo, and that PSD-95 maintains normal receptor expression by promoting apical dendritic targeting and stabilizing receptor turnover in vivo. Significantly, 5-HT2A and 5-HT2C-mediated downstream signaling is impaired in PSD-95null mice, and the 5-HT2A-mediated head twitch response is abnormal. Furthermore, the ability of 5-HT2A inverse agonists to normalize behavioral changes induced by glutamate receptor antagonists is abolished in the absence of PSD-95 in vivo. These results demonstrate that PSD-95, in addition to the well known role it plays in scaffolding macromolecular glutamatergic signaling complexes, profoundly modulates metabotropic 5-HT2A and 5-HT2C receptor function. PMID:19494135

  5. Atypical antipsychotics and the neural regulation of food intake and peripheral metabolism.

    PubMed

    Teff, Karen L; Kim, Sangwon F

    2011-09-26

    The atypical antipsychotics (AAPs) are associated with weight gain and an increased incidence of metabolic disease including type 2 diabetes mellitus. Epidemiological, cross-sectional and prospective studies suggest that two of the AAPs, olanzapine and clozapine, cause the most dramatic weight gain and metabolic impairments including increased fasting glucose, insulin and triglycerides. Relative to the other AAPs, both olanzapine and clozapine exhibit a particularly high antagonistic affinity for histamine and muscarinic receptors which have been hypothesized as mediators of the reported increase in weight and glucose abnormalities. In this article, we review the current evidence for the AAP associated weight gain and abnormal glucose metabolism. We postulate that the effects of the AAPs on food intake and peripheral metabolism are initially independently regulated but with increasing body adiposity, the early AAP-induced impairments in peripheral metabolism will be exacerbated, thereby establishing a vicious cycle such that the effects of the AAP are magnified by the known pathophysiological consequences of obesity. Furthermore, we examine how inhibition of the histaminergic pathway may mediate increases in food intake and the potential role of the vagus nerve in the reported peripheral metabolic effects. PMID:21664918

  6. Effects of switching to aripiprazole from current atypical antipsychotics on subsyndromal symptoms and tolerability in patients with bipolar disorder.

    PubMed

    Woo, Young Sup; Bahk, Won-Myong; Park, Young-Min; Chung, Sangkeun; Yoon, Bo-Hyun; Won, Seunghee; Lee, Jeong Goo; Lee, Hwang-Bin; Kim, Won; Jeong, Jong-Hyun; Lee, Kwanghun; Kim, Moon-Doo

    2016-09-01

    We evaluated the effectiveness of aripiprazole among bipolar patients who had switched to this medication as a result of difficulty maintaining on their prestudy atypical antipsychotics (AAPs) because of subsyndromal mood symptoms or intolerance. This study included 77 bipolar patients who were in syndromal remission with an AAP as monotherapy or with an AAP combined with a mood stabilizer(s) who needed to switch from their present AAP because of subsyndromal symptoms or intolerance. At 24 weeks after switching to aripiprazole, the remission rates on the Montgomery-Åsberg Depression Rating Scale (MADRS) and on both the MADRS and the Young Mania Rating Scale were increased significantly in the full sample and in the inefficacy subgroup. In the inefficacy subgroup, the MADRS score change was significant during the 24 weeks of study. Total cholesterol and prolactin decreased significantly after switching to aripiprazole. The proportion of patients who had abnormal values for central obesity and hypercholesterolemia decreased significantly from baseline to week 24. These findings suggest that a change from the current AAP to aripiprazole was associated with improvement in subsyndromal mood symptoms and several lipid/metabolic or safety profile parameters in patients with bipolar disorder with tolerability concerns or subsyndromal mood symptoms. PMID:27487259

  7. Evidence for a SULT4A1 haplotype correlating with baseline psychopathology and atypical antipsychotic response

    PubMed Central

    Ramsey, Timothy L; Meltzer, Herbert Y; Brock, Guy N; Mehrotra, Bharat; Jayathilake, Karu; Bobo, William V; Brennan, Mark D

    2011-01-01

    Aim This study evaluated the impact of SULT4A1 gene variation on psychopathology and antipsychotic drug response in Caucasian subjects from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study and a replication sample. Patients & methods SULT4A1 haplotypes were determined using SNP data. The relationship to baseline psychopathology was evaluated using linear regression of Positive and Negative Syndrome Scale (PANSS) total score. Drug response was evaluated using Mixed Model Repeat Measures (MMRM) for change in PANSS. Results For the CATIE sample, patients carrying a haplotype designated SULT4A1-1(+) displayed higher baseline PANSS (p = 0.03) and, when treated with olanzapine, demonstrated a significant interaction with time (p = 0.009) in the MMRM. SULT4A1-1(+) patients treated with olanzapine displayed improved response compared with SULT4A1-1(−) patients treated with olanzapine (p = 0.008) or to SULT4A1-1(+) patients treated with risperidone (p = 0.006). In the replication sample, SULT4A1-1(+) patients treated with olanzapine demonstrated greater improvement than SULT4A1-1(−) patients treated with olanzapine (p = 0.05) or than SULT4A1-1(+) patients treated with risperidone (p = 0.05). Conclusion If validated, determination of SULT4A1-1 haplotype status might be useful for identifying patients who show an enhanced response to long-term olanzapine treatment. PMID:21521020

  8. Metabolic Disturbances Independent of Body Mass in Patients with Schizophrenia Taking Atypical Antipsychotics

    PubMed Central

    Lee, Jong Il

    2015-01-01

    Objective Atypical antipsychotic (AAP) treatment is associated with weight gain and metabolic disturbances such as dyslipidemia and dysglycemia. The metabolic disturbances are usually considered to develop secondary to weight gain. We performed the comparison of metabolic disturbances of three AAP group with different risk of metabolic side effect after adjusting for body mass to investigate whether any metabolic disturbances develop independently from body mass index (BMI). Methods This cross-sectional study included 174 subjects with schizophrenia who were on 1) monotherapy with clozapine (CL), olanzapine (OL), or quetiapine (QT) (n=61), 2) monotherapy with risperidone (RSP) (n=89), or 3) monotherapy with aripiprizole (ARP), or ziprasidone (ZPS) (n=24) more than 1 year. Association between the prevalence of metabolic disturbances and groups were analysed using logistic regression after adjusting confounding variables including BMI. Analysese of covariance were used to compare the AAP groups in terms of the levels of metabolic parameters. Results There were significant differences among groups in terms of the prevalence of hypertriglyceridemia (p=0.015), low HDL-cholesterol (p=0.017), and hyperglycemia (p=0.022) after adjusting for BMI. Triglyceride level (p=0.014) and the ratio of triglyceride to HDL-cholesterol (p=0.004) were significantly different among groups after adjusting for BMI. Conclusion In conclusion, metabolic disturbances are significantly different in AAP groups even after adjusting BMI. AAPs may have direct effect on metabolic parameters. Blood lipid and glucose levels should be monitored regularly regardless of whether patients tend to gain weight. PMID:25866526

  9. Aripiprazole an atypical antipsychotic protects against ethanol induced gastric ulcers in rats

    PubMed Central

    Asmari, Abdulrahman Al; Arshaduddin, Mohammed; Elfaki, Ibrahim; Kadasah, Saeed; Robayan, Abdulrahman Al; Asmary, Saeed Al

    2014-01-01

    The present investigation was undertaken, to study the gastro-protective potential of aripiprazole (ARI) an atypical antipsychotic drug in ethanol induced gastric ulcers in rats. ARI (10, 30, 100 mg/kg) was tested for gastric secretion and antiulcer activity in different groups of male Sprague Dawley rats. Gastric secretion and acidity studies were performed in pylorus ligated rats while indices of gastric ulcers were measured in ethanol (1 ml-100%) induced gastric ulcers. Histological changes and the levels of gastric wall mucus, malondialdehyde (MDA), non-protein sulfhydryls (NP-SH), myeloperoxidase (MPO), and serotonin were used to assess ethanol induced gastric mucosal injuries. Exposure of rats to ethanol resulted in gastric mucosal injury and a high index of ulcer. Pretreatment with ARI significantly (P < 0.001), reduced the gastric lesions induced by ethanol and also resulted in a significant decrease in the gastric secretion, and total acidity in pylorus ligated rats. ARI also significantly attenuated the ethanol induced reduction in the levels of gastric wall mucus, and NP-SH (P < 0.001). The histological changes and the increased MDA and MPO activity were also significantly (P < 0.001) inhibited by ARI. Ethanol induced depletion in the levels of serotonin in the gastric tissue were also significantly restored by pretreatment with ARI (p < 0.001). ARI showed significant antiulcer and gastroprotective activity against ethanol induced gastric ulcers. The gastroprotective effects of ARI may be due to its anti-secretory, antioxidant and anti-inflammatory action and also due to the restoration of the depleted gastric serotonin levels. PMID:25232384

  10. Effects of divalproex and atypical antipsychotic drugs on dopamine and acetylcholine efflux in rat hippocampus and prefrontal cortex.

    PubMed

    Huang, Mei; Li, Zhu; Ichikawa, Junji; Dai, Jin; Meltzer, Herbert Y

    2006-07-12

    Mood stabilizers (e.g., valproic acid) and antipsychotic drugs (APDs) are commonly co-administered in the treatment of bipolar disorder and schizophrenia. The basis for any synergism between these classes of drugs in either group of disorders has been little studied. Previous studies have shown that atypical APDs (e.g., clozapine) preferentially increases dopamine (DA) and acetylcholine (ACh) efflux in rat medial prefrontal cortex (mPFC) and hippocampus (HIP), both of which have been suggested to contribute to their ability to improve cognition in patients with schizophrenia. We have recently reported that the anticonvulsant mood stabilizers (AMS), valproic acid, carbamazepine, and zonisamide, but not lithium, also preferentially increase DA efflux in the rat mPFC, and that, at subthreshold doses, the AMS also augment the ability of the atypical APDs clozapine and risperidone to increase DA but not ACh efflux in the mPFC. The present study examined the ability of divalproex (DVX), which is chemically related to valproic acid, to enhance DA and ACh efflux in the HIP and to augment the effect of atypical APDs on ACh efflux in the HIP and mPFC. DVX, 500 mg/kg, significantly increased DA and ACh efflux in the HIP, and DA, but not ACh, efflux in the mPFC, whereas a lower dose of DVX, 50 mg/kg, had no effect on DA or ACh in either region. However, DVX, 50 mg/kg, combined with the atypical APDs olanzapine (1.0 mg/kg) or aripiprazole (0.3 mg/kg) significantly potentiated the effect of both APDs on DA, but not ACh efflux in the HIP and mPFC. Pretreatment of olanzapine or aripiprazole with the selective serotonin 5-HT(1A) antagonist, WAY100635 (1.0 mg/kg) partially but significantly blocked the effect of the combination of DVX, 50 mg/kg, and olanzapine or aripiprazole, on DA efflux in both the HIP and mPFC. WAY100635 did not affect the ability of the combination of olanzapine or aripiprazole and DVX to enhance ACh efflux in the HIP or mPFC. Subchronic administration of the

  11. GLP-1 receptor agonist liraglutide reverses long-term atypical antipsychotic treatment associated behavioral depression and metabolic abnormalities in rats.

    PubMed

    Sharma, Ajaykumar N; Ligade, Sagar S; Sharma, Jay N; Shukla, Praveen; Elased, Khalid M; Lucot, James B

    2015-04-01

    Mood disorder patients that are on long-term atypical antipsychotics treatment frequently experience metabolic dysfunctions. In addition to this, accumulating evidences points to increased risk of structural abnormalities, brain volume changes, altered neuroplasticity and behavioral depression with long-term antipsychotics use. However, there is paucity of preclinical evidences for long-term antipsychotic associated depression-like behavior. The objectives of the present study were: (1) to evaluate influence of long-term antipsychotic (olanzapine) treatment on rat behavior in forced swim test (FST) as a model for depression and; (2) to examine impact of glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide - an antidiabetic medication for type II diabetes, on long-term olanzapine associated metabolic and behavioral changes in rats. Daily olanzapine treatment (0.5 mg/kg; p.o.) for 8-9 weeks significantly increased body weights, food and water intake, plasma cholesterol and triglycerides and immobility time in FST with parallel reduction in plasma HDL cholesterol levels. These results points to development of metabolic abnormalities and depression-like behavior with long-term olanzapine treatment. Acute liraglutide (50 μg/kg; i.p.) and imipramine (10 mg/kg, i. p.) treatment per se significantly decreased duration of immobility in FST compared to vehicle treated rats. Additionally, 3-week liraglutide treatment (50 μg/kg; i.p., daily) partially reversed metabolic abnormalities and depression-like behavior with long-term olanzapine-treatment in rats. None of these treatment regimens affected locomotor behavior of rats. In summary, add-on GLP-1 receptor agonists promise novel alternatives to counteract long-term antipsychotics associated behavioral and metabolic complications. PMID:25023888

  12. Relationship between Dose, Drug Levels, and D2 Receptor Occupancy for the Atypical Antipsychotics Risperidone and Paliperidone

    PubMed Central

    Votaw, J. R.; Ritchie, J.; Howell, L. L.

    2012-01-01

    Blockade of D2 family dopamine receptors (D2Rs) is a fundamental property of antipsychotics, and the degree of striatal D2R occupancy has been related to antipsychotic and motor effects of these drugs. Recent studies suggest the D2R occupancy of antipsychotics may differ in extrastriatal regions compared with the dorsal striatum. We studied this issue in macaque monkeys by using a within-subjects design. [18F]fallypride positron emission tomography scans were obtained on four different doses of risperidone and paliperidone (the 9-OH metabolite of risperidone) and compared with multiple off-drug scans in each animal. The half-life of the two drugs in these monkeys was determined to be between 3 and 4 h, and drug was administered by a constant infusion through an intragastric catheter. The D2R occupancy of antipsychotic was determined in the caudate, putamen, ventral striatum, and four prefrontal and temporal cortical regions and was related to serum and cerebrospinal fluid drug levels. Repeated 2-week treatment with risperidone or paliperidone did not produce lasting changes in D2R binding potential in any region examined. As expected, D2R binding potential was highest in the caudate and putamen and was approximately one-third that level in the ventral striatum and 2% of that level in the cortical regions. We found dose-dependent D2R occupancy for both risperidone and paliperidone in both basal ganglia and cortical regions of interest. We could not find evidence of regional variation in D2R occupancy of either drug. Comparison of D2R occupancy and serum drug levels supports a target of 40 to 80 ng/ml active drug for these two atypical antipsychotics. PMID:22214649

  13. Comparison of Medicaid spending in schizoaffective patients treated with once monthly paliperidone palmitate or oral atypical antipsychotics.

    PubMed

    Xiao, Yongling; Muser, Erik; Fu, Dong-Jing; Lafeuille, Marie-Hélène; Pilon, Dominic; Emond, Bruno; Wu, Allen; Duh, Mei Sheng; Lefebvre, Patrick

    2016-04-01

    Background Compared to oral atypical antipsychotics (OAAs), long-acting injectable antipsychotics require less frequent administration, and thus may improve adherence and reduce risk of relapse in schizoaffective disorder (SAD) patients. Objective To evaluate the impact of once monthly paliperidone palmitate (PP) versus OAAs on healthcare resource utilization, Medicaid spending, and hospital readmission among SAD patients. Methods Using FL, IA, KS, MS, MO, and NJ Medicaid data (January 2009-December 2013), adults with ≥2 SAD diagnoses initiated on PP or OAA (index date) were identified. Baseline characteristics and outcomes were assessed during the 12month pre- and post-index periods, respectively. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to reduce confounding and compare the estimated treatment effect for PP versus OAA. Results A total of 10,778 OAA-treated patients and 876 PP-treated patients were selected. Compared to OAAs, PP was associated with significantly lower medical costs (PSM: mean monthly cost difference [MMCD] = -$383, p < 0.001; IPTW: MMCD = -$403, p = 0.016), which offset the higher pharmacy costs associated with PP (PSM: MMCD = $270, p < 0.001; IPTW: MMCD = $350, p < 0.001) and resulted in similar total healthcare cost (PSM: MMCD = -$113, p = 0.414; IPTW: MMCD = -$53, p = 0.697) for PP versus OAA. Reduced risk of hospitalization (PSM: incidence rate ratio [IRR] = 0.85, p = 0.128; IPTW: IRR = 0.96, p = 0.004) and fewer hospitalization days (PSM: IRR = 0.74, p = 0.008; IPTW: IRR = 0.85, p < 0.001) were observed in PP versus OAA patients. Among hospitalized patients, PP was associated with a lower risk of 30 day hospital readmission compared to OAA (IPTW: odds ratio = 0.89, p = 0.041). Limitations The Medicaid data may not be representative of the nation or other states, and includes pre-rebate pharmacy costs

  14. Do we need to consider ethno-cultural variation in the use of atypical antipsychotics for Asian patients with major depressive disorder?

    PubMed

    Han, Changsu; Pae, Chi-Un

    2013-05-01

    Asian and western countries differ in the prevalence, symptom manifestation, diagnostic procedures, patient recognition and treatments of major depressive disorder (MDD), according to a number of studies. Ethnic differences in pharmacological profiles are also important in the prescription of certain antipsychotic medications because they may impact treatment outcomes and adverse events. Differential pharmacokinetic and pharmacodynamic properties of antipsychotics may be practically useful in the control of specific depressive symptoms. Furthermore, patient compliance with prescribed medications has been found to be different across races and ethnicities. Therefore, this article explores practical clinical issues for the use of atypical antipsychotics in patients with MDD, focusing on ethno-cultural differences. PMID:23709361

  15. Supplement use by women during pregnancy: data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics.

    PubMed

    Freeman, Marlene P; Sosinsky, Alexandra Z; Moustafa, Danna; Viguera, Adele C; Cohen, Lee S

    2016-06-01

    Women of reproductive age commonly use integrative treatments. However, the reproductive safety for most complementary products lacks systematic study. We aimed to study the use of supplements by women in a prospective pregnancy registry. The Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics was established to evaluate the reproductive safety of atypical antipsychotics. Exposed and control participants were systematically queried about the use of vitamins and supplements. Slightly greater than half (53.2 %) of the participants eligible for analysis (N = 534) were using at least one vitamin or supplement at the time of enrollment, not including prenatal vitamins or folic acid. The most common supplements used were omega-3 fatty acids (38.0 %), vitamin D (11.0 %), calcium (8.2 %), and iron (4.7 %). Probiotics and melatonin were used by 2.6 and 0.9 %, respectively. In this prospective pregnancy registry, we found that over half of the participants were taking supplements or vitamins other than prenatal vitamins and folic acid. These findings underscore the need for active query on the part of health care providers about the use of supplements during pregnancy, and the need to obtain rigorous reproductive safety and efficacy data for supplements used by pregnant women and reproductive aged women. PMID:26472040

  16. 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

  17. 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…

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

    PubMed

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

    2014-08-01

    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 and adiponectin, suggesting that both glucose and fat metabolism may be affected by these drugs. These data further suggest that antipsychotic treatments in patients alter the gene expression patterns in adipocytes in a coordinated fashion and priming them for a low-level inflammatory state. PMID:25019983

  19. Important clinical features of atypical antipsychotics in acute bipolar depression that inform routine clinical care: a review of pivotal studies with number needed to treat.

    PubMed

    Gao, Keming; Yuan, Chengmei; Wu, Renrong; Chen, Jun; Wang, Zuowei; Fang, Yiru; Calabrese, Joseph R

    2015-10-01

    English-language literature cited in MEDLINE from January, 1980 to October 30, 2014 was searched by using terms of antipsychotic, generic and brand names of atypical antipsychotics, "bipolar depression/bipolar disorder", "placebo", and "trial". The parameters of response (≥50% improvement on MADRS, Montgomery-Asberg Depression Rating Scale total score), remission (either ≤12 or 8 on MADRS total score at endpoint), discontinuation due to adverse events (DAEs), somnolence, ≥7% weight gain, overall extrapyramidal side-effects (EPSs), and akathisia, were extracted from originally published primary outcome papers. The number needed to treat to benefit (NNT) for response and remission or harm (NNH) for DAEs or other side effects relative to placebo were estimated and presented with the estimate and 95% confidence interval. Olanzapine monotherapy, olanzapine-fluoxetine combination (OFC), quetiapine-IR monotherapy, quetiapine-XR monotherapy, lurasidone monotherapy, and lurasidone adjunctive therapy were superior to placebo with NNTs for responses of 11-12, 4, 7-8, 4, 4-5, and 7, and NNTs for remission of 11-12, 4, 5-11, 7, 6-7, and 6, respectively. There was no significant difference between OFC and lamotrigine, and between aripiprazole or ziprasidone and placebo in response and remission. Olanzapine monotherapy, quetiapine-IR, quetiapine-XR, aripiprazole, and ziprasidone 120-160 mg/day had significantly increased risk for DAEs with NNHs of 24, 8-14, 9, 12, and 10, respectively. For somnolence, quetiapine-XR had the smallest NNH of 4. For ≥7% weight gain, olanzapine monotherapy and OFC had the smallest NNHs with both of 5. For akathisia, aripiprazole had the smallest NNH of 5. These findings suggest that among the FDA-approved agents including OFC, quetiapine-IR and -XR, lurasidone monotherapy and adjunctive therapy to a mood stabilizer, the differences in the NNTs for response and remission are small, but the differences in NNHs for DAEs and common side

  20. Anti-atherogenic properties of high-density lipoproteins in psychiatric patients before and after two months of atypical anti-psychotic therapy.

    PubMed

    Hussein, Osamah; Izikson, Lidia; Bathish, Yunis; Dabur, Enas; Hanna, Alaa; Zidan, Jamal

    2015-12-01

    Some of the medications used for the management of schizophrenia are associated with clinically significant increases in weight and adverse alterations in serum lipid levels. The aim of the study was to investigate the effect of short-term (two months) treatment with atypical anti-psychotics on coronary heart disease risk factors, including the functional properties of high-density lipoprotein (HDL), in psychiatric patients. Nineteen patients diagnosed with schizophrenia, schizoaffective, and bipolar disorder and ten healthy volunteers were enrolled in the study. In the present study blood was drawn at baseline and after two months of atypical anti-psychotic treatment. Wilcoxon non-parametric-test was used to examine differences in the psychotic group before and two months after treatment.Waist circumference and oxidative stress in psychiatric patients were higher compared with the control group. Serum-mediated cholesterol efflux capacity was lower in psychotic patients compared to controls. Two months of anti-psychotic therapy was associated with increased abdominal obesity, decreased paraoxonase lactonase activity, but with no further change in serum-mediated cholesterol efflux from macrophages. Psychotic patients have low serum-mediated cholesterol efflux from macrophages as a parameter of HDL functionality. Atypical anti-psychotic treatment for two months increased metabolic derangements in these patients but without further decrement in serum-mediated cholesterol efflux. PMID:26253619

  1. The atypical antipsychotic blonanserin reverses (+)-PD-128907- and ketamine-induced deficit in executive function in common marmosets.

    PubMed

    Kotani, Manato; Enomoto, Takeshi; Murai, Takeshi; Nakako, Tomokazu; Iwamura, Yoshihiro; Kiyoshi, Akihiko; Matsumoto, Kenji; Matsumoto, Atsushi; Ikejiri, Masaru; Nakayama, Tatsuo; Ogi, Yuji; Ikeda, Kazuhito

    2016-05-15

    Antagonism of the dopamine D3 receptor is considered a promising strategy for the treatment of cognitive impairment associated with schizophrenia. We have previously reported that the atypical antipsychotic blonanserin, a dopamine D2/D3 and serotonin 5-HT2A receptor antagonist, highly occupies dopamine D3 receptors at its antipsychotic dose range in rats. In the present study, we evaluated the effects of blonanserin on executive function in common marmosets using the object retrieval with detour (ORD) task. The dopamine D3 receptor-preferring agonist (+)-PD-128907 at 1mg/kg decreased success rate in the difficult trial, but not in the easy trial. Since the difference between the two trials is only cognitive demand, our findings indicate that excess activation of dopamine D3 receptors impairs executive function in common marmosets. Blonanserin at 0.1mg/kg reversed the decrease in success rate induced by (+)-PD-128907 in the difficult trial. This finding indicates that blonanserin has beneficial effect on executive function deficit induced by activation of the dopamine D3 receptor in common marmosets. Next, and based on the glutamatergic hypothesis of schizophrenia, the common marmosets were treated with the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine. Ketamine at sub-anesthetic doses decreased success rate in the difficult trial, but not in the easy trial. Blonanserin at 0.1mg/kg reversed the decrease in success rate induced by ketamine in the difficult trial. The findings of this study suggest that blonanserin might have beneficial effect on executive dysfunction in patients with schizophrenia. PMID:26970575

  2. 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

  3. 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

  4. 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

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

    PubMed Central

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

    2016-01-01

    Abstract 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

  6. 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

  7. Treatment with the atypical antipsychotic, olanzapine, prevents the expression of amphetamine-induced place conditioning in the rat.

    PubMed

    Mechanic, Jordan A; Maynard, Brian T; Holloway, Frank A

    2003-02-01

    Place conditioning (PC) experiments were conducted as a means to further elaborate the treatment potential of the atypical antipsychotic, olanzapine (OLZ), for stimulant abuse. The resulting preference/aversion provides an indirect measure of the incentive salience (i.e., euphoria/dysphoria) produced by a drug. Male Sprague-Dawley rats (n=48) were conditioned in two unique environments (i.e., vertical vs. horizontal stripped walls, large vs. small grid flooring) using injections (1.0 mg/kg ip) of either amphetamine (AMPH) or saline (SAL). On average, animals displayed a significant preference for the AMPH-paired location after 2.5 weeks of conditioning (five pairings each of AMPH and SAL). Once the preference was established, animals were pretreated (60 min) with a single dose of OLZ (0.0, 0.56, 1.0 or 1.5 mg/kg sc) given on the test (AMPH-free) day. For the following week's test, animals were injected with SAL (1.0 mg/kg ip) in an attempt to recapture the side preference exhibited before OLZ treatment. OLZ treatment prevented the expression of the AMPH-conditioned preference and reduced locomotor activity. Inhibition of preference resulted from the highest dose of OLZ (1.5 mg/kg), while the inhibition of locomotor activity occurred across all three doses. Additionally, while the effects on preference were no longer apparent by the SAL test the following week (reversible), the activity was still depressed during the SAL tests in animals that had experienced the highest dose of OLZ (1.5 mg/kg). Control experiments, in which OLZ was used as the conditioning drug, suggest that OLZ itself possesses no aversive effects in the PC paradigm, and may even produce a preference for the drug-paired chamber. Because the AMPH preference is dependent on dopamine (DA) release in the nucleus accumbens (NAcc), these experiments suggest that OLZ pretreatment interferes with the rewarding, as well as the subjective effects of AMPH. PMID:12551725

  8. Dietary, Lifestyle and Pharmacogenetic Factors Associated with Arteriole Endothelial Dependent Vasodilatation In Schizophrenia Patients Treated with Atypical Antipsychotics (AAPs)

    PubMed Central

    Ellingrod, Vicki L.; Taylor, Stephan F.; Brook, Robert D.; Evans, Simon J.; Zöllner, Sebastian K.; Grove, Tyler B.; Gardner, Kristen M.; Bly, Michael J.; Pop-Busui, Rodica; Dalack, Gregory

    2011-01-01

    Purpose Within schizophrenia cardiovascular disease (CVD) is highly prevalent secondary to atypical antipsychotic (AAP) use. Thorough assessments of diet, lifestyle, and endothelial functioning have not been done in this population. Omega 3 Fatty Acids (N-3 FAs) have garnered attention in relation to psychopathology as well as cardioprotection. This study examined the status of endothelial function within the schizophrenia population and determined pharmacogenetic, medication, dietary, and lifestyle factors associated with this functioning. Methods Schizophrenia subjects were screened for the metabolic syndrome along with physical activity, smoking, and variants related to folate pharmacogenetics in this cross-sectional analysis. Arteriole endothelial-dependent vasodilatation was measured using non-invasive peripheral arterial tonometry (RH-PAT, EndoPAT2000). A 24 hour dietary food recall was used to construct intake profiles using the Nutrition Data Systems for Research software (NDSR). We examined associations between AAP use and RH-PAT values, and the influence of N-3 FA dietary intake on this measure. Preliminary data are reported in 83 subjects with a mean age (± s.d.) of 45.89 (± 11.49), 64% were Caucasian (n = 53), 64% were male (n = 53), and 77% were receiving AAP treatment (n = 63). Results A significant positive relationship was found between RH-PAT values and N-3 FA intake (F=17.7(1,16), p=0.0007) in subjects not receiving AAPs. This relationship was lost in those treated with AAPs (F=0.25(1,43), p>0.6). Regression analysis confirmed the interaction effect of AAP treatment on the relationship between RH-PAT and N-3 FAs (p=0.0105). Endothelial dysfunction was also related to folate pharmacogenetic variants. Conclusions AAPs may counteract some vascular health benefits of a diet high in N-3 FAs. AAP use may necessitate a higher N-3 FA dose to regain these effects, but additional research is necessary to strengthen the preliminary findings

  9. 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. PMID:24919175

  10. Quality of life in patients with schizophrenia: the impact of socio-economic factors and adverse effects of atypical antipsychotics drugs.

    PubMed

    de Araújo, Aurigena Antunes; de Araújo Dantas, Diego; do Nascimento, Gemma Galgani; Ribeiro, Susana Barbosa; Chaves, Katarina Melo; de Lima Silva, Vanessa; de Araújo, Raimundo Fernandes; de Souza, Dyego Leandro Bezerra; de Medeiros, Caroline Addison Carvalho Xavier

    2014-09-01

    This cross-sectional study compared the effects of treatment with atypical antipsychotic drugs on quality of life (QoL) and side effects in 218 patients with schizophrenia attending the ambulatory services of psychiatric in Rio Grande do Norte, Brazil. Socio-economic variables were compared. The five-dimension EuroQoL (EQ-5D) was used to evaluate QoL, and side effects were assessed using the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale and the Simpson-Angus Scale. Data were analysed using the χ (2) test and Student's t test, with a significance level of 5 %. Average monthly household incomes in the medication groups were 1.1-2.1 minimum wages ($339-$678). UKU Scale scores showed significant differences in side effects, mainly, clozapine, quetiapine and ziprasidone (p < 0.05). EQ-5D scores showed that all drugs except olanzapine significantly impacted mobility (p < 0.05), and proportions of individuals reporting problems in other dimensions were high: 63.6 % of clozapine users reported mobility problems, 63.7 and 56.3 % of clozapine and ziprasidone users, respectively, had difficulties with usual activities, 68.8 and 54.5 % of ziprasidone and clozapine users, respectively, experienced pain and/or discomfort, and 72.8 % of clozapine users reported anxiety and/or depression. Psychiatric, neurological, and autonomous adverse effects, as well as other side effects, were prevalent in users of atypical antipsychotic drugs, especially clozapine and ziprasidone. Olanzapine had the least side effects. QoL was impacted by side effects and economic conditions in all groups. Thus, the effects of these antipsychotic agents appear to have been masked by aggravating social and economic situations. PMID:24789610

  11. Adjunctive α-lipoic acid reduces weight gain compared with placebo at 12 weeks in schizophrenic patients treated with atypical antipsychotics: a double-blind randomized placebo-controlled study.

    PubMed

    Kim, Nam Wook; Song, Yul-Mai; Kim, Eosu; Cho, Hyun-Sang; Cheon, Keun-Ah; Kim, Su Jin; Park, Jin Young

    2016-09-01

    α-Lipoic acid (ALA) has been reported to be effective in reducing body weight in rodents and obese patients. Our previous open trial showed that ALA may play a role in reducing weight gain in patients with schizophrenia on atypical antipsychotics. The present study evaluated the efficacy of ALA in reducing weight and BMI in patients with schizophrenia who had experienced significant weight gain since taking atypical antipsychotics. In a 12-week, double-blind randomized placebo-controlled study, 22 overweight and clinically stable patients with schizophrenia were randomly assigned to receive ALA or placebo. ALA was administered at 600-1800 mg, as tolerated. Weight, BMI, abdomen fat area measured by computed tomography, and metabolic values were determined. Adverse effects were also assessed to examine safety. Overall, 15 patients completed 12 weeks of treatment. There was significant weight loss and decreased visceral fat levels in the ALA group compared with the placebo group. There were no instances of psychopathologic aggravation or severe ALA-associated adverse effects. ALA was effective in reducing weight and abdominal obesity in patients with schizophrenia who had experienced significant weight gain since beginning an atypical antipsychotic regimen. Moreover, ALA was well tolerated throughout this study. ALA might play an important role as an adjunctive treatment in decreasing obesity in patients who take atypical antipsychotics. PMID:27276401

  12. 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

  13. Attenuation of phencyclidine-induced object recognition deficits by the combination of atypical antipsychotic drugs and pimavanserin (ACP 103), a 5-hydroxytryptamine(2A) receptor inverse agonist.

    PubMed

    Snigdha, S; Horiguchi, M; Huang, M; Li, Z; Shahid, M; Neill, J C; Meltzer, H Y

    2010-02-01

    Subchronic administration of the N-methyl-d-aspartate receptor antagonist, phencyclidine (PCP), in rodents has been shown to produce impairment in novel object recognition (NOR), a model of visual learning and memory. We tested the hypothesis that the selective 5-HT(2A) inverse agonists, pimavanserin and (R)-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl]-4-piperidinemethanol (M100907), would potentiate subeffective doses of atypical antipsychotic drugs (APDs) to reverse the NOR deficits. Female rats received vehicle or PCP (2 mg/kg b.i.d.) for 7 days, followed by a 7-day washout. Pimavanserin (3 mg/kg) or M100907 (1 mg/kg) alone, or four atypicial APDs, risperidone (0.05-0.1 mg/kg), melperone (1-3 mg/kg), olanzapine (1-2 mg/kg), or N-desmethylclozapine (1-2 mg/kg), and the typical APD, haloperidol (0.05-0.1 mg/kg), were administered alone, or in combination with pimavanserin or M100907, before NOR testing. The exploration times of objects during 3-min acquisition and retention trials, separated by a 1-min interval, were compared by analysis of variance. Vehicle-, but not PCP-treated, animals, explored the novel object significantly more than the familiar in the retention trial (p < 0.05-0.01). Pretreatment with the higher doses of the atypical APDs, but not pimavanserin, M100907, or haloperidol alone, reversed the effects of PCP. The effect of risperidone was blocked by haloperidol pretreatment. Coadministration of pimavanserin or M100907, with ineffective doses of the atypical APDs, but not haloperidol, also reversed the PCP-induced deficit in NOR. These results support the importance of 5-hydroxytryptamine(2A) receptor blockade relative to D(2) receptor blockade in the ability of atypicals to ameliorate the effect of subchronic PCP, a putative measure of cognitive dysfunction in schizophrenia. PMID:19864614

  14. 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

  15. 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

  16. [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. PMID:18379518

  17. 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

  18. Improving metabolic parameters of antipsychotic child treatment (IMPACT) study: rationale, design, and methods

    PubMed Central

    2013-01-01

    Background Youth with serious mental illness may experience improved psychiatric stability with second generation antipsychotic (SGA) medication treatment, but unfortunately may also experience unhealthy weight gain adverse events. Research on weight loss strategies for youth who require ongoing antipsychotic treatment is quite limited. The purpose of this paper is to present the design, methods, and rationale of the Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) study, a federally funded, randomized trial comparing two pharmacologic strategies against a control condition to manage SGA-related weight gain. Methods The design and methodology considerations of the IMPACT trial are described and embedded in a description of health risks associated with antipsychotic-related weight gain and the limitations of currently available research. Results The IMPACT study is a 4-site, six month, randomized, open-label, clinical trial of overweight/obese youth ages 8–19 years with pediatric schizophrenia-spectrum and bipolar-spectrum disorders, psychotic or non-psychotic major depressive disorder, or irritability associated with autistic disorder. Youth who have experienced clinically significant weight gain during antipsychotic treatment in the past 3 years are randomized to either (1) switch antipsychotic plus healthy lifestyle education (HLE); (2) add metformin plus HLE; or (3) HLE with no medication change. The primary aim is to compare weight change (body mass index z-scores) for each pharmacologic intervention with the control condition. Key secondary assessments include percentage body fat, insulin resistance, lipid profile, psychiatric symptom stability (monitored independently by the pharmacotherapist and a blinded evaluator), and all-cause and specific cause discontinuation. This study is ongoing, and the targeted sample size is 132 youth. Conclusion Antipsychotic-related weight gain is an important public health issue for youth requiring

  19. 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

  20. Sub-chronic treatment with classical but not atypical antipsychotics produces morphological changes in rat nigro-striatal dopaminergic neurons directly related to "early onset" vacuous chewing.

    PubMed

    Marchese, Giorgio; Casu, Maria Antonietta; Bartholini, Francesco; Ruiu, Stefania; Saba, Pierluigi; Gessa, Gian Luigi; Pani, Luca

    2002-04-01

    In the present work, we investigated if an impairment of dopaminergic neurons after subchronic haloperidol treatment might be a possible physiopathologic substrate of the "early onset" vacuous chewing movements (VCMs) in rats. For this purpose, different antipsychotics were used to analyse a possible relationship between VCMs development and morphological alterations of tyrosine-hydroxylase-immunostained (TH-IM) neurons. Rats treated twice a day with haloperidol displayed a significant increase of VCMs that was both time- (2-4 weeks) and dose (0.1-1 mg/kg) dependent. Immunocytochemical analysis showed a shrinkage of TH-IM cell bodies in substantia nigra pars compacta and reticulata and a reduction of TH-immunostaining in the striatum of haloperidol treated rats with the arising of VCMs. No differences were observed in TH-IM neurons of ventral tegmental area and nucleus accumbens vs. control rats. The atypical antipsychotics risperidone (2 mg/kg, twice a day), amisulpride (20 mg/kg, twice a day) and clozapine (10 mg/kg, twice a day) did not produce any nigro-striatal morphological changes or VCMs. TH-IM nigro-striatal neuron morphological alterations and VCMs were still present after three days of withdrawal in rats treated for four weeks with haloperidol (1 mg/kg). Both the main morphological changes and the behavioural correlate disappeared after three weeks of withdrawal. These results suggest that haloperidol induces a morphological impairment of the dopaminergic nigro-striatal neurons which is directly associated with the arising, permanency and disappearance of VCMs in rats. PMID:11982629

  1. 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

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

    PubMed Central

    Hall, Ian; Shah, Amar; Thomson, Helen

    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

  3. Development and validation of a stability-indicating gas chromatographic method for quality control of residual solvents in blonanserin: a novel atypical antipsychotic agent.

    PubMed

    Peng, Ming; Liu, Jin; Lu, Dan; Yang, Yong-Jian

    2012-09-01

    Blonanserin is a novel atypical antipsychotic agent for the treatment of schizophrenia. Ethyl alcohol, isopropyl alcohol and toluene are utilized in the synthesis route of this bulk drug. A new validated gas chromatographic (GC) method for the simultaneous determination of residual solvents in blonanserin is described in this paper. Blonanserin was dissolved in N, N-dimethylformamide to make a sample solution that was directly injected into a DB-624 column. A postrun oven temperature at 240°C for approximately 2 h after the analysis cycle was performed to wash out blonanserin residue in the GC column. Quantitation was performed by external standard analyses and the validation was carried out according to International Conference on Harmonization validation guidelines Q2A and Q2B. The method was shown to be specific (no interference in the blank solution), linear (correlation coefficients ≥0.99998, n = 10), accurate (average recoveries between 94.1 and 101.7%), precise (intra-day and inter-day precision ≤2.6%), sensitive (limit of detection ≤0.2 ng, and limit of quantitation ≤0.7 ng), robust (small variations of carrier gas flow, initial oven temperature, temperature ramping rate, injector and detector temperatures did not significantly affect the system suitability test parameters and peak areas) and stable (reference standard and sample solutions were stable over 48 h). This extensively validated method is ready to be used for the quality control of blonanserin. PMID:22595261

  4. 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

  5. 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

  6. Does the Addition of a Second Antipsychotic Drug Improve Clozapine Treatment?

    PubMed Central

    Barbui, Corrado; Signoretti, Alessandra; Mulè, Serena; Boso, Marianna; Cipriani, Andrea

    2009-01-01

    In patients with schizophrenia who do not have an optimal response to clozapine, it remains unclear if there is an evidence base to support a second antipsychotic in combination with clozapine. The present systematic review was therefore carried out to determine the efficacy of various clozapine combination strategies with antipsychotics. Relevant studies were located by searching the Cochrane Schizophrenia Group Trials Register, Medline, and Embase (up to November 2007). Only studies randomly allocating patients to clozapine plus another antipsychotic vs clozapine monotherapy were included. The search yielded 21 studies suitable for reanalysis. In 3 trials, clozapine was combined with a phenothiazine, in 8 trials with a benzamide, and in the remaining trials with risperidone. While the majority of randomized trials were not double blind, 6 studies were double-blind placebo-controlled trials. A total of 14 randomized open studies significantly favored clozapine combination strategy in terms of mean difference (random effect standardized mean difference [SMD] = −0.80, 95% confidence interval [CI] = −1.14 to −0.46); however, data extracted from 6 randomized double-blind studies did not show a statistically significant positive effect of this combination strategy in terms of mean difference (SMD = −0.12, 95% CI = −0.57 to 0.32). In terms of percentage of patients failing to show an improvement, a total of 10 randomized open studies significantly favored clozapine combination strategy (random effect relative risk [RR] = 0.64, 95% CI = 0.42 to 0.97), but data extracted from 6 randomized double-blind studies did not show a statistically significant positive effect of this combination strategy (RR = 0.91, 95% CI = 0.75 to 1.11). We conclude that the evidence base supporting a second antipsychotic in addition to clozapine in partially responsive patients with schizophrenia is weak. This weak evidence indicates modest to absent benefit. PMID:18436527

  7. Role and clinical implications of atypical antipsychotics in anxiety disorders, obsessive-compulsive disorder, trauma-related, and somatic symptom disorders: a systematized review.

    PubMed

    Albert, Umberto; Carmassi, Claudia; Cosci, Fiammetta; De Cori, David; Di Nicola, Marco; Ferrari, Silvia; Poloni, Nicola; Tarricone, Ilaria; Fiorillo, Andrea

    2016-09-01

    Atypical antipsychotics (AAs) may play a role in the treatment of anxiety disorders, obsessive-compulsive disorder (OCD), and trauma-related disorders. No reviews on their differential use in these different disorders have been performed recently. The aim of this systematized review was to obtain data on efficacy and comparative effectiveness of AAs as a treatment of anxiety disorders, OCD, and trauma-related disorders to provide guidance for clinicians on when and which AA to use. We searched on PubMed, Psychnet, and Cochrane Libraries from inception to July 2015. Search results were limited to randomized, placebo-controlled trials of adult patients. Evidence of efficacy was considered the presence of positive results in two or more double-blind placebo-controlled studies. Our systematized search identified 1298 papers, of which 191 were subjected to a full-text review and 56 were included. Quetiapine extended-release showed a role in both acute and maintenance treatment of uncomplicated generalized anxiety disorder, whereas more studies are needed before drawing practical recommendations on the use of olanzapine and risperidone; aripiprazole and risperidone are effective in resistant OCD as augmentation treatments. Risperidone and olanzapine add-on may have a role in resistant or chronic post-traumatic stress disorder patients, although only risperidone addition can be recommended on the basis of the criterion of two or more positive placebo-controlled trials. This systematized review supports the evidence that only a few AAs are effective in only a minority of the off-label conditions in which they are currently used and confirms that AAs are not all the same. Their use should be on the basis of a balance between efficacy and side effects, and the characteristics as well as the preference of the patient. PMID:26974213

  8. Treatment Patterns, Resource Use, and Economic Outcomes Associated With Atypical Antipsychotic Prescriptions in Children and Adolescents With Attention-Deficit Hyperactivity Disorder in Quebec

    PubMed Central

    Lachaine, Jean; De, Gourab; Sikirica, Vanja; van Stralen, Judy; Hodgkins, Paul; Yang, Hongbo; Heroux, Julie; Ben Amor, Leila

    2014-01-01

    Objective: To assess treatment patterns, health care resource utilization (HRU), and costs among previously stimulant-treated children and adolescents with attention-deficit hyperactivity disorder (ADHD) receiving atypical antipsychotic (AAP) prescriptions in Quebec. Methods: Health care claims data extracted from Quebec’s provincial health plan database between March 2007 and February 2012 were analyzed. Children and adolescents (6 to 17 years) with ADHD who were taking a stimulant and either switched to, or augmented with, an AAP (with the first AAP defined as the index AAP) without a documented diagnosis for which AAPs are Health Canada–approved were included. Discontinuation, augmentation, and switching of the index AAP during the 12-month, follow-up period were estimated using Kaplan–Meier survival analysis. HRU and costs for the 6 months before (baseline period) and after initiation of the index AAP were compared. Results: A total of 453 children and adolescents with ADHD, mostly male (74.6%) and aged 6 to 12 years (73.7%), met the inclusion criteria. The 12-month discontinuation, augmentation, and switching rates were 45.5%, 68.2%, and 80.7%, respectively. Patients had, on average, more all-cause prescription fills (22.2, compared with 13.3) and incurred more all-cause pharmacy ($889, compared with $710), total medical ($1096, compared with $644), and total health care ($1985, compared with $1354) costs during the 6-month study period than during the 6-month baseline period (all P < 0.05). Similarly, ADHD-related total health care costs were higher during the study period ($1269, compared with $835; P < 0.05); all-cause and ADHD-related total health care costs increased by 46.6% and 52.0%, respectively. Conclusion: Use of an AAP among stimulant-treated children and adolescents with ADHD in Quebec was associated with high rates of therapy changes and increased HRU and costs. PMID:25565476

  9. 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.

  10. 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

  11. 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

  12. The atypical antipsychotic profile of NRA0045, a novel dopamine D4 and 5-hydroxytryptamine2A receptor antagonist, in rats

    PubMed Central

    Okuyama, Shigeru; Chaki, Shigeyuki; Kawashima, Naoya; Suzuki, Yoshiko; Ogawa, Shin-ichi; Kumagai, Toshihito; Nakazato, Atsuro; Nagamine, Masashi; Yamaguchi, Kazumasa; Tomisawa, Kazuyuki

    1997-01-01

    The atypical antipsychotic profile of (R)-(+)-2-amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl] pyrrolidin-3-yl] thiazole (NRA0045), a potent dopamine D4 and 5-hydroxytryptamine (5-HT)2A receptor antagonist, was examined in rats. Spontaneous locomotor activity was decreased dose-dependently with i.p. administration of clozapine (ED50 3.7 mg kg−1), haloperidol (ED50 0.1 mg kg−1) and chlorpromazine (ED50 0.9 mg kg−1), whereas inhibition of this type of behaviour induced by i.p. administration of NRA0045, at doses up to 10 mg kg−1, did not exceed 50%. Locomotor hyperactivity induced by methamphetamine (MAP, 2 mg kg−1, i.p.) in rats (a model of antipsychotic activity) was dose-dependently antagonized by NRA0045 (ED50 0.4 mg kg−1, i.p., and 0.3 mg kg−1, p.o., respectively), clozapine (ED50 0.3 mg kg−1, i.p. and 0.8 mg kg−1, p.o., respectively), haloperidol (ED50 0.02 mg kg−1, i.p. and 0.1 mg kg−1, p.o., respectively), chlorpromazine (ED50 0.3 mg kg−1, i.p. and 3.3 mg kg−1, p.o., respectively). In contrast, the MAP (3 mg kg−1, i.v.)-induced stereotyped behaviour in rats (a model of extrapyramidal symptoms) was not affected by NRA0045 or clozapine, at the highest dose given (30 mg kg−1, i.p.). Haloperidol (ED50 0.3 mg kg−1, i.p.) and chlorpromazine (ED50 4.8 mg kg−1, i.p.) strongly blocked the MAP-induced stereotyped behaviour. NRA0045 and clozapine selectively blocked behaviour associated with activation of the mesolimbic/mesocortical dopamine neurones rather than nigrostriatal dopamine neurones. Extracellular single-unit recording studies demonstrated that MAP (1 mg kg−1, i.v.) decreased the firing rate in the substantia nigra (A9) and ventral tegmental area (A10) dopamine neurones in anaesthetized rats. NRA0045 completely reversed the inhibitory effects of MAP on A10 dopamine neurones (ED50 0.1 mg kg−1, i.v.), whereas the inhibitory effects of

  13. [Antipsychotics in bipolar disorders].

    PubMed

    Vacheron-Trystram, M-N; Braitman, A; Cheref, S; Auffray, L

    2004-01-01

    may worsen depressive symptoms when used for a long term maintenance therapy. Additionally, mixed mania, rapid cycling type patients and bipolar disorder associated with substance abuse do not respond well to lithium therapy. In addition to the lithium therapy or in place of a lithium therapy, one can report the frequent use of antipsychotic agents in respect of patients with bipolar disorder during both the acute and maintenance phases of treatment. Antipsychotic agents have been used for almost forty years and may be used in combination with a lithium therapy. Conventional antipsychotics are effective but they may induce late dyskinesia, weight gain, sedation, sexual dysfunction and depression. These adverse side effects often lead to non compliance in particular in circumstances where antipsychotic agents are combined with a lithium therapy. A number of alternative somatic treatment approaches have been reported for patients who do not respond well or who are intolerant to lithium therapy. As such, valproate has received regulatory approval for the acute treatment of mania and carbamazepine has been indicated for this condition in a number of countries. Divalproex (Depakote) has recently obtained the authorization to market in France and may be prescribed for manic states or hypomanic states that do not tolerate lithium therapy or for which lithium therapy is contraindicated. A number of other anticonvulsants (lamotrigine, gabapentin and topiramate) are currently being tested. Because of the side effects of the conventional antipsychotic agents, atypical antipsychotic agents are currently on trial and appear to be of interest in the treatment of bipolar disorders. Currently, a number of prospective studies are available with clozapine, risperidone and olanzapine in the treatment of bipolar disorder. Most are short-term studies. Recent randomised, double-blind, placebo-controlled studies have shown clozapine, risperidone and olanzapine to be effective with antimanic

  14. Antipsychotics and amotivation.

    PubMed

    Fervaha, Gagan; Takeuchi, Hiroyoshi; Lee, Jimmy; Foussias, George; Fletcher, Paul J; Agid, Ofer; Remington, Gary

    2015-05-01

    Antipsychotic drugs are thought to produce secondary negative symptoms, which can also exacerbate primary negative symptoms. In the present study, we examined whether motivational deficits in particular were related to antipsychotic treatment in patients with schizophrenia in a dose-dependent manner. Five hundred and twenty individuals with schizophrenia who were receiving antipsychotic monotherapy for at least 6 months and followed prospectively were included in the present study. Participants were receiving one of five antipsychotic medications (olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone), and analyses were conducted for patients receiving each drug separately. Analysis of covariance models were constructed to examine the effect of antipsychotic dose on level of motivational impairment, controlling for selected demographic and clinical variables (eg, positive symptoms). Level of motivation, or deficits therein, were evaluated using a derived measure from the Quality of Life Scale, and in addition with scores derived from the Positive and Negative Syndrome Scale. Antipsychotic dose was not related to the level of amotivation for any of the medications examined. Moreover, severity of sedation was not significantly related to the degree of amotivation. One hundred and twenty-one individuals were identified as antipsychotic-free at baseline, and after 6 months of antipsychotic treatment, no change in motivation was found. Chronic treatment with antipsychotics does not necessarily impede or enhance goal-directed motivation in patients with schizophrenia. It is possible that the negative impact of antipsychotics in this regard is overstated; conversely, the present results also indicate that we must look beyond antipsychotics in our efforts to improve motivation. PMID:25567425

  15. [Antipsychotics in geriatric institutions].

    PubMed

    Szulik, Judith

    2007-01-01

    The present paper approaches the use of antipsychotics in elder people in general, and particularly in geriatric institutions. During the last few years, prescription of antipsychotics in geriatric institutions increased, especially because of the availability of the atypicals, and their use was extended beyond the indications these drugs had been approved for. In dementia they are suggested for treatment of behavioral symptoms, despite having been approved only for cases of aggressiveness and risk of damage. There is a common tendency of perpetuating antipsychotic medication in elder people, with its consequent collateral effects as well. Few years ago, the increase of both risk of cerebrovascular events and of mortality in dementia patients treated with atypical agents was noticed. This generated controversy regarding their use in those kind of patients. Diverse factors associated to caregivers affect the decision of prescribing an antipsychotic in elder people. Non-pharmacological interventions are the first choice when treating behavioral symptoms; pharmacological interventions must take place with the lowest doses possible, with limited durations. PMID:18273435

  16. 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

  17. 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

    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 clinically

  18. 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

  19. The selective glycine uptake inhibitor org 25935 as an adjunctive treatment to atypical antipsychotics in predominant persistent negative symptoms of schizophrenia: results from the GIANT trial.

    PubMed

    Schoemaker, Joep H; Jansen, Wim T; Schipper, Jacques; Szegedi, Armin

    2014-04-01

    Using a selective glycine uptake inhibitor as adjunctive to second-generation antipsychotic (SGA) was hypothesized to ameliorate negative and/or cognitive symptoms in subjects with schizophrenia. Subjects with predominant persistent negative symptoms (previously stabilized ≥3 months on an SGA) were enrolled in a randomized, placebo-controlled trial to investigate adjunctive treatment with Org 25935, a selective inhibitor of type 1 glycine transporter, over 12 weeks in a flexible dose design. Org 25935 was tested at 4 to 8 mg twice daily and 12 to 16 mg twice daily versus placebo. Primary efficacy outcome was mean change from baseline in Scale for Assessment of Negative Symptoms composite score. Secondary efficacy end points were Positive and Negative Syndrome Scale total and subscale scores, depressive symptoms (Calgary Depression Scale for Schizophrenia), global functioning (Global Assessment of Functioning scale), and cognitive measures using a computerized battery (Central Nervous System Vital Signs). Responder rates were assessed post hoc. A total of 215 subjects were randomized, of which 187 (87%) completed the trial. Both dose groups of Org 25935 did not differ significantly from placebo on Scale for Assessment of Negative Symptoms, Positive and Negative Syndrome Scale (total or subscale scores), Global Assessment of Functioning, or the majority of tested cognitive domains. Org 25935 was generally well tolerated within the tested dose range, with no meaningful effects on extrapyramidal symptoms and some reports of reversible visual adverse effects. Org 25935 did not differ significantly from placebo in reducing negative symptoms or improving cognitive functioning when administered as adjunctive treatment to SGA. In our study population, Org 25935 appeared to be well tolerated in the tested dose ranges. PMID:24525661

  20. Antipsychotic efficacy: relationship to optimal D2-receptor occupancy.

    PubMed

    Pani, Luca; Pira, Luigi; Marchese, Giorgio

    2007-07-01

    Clinically important differences exist between antipsychotic agents and formulations in terms of safety and tolerability. Features of the biochemical interaction between the antipsychotic and the D2-receptor may underlie these differences. This article reviews current information on the relationship between antipsychotic receptor occupancy and clinical response. A literature search was performed using the keywords 'antipsychotic or neuroleptic', 'receptor' and 'occupancy' and 'dopamine' and 'D2' supplemented by the authors' knowledge of the literature. Imaging and clinical data have generally supported the hypotheses that optimal D2-receptor occupancy in the striatum lies in a 'therapeutic window' between approximately 65 and approximately 80%, however, pharmacokinetic and pharmacodynamic properties of a drug should also be taken into account to fully evaluate its therapeutic effects. Additional research, perhaps in preclinical models, is needed to establish D2-receptor occupancy in various regions of the brain and the optimal duration of D2-receptor blockade in order to maximise efficacy and tolerability profiles of atypical antipsychotics and thereby improve treatment outcomes for patients with schizophrenia. PMID:17419008

  1. 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. PMID:14651433

  2. [Differential indications for atypical neuroleptics: Amisulprid, Clozapin, Olanzapin, Quetiapin und Risperidon. Results of a pilot study of prescription habits in psychiatric clinical usage in the BRD].

    PubMed

    Günther, W; Laux, G; Trapp, W; Müller, N; Mitznegg, N; Schulze-Mönking, H; Steinberg, R; Wolfersdorf, M

    2005-03-01

    With the introduction of atypical neuroleptics, the therapy of schizophrenia has been improved by a group of antipsychotic substances characterized by better tolerability concerning extrapyramidal side effects and higher efficiency against negative symptoms. However, these atypical antipsychotics are not a homogeneous class of drugs but rather represent a group of substances with very different neurobiologic, pharmacologic, and clinical features. This fact and the growing variety of available atypical neuroleptics illustrate the difficulty in choosing the "right" antipsychotic drug for each patient. The aim of this investigation was to evaluate preliminary empirical data for possible differential indication of atypical neuroleptics by a questionnaire-based survey of 192 physicians in ten psychiatric hospitals active in the biological psychiatry work group of the German Federal Directors' Conference. PMID:15448910

  3. Atypical neuroleptic malignant syndrome.

    PubMed

    Collins, Ann; Davies, Drew; Menon, Sharmila

    2016-01-01

    A 57-year-old man was admitted to a psychiatric ward in a confused state. He had a 30-year history of lately stable schizophrenia and antipsychotic medication had recently been reduced. The clinical picture was characterised by confusion, agitation, autonomic instability, muscle rigidity and elevated creatine kinase. Despite no other identifiable cause, physicians were reluctant to accept a diagnosis of neuroleptic malignant syndrome (NMS) due to the absence of fever. Despite acute renal failure, the patient was repeatedly transferred between medical and psychiatric wards; diagnosis and management were delayed, with potentially catastrophic consequences. NMS is a rare, life-threatening neurological disorder that can present atypically and requires emergency medical rather than psychiatric care. Clinicians must proactively distinguish between medical emergencies (including acute confusional states/delirium) and mental illness. Prompt, accurate diagnosis, management on the appropriate ward and effective teamwork between specialties are essential to improve patient outcomes in this potentially fatal condition. PMID:27298291

  4. Switching antipsychotic therapy: what to expect and clinical strategies for improving therapeutic outcomes.

    PubMed

    Lambert, Tim J

    2007-01-01

    When a patient taking an antipsychotic is not experiencing symptomatic remission, or is experiencing adverse effects (AEs) that are intolerable or damaging to his or her physical health, a change in medication may be the best path to a good outcome. However, many clinicians are reluctant to switch medications in all but the clearest cases of failure. This reluctance is intensified by the occurrence of AEs caused by transitioning patients too rapidly between agents with different receptor-binding profiles. Emergent antipsychotic-switching syndromes include the "withdrawal triad," comprised of cholinergic rebound, supersensitivity psychosis, and emergent withdrawal dyskinesias (and other motor syndromes). More recently, another element has been observed consistent with an activation syndrome. This activation syndrome may occur as a consequence of switching from highly sedative agents or as a consequence of initial prodopaminergic drive. All of these effects can be minimized by careful planning of gradual switch procedures and judicious use of adjunctive medications. PMID:17650054

  5. Efficacy and acceptability of atypical antipsychotics for the treatment of post-traumatic stress disorder: a meta-analysis of randomized, double-blind, placebo-controlled clinical trials.

    PubMed

    Liu, Xiao-hui; Xie, Xin-hui; Wang, Ke-yong; Cui, Hong

    2014-11-30

    As some evidences demonstrated that atypical antipsychotics (AA) may be efficacious in treating post-traumatic stress disorder (PTSD), we preformed a meta-analysis of randomized, double-blind, placebo-controlled clinical trials (RCTs) of AAs for the treatment of PTSD. Two hundred and fifty one papers were searched and screened. Eight RCTs met the inclusion criteria. AAs may be superior to placebo in the treatment of PTSD, as indicated by the changes in Clinician Administered PTSD Scale (CAPS) total scores (weighted mean differences (WMD)=-5.89, 95% confidence interval (CI) [-9.21, -2.56], P=0.0005) and also in CAPS subscale intrusion (WMD=-2.58, 95% CI[-3.83, -1.33], P<0.0001 ) and subscale hyperarousal (WMD=-2.94, 95% CI[-5.45, -0.43], P=0.02). The acceptability measured by dropout rates between AAs and placebo showed no statistical difference (OR=1.24, 95%CI [0.78, 1.97], P=0.36). PTSD symptom cluster, especially in intrusion and hyperarousal. However, we should be careful to generalize the conclusion because of the small number of included trails. We expect more RCTs will be done in the future so as to clarify the specific value of AAs for PTSD. PMID:25015709

  6. 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

  7. 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

  8. Correlation between changes in quality of life and symptomatic improvement in Chinese patients switched from typical antipsychotics to olanzapine

    PubMed Central

    Montgomery, William; Kadziola, Zbigniew; Ye, Wenye; Xue, Hai Bo; Liu, Li; Treuer, Tamás

    2015-01-01

    Purpose The aim of this study was to investigate the correlation between changes in symptoms and changes in self-reported quality of life among Chinese patients with schizophrenia who were switched from a typical antipsychotic to olanzapine during usual outpatient care. Patients and methods This post hoc analysis was conducted using data from the Chinese subgroup (n=475) of a multicountry, 12-month, prospective, noninterventional, observational study. The primary publication previously reported the efficacy, safety, and quality of life among patients who switched from a typical antipsychotic to olanzapine. Patients with schizophrenia were included if their symptoms were inadequately controlled with a typical antipsychotic and they were switched to olanzapine. Symptom severity was measured using the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions-Severity scale (CGI-S). Health-Related Quality of Life (HRQOL) was assessed using the World Health Organization Quality of Life–Abbreviated (WHOQOL-BREF). Paired t-tests were performed to assess changes from baseline to endpoint. Pearson’s correlation coefficients (r) were used to assess the correlations between change in symptoms (BPRS and CGI-S scores) and change in HRQOL (WHOQOL-BREF scores). Results Symptoms and HRQOL both improved significantly over the 12 months of treatment (P<0.001). Significant correlations were observed between changes from baseline to end of study on the BPRS and the CGI-S and each of the WHOQOL-BREF four domain scores and two overall quality-of-life questions. The correlation coefficients ranged from r=−0.45 to r=−0.53 for the BPRS and WHOQOL-BREF. The correlation coefficients were slightly smaller between the CGI-S and WHOQOL-BREF, ranging from r=−0.33 to r=−0.40. Conclusion For patients with schizophrenia, assessing quality of life has the potential to add valuable information to the clinical assessment that takes into account the patient’s own

  9. 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

  10. 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

  11. Medicaid Cost Control Measures Aimed at Second Generation Antipsychotics Led to Less Use of All Antipsychotics

    PubMed Central

    Vogt, William B.; Joyce, Geoffrey; Xia, Jing; Dirani, Riad; Wan, George; Goldman, Dana

    2013-01-01

    Atypical antipsychotics and other psychotherapeutics are increasingly subject to prior authorization and other restrictions in state Medicaid programs, begging the question of how these formulary restrictions affect the drug treatments being delivered. To find an answer we collected drug-level information on utilization management for 30 state Medicaid programs over the past 10 years and drug-level utilization data for state Medicaid programs. We find that prior authorization requirements on atypical antipsychotics and other psychotherapeutics greatly reduced the utilization of these drugs and this reduction is not offset by substitution to other drugs in the same drug classes—with the adverse consequence that fewer patients are receiving pharmacotherapy. PMID:22147863

  12. A Longitudinal Study of Relation between Side-effects and Clinical Improvement in Schizophrenia: Is There a Neuro-metabolic Threshold for Second Generation Antipsychotics?

    PubMed Central

    Rao, Naren P.; Arasappa, Rashmi; Kalmady, Sunil V.; Gangadhar, Bangalore N.

    2013-01-01

    Objective Classical studies demonstrated Neuroleptic Induced Extrapyramidal Side-effects (NIES; Neuroleptic threshold) to correlate with the efficacy of first generation antipsychotics. Second generation antipsychotics (SGAs), in addition to the extrapyramidal side effects, are also associated with metabolic side effects. This prospective study on antipsychotic-naïve schizophrenia patients, for the first-time, examined concurrently the relationship between clinical improvement and these side-effects NIES and Neuroleptic Induced Metabolic Side-effects. Methods Thirty six-antipsychotic-naïve schizophrenia (DSM-IV) patients were examined at baseline and after 5 weeks of treatment with antipsychotics. At baseline and follow-up, we recorded the body mass index (BMI) and assessed psychopathology using Scale for Assessment of Positive-symptoms (SAPS) and Scale for Assessment of Negative-symptoms (SANS), extrapyramidal symptoms using Simpson-Angus Extra Pyramidal Scale (SAEPS) and improvement using Clinical Global Impression Improvement (CGI). Results After treatment, patients showed significant reduction in SAPS (baseline, 27.97±14.47; follow-up, 14.63±13.25; p<0.001) and SANS total scores (baseline, 63.77±28.96; follow-up, 49.30±28.77; p=0.001) and a significant increase in BMI (baseline, 18.5±3.37; follow-up, 19.13±3.17; p<0.001). At follow-up CGI-Improvement score was (2.55±0.65) and SAEPS score was (0.8±1.32). CGI-Improvement score had a significant negative correlation with magnitude of increase in BMI (rs=-0.39; p=0.01) and SAEPS symptom score at follow-up (rs=-0.58; p<0.001). In addition, magnitude of increase in BMI showed positive correlation with the magnitude of reduction in SAPS total score (rs=0.33; p=0.04). Conclusion The study findings suggest a possible relation between clinical improvement and antipsychotic-induced neuroleptic as well as metabolic side-effects in schizophrenia. Though the mechanism of this relation is yet to be elucidated

  13. [Atipical antipsychotics in relation with social functioning].

    PubMed

    Vrdoljak, Marijo; Sesar, Marijan Alfonso; Ivezić, Sladana Strkalj

    2007-01-01

    We studied influence of type of antipsychotics in relation with social functioning in sample of 123 patients diagnozed with schizophrenia accordingto lCD 10 criteria. On atypicals (olanzapin, risperidon, clozapin) were 39 patients, 26 female and 13 male. The social functioning scale according to Bellak et al was used for assessment of social functioning. Results of our study show that there is no difference in social functioning between patients on atypical in comapration with patients on typical antipsychotics. We observed a positive trend of better social functioning in group of patients who takes atypicals. Results also showed that women had better social functioning comparing to males Education and duration of illness were not in relation with social functioning. PMID:18298001

  14. 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

  15. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug.

    PubMed

    Zuardi, A W; Crippa, J A S; Hallak, J E C; Moreira, F A; Guimarães, F S

    2006-04-01

    A high dose of delta9-tetrahydrocannabinol, the main Cannabis sativa (cannabis) component, induces anxiety and psychotic-like symptoms in healthy volunteers. These effects of delta9-tetrahydrocannabinol are significantly reduced by cannabidiol (CBD), a cannabis constituent which is devoid of the typical effects of the plant. This observation led us to suspect that CBD could have anxiolytic and/or antipsychotic actions. Studies in animal models and in healthy volunteers clearly suggest an anxiolytic-like effect of CBD. The antipsychotic-like properties of CBD have been investigated in animal models using behavioral and neurochemical techniques which suggested that CBD has a pharmacological profile similar to that of atypical antipsychotic drugs. The results of two studies on healthy volunteers using perception of binocular depth inversion and ketamine-induced psychotic symptoms supported the proposal of the antipsychotic-like properties of CBD. In addition, open case reports of schizophrenic patients treated with CBD and a preliminary report of a controlled clinical trial comparing CBD with an atypical antipsychotic drug have confirmed that this cannabinoid can be a safe and well-tolerated alternative treatment for schizophrenia. Future studies of CBD in other psychotic conditions such as bipolar disorder and comparative studies of its antipsychotic effects with those produced by clozapine in schizophrenic patients are clearly indicated. PMID:16612464

  16. [Negative symptoms: which antipsychotics?].

    PubMed

    Maurel, M; Belzeaux, R; Adida, M; Azorin, J-M

    2015-12-01

    Treating negative symptoms of schizophrenia is a major issue and a challenge for the functional and social prognosis of the disease, to which they are closely linked. First- and second-generation antipsychotics allow a reduction of all negative symptoms. The hope of acting directly on primary negative symptoms with any antipsychotic is not supported by the literature. However, the effectiveness of first- and second-generation antipsychotics is demonstrated on secondary negative symptoms. PMID:26776390

  17. Antipsychotics-induced metabolic alterations: focus on adipose tissue and molecular mechanisms.

    PubMed

    Gonçalves, Pedro; Araújo, João Ricardo; Martel, Fátima

    2015-01-01

    The use of antipsychotic drugs for the treatment of mood disorders and psychosis has increased dramatically over the last decade. Despite its consumption being associated with beneficial neuropsychiatric effects in patients, atypical antipsychotics (which are the most frequently prescribed antipsychotics) use is accompanied by some secondary adverse metabolic effects such as weight gain, dyslipidemia and glucose intolerance. The molecular mechanisms underlying these adverse effects are not fully understood but have been suggested to involve a dysregulation of adipose tissue homeostasis. As such, the aim of this paper is to review and discuss the role of adipose tissue in the development of secondary adverse metabolic effects induced by atypical antipsychotics. Data analyzed in this article suggest that atypical antipsychotics may increase adipose tissue (particularly visceral adipose tissue) lipogenesis, differentiation/hyperplasia, pro-inflammatory mediator secretion and insulin resistance and decrease adipose tissue lipolysis. Consequently, patients receiving antipsychotic medication could be at risk of developing obesity, type 2 diabetes and cardiovascular disease. A better knowledge of the impact of these drugs on adipose tissue homeostasis may unveil strategies to develop novel antipsychotic drugs with less adverse metabolic effects and to develop adjuvant therapies (e.g. behavioral and nutritional therapies) to neuropsychiatric patients receiving antipsychotic medication. PMID:25523882

  18. A review of the adverse side effects associated with antipsychotics as related to their efficacy.

    PubMed

    Pakpoor, Jina; Agius, Mark

    2014-11-01

    Since the introduction of antipsychotic medication for the treatment of psychosis, a wide range of different types of antipsychotic drugs have been developed while their side effects have become evident. The side effects of both the typical and atypical generation of antipsychotics have important consequences for the quality of life of recipients, stigma experienced and also the level of care of patients. It is well acknowledged that the side effects of antipsychotics reduce compliance with the medication. In this review the data for an association between typical and atypical antipsychotics and the main side effects that are well-supported in the literature was explored: weight gain and associated metabolic effects; extrapyramidal symptoms and tardive dyskinesia; prolactin elevation and associated sexual effects; QTc elongation; and a group of miscellaneous side effects. It has been demonstrated that the production of adverse effects following the use of antipsychotic medication differs widely both between atypical and typical drugs but also within these subgroups. Considering the wide range of antipsychotics available amongst both groups and the differing effects they have on patients in terms of side effects, there is reason to believe that a more personalised approach to antipsychotic treatment should be considered. Additionally, screening for risk factors, screening for the appearance of side effects, as well as good communication with patients about the side effects and other options available are important tasks for clinicians in order to optimise concordance with medication. PMID:25413553

  19. Developments in antipsychotic drugs - an update.

    PubMed

    Reynolds, G P

    1998-02-01

    Antipsychotic drug research has recently made much progress. Over the past two years several new drugs have been introduced for the treatment of schizophrenia and more compounds are shortly to be released. Pharmacological studies, improved behavioural models and modern imaging techniques have all contributed to a better understanding of the mechanisms of antipsychotic drug action. Some of the developments that have been made over the past year are reviewed here. PMID:15991957

  20. 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

  1. Antipsychotics and associated risk of out-of-hospital cardiac arrest.

    PubMed

    Weeke, P; Jensen, A; Folke, F; Gislason, G H; Olesen, J B; Fosbøl, E L; Wissenberg, M; Lippert, F K; Christensen, E F; Nielsen, S L; Holm, E; Kanters, J K; Poulsen, H E; Køber, L; Torp-Pedersen, C

    2014-10-01

    Antipsychotic drugs have been associated with sudden cardiac death, but differences in the risk of out-of-hospital cardiac arrest (OHCA) associated with different antipsychotic drug classes are not clear. We identified all OHCAs in Denmark (2001-2010). The risk of OHCA associated with antipsychotic drug use was evaluated by conditional logistic regression analysis in case-time-control models. In total, 2,205 (7.6%) of 28,947 OHCA patients received treatment with an antipsychotic drug at the time of the event. Overall, treatment with any antipsychotic drug was associated with OHCA (odds ratio (OR) = 1.53, 95% confidence interval (CI): 1.23-1.89), as was use with typical antipsychotics (OR = 1.66, CI: 1.27-2.17). By contrast, overall, atypical antipsychotic drug use was not (OR = 1.29, CI: 0.90-1.85). Two individual typical antipsychotic drugs, haloperidol (OR = 2.43, CI: 1.20-4.93) and levomepromazine (OR = 2.05, CI: 1.18-3.56), were associated with OHCA, as was one atypical antipsychotic drug, quetiapine (OR = 3.64, CI: 1.59-8.30). PMID:24960522

  2. Atypical pneumonia

    MedlinePlus

    ... that cause typical pneumonia. These include Legionella pneumophila , Mycoplasma pneumoniae , and Chlamydophila pneumoniae . Atypical pneumonia also tends to have milder symptoms than typical pneumonia. Causes Mycoplasma pneumonia is a type of atypical pneumonia. It ...

  3. Second-Generation Antipsychotics and Extrapyramidal Adverse Effects

    PubMed Central

    Jakovcevski, Igor

    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

  4. Schizophrenia Gene Expression Profile Reverted to Normal Levels by Antipsychotics

    PubMed Central

    Crespo-Facorro, Benedicto; Prieto, Carlos

    2015-01-01

    Background: Despite the widespread use of antipsychotics, little is known of the molecular bases behind the action of antipsychotic drugs. A genome-wide study is needed to characterize the genes that affect the clinical response and their adverse effects. Methods: Here we show the analysis of the blood transcriptome of 22 schizophrenia patients before and after medication with atypical antipsychotics by next-generation sequencing. Results: We found that 17 genes, among the 21 495 genes analyzed, have significantly-altered expression after medication (p-value adjusted [Padj] <0.05). Six genes (ADAMTS2, CD177, CNTNAP3, ENTPD2, RFX2, and UNC45B) out of the 17 are among the 200 genes that we characterized with differential expression in a previous study between antipsychotic-naïve schizophrenia patients and controls (Sainz et al., 2013). This number of schizophrenia-altered expression genes is significantly higher than expected by chance (Chi-test, Padj 1.19E-50), suggesting that at least part of the antipsychotic beneficial effects is exerted by modulating the expression of these genes. Interestingly, all six of these genes were overexpressed in patients and reverted to control levels of expression after treatment. We also found a significant enrichment of genes related to obesity and diabetes, known adverse affects of antipsychotics. Conclusions: These results may facilitate understanding of unknown molecular mechanisms behind schizophrenia symptoms and the molecular mechanisms of antipsychotic drugs. PMID:25522406

  5. 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

  6. 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

  7. Proteome effects of antipsychotic drugs: Learning from preclinical models.

    PubMed

    Carboni, Lucia; Domenici, Enrico

    2016-04-01

    Proteome-wide expression analyses are performed in the brain of schizophrenia patients to understand the biological basis of the disease and discover molecular paths for new clinical interventions. A major issue with postmortem analysis is the lack of tools to discern molecular modulation related to the disease from dysregulation due to medications. We review available proteome-wide analysis of antipsychotic treatment in rodents, highlighting shared dysregulated pathways that may contribute to an extended view of molecular processes underlying their pharmacological activity. Fourteen proteomic studies conducted with typical and atypical antipsychotic treatments were examined; hypothesis-based approaches are also briefly discussed. Treatment with antipsychotics mainly affects proteins belonging to metabolic pathways involved in energy generation, both in glycolytic and oxidative phosphorylation pathways, suggesting antipsychotics-induced impairments in metabolism. Nevertheless, schizophrenic patients show impaired glucose metabolism and mitochondrial dysfunctions independent of therapy. Other antipsychotics-induced changes shared by different studies implicate cytoskeletal and synaptic function proteins. The mechanism can be related to the reorganization of dendritic spines resulting from neural plasticity events induced by treatments affecting neurotransmitter circuitry. However, metabolic and plasticity pathways activated by antipsychotics can also play an authentic role in the etiopathological basis of schizophrenia. PMID:26548651

  8. 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

  9. Intramuscular preparations of antipsychotics: uses and relevance in clinical practice.

    PubMed

    Altamura, A Cario; Sassella, Francesca; Santini, Annalisa; Montresor, Clauno; Fumagalli, Sara; Mundo, Emanuela

    2003-01-01

    Intramuscular formulations of antipsychotics can be sub-divided into two groups on the basis of their pharmacokinetic features: short-acting preparations and long-acting or depot preparations. Short-acting intramuscular formulations are used to manage acute psychotic episodes. On the other hand, long-acting compounds, also called "depot", are administered as antipsychotic maintenance treatment to ensure compliance and to eliminate bioavailability problems related to absorption and first pass metabolism. Adverse effects of antipsychotics have been studied with particular respect to oral versus short- and long-acting intramuscular formulations of the different compounds. For short-term intramuscular preparations the main risk with classical compounds are hypotension and extrapyramidal side effects (EPS). Data on the incidence of EPS with depot formulations are controversial: some studies point out that the incidence of EPS is significantly higher in patients receiving depot preparations, whereas others show no difference between oral and depot antipsychotics. Studies on the strategies for switching patients from oral to depot treatment suggest that this procedure is reasonably well tolerated, so that in clinical practice depot antipsychotic therapy is usually begun while the oral treatment is still being administered, with gradual tapering of the oral dose. Efficacy, pharmacodynamics and clinical pharmacokinetics of haloperidol decanoate, fluphenazine enanthate and decanoate, clopenthixol decanoate, zuclopenthixol decanoate and acutard, flupenthixol decanoate, perphenazine enanthate, pipothiazine palmitate and undecylenate, and fluspirilene are reviewed. In addition, the intramuscular preparations of atypical antipsychotics and clinical uses are reviewed. Olanzapine and ziprasidone are available only as short-acting preparations, while risperidone is to date the only novel antipsychotic available as depot formulation. To date, acutely ill, agitated psychotic patients

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

    PubMed Central

    Krause, Beatrix; Cohen Kadosh, Roi

    2013-01-01

    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

  11. 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

  12. Second-Generation Antipsychotics and Tardive Syndromes in Affective Illness: A Public Health Problem With Neuropsychiatric Consequences

    PubMed Central

    2015-01-01

    Food and Drug Administration–approved information and public advertisements belie neurodegenerative risks for second-generation antipsychotics in affective illness. Package inserts label tardive syndromes “potentially reversible” while uniformly omitting patient counseling for long-term neurodegenerative side effects. I found that only 2 of 78 outpatients exposed to second-generation antipsychotics reported awareness of tardive syndromes. Updated literature challenges safety advantages of atypical versus typical antipsychotics. Physician and patient information regarding tardive syndromes from second-generation antipsychotics approved for affective illness is inadequate. PMID:25521884

  13. Second-generation antipsychotics and tardive syndromes in affective illness: a public health problem with neuropsychiatric consequences.

    PubMed

    Jacobsen, Frederick M

    2015-02-01

    Food and Drug Administration-approved information and public advertisements belie neurodegenerative risks for second-generation antipsychotics in affective illness. Package inserts label tardive syndromes "potentially reversible" while uniformly omitting patient counseling for long-term neurodegenerative side effects. I found that only 2 of 78 outpatients exposed to second-generation antipsychotics reported awareness of tardive syndromes. Updated literature challenges safety advantages of atypical versus typical antipsychotics. Physician and patient information regarding tardive syndromes from second-generation antipsychotics approved for affective illness is inadequate. PMID:25521884

  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. 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

  16. Antipsychotic agents: efficacy and safety in schizophrenia

    PubMed Central

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

    2012-01-01

    Antipsychotics have provided a great improvement in the management of people with schizophrenia. The first generation antipsychotics could establish the possibility of managing many psychotic subjects in an outpatient setting. With the advent of the second (SGA) and third generation antipsychotics (TGA), other psychiatric disorders such as bipolar depression, bipolar mania, autism, and major depressive disorder have now been approved for the use of these drugs for their treatment. Also, the administration of more specific assessment tools has allowed for better delineation of the repercussions of these drugs on symptoms and the quality of life of patients who use antipsychotic agents. In general, the SGA share similar mechanisms of action to achieve these results: dopamine-2 receptor antagonism plus serotonin-2A receptor antagonism. The TGA (eg, aripiprazole) have partial agonist activity at the dopamine-2 receptor site, and are also called dopaminergic stabilizers. The pharmacological profile of SGA and TGA may provide better efficacy against negative symptoms, and are less likely to produce extrapyramidal symptoms; however, the SGA and TGA are associated with many other adverse events. The clinician has to balance the risks and benefits of these medications when choosing an antipsychotic for an individual patient. PMID:23236256

  17. Rethinking Antipsychotic Formulary Policy

    PubMed Central

    Rosenheck, R.A.; Leslie, D.L.; Busch, Susan; Rofman, Ethan S.; Sernyak, Michael

    2008-01-01

    In this commentary, we review recent research suggesting that (a) second-generation antipsychotics (SGAs) may be no more effective than first-generation antipsychotics (FGAs), (b) the reduced risk of EPS and tardive dyskinesia with SGAs is more weakly supported by the research literature than has been appreciated, and (c) benefits may be offset by greater metabolic risks of some SGAs and their substantially greater cost. Bearing in mind, as well, that risperidone, currently the least expensive SGA, will soon be available as an even less expensive generic drug, we propose a new algorithm for maintenance antipsychotic therapy. We further outline a cautious implementation procedure that relies on standardized documentation and feedback, without a restrictive formulary that would limit physician choice. The algorithm outlined here and the process for its implementation are intended as a stimulus for discussion of potential policy responses, not as a finalized proposition. PMID:17634413

  18. Effect of Different Antipsychotic Drugs on Short-Term Mortality in Stroke Patients

    PubMed Central

    Wang, Jen-Yu; Wang, Cheng-Yi; Tan, Chen-Hui; Chao, Ting-Ting; Huang, Yung-Sung; Lee, Ching-Chih

    2014-01-01

    Abstract The safety, tolerability, and efficacy data for antipsychotic drugs used in the acute phase of stroke are limited. The primary aim of this study was to examine the effectiveness and safety of typical and atypical antipsychotics on acute ischemic stroke mortality. This observational study was conducted in a retrospective cohort of patients selected from the 2010–2011 National Health Research Institute database in Taiwan. Patients were tracked for 1 month from the time of their first hospitalization for acute ischemic stroke. A nested case–control analysis was used to estimate the odds ratio (OR) of 30-day mortality associated with antipsychotic drug, adjusted for age, gender, disease severity, and comorbidities. The study cohort included 47,225 subjects with ischemic stroke, including 9445 mortality cases and 37,780 matched controls. After adjustment for the covariates, antipsychotics users before ischemic stroke are associated with a 73% decrease in the rate of mortality (OR 0.27; 95% CI 0.23–0.31). After ischemic stroke, the use of antipsychotics is associated with 87% decrease in the rate of mortality (OR 0.13; 95% CI 0.1–0.16). The users of conventional antipsychotics are associated with a 78% decrease in the rate of mortality (OR 0.22; 95% CI 0.18–0.26). The users of atypical antipsychotics are also associated with a 86% decrease in the rate of mortality (OR 0.14; 95% CI 0.12–0.17). We found that 1-month mortality among acute stroke patients treated with antipsychotics is significantly lower. The benefit on lower mortality was found not only among ischemic stroke patients who had received antipsychotics previously but also among patients who start antipsychotics after their stroke. PMID:25437033

  19. Antipsychotics as antidepressants.

    PubMed

    Roberts, Rona Jeannie; Lohano, Kavita K; El-Mallakh, Rif S

    2016-09-01

    Three second-generation antipsychotic (SGA) agents have received FDA approval for adjunctive treatment, to antidepressant, of major depressive disorder: quetiapine, aripiprazole, and olanzapine. Additionally, quetiapine and lurasidone have been approved for the treatment of bipolar depression. There are data suggesting that quetiapine is effective for major depressive disorder as monotherapy. These agents are effective for depression only at subantipsychotic doses. Receptor profiles predict that all SGA will have anxiolytic effects as subantipsychotic doses but that all will be dysphorogenic at full antipsychotic doses (i.e., produce a depression-like clinical picture). The antidepressant effect appears to be unique to some agents, with direct evidence of insignificant antidepressant action for ziprasidone. Three general principles can guide the use of antipsychotics as antidepressants: (i) All SGAs may have anxiolytic effects; (ii) full antipsychotic doses are dysphorogenic, and therefore, subantipsychotic doses are to be used; and (iii) SGAs do not have a general antidepressant effect, rather, this appears to be unique to quetiapine and aripiprazole, and possibly lurasidone. PMID:25963405

  20. The fast-off hypothesis revisited: A functional kinetic study of antipsychotic antagonism of the dopamine D2 receptor.

    PubMed

    Sahlholm, Kristoffer; Zeberg, Hugo; Nilsson, Johanna; Ögren, Sven Ove; Fuxe, Kjell; Århem, Peter

    2016-03-01

    Newer, "atypical" antipsychotics carry a lower risk of motor side-effects than older, "typical" compounds. It has been proposed that a ~100-fold faster dissociation from the dopamine D2 receptor (D2R) distinguishes atypical from typical antipsychotics. Furthermore, differing antipsychotic D2R affinities have been suggested to reflect differences in dissociation rate constants (koff), while association rate constants (kon) were assumed to be similar. However, it was recently demonstrated that lipophilic accumulation of ligand in the cell interior and/or membrane can cause underestimation of koff, and as high-affinity D2R antagonists are frequently lipophilic, this may have been a confounding factor in previous studies. In the present work, a functional electrophysiology assay was used to measure the recovery of dopamine-mediated D2R responsivity from antipsychotic antagonism, using elevated concentrations of dopamine to prevent the potential bias of re-binding of lipophilic ligands. The variability of antipsychotic kon was also reexamined, capitalizing on the temporal resolution of the assay. kon was estimated from the experimental recordings using a simple mathematical model assumed to describe the binding process. The time course of recovery from haloperidol (typical antipsychotic) was only 6.4- to 2.5-fold slower than that of the atypical antipsychotics, amisulpride, clozapine, and quetiapine, while antipsychotic kons were found to vary more widely than previously suggested. Finally, affinities calculated using our kon and koff estimates correlated well with functional potency and with affinities reported from radioligand binding studies. In light of these findings, it appears unlikely that typical and atypical antipsychotics are primarily distinguished by their D2R binding kinetics. PMID:26811292

  1. Determinants of physical health parameters in individuals with intellectual disability who use long-term antipsychotics.

    PubMed

    de Kuijper, Gerda; Mulder, Hans; Evenhuis, Heleen; Scholte, Frans; Visser, Frank; Hoekstra, Pieter J

    2013-09-01

    Individuals with intellectual disability frequently use antipsychotics for many years. This may have detrimental health effects, including neurological symptoms and metabolic and hormonal dysregulation, the latter possibly affecting bone metabolism. There is large variability in the degree in which antipsychotic agents lead to these health problems. In the current study we investigated potential determinants of physical symptoms and biological parameters known to be associated with use of antipsychotics in a convenience sample of 99 individuals with intellectual disability who had used antipsychotics for more than one year for behavioural symptoms. We focused on extrapyramidal symptoms; on overweight and presence of components of the metabolic syndrome; and on elevated plasma prolactin and bone turnover parameters. As predictor variables, we used patient (sex, age, genetic polymorphisms, and severity of intellectual disability) and medication use (type and dosage) characteristics. We found extrapyramidal symptoms to be present in 53%, overweight or obesity in 46%, and the metabolic syndrome in 11% of participants. Hyperprolactineaemia and one or more elevated bone turnover markers were present in 17% and 25%, respectively. Higher age and more severe intellectual disability were associated with dyskinesia and a higher dosage of the antipsychotic drug was associated with parkinsonism. Less severe intellectual disability was related to higher Body Mass Index. Use of atypical antipsychotics was associated with higher diastolic blood pressure and elevated fasting glucose. Clinicians who prescribe antipsychotics in individuals with intellectual disability should carefully balance the potential benefits of prolonged treatment against the risk of health hazards associated with the use of antipsychotics. PMID:23792429

  2. Improvement in verbal memory following SSRI augmentation of antipsychotic treatment is associated with changes in the expression of mRNA encoding for the GABA-A receptor and BDNF in PMC of schizophrenic patients.

    PubMed

    Silver, Henry; Mandiuk, Nina; Einoch, Reef; Susser, Ehud; Danovich, Lena; Bilker, Warren; Youdim, Moussa; Weinreb, Orly

    2015-05-01

    Verbal memory impairment in schizophrenia is associated with abnormalities in gamma-aminobutyric acid (GABA)-ergic and brain-derived neurotrophic factor (BDNF) systems. Recent evidence from animal and clinical studies that adding fluvoxamine to antipsychotics alters the expression of transcripts encoding for the GABA-A receptor and BDNF led us to postulate that fluvoxamine augmentation may improve memory in schizophrenia. To test this, we examined the effect of add-on fluvoxamine on verbal memory and other cognitive functions and related it to the expression of mRNA coding for the GABA-A receptor and BDNF in peripheral mononuclear cells (PMC) of schizophrenic patients. Twenty-nine patients completed a 6-week study in which fluvoxamine (100 mg/day) was added to ongoing antipsychotic treatment. Verbal memory, abstraction working memory, object and face recognition, and psychomotor speed and clinical symptoms were assessed at baseline and after 3 and 6 weeks of treatment. Blood samples were taken at baseline and weeks 1, 3, and 6 and PMC was assayed for the GABA-A beta3 receptor and BDNF mRNA by quantitative real-time reverse transcription-PCR. Associative and logical verbal memory improved significantly and showed a significant correlation with changes in PMC BDNF and GABA-A beta3 receptor mRNA, which increased during treatment. Abstraction and object recognition improved, but this did not correlate with PMC measures. Negative and positive symptoms improved significantly; the latter showed significant correlations with changes in PMC measures. Addition of fluvoxamine to antipsychotics improves verbal memory. It is postulated that the mechanism involves enhanced GABA-A receptor/BDNF-dependent synaptic plasticity in the hippocampus. PMID:25756551

  3. 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

  4. 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

  5. [Anticonvulsants and antipsychotics in the treatment of bipolar disorder].

    PubMed

    Moreno, Ricardo Alberto; Moreno, Doris Hupfeld; Soares, Márcia Britto de Macedo; Ratzke, Roberto

    2004-10-01

    Bipolar disorder is a complex medical condition, and up to the date there is no single treatment with proven efficacy in the control of all aspects of the illness. The available literature on the use of anticonvulsants (valproate, carbamazepine, oxcarbazepine, lamotrigine, gabapentin, topiramate, clonazepam) and atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole) for acute and prophylactic treatment of bipolar disorder was reviewed. There is a large amount of evidence that lithium is efficacious in the prophylaxis of episodes and better for acute mania than for depressive episodes. Other data show that carbamazepine and valproate are effective in acute manic episodes. Lamotrigine has been shown to reduce cycling and effective in depressive episodes. Based on the available data, olanzapine was found to be the most appropriate atypical antipsychotic agent for the treatment of manic bipolar patients, although there are also studies suggesting the efficacy of risperidone, aripiprazole and clozapine. The preliminary data evaluating the efficacy of quetiapine and ziprasidone in bipolar disorder are still very limited. There is no consistent information supporting the prophylactic use of newer antipsychotics. PMID:15597138

  6. 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

  7. [Atypical odontalgia].

    PubMed

    Türp, Jens Christoph

    2005-01-01

    In spite of its first description by the English surgeon JOHN HUNTER more than 200 years ago, atypical odontalgia (AO), or phantom tooth pain, is not universally known among dentists. AO is a persistent neuropathic pain which may be initiated after deafferentiation of trigeminal nerve fibers following root canal treatment, apicectomy, or tooth extraction. In the absence of pathological clinical or radiological findings, the diagnosis is made by exclusion. After a thorough patient education about the condition, pharmacological and psychological pain management is required. Invasive and irreversible treatment attempts are contraindicated. PMID:16342640

  8. Atypical Inflammasomes.

    PubMed

    Janowski, Ann M; Sutterwala, Fayyaz S

    2016-01-01

    Pattern recognition receptors, including members of the NLR and PYHIN families, are essential for recognition of both pathogen- and host-derived danger signals. A number of molecules in these families are capable of forming multiprotein complexes termed inflammasomes that result in the activation of caspase-1. In addition to NLRP1, NLRP3, NLRC4, and AIM2, which form well-described inflammasome complexes, IFI16, NLRP6, NLRP7, NLRP12, and NLRC5 have also been proposed to form inflammasomes under specific conditions. The structure and function of these atypical inflammasomes will be highlighted here. PMID:27221480

  9. 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. PMID:26156500

  10. Polymorphisms of the LEP- and LEPR gene and obesity in patients using antipsychotic medication.

    PubMed

    Gregoor, Jochem G; van der Weide, Jan; Mulder, Hans; Cohen, Dan; van Megen, Harold J G M; Egberts, Antoine C G; Heerdink, Eibert R

    2009-02-01

    Weight gain is one of the most serious adverse effects of atypical antipsychotic agents. Genetic factors influence the risk of an individual to gain weight. The objective of our study was to determine whether the LEPR Q223R polymorphism and the LEP promoter 2548G/A polymorphism are associated with obesity in a group of male and female patients using atypical antipsychotic drugs. A cross-sectional study design was used. The study population consisted of 200 patients aged between 18 and 65 years, diagnosed with a psychotic disorder, all of whom had been using an atypical antipsychotic for at least 3 months. The primary outcome measure was the presence of obesity. Determinants were the LEPR Q223R (rs1137101) polymorphism and the LEP promoter 2548G/A single nucleotide polymorphism ([SNP] rs7799039). Of the 200 included patients, 61 (31%) were obese. In females, the LEPR 223QR (adjusted odds ratio, 0.11; 95% confidence interval [CI], 0.02-0.54) and LEPR 223RR (adjusted odds ratio, 0.07; 95% CI, 0.01-0.63) genotypes were associated with a lower risk of obesity. In males, this association was not found. In females, the average body weight was 13.6 kg more (95% CI, 1.11-26.1) in the LEPR 223QQ group compared with the LEPR 223RR group. No significant association was found between the LEP promoter 2548G/A polymorphism and obesity. Taken together, the results of our study show that the LEPR Q223R polymorphism may be associated with obesity in women with a psychotic disorder treated with atypical antipsychotic drugs and stress the importance of stratification for gender when investigating the role of variations of the LEP- and LEPR genes on the metabolic side effects of antipsychotic medications. PMID:19142102

  11. Medical complications of new antipsychotic drugs.

    PubMed

    Umbricht, D; Kane, J M

    1996-01-01

    Although antipsychotic drugs have a high therapeutic index (ratio of clinical benefit to adverse effects), they are associated with a range of adverse effects in most patients. The majority of these side effects are tolerable, readily managed, and not life threatening. The most troublesome side effects are neurological. Two new antipsychotics (clozapine and risperidone) have recently been introduced and are the first of a new generation of compounds that may further improve the therapeutic index of routine antipsychotic drug administration. Clozapine clearly has a reduced risk of drug-induced parkinsonism, akathisia, and tardive dyskinesia, while producing an increased risk of agranulocytosis, seizures, and weight gain. Risperidone at low doses produces relatively few parkinsonian side effects, but it can cause tardive dyskinesia (though relative risk remains to be established). Risperidone has not been associated with blood dyscrasias or increased risk of seizures, but weight gain can be a problem for some patients. Neuroleptic malignant syndrome has been reported with both drugs, but relative risk has not been established. PMID:8873298

  12. The novel phosphodiesterase 10A inhibitor THPP-1 has antipsychotic-like effects in rat and improves cognition in rat and rhesus monkey.

    PubMed

    Smith, Sean M; Uslaner, Jason M; Cox, Christopher D; Huszar, Sarah L; Cannon, Christopher E; Vardigan, Joshua D; Eddins, Donnie; Toolan, Dawn M; Kandebo, Monika; Yao, Lihang; Raheem, Izzat T; Schreier, John D; Breslin, Michael J; Coleman, Paul J; Renger, John J

    2013-01-01

    Phosphodiesterase 10A (PDE10A) is a novel target for the treatment of schizophrenia that may address multiple symptomatic domains associated with this disorder. PDE10A is highly expressed in the brain and functions to metabolically inactivate the important second messengers cAMP and cGMP. Here we describe effects of a potent and orally bioavailable PDE10A inhibitor [2-(6-chloropyridin-3-yl)-4-(2-methoxyethoxy)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl](imidazo[1,5-a]pyridin-1-yl)methanone] (THPP-1) on striatal signaling pathways, in behavioral tests that predict antipsychotic potential, and assays that measure episodic-like memory in rat and executive function in rhesus monkey. THPP-1 exhibits nanomolar potency on the PDE10A enzyme, demonstrates excellent pharmacokinetic properties in multiple preclinical animal species, and is selective for PDE10A over other PDE families of enzymes. THPP-1 significantly increased phosphorylation of proteins in the striatum involved in synaptic plasticity, including the a-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor (AMPA) GluR1 subunit, extracellular receptor kinase (ERK), and cAMP-response element binding protein (CREB). THPP-1 produced dose-dependent effects in preclinical assays predictive of antipsychotic activity including attenuation of MK-801-induced psychomotor activation and condition avoidance responding in rats. At similar plasma exposures, THPP-1 significantly increased object recognition memory in rat and attenuated a ketamine-induced deficit in the object retrieval detour task in rhesus monkey. These findings suggest that PDE10A inhibitors have the potential to impact multiple symptomatic domains of schizophrenia including positive symptoms and cognitive impairment. This article is part of a Special Issue entitled 'Cognitive Enhancers'. PMID:22750078

  13. 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

  14. 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

  15. Antipsychotic Management of Schizoaffective Disorder: A Review.

    PubMed

    Lindenmayer, Jean-Pierre; Kaur, Amandeep

    2016-04-01

    Schizoaffective disorder (SAD) is an incapacitating illness that presents clinicians with challenges in terms of both its diagnosis and its psychopharmacological management. Most studies conducted on the psychopharmacological treatment of SAD also include patients with schizophrenia or other psychotic illnesses, thereby providing an unspecific view to the clinician as to the best way of treating patients with SAD. The objective of this article is to review studies on evidence-based treatment of patients with SAD. We conducted a systematic literature search in MEDLINE/PubMed for full-text studies in the English language using the terms 'Schizoaffective and treatment' or 'antipsychotic schizoaffective'. Our review found relatively few studies with either an active comparator or placebo that examined the efficacy of antipsychotics for patients with SAD without an admixture of patients with schizophrenia. Only oral paliperidone extended release (ER), paliperidone long-acting injection (LAI), and risperidone have been shown to be effective and safe in reducing psychotic as well as affective components in acutely ill SAD patients in controlled studies. Paliperidone ER and LAI have also been shown to be efficacious in the maintenance treatment phase of SAD patients. While no supportive data exist, it is possible that other atypical antipsychotics may have similar efficacy to the two mentioned above. We conclude with a number of research recommendations for the study of treatment options for patients with SAD. First, there is a need for studies with patients specifically diagnosed with SAD for both the acute and the maintenance phase. The sample size needs to be adequate to allow a primary analysis of efficacy and to allow for analysis of the SAD subtypes: depressed and bipolar. Another recommendation is the need for studies of patients with SAD stratified into patients with and without mood stabilizers or antidepressants to allow the examination of the adjunctive role of

  16. Effects of adjunct galantamine to risperidone, or haloperidol, in animal models of antipsychotic activity and extrapyramidal side-effect liability: involvement of the cholinergic muscarinic receptor.

    PubMed

    Wadenberg, Marie-Louise G; Fjällström, Ann-Kristin; Federley, Malin; Persson, Pernilla; Stenqvist, Pia

    2011-06-01

    The acetylcholine esterase inhibitor/cholinergic nicotinic receptor (nAChR) allosteric modulator galantamine (Gal) is used against cognitive impairment in Alzheimer's disease. Negative/cognitive and psychotic symptom improvement in schizophrenia by adjunct Gal to antipsychotic drugs (APDs) has been reported. Cognitive symptoms in schizophrenia may involve brain prefrontal hypo-dopaminergia. Experimental data by others indicate nAChR involvement in animal pro-cognitive effects of Gal. The role of nAChRs in antipsychotic effects by Gal has, however, not been elucidated. Using the conditioned avoidance response (CAR) and the catalepsy tests for antipsychotic activity and extrapyramidal side-effect (EPS) liability, respectively, we here investigated the effects of adjunct Gal (1.25 mg/kg) to the typical APD haloperidol (Hal) (0.05 mg/kg), or the atypical APD risperidone (Ris) (0.2 mg/kg), in rats. Adjunct Gal significantly enhanced APD-like effects by low doses of Hal or Ris, but showed a safe EPS liability profile only in combination with Ris. Pretreatment with the muscarinic receptor (mAChR) antagonist scopolamine, but not the nAChR antagonist mecamylamine, completely reversed the enhancing effects of adjunct Gal to Hal treatment, in the CAR test. While the nAChR-modulating properties of Gal probably contribute to pro-cognitive activity, as shown by others, the present data suggest that any contribution to antipsychotic activity by Gal is mediated primarily via mAChRs. This property combination of Gal may offer a unique, favourable therapeutic profile for schizophrenia treatment. PMID:20701827

  17. Treatment patterns and characteristics of older antipsychotic users in Germany.

    PubMed

    Schmedt, Niklas; Jobski, Kathrin; Kollhorst, Bianca; Krappweis, Jutta; Rüther, Eckart; Schink, Tania; Garbe, Edeltraut

    2016-05-01

    The aim of this study was to investigate the characteristics and treatment patterns of older antipsychotic (AP) users in Germany. We carried out a cohort study in the German Pharmacoepidemiological Research Database and identified new AP users aged at least 65 years between 2005 and 2011. Possible indications, comedication, and information on persistence and adherence, concurrent multiple use, and switch of APs were assessed. Overall, 298 847 individuals were included in the cohort. Almost 70% entered the cohort with a typical antipsychotic (TAP). Melperone (23.4%) was used most frequently, followed by promethazine (18.3%), sulpiride (11.0%), and risperidone (10.3%). AP users had a low prevalence of schizophrenia and bipolar disorders in contrast to dementia. Initiators of atypical antipsychotics had more treatment episodes compared with TAPs (median 3 vs. 2), but lower median persistence (14 vs. 22 days). Persistence was also lower in patients with, rather than without, dementia. The overall percentage of concurrent multiple use and switch to other APs was low with 5.6%, but higher in patients with, rather than without, dementia. In conclusion, APs were used for a broad range of indications, mostly other than schizophrenia and bipolar disorders. Low persistence and a high number of treatment episodes suggest frequent 'as-needed' treatment, especially in dementia patients. PMID:26871678

  18. Informed consent for antipsychotic medication.

    PubMed Central

    Schachter, D.; Kleinman, I.; Williams, J. I.

    1999-01-01

    OBJECTIVE: To determine family physicians' attitudes and practices regarding documentation of informed consent for antipsychotic medication. DESIGN: Pilot cross-sectional study. SETTING: Teaching and non-teaching hospitals in Toronto, Ont. PARTICIPANTS: Thirty family physicians were selected in equal numbers from teaching and non-teaching hospitals with no more than five physicians from a given hospital. Participants were treating at least 10 patients with antipsychotic medication. Participants' mean age was 44.3 years; 83% were men. MAIN OUTCOME MEASURES: Documentation of consent and of disclosure of consent for antipsychotic medication in patients' charts. RESULTS: Documentation was found in only 13% of charts. Whether it was there or not did not correlate with information disclosed, score on an attitude scale, or demographics. Physicians who found documentation time-consuming were less likely to document. Most physicians disclosed reasons for antipsychotic medication, but less than half described tardive dyskinesia, a potentially irreversible movement disorder that affects about 25% of patients on long-term treatment. CONCLUSIONS: The low rate of documentation observed in this sample was consistent with reports of similar samples and might indicate that family physicians are unaware of recommendations for documentation or simply do not have time to keep abreast of current recommendations. Many physicians thought signed consent forms unnecessary for psychotic patients, and even more believed seeking consent for antipsychotic medications would increase patient anxiety. PMID:10386214

  19. Analysis of differential clinical profiles of different antipsychotic molecules in the first psychotic episode: a retrospective study.

    PubMed

    Spanarello, S; Beoni, A M; Mina, G; Amantini, K; Colotto, A

    2005-01-01

    Our study starts from the supposition that the ideal pharmacological treatment should improve the patient's global behaviour, as a consequence of the therapeutic activity on positive, negative, behavioural, affective and cognitive symptoms. It should have few secondary effects, both in the short and long term, thus assuring a good life-quality, the fundamental condition for the patient's compliance and adherence. Currently only few studies have been published evaluating atypical antipsychotic effects vs. typical ones in the first psychotic episode, particularly studying different profile evaluations and different molecule rating standards. Our aim has been the therapeutic profile evaluation of atypical anti-psychotic molecules vs. typical ones, using "Liège's star" parameters (anti- manic, anti-autistic, anti-delusional, extra-pyramidal, ataraxic-sedative and adrenolitic). We added 2 complex scales, the first for loss in affectiveness, the second for cognitive and behavioural disorganization. We utilized Aosta's Psychiatric Service data-base, evaluating patients in their first psychotic episode diagnosed with various schizophrenic disorders per DSM IV criteria. We considered everyone who received, as monotherapy, or a typical molecule or an atypical one and who had been tested, at the beginning and at the end of the psychotic episode, with MMPI and PANSS Rating Scale. We evaluated 107 patients, 68 men and 39 women, whose mean age was 25,04 years (SD=3,789): 21 schizo-affective, 27 schizophreniform, 23 brief reactive psychosis and 36 paranoid- type schizophrenic disorders. The mean observation time was 117,18 days. Monotherapy was with olanzapine (23), quetiapine (8), risperidon (19), haloperidol (20), clopentixol (9), chlorpromazine (10), pimozide (8) and sulpiride (10). For the evaluation of adrenolitic, sedative and extrapyramidal effects we utilized clinical data and specific drugs administrations. We based our estimate for anti-delusional activity on P1, p3, p

  20. Third generation antipsychotic drugs: partial agonism or receptor functional selectivity?

    PubMed Central

    Mailman, Richard B.; Murthy, Vishakantha

    2010-01-01

    Functional selectivity is the term that describes drugs that cause markedly different signaling through a single receptor (e.g., full agonist at one pathway and antagonist at a second). It has been widely recognized recently that this phenomenon impacts the understanding of mechanism of action of some drugs, and has relevance to drug discovery. One of the clinical areas where this mechanism has particular importance is in the treatment of schizophrenia. Antipsychotic drugs have been grouped according to both pattern of clinical action and mechanism of action. The original antipsychotic drugs such as chlorpromazine and haloperidol have been called typical or first generation. They cause both antipsychotic actions and many side effects (extrapyramidal and endocrine) that are ascribed to their high affinity dopamine D2 receptor antagonism. Drugs such as clozapine, olanzapine, risperidone and others were then developed that avoided the neurological side effects (atypical or second generation antipsychotics). These compounds are divided mechanistically into those that are high affinity D2 and 5-HT2A antagonists, and those that also bind with modest affinity to D2, 5-HT2A, and many other neuroreceptors. There is one approved third generation drug, aripiprazole, whose actions have been ascribed alternately to either D2 partial agonism or D2 functional selectivity. Although partial agonism has been the more widely accepted mechanism, the available data are inconsistent with this mechanism. Conversely, the D2 functional selectivity hypothesis can accommodate all current data for aripiprazole, and also impacts on discovery compounds that are not pure D2 antagonists. PMID:19909227

  1. Molecular pathophysiology of metabolic effects of antipsychotic medications.

    PubMed

    Ballon, Jacob S; Pajvani, Utpal; Freyberg, Zachary; Leibel, Rudolph L; Lieberman, Jeffrey A

    2014-11-01

    Antipsychotic medications are associated with major metabolic changes that contribute to medical morbidity and a significantly shortened life span. The mechanisms for these changes provide us with a broader understanding of central nervous and peripheral organ-mediated metabolic regulation. This paper reviews an extensive literature regarding putative mechanisms for effects of antipsychotic medications on weight regulation and glucose homeostasis as well as potential inherent metabolic risks of schizophrenia itself. We present a model suggesting that peripheral antipsychotic targets play a critical role in drug-induced weight gain and diabetes. We propose that a better understanding of these mechanisms will be crucial to developing improved treatments for serious mental illnesses as well as providing potentially novel therapeutic targets of metabolic disorders including diabetes. PMID:25190097

  2. How antipsychotics work-from receptors to reality.

    PubMed

    Kapur, Shitij; Agid, Ofer; Mizrahi, Romina; Li, Ming

    2006-01-01

    How does a small molecule blocking a few receptors change a patients' passionately held paranoid belief that the FBI is out to get him? To address this central puzzle of antipsychotic action, we review a framework linking dopamine neurochemistry to psychosis, and then link this framework to the mechanism of action of antipsychotics. Normal dopamine transmission has a role in predicting novel rewards and in marking and responding to motivationally salient stimuli. Abnormal dopamine transmission alters these processes and results in an aberrant sense of novelty and inappropriate assignment of salience leading to the experience of psychosis. Antipsychotics improve psychosis by diminishing this abnormal transmission by blocking the dopamine D2/3 receptor (not D1 or D4), and although several brain regions may be involved, it is suggested that the ventral striatal regions (analog of the nucleus accumbens in animals) may have a particularly critical role. Contrary to popular belief, the antipsychotic effect is not delayed in its onset, but starts within the first few days. There is more improvement in the first 2 weeks, than in any subsequent 2-week period thereafter. However, a simple organic molecule cannot target the complex phenomenology of the individual psychotic experience. Antipsychotics diminish dopamine transmission and thereby dampen the salience of the pre-occupying symptoms. Therefore, in the initial stage of an antipsychotic response, the patients experience a detachment from symptoms, a relegation of the delusions and hallucinations to the back of their minds, rather than a complete erasure of the symptoms. Only with time, and only in some, via the mediation of new learning and plasticity, is there a complete resolution of symptoms. The implications of these findings for clinical care, animal models, future target discovery and drug development are discussed. PMID:16490410

  3. 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

  4. A critical review of the antipsychotic effects of cannabidiol: 30 years of a translational investigation.

    PubMed

    Zuardi, Antonio Waldo; Crippa, Jose Alexandre S; Hallak, Jaime E C; Bhattacharyya, Sagnik; Atakan, Zerrin; Martin-Santos, Rocio; McGuire, Philip K; Guimarães, Francisco Silveira

    2012-01-01

    Δ(9)-tetrahydrocannabinol (Δ(9)-THC) is the main compound of the Cannabis Sativa responsible for most of the effects of the plant. Another major constituent is cannabidiol (CBD), formerly regarded to be devoid of pharmacological activity. However, laboratory rodents and human studies have shown that this cannabinoid is able to prevent psychotic-like symptoms induced by high doses of Δ(9)- THC. Subsequent studies have demonstrated that CBD has antipsychotic effects as observed using animal models and in healthy volunteers. Thus, this article provides a critical review of the research evaluating antipsychotic potential of this cannabinoid. CBD appears to have pharmacological profile similar to that of atypical antipsychotic drugs as seem using behavioral and neurochemical techniques in animal models. Additionally, CBD prevented human experimental psychosis and was effective in open case reports and clinical trials in patients with schizophrenia with a remarkable safety profile. Moreover, fMRI results strongly suggest that the antipsychotic effects of CBD in relation to the psychotomimetic effects of Δ(9)-THC involve the striatum and temporal cortex that have been traditionally associated with psychosis. Although the mechanisms of the antipsychotic properties are still not fully understood, we propose a hypothesis that could have a heuristic value to inspire new studies. These results support the idea that CBD may be a future therapeutic option in psychosis, in general and in schizophrenia, in particular. PMID:22716160

  5. Combining antipsychotics; is this strategy useful?

    PubMed

    Christy, Jill; Burnside, David; Agius, Mark

    2014-11-01

    Antipsychotic drugs are commonly combined in psychiatric practice in an attempt to treat schizophrenia. Such practice is widespread, despite the lack of explicit endorsement by many of the main regulatory bodies. There are varying rationales behind combining these potent drugs-either to augment the effect of a drug whose action alone is inadequate for patients with treatment resistant schizophrenia (TRS), or to improve the side effects seen due to treatment. Augmentations are most frequently observed with clozapine, a drug reserved for use when other antipsychotic medications have failed. Several drugs have been chosen as adjuvants, including aripiprazole, sulpiride, amisulpiride and risperidone. A small number of RCTs (randomized controlled trials) have been performed but, despite this data and numerous case reports showing positive changes in symptomatology, Cochrane reviews of available studies have been unable to definitively confirm the efficacy of these combinations, frequently citing the need for larger, longer term, prospective studies.Evidence for benefits of combination therapy on side effects is also inadequate. Some RCTs and case series have shown they can positively alter side effects due to drugs such as clozapine, e.g. metabolic side effects. However, despite many of the combinations being relatively well tolerated, there is some evidence they can cause adverse effects of their own. More evidence is essential as, on the current data alone, it is not possible to make a firm recommendation on the efficacy and safety of antipsychotic combinations. In addition it is vital that the importance of a fair trial of monotherapy at adequate dosages is reinforced to clinicians, so that patients are not put onto these relatively unknown treatment strategies unnecessarily. PMID:25413558

  6. 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

  7. Antipsychotic prescription use and costs for persons with schizophrenia in the 1990s: current trends and five year time series forecasts.

    PubMed

    Martin, B C; Miller, L S; Kotzan, J A

    2001-03-01

    Real advances in schizophrenia pharmacotherapy have been made over this decade with the development of more efficacious treatment options with fewer side-effects. These advances have high per-unit direct costs that may have a profound effect on drug budgets of systems caring for persons with schizophrenia. The objective of this study was to describe the changes in utilization and cost for antipsychotic prescriptions by atypical, clozapine, decanoate products, and traditional neuroleptics in a large naturalistic setting, i.e. the Georgia Medicaid population. Secondly, this study forecasted the categorized antipsychotic prescription utilization through the year 2002. Administrative claims data spanning 1990-1997 for Medicaid eligible persons suffering from schizophrenia in the state of Georgia were supplemented with psychiatric institutional data obtained from the Georgia Department of Human Resources. A total of 16227 Medicaid-eligible recipients had a code indicative of schizophrenia (ICD-9-CM=295.(**)) and were at least 16 years of age at the time of their first diagnosis. The mean recipient prescription use and expenditures were tallied for each month of the study and stratified by prescription category (atypical, clozapine, decanoate, and traditional antipsychotic). ARIMA time series models were identified and estimated using these monthly PMPM utilization and expenditures estimates to forecast 5 years beyond the last month of the study. The total use of antipsychotics increased modestly throughout the study period, and the use of atypicals, clozapine, and decanoate products increased substantially, while a decrease was observed for traditional antipsychotics. In 1995 dollars, antipsychotic expenditures increased from a mean of approximately $10 PMPM in 1990 to $95 projected for the year 2002. This transition from traditional oral antipsychotics to atypicals and decanoate products has a profound effect on drug expenditures for systems paying for the care of

  8. 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

  9. The relationship of antipsychotic medication class and adherence with treatment outcomes and costs for Florida Medicaid beneficiaries with schizophrenia.

    PubMed

    Becker, Marion A; Young, M Scott; Ochshorn, Ezra; Diamond, Ronald J

    2007-05-01

    While some studies show a significant advantage in adherence rates with use of atypical versus typical antipsychotic medication, others show no advantage or mixed results (Jones et al. (2006). Archives of General Psychiatry, 63, 1079-1087; Rosenheck, (2006). Archives of General Psychiatry, 63, 1074-1076). This study examined treatment outcomes and costs associated with adherence rates by antipsychotic medication class for adult Medicaid beneficiaries in Florida diagnosed with schizophrenia. Outcomes examined include arrests, involuntary commitments, and physical and behavioral healthcare costs. Study findings demonstrate that medication adherence for persons with schizophrenia may be as important to treatment costs and benefits as the class of medication used. PMID:17211716

  10. Costs, Control or Just Good Clinical Practice? The Use of Antipsychotic Medications and Formulary Decision-Making in Large U.S. Prisons and Jails

    ERIC Educational Resources Information Center

    Veysey, Bonita M.; Stenius, Vanja; Mazade, Noel; Schacht, Lucille

    2007-01-01

    Medications are central to the psychiatric armamentorium in U.S. jails and prisons. Psychiatric medications are used both to stabilize acute symptoms as well as maintain mental health once symptoms are reduced. Both jails and prisons rely heavily on traditional antipsychotics, but both have a full array of atypical medications in their…

  11. 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

  12. Risks versus benefits of different types of long-acting injectable antipsychotics.

    PubMed

    McEvoy, Joseph P

    2006-01-01

    Since their introduction into clinical practice in the early 1960s, long-acting depot antipsychotics have been widely used as maintenance therapy for patients with schizophrenia. The improved pharmacokinetics of injectable long-acting antipsychotic therapies have provided more reliable drug delivery and reduced differences in peak and trough plasma levels of the drug. Studies that have compared short-acting oral antipsychotics with long-acting injectable antipsychotics, although imperfect, support injectable antipsychotics as having real benefit over oral antipsychotics on patient outcome owing largely to improved adherence. If patients forget or refuse to take their prescribed oral medications, weeks or months may go by before they experience an exacerbation; the effects of nonadherence become apparent too late to preempt the problem. On the other hand, if a patient fails to show up for an injection, the problem of nonadherence can be immediately addressed. When injectable medication is combined with an active psychosocial treatment program that will respond assertively to nonadherence, relapse rates may be reduced. By preventing or delaying relapse, consistent treatment can improve the patient's quality of life and lead to an overall reduction in the cost of care. PMID:16822092

  13. Bitropic D3 Dopamine Receptor Selective Compounds s Potential Antipsychotics.

    PubMed

    Luedtke, Robert R; Rangel-Barajas, Claudia; Malik, Mahinder; Reichert, David E; Mach, R H

    2015-01-01

    Neuropsychiatric disorders represent a substantial social and health care issue. The National Institutes of Health estimates that greater than 2 million adults suffer from neuropsychiatric disorders in the USA. These individuals experience symptoms that can include auditory hallucinations, delusions, unrealistic beliefs and cognitive dysfunction. Although antipsychotic medications are available, suboptimal therapeutic responses are observed for approximately one-third of patients. Therefore, there is still a need to explore new pharmacotherapeutic strategies for the treatment of neuropsychiatric disorders. Many of the medications that are used clinically to treat neuropsychiatric disorders have a pharmacological profile that includes being an antagonist at D2-like (D2, D3 and D4) dopamine receptor subtypes. However, dopamine receptor subtypes are involved in a variety of neuronal circuits that include movement coordination, cognition, emotion, affect, memory and the regulation of prolactin. Consequently, antagonism at D2-like receptors can also contribute to some of the adverse side effects associated with the long-term use of antipsychotics including the a) adverse extrapyramidal symptoms associated with the use of typical antipsychotics and b) metabolic side effects (weight gain, hyperglycemia, increased risk of diabetes mellitus, dyslipidemia and gynecomastia) associated with atypical antipsychotic use. Preclinical studies suggest that D3 versus D2 dopamine receptor selective compounds might represent an alternative strategy for the treatment of the symptoms of schizophrenia. In this review we discuss a) how bitropic Nphenylpiperazine D3 dopamine receptor selective compounds have been developed by modification of the primary (orthosteric) and secondary (allosteric or modulatory) pharmacophores to optimize D3 receptor affinity and D2/D3 binding selectivity ratios and b) the functional selectivity of these compounds. Examples of how these compounds might be

  14. Pharmacogenetics of leptin in antipsychotic-associated weight gain and obesity-related complications

    PubMed Central

    Lee, Amy K; Bishop, Jefrey R

    2013-01-01

    Second-generation antipsychotics can greatly improve symptoms of psychosis-spectrum disorders. Unfortunately, these drugs are associated with weight gain, which increases a patient’s risk for developing chronic diseases including Type 2 diabetes, cardiovascular diseases or other obesity-related complications. There are interindividual differences in weight gain resulting from antipsychotic drug use that may be explained by pharmacodynamic characteristics of these agents as well as clinical factors. In addition, genetic variations in pathways associated with satiety are increasingly recognized as potential contributors to antipsychotic-associated weight gain. Polymorphisms in the leptin gene, as well as the leptin receptor gene, are potential pharmacogenetic markers associated with these outcomes. This article summarizes evidence for the associations of the leptin gene and the leptin receptor gene polymorphisms with antipsychotic-induced weight gain, potential mechanisms underlying these relationships, and discusses areas for future pharmacogenetic investigation. PMID:21787190

  15. 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

  16. Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats

    PubMed Central

    Bordia, Tanuja; McIntosh, J. Michael

    2012-01-01

    Antipsychotics are an important class of drugs for the management of schizophrenia and other psychotic disorders. They act by blocking dopamine receptors; however, because these receptors are present throughout the brain, prolonged antipsychotic use also leads to serious side effects. These include tardive dyskinesia, repetitive abnormal involuntary movements of the face and limbs for which there is little treatment. In this study, we investigated whether nicotine administration could reduce tardive dyskinesia because nicotine attenuates other drug-induced abnormal movements. We used a well established model of tardive dyskinesia in which rats injected with the commonly used antipsychotic haloperidol develop vacuous chewing movements (VCMs) that resemble human orofacial dyskinesias. Rats were first administered nicotine (minipump; 2 mg/kg per day). Two weeks later, they were given haloperidol (1 mg/kg s.c.) once daily. Nicotine treatment reduced haloperidol-induced VCMs by ∼20% after 5 weeks, with a significant ∼60% decline after 13 weeks. There was no worsening of haloperidol-induced catalepsy. To understand the molecular basis for this improvement, we measured the striatal dopamine transporter and nicotinic acetylcholine receptors (nAChRs). Both haloperidol and nicotine treatment decreased the transporter and α6β2* nAChRs (the asterisk indicates the possible presence of other nicotinic subunits in the receptor complex) when given alone, with no further decline with combined drug treatment. By contrast, nicotine alone increased, while haloperidol reduced α4β2* nAChRs in both vehicle and haloperidol-treated rats. These data suggest that molecular mechanisms other than those directly linked to the transporter and nAChRs underlie the nicotine-mediated improvement in haloperidol-induced VCMs in rats. The present results are the first to suggest that nicotine may be useful for improving the tardive dyskinesia associated with antipsychotic use. PMID:22144565

  17. 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

  18. Clinical predictors of therapeutic response to antipsychotics in schizophrenia

    PubMed Central

    Carbon, Maren; Correll, Christoph U.

    2014-01-01

    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. PMID:25733955

  19. 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

  20. 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

  1. Low dose morphine adjuvant therapy for enhanced efficacy of antipsychotic drug action: potential involvement of endogenous morphine in the pathophysiology of schizophrenia.

    PubMed

    Stefano, George B; Králíčková, Milena; Ptacek, Radek; Kuzelova, Hana; Esch, Tobias; Kream, Richard M

    2012-07-01

    Major thematic threads linking extensive preclinical and clinical efforts have established a working mechanistic scheme whereby atypical antipsychotic drugs ameliorate negative DSM IV diagnostic criteria by effecting relatively potent blockade of serotonin (5-HT)(2A) receptors coupled with weaker antagonism of dopamine D(2) receptors in frontal cortical areas. These contentions are more or less supported by in vitro binding experiments employing cloned receptors on cultured cells, although significant functional involvement of 5-HT(2C) receptors has also been proposed. It is interesting that a key statistical analysis indicates a major shift in usage back to typical antipsychotic agents for management of schizophrenia from 1995-2008, whereas off-label usage of atypical antipsychotic agents was markedly increased or expanded for bipolar affective disorder. Importantly, meta-analyses generally did not support efficacy differences between the other atypical antipsychotics compared with the older typical agents. A critical examination of putative functional linkages of morphine and its type-selective mu opioid receptor to higher order cortical regulation of cognitive processes may provide novel insights into human behavioral processes that are severely impaired in schizophrenia spectrum disorders. PMID:22739740

  2. Antipsychotic treatment in breast cancer patients.

    PubMed

    Rahman, Tahir; Clevenger, Charles V; Kaklamani, Virginia; Lauriello, John; Campbell, Austin; Malwitz, Kari; Kirkland, Robert S

    2014-06-01

    Special consideration is required when prescribing antipsychotic drugs for patients with an existing diagnosis of breast cancer. The package inserts of all approved antipsychotics contain precautions regarding their administration in this patient group. These drugs are well known to elevate serum prolactin levels to varying degrees. Overexpression of the prolactin receptor is seen in more than 95% of human breast cancers. Many genes that are activated by the prolactin receptor are associated with tumorigenesis and cancer cell proliferation. The authors discuss the pathophysiology, clinical implications, and pertinent preclinical data and make specific recommendations regarding the use of antipsychotics in patients with breast cancer. PMID:24880509

  3. Attitudes towards the administration of long-acting antipsychotics: a survey of physicians and nurses

    PubMed Central

    2013-01-01

    Background Discontinuation of antipsychotic treatment for schizophrenia can interrupt improvement and exacerbate the illness. Reasons for discontinuing treatment are multifactorial and include adherence, efficacy and tolerability issues. Poor adherence may be addressed through non-pharmacological approaches as well as through pharmacological ones, ie ensured delivery of medication, such as that achieved with long-acting injectable (LAI) antipsychotics. However, attitudes of healthcare professionals (HCPs) towards LAI antipsychotics may influence their prescribing decisions and may influence medication choices offered to patients. We therefore conducted a survey to investigate factors driving LAI use as well as physician and nurse attitudes to LAI antipsychotics and to different injection sites. Methods An independent market research agency conducted the survey of HCPs across Europe. Participants were recruited by telephone and completed the survey online. Using conjoint analyses (a multivariate statistical technique analysing preferences on the basis of ranking a limited number of attributes which are presented repetitively), attitudes to oral versus LAI medication and gluteal versus deltoid injection routes were assessed. Results A total of 891 HCPs across Europe were surveyed. Of these, 40% would choose LAI antipsychotics for first episode patients whereas 90% would select LAI antipsychotics for chronic patients with two to five psychotic episodes. Dominant elements in antipsychotic choice were low sedation but no tardive dyskinesia, no or mild pain at injection and low risk of embarrassment or impact upon therapeutic alliance. Eighty-six per cent of respondents considered that having the choice of a deltoid as well as gluteal administration site was beneficial over not having that choice. Two thirds of respondents said they agreed that medication administration via the deltoid muscle may reduce social embarrassment associated with LAI antipsychotics and most

  4. Guidelines for the use and management of long-acting injectable antipsychotics in serious mental illness

    PubMed Central

    2013-01-01

    Background Long-acting injectable (LAI) formulations are not widely used in routine practice even though they offer advantages in terms of relapse prevention. As part of a process to improve the quality of care, the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) elaborated guidelines for the use and management of antipsychotic depots in clinical practice. Methods Based on a literature review, a written survey was prepared that asked about 539 options in 32 specific clinical situations concerning 3 fields: target-population, prescription and use, and specific populations. We contacted 53 national experts, 42 of whom (79%) completed the survey. The options were scored using a 9-point scale derived from the Rand Corporation and the University of California in the USA. According to the answers, a categorical rank (first-line/preferred choice, second-line/alternate choice, third-line/usually inappropriate) was assigned to each option. The first-line option was defined as a strategy rated as 7–9 (extremely appropriate) by at least 50% of the experts. The following results summarize the key recommendations from the guidelines after data analysis and interpretation of the results of the survey by the scientific committee. Results LAI antipsychotics are indicated in patients with schizophrenia, schizoaffective disorder, delusional disorder and bipolar disorder. LAI second-generation antipsychotics are recommended as maintenance treatment after the first episode of schizophrenia. LAI first-generation antipsychotics are not recommended in the early course of schizophrenia and are not usually appropriate in bipolar disorder. LAI antipsychotics have long been viewed as a treatment that should only be used for a small subgroup of patients with non-compliance, frequent relapses or who pose a risk to others. The panel considers that LAI antipsychotics should be considered and systematically proposed to any patients for whom maintenance

  5. 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— ...

  6. 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

  7. Antipsychotics in pregnancy and lactation

    PubMed Central

    Babu, Girish N.; Desai, Geetha; Chandra, Prabha S.

    2015-01-01

    Research on psychotropic medications during pregnancy and lactation is limited as often involves complex ethical issues. Information on safety of psychotropic drugs during these critical phases is either inconclusive or undetermined. Many women with severe mental illness have unplanned pregnancies and require antipsychotic medication during pregnancy and lactation. Multiple issues have to be considered while choosing safe treatments for pregnant and lactating women and the best approach is to individualize the treatment. Medication should be guided primarily by its safety data and by the psychiatric history of the patient. Important issues to be kept in mind include pre-pregnancy counseling for all women, including planning pregnancies; folate supplementation, discussion with patient and family regarding options, and active liaison with obstetricians, ultrasonologists and pediatricians. Whenever possible, non-pharmacological approaches should be used in addition. PMID:26330648

  8. Iminodibenzyl class antipsychotics for schizophrenia: a systematic review and meta-analysis of carpipramine, clocapramine, and mosapramine

    PubMed Central

    Kishi, Taro; Matsunaga, Shinji; Matsuda, Yuki; Iwata, Nakao

    2014-01-01

    Background We conducted a meta-analysis of the iminodibenzyl antipsychotics carpipramine, clocapramine, and mosapramine, which are classified as second-generation antipsychotics (SGAs) for schizophrenia treatment. Methods We searched data that had been published in PubMed, the Cochrane Library databases, PsycINFO, CiNii, and the Japan Medical Abstracts Society up to August 29, 2014. Randomized controlled trials that compared iminodibenzyl antipsychotics with other antipsychotics in patients with schizophrenia were included. Odds ratios and standardized mean differences were evaluated. Results We included four randomized controlled trials on carpipramine (number of patients [n]=290), six on clocapramine (n=1,048), and five on mosapramine (n=986) in the meta-analysis. There were no significant differences in the response rates or in the discontinuation rates either between carpipramine and the other pooled antipsychotics or between clocapramine and the other pooled antipsychotics. On the Positive and Negative Syndrome Scale, mosapramine’s positive subscale scores were superior to those of the other pooled antipsychotics (standard mean of difference =−0.22); however, on that same scale, there were no significant differences in total scores, negative scores, general subscale scores, response rates, or the discontinuation rates between mosapramine and the other pooled antipsychotics. Furthermore, the incidences of extrapyramidal symptoms and of hyperprolactinemia were significantly greater with mosapramine than with the other pooled antipsychotics. Conclusion The pharmacological profiles of carpipramine and clocapramine, which are classified as SGAs, were similar to those of first-generation antipsychotics because there were no significant differences in efficacy and safety outcomes. However, mosapramine was associated with a greater risk of extrapyramidal symptoms and hyperprolactinemia than the other SGAs were, although it may be beneficial for the improvement of

  9. 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.

  10. Managing patients on antipsychotics: your domain, too.

    PubMed

    Moore, Richard; DeJoseph, Daniel; Simmons, B Brent

    2014-03-01

    Primary care physicians are increasingly likely to care for patients taking antipsychotics. Here's what you need to know about the common adverse effects, major risks, and monitoring required. PMID:24701600

  11. 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

  12. The Potential Risks of Commonly Prescribed Antipsychotics

    PubMed Central

    Aneja, Alka; Rahman, Atiq; Megna, James; Freemont, Wanda; Shiplo, Mohammed; Nihilani, Nikil; Lee, Kathy

    2005-01-01

    Chlorpromazine, haloperidol, fluphenazine, clozapine, risperidone, quetiapine, olanzapine, ziprasidone, and aripiprazole are antipsychotics commonly used in psychiatric medicine. Approximately one third of pregnant women with psychotic symptoms use antipsychotics at least once. This review will discuss the effects of antipsychotic use during pregnancy and lactation on the fetus and infant. Although adequate and well-controlled studies have not been done in any one of these antipsychotic drugs, animal studies have revealed evidence of teratogenic or embryo/fetotoxic effects in all of them. Toxicities include skeletal malformations, central nervous system (CNS) defects, cleft palate, cardiac abnormalities, decreased fetal growth, and fetal death. For example, in pregnant women, congenital malformations and perinatal death have been reported with chlorpromazine use. Both chlorpromazine and fluphenazine in monotherapy have been shown to cause extrapyramidal symptoms and respiratory distress in infants born to mothers treated with these medications. Haloperidol use during pregnancy has been linked to severe limb reduction defects. Effects of antipsychotic use in lactating mothers are mostly unknown. However, the use of chlorpromazine has been reported to result in drowsiness and lethargy in breastfed infants. Additionally, clozapine has been reported to cause sedation, decreased suckling, restlessness, irritability, seizures, and cardiovascular instability of infants were also reported with clozapine use in lactating mother. Use of antipsychotic drugs by pregnant and lactating mother may only be justified if the potential benefit outweighs the potential risk to the fetus. PMID:21152171

  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. PMID:26781158

  14. Preliminary examination of microRNA expression profiling in bipolar disorder I patients during antipsychotic treatment.

    PubMed

    Lim, Chor Hong; Zainal, Nor Zuraida; Kanagasundram, Sharmilla; Zain, Shamsul Mohd; Mohamed, Zahurin

    2016-09-01

    Although major progress has been achieved in research and development of antipsychotic medications for bipolar disorder (BPD), knowledge of the molecular mechanisms underlying this disorder and the action of atypical antipsychotics remains incomplete. The levels of microRNAs (miRNAs)-small non-coding RNA molecules that regulate gene expression, including genes involved in neuronal function and plasticity-are frequently altered in psychiatric disorders. This study aimed to examine changes in miRNA expression in bipolar mania patients after treatment with asenapine and risperidone. Using a miRNA microarray, we analyzed miRNA expression in the blood of 10 bipolar mania patients following 12 weeks of treatment with asenapine or risperidone. Selected miRNAs were validated by using real-time PCR. A total of 16 miRNAs were differentially expressed after treatment in the asenapine group, 14 of which were significantly upregulated and the other two significantly downregulated. However, all three differentially expressed miRNAs in the risperidone group were downregulated. MiRNA target gene prediction and gene ontology analysis revealed significant enrichment for pathways associated with immune system response and regulation of programmed cell death and transcription. Our results suggest that candidate miRNAs may be involved in the mechanism of action of both antipsychotics in bipolar mania. © 2016 Wiley Periodicals, Inc. PMID:27177356

  15. 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

  16. 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.

  17. 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

  18. Atypical Optic Neuritis.

    PubMed

    Gaier, Eric D; Boudreault, Katherine; Rizzo, Joseph F; Falardeau, Julie; Cestari, Dean M

    2015-12-01

    Classic demyelinative optic neuritis is associated with multiple sclerosis and typically carries a good prognosis for visual recovery. This disorder is well characterized with respect to its presentation and clinical features by baseline data obtained through the optic neuritis treatment trial and numerous other studies. Atypical optic neuritis entails clinical manifestations that deviate from this classic pattern of features. Clinical signs and symptoms that deviate from the typical presentation should prompt consideration of less common etiologies. Atypical features to consider include lack of pain, simultaneous or near-simultaneous onset, lack of response to or relapse upon tapering from corticosteroids, or optic nerve head or peripapillary hemorrhages. The most important alternative etiologies to consider and the steps towards their respective diagnostic evaluations are suggested for these atypical features. PMID:26467052

  19. 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. PMID:26513177

  20. 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

  1. Weight Gain, Schizophrenia and Antipsychotics: New Findings from Animal Model and Pharmacogenomic Studies

    PubMed Central

    Panariello, Fabio; De Luca, Vincenzo; de Bartolomeis, Andrea

    2011-01-01

    Excess body weight is one of the most common physical health problems among patients with schizophrenia that increases the risk for many medical problems, including type 2 diabetes mellitus, coronary heart disease, osteoarthritis, and hypertension, and accounts in part for 20% shorter life expectancy than in general population. Among patients with severe mental illness, obesity can be attributed to an unhealthy lifestyle, personal genetic profile, as well as the effects of psychotropic medications, above all antipsychotic drugs. Novel “atypical” antipsychotic drugs represent a substantial improvement on older “typical” drugs. However, clinical experience has shown that some, but not all, of these drugs can induce substantial weight gain. Animal models of antipsychotic-related weight gain and animal transgenic models of knockout or overexpressed genes of antipsychotic receptors have been largely evaluated by scientific community for changes in obesity-related gene expression or phenotypes. Moreover, pharmacogenomic approaches have allowed to detect more than 300 possible candidate genes for antipsychotics-induced body weight gain. In this paper, we summarize current thinking on: (1) the role of polymorphisms in several candidate genes, (2) the possible roles of various neurotransmitters and neuropeptides in this adverse drug reaction, and (3) the state of development of animal models in this matter. We also outline major areas for future research. PMID:22988505

  2. 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

  3. 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

  4. A Multimodal Analysis of Antipsychotic Effects on Brain Structure and Function in First-Episode Schizophrenia

    PubMed Central

    Lesh, Tyler A.; Tanase, Costin; Geib, Benjamin R.; Niendam, Tara A.; Yoon, Jong H.; Minzenberg, Michael J.; Ragland, J. Daniel; Solomon, Marjorie; Carter, Cameron S.

    2016-01-01

    IMPORTANCE Recent data suggest that treatment with antipsychotics is associated with reductions in cortical gray matter in patients with schizophrenia. These findings have led to concerns about the effect of antipsychotic treatment on brain structure and function; however, no studies to date have measured cortical function directly in individuals with schizophrenia and shown antipsychotic-related reductions of gray matter. OBJECTIVE To examine the effects of antipsychotics on brain structure and function in patients with first-episode schizophrenia, using cortical thickness measurements and administration of the AX version of the Continuous Performance Task (AX-CPT) during event-related functional magnetic resonance imaging. DESIGN, SETTING, AND PARTICIPANTS This case-control cross-sectional study was conducted at the Imaging Research Center of the University of California, Davis, from November 2004 through July 2012. Participants were recruited on admission into the Early Diagnosis and Preventive Treatment Clinic, an outpatient clinic specializing in first-episode psychosis. Patients with first-episode schizophrenia who received atypical antipsychotics (medicated patient group) (n = 23) and those who received no antipsychotics (unmedicated patient group) (n = 22) and healthy control participants (n = 37) underwent functional magnetic resonance imaging using a 1.5-T scanner. MAIN OUTCOMES AND MEASURES Behavioral performance was measured by trial accuracy, reaction time, and d′-context score. Voxelwise statistical parametric maps tested differences in functional activity during the AX-CPT, and vertexwise maps of cortical thickness tested differences in cortical thickness across the whole brain. RESULTS Significant cortical thinning was identified in the medicated patient group relative to the control group in prefrontal (mean reduction [MR], 0.27 mm; P < .001), temporal (MR, 0.34 mm; P = .02), parietal (MR, 0.21 mm; P = .001), and occipital (MR, 0.24 mm; P = .001

  5. 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

  6. 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

  7. Paranoid Personality Masking an Atypical Case of Frontotemporal Dementia

    PubMed Central

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

    2015-01-01

    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. PMID:25780487

  8. 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. PMID:25780487

  9. 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

  10. Endocervical Atypical Polypoid Adenomyoma.

    PubMed

    Protopapas, Athanasios; Sotiropoulou, Maria; Athanasiou, Stavros; Loutradis, Dimitrios

    2016-01-01

    Atypical polypoid adenomyomas (APAMs) are rare uterine tumors that occur predominantly in premenopausal women, with less than 250 cases reported so far, worldwide. They may recur after treatment, and they may coexist with, or precede development of an endometrial adenocarcinoma. For this reason cases managed with conservative surgery or medical therapies require long-term follow-up. We report the case of a 41 years old nulliparous patient who during a diagnostic hysteroscopy was found with an endocervical atypical polypoid adenomyoma (APAM). The patient was desirous of a pregnancy, reported menometrorrhagia, and had a coexistent 5 cm, grade 2, submucous myoma, 3 endometrial polyps, and diffuse adenomyosis. She was treated with hysteroscopic resection of the APAM and polyps, plus laparoscopic myomectomy and wedge resection of adenomyosis. She is on an IVF list and after 4 months she is symptoms-free. PMID:26304721

  11. 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

  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. 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

  14. Glutamate Levels in the Associative Striatum Before and After 4 Weeks of Antipsychotic Treatment in First-Episode Psychosis

    PubMed Central

    de la Fuente-Sandoval, Camilo; León-Ortiz, Pablo; Azcárraga, Mariana; Stephano, Sylvana; Favila, Rafael; Díaz-Galvis, Leonardo; Alvarado-Alanis, Patricia; Ramírez-Bermúdez, Jesús; Graff-Guerrero, Ariel

    2013-01-01

    IMPORTANCE Increased glutamate levels in the right associative striatum have been described in patients during a first episode of psychosis. Whether this increase would persist after effective antipsychotic treatment is unknown. OBJECTIVES To compare the glutamate levels in antipsychotic-naive patients with first-episode psychosis in the right associative striatum and right cerebellar cortex using proton magnetic resonance spectroscopy before and 4 weeks after antipsychotic treatment and to compare these results with normative data from sex-matched healthy control subjects. DESIGN, SETTING, AND PARTICIPANTS Before-after trial in an inpatient psychiatric research unit among 24 antipsychotic-naive patients with first-episode psychosis and 18 healthy controls matched for age, sex, handedness, and cigarette smoking. INTERVENTIONS Participants underwent 2 proton magnetic resonance spectroscopy studies: patients were imaged at baseline and after 4 weeks of antipsychotic treatment, while controls were imaged at baseline and at 4 weeks after the baseline measurement. Patients were treated with oral risperidone (open label) for 4 weeks with dosages that were titrated on the basis of clinical judgment. MAIN OUTCOMES AND MEASURES Glutamate levels were estimated using LCModel (version 6.2-1T) and were corrected for the cerebrospinal fluid proportion within the voxel. RESULTS Patients with first-episode psychosis had higher levels of glutamate in the associative striatum and the cerebellum during the antipsychotic-naive condition compared with controls. After clinically effective antipsychotic treatment, glutamate levels significantly decreased in the associative striatum, with no significant change in the cerebellum. No differences in glutamate levels were observed between groups at 4 weeks. CONCLUSIONS AND RELEVANCE Increased glutamate levels observed at baseline in patients with first-episode psychosis normalized after 4 weeks of clinically effective antipsychotic treatment

  15. Genetic Variations of PIP4K2A Confer Vulnerability to Poor Antipsychotic Response in Severely Ill Schizophrenia Patients

    PubMed Central

    Kaur, Harpreet; Jajodia, Ajay; Grover, Sandeep; Baghel, Ruchi; Gupta, Meenal; Jain, Sanjeev; Kukreti, Ritushree

    2014-01-01

    Literature suggests that disease severity and neurotransmitter signaling pathway genes can accurately identify antipsychotic response in schizophrenia patients. However, putative role of signaling molecules has not been tested in schizophrenia patients based on severity of illness, despite its biological plausibility. In the present study we investigated the possible association of polymorphisms from five candidate genes RGS4, SLC6A3, PIP4K2A, BDNF, PI4KA with response to antipsychotic in variably ill schizophrenia patients. Thus in present study, a total 53 SNPs on the basis of previous reports and functional grounds were examined for their association with antipsychotic response in 423 schizophrenia patients segregated into low and high severity groups. Additionally, haplotype, diplotype, multivariate logistic regression and multifactor-dimensionality reduction (MDR) analyses were performed. Furthermore, observed associations were investigated in atypical monotherapy (n = 355) and risperidone (n = 260) treated subgroups. All associations were estimated as odds ratio (OR) and 95% confidence interval (CI) and test for multiple corrections was applied. Single locus analysis showed significant association of nine variants from SLC6A3, PIP4K2A and BDNF genes with incomplete antipsychotic response in schizophrenia patients with high severity. We identified significant association of six marker diplotype ATTGCT/ATTGCT (rs746203-rs10828317-rs7094131-rs2296624-rs11013052-rs1409396) of PIP4K2A gene in incomplete responders (corrected p-value = 0.001; adjusted-OR = 3.19, 95%-CI = 1.46–6.98) with high severity. These associations were further observed in atypical monotherapy and risperidone sub-groups. MDR approach identified gene-gene interaction among BDNF_rs7103411-BDNF_rs1491851-SLC6A3_rs40184 in severely ill incomplete responders (OR = 7.91, 95%-CI = 4.08–15.36). While RGS4_rs2842026-SLC6A3_rs2975226 interacted synergistically in

  16. Placebo Response in Antipsychotic Clinical Trials: A Meta-Analysis

    PubMed Central

    Rutherford, Bret R; Pott, Emily; Tandler, Jane M.; Wall, Melanie M.; Roose, Steven P.; Lieberman, Jeffrey A.

    2014-01-01

    severity, and with increasing study duration. Medication treatment in comparator studies was associated with significantly more improvement than medication treatment in placebo-controlled trials (t = 2.73, df 93, p = 0.008). Conclusions and Relevance The average treatment change associated with placebo treatment in antipsychotic trials rose since 1960, while the change associated with medication treatment decreased. RCT changes leading to increased baseline score inflation, enrolling less severely ill subjects, and inducing higher patient expectancy may be responsible. PMID:25321611

  17. Long-term depot antipsychotics. A risk-benefit assessment.

    PubMed

    Barnes, T R; Curson, D A

    1994-06-01

    The main advantage of depot antipsychotic medication is that it overcomes the problem of covert noncompliance. Patients receiving depot treatment who refuse their injection or fail to receive it for any other reason can be immediately identified and appropriate action taken. In the context of a carefully monitored management programme, depot treatment can have a major impact on compliance and, consequently, the risk of relapse and hospitalisation can be reduced. Another major advantage is that the considerable individual variation in bioavailability and metabolism with oral antipsychotic drugs is markedly reduced with depot treatment. A better correlation between the dose administered and the concentration of medication found in blood or plasma is achieved with depot treatment, and thus, the clinician has greater control over the amount of drug being delivered to the site of activity. A further benefit of depot treatment is the achievement of stable plasma concentrations over long periods, allowing injections to be given every few weeks. However, this also represents a potential disadvantage in that there is a lack of flexibility of administration. Should adverse effects develop, the drug cannot be rapidly withdrawn. Furthermore, adjustment to the optimal dose becomes a long term strategy. The controlled studies of low dose maintenance therapy with depot treatment suggest that it can take months or years for the consequences of dose reduction, in terms of increased risk of relapse, to become manifest. When weighing up the risks and benefits of long term antipsychotic treatment for the individual patient with schizophrenia, the clinician must take into account the nature, severity and frequency of past relapses, and the degree of distress and disability related to any adverse effects. However, the clinical decision to prescribe either a depot or an oral antipsychotic for maintenance treatment will probably rest largely on an assessment of the risk of poor compliance

  18. Atypical odontalgia--an update.

    PubMed

    Patel, Seena B; Boros, Audrey L; Kumar, Satish K S

    2012-09-01

    Atypical odontalgia is a commonly misdiagnosed condition that frequently leads to unnecessary dental treatments such as extraction and endodontic therapy. These treatments often worsen the pain. Despite greater recognition and understanding of this condition, proper diagnosis and treatment remains a challenge. It is believed that atypical odontalgia is a neuropathic condition. This article updates the current understanding of the etiology and pathophysiology of atypical odontalgia, and provides appropriate diagnostic and management approaches for this condition. PMID:23097829

  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. The Pharmacogenetics of Symptom Response to Antipsychotic Drugs

    PubMed Central

    2012-01-01

    Antipsychotic drugs are limited in their efficacy by the relatively poor response of negative and cognitive symptoms of schizophrenia as well as by the substantial variability in response between patients. Pharmacogenetic studies have sought to identify the genetic factors that underlie the individual variability in response to treatment, with a past emphasis on dopamine and serotonin receptors as candidate genes. Few studies have separated effects on positive and negative symptoms, despite the established differences in response to drug treatment between these syndromes. Where this has been done most findings are consistent with the conclusion that dopamine receptor polymorphisms relate to positive symptom response, while negative symptom improvement is influenced by polymorphisms of genes involved in 5-HT neurotransmission. A wide range of polymorphisms in other candidate genes have been investigated, with some positive findings in those genes associated with glutamatergic transmission and/or risk factors for schizophrenia. However, there remains a lack of good replicated findings; furthermore there is little evidence to support drug-specific genetic associations with treatment response. While most past studies focused on single candidate genes, technology now permits genome-wide association studies with response to antipsychotics. Although not without major limitations, these "hypothesis-free" approaches are beginning to identify further important risk factors for treatment response. Again there is little consistency between various studies, although some of the polymorphisms identified are in genes involved in neurodevelopment, which is increasingly being recognized as important in the pathophysiology of schizophrenia. PMID:22396678

  1. The pharmacogenetics of symptom response to antipsychotic drugs.

    PubMed

    Reynolds, Gavin P

    2012-03-01

    Antipsychotic drugs are limited in their efficacy by the relatively poor response of negative and cognitive symptoms of schizophrenia as well as by the substantial variability in response between patients. Pharmacogenetic studies have sought to identify the genetic factors that underlie the individual variability in response to treatment, with a past emphasis on dopamine and serotonin receptors as candidate genes. Few studies have separated effects on positive and negative symptoms, despite the established differences in response to drug treatment between these syndromes. Where this has been done most findings are consistent with the conclusion that dopamine receptor polymorphisms relate to positive symptom response, while negative symptom improvement is influenced by polymorphisms of genes involved in 5-HT neurotransmission. A wide range of polymorphisms in other candidate genes have been investigated, with some positive findings in those genes associated with glutamatergic transmission and/or risk factors for schizophrenia. However, there remains a lack of good replicated findings; furthermore there is little evidence to support drug-specific genetic associations with treatment response. While most past studies focused on single candidate genes, technology now permits genome-wide association studies with response to antipsychotics. Although not without major limitations, these "hypothesis-free" approaches are beginning to identify further important risk factors for treatment response. Again there is little consistency between various studies, although some of the polymorphisms identified are in genes involved in neurodevelopment, which is increasingly being recognized as important in the pathophysiology of schizophrenia. PMID:22396678

  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. Testing atypical depression definitions.

    PubMed

    Benazzi, Franco

    2005-01-01

    The evidence supporting the DSM-IV definition of atypical depression (AD) is weak. This study aimed to test different definitions of AD. Major depressive disorder (MDD) patients (N = 254) and bipolar-II (BP-II) outpatients (N = 348) were interviewed consecutively, during major depressive episodes, with the Structured Clinical Interview for DSM-IV. DSM-IV criteria for AD were followed. AD validators were female gender, young onset, BP-II, axis I comorbidity, bipolar family history. Frequency of DSM-IV AD was 43.0%. AD, versus non-AD, was significantly associated with all AD validators, apart from comorbidity when controlling for age and sex. Factor analysis of atypical symptoms found factor 1 including oversleeping, overeating and weight gain (leaden paralysis at trend correlation), and factor 2 including interpersonal sensitivity, mood reactivity, and leaden paralysis. Multiple logistic regression of factor 1 versus AD validators found significant associations with several validators (including bipolar family history), whereas factor 2 had no significant associations. Findings may support a new definition of AD based on the state-dependent features oversleeping and overeating (plus perhaps leaden paralysis) versus the current AD definition based on a combination of state and trait features. Pharmacological studies are required to support any new definition of AD, as the current concept of AD is based on different response to TCA antidepressants versus non-AD. PMID:16175877

  4. Review of antipsychotics in children and adolescents.

    PubMed

    Kapetanovic, Suad; Simpson, George M

    2006-10-01

    The use of antipsychotics in children and adolescents in the clinical setting is increasing. This article reviews 77 clinical trials published in the last 10 years, investigating their efficacy, effectiveness, safety and pharmacokinetic data in paediatric populations. The diagnostic categories in which the antipsychotics are commonly used (schizophrenia, pervasive developmental disorders, Tourette's disorder, mental retardation/subaverage intelligence, mood disorders and disruptive behaviour disorders) were used in order to review the evidence and effectiveness. All randomised, double-blind, placebo-controlled trials from the past decade are also summarised. This review refers to recent relevant practice parameters, guidelines and reviews throughout the text. Consistent with previous reviews, it is concluded that the recent trend of increased use of antipsychotics in children and adolescents is not adequately supported by evidence. Specific suggestions have been provided on how to incorporate the existing evidence base into clinical decision making. The review ends with the authors' opinion on the clinical and research implications for the field and future directions. PMID:17020414

  5. 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

  6. Atypical teratoid rhabdoid tumor: improved long-term survival with an intensive multimodal therapy and delayed radiotherapy. The Medical University of Vienna Experience 1992–2012

    PubMed Central

    Slavc, Irene; Chocholous, Monika; Leiss, Ulrike; Haberler, Christine; Peyrl, Andreas; Azizi, Amedeo A; Dieckmann, Karin; Woehrer, Adelheid; Peters, Christina; Widhalm, Georg; Dorfer, Christian; Czech, Thomas

    2014-01-01

    Atypical teratoid rhabdoid tumors (ATRTs) are recently defined highly aggressive embryonal central nervous system tumors with a poor prognosis and no definitive guidelines for treatment. We report on the importance of an initial correct diagnosis and disease-specific therapy on outcome in 22 consecutive patients and propose a new treatment strategy. From 1992 to 2012, nine patients initially diagnosed correctly as ATRT (cohort A, median age 24 months) were treated according to an intensive multimodal regimen (MUV-ATRT) consisting of three 9-week courses of a dose-dense regimen including doxorubicin, cyclophosphamide, vincristine, ifosfamide, cisplatin, etoposide, and methotrexate augmented with intrathecal therapy, followed by high-dose chemotherapy (HDCT) and completed with local radiotherapy. Thirteen patients were treated differently (cohort B, median age 30 months) most of whom according to protocols in use for their respective diagnoses. As of July 2013, 5-year overall survival (OS) and event-free survival (EFS) for all 22 consecutive patients was 56.3 ± 11.3% and 52.9 ± 11.0%, respectively. For MUV-ATRT regimen-treated patients (cohort A) 5-year OS was 100% and EFS was 88.9 ± 10.5%. For patients treated differently (cohort B) 5-year OS and EFS were 28.8 ± 13.1%. All nine MUV-ATRT regimen-treated patients are alive for a median of 76 months (range: 16–197), eight in first complete remission. Our results compare favorably to previously published data. The drug combination and sequence used in the proposed MUV-ATRT regimen appear to be efficacious in preventing early relapses also in young children with M1–M3 stage disease allowing postponement of radiotherapy until after HDCT. PMID:24402832

  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. Bioenergetic disruption of human micro-vascular endothelial cells by antipsychotics.

    PubMed

    Elmorsy, Ekramy; Smith, Paul A

    2015-05-01

    Antipsychotics (APs) are widely used medications, however these are not without side effects such as disruption of blood brain barrier function (BBB). To investigate this further we have studied the chronic effects of the typical APs, chlorpromazine (CPZ) and haloperidol (HAL) and the atypical APs, risperidone (RIS) and clozapine (CLZ), on the bioenergetics of human micro-vascular endothelial cells (HBVECs) of the BBB. Alamar blue (AB) and ATP assays showed that these APs impair bioenergenesis in HBVECs in a concentration and time dependent manner. However since these effects were incomplete they suggest a population of cell bioenergetically heterogeneous, an idea supported by the bistable nature by which APs affected the mitochondrial transmembrane potential. CPZ, HAL and CLZ inhibited the activity of mitochondrial complexes I and III. Our data demonstrates that at therapeutic concentrations, APs can impair the bioenergetic status of HBVECs, an action that help explains the adverse side effects of these drugs when used clinically. PMID:25824037

  9. [Pros and cons of antipsychotics in children and adolescents].

    PubMed

    Schmeck, Klaus

    2015-08-01

    In the last decade the indication of antipsychotics has been expanded from the treatment of psychoses to the treatment of impulsive-aggressive behaviors in mentally retarded children and adolescents with conduct disorder or autism spectrum disorders. As a consequence the use of antipsychotics in children and adolescents has increased worldwide. This increase of prescriptions is under critical discussion. In this paper the indication and the potential side-effects of antipsychotics in children and adolescents are described. The risks of antipsychotic medication are contrasted with the potential benefits to arrive at rational treatment recommendations. PMID:26242421

  10. A bibliometric study of scientific research conducted on second-generation antipsychotic drugs in Singapore

    PubMed Central

    López-Muñoz, Francisco; Sim, Kang; Shen, Winston Wu; Huelves, Lorena; Moreno, Raquel; Molina, Juan de Dios; Rubio, Gabriel; Noriega, Concha; Ángel Miguel, Pérez-Nieto; Álamo, Cecilio

    2014-01-01

    INTRODUCTION A bibliometric study was carried out to ascertain the volume and impact of scientific literature published on second-generation antipsychotic drugs (SGAs) in Singapore from 1997 to 2011. METHODS A search of the EMBASE and MEDLINE databases was performed to identify articles originating from Singapore that included the descriptors ‘atypic* antipsychotic*’, ‘second-generation antipsychotic*’, ‘clozapine’, ‘risperidone’, ‘olanzapine’, ‘ziprasidone’, ‘quetiapine’, ‘sertindole’, ‘aripiprazole’, ‘paliperidone’, ‘amisulpride’, ‘zotepine’, ‘asenapine’, ‘iloperidone’, ‘lurasidone’, ‘perospirone’ and ‘blonanserin’ in the article titles. Certain bibliometric indicators of production and dispersion (e.g. Price's Law on the increase of scientific literature, and Bradford's Law) were applied, and the participation index of various countries was calculated. The bibliometric data was also correlated with some social and health data from Singapore, such as the total per capita expenditure on health and gross domestic expenditure on research and development. RESULTS From 1997 to 2011, a total of 51 articles on SGAs in Singapore were published. Our results suggested non-fulfilment of Price's Law (r = 0.0648 after exponential adjustment vs. r = 0.2140 after linear adjustment). The most widely studied drugs were clozapine (21 articles), risperidone (16 articles) and olanzapine (8 articles). Division into Bradford zones yielded a nucleus occupied by the Journal of Clinical Psychopharmacology (6 articles) and the Singapore Medical Journal (4 articles). The analysed material was published in a total of 30 journals, with the majority from six journals. Four of these six journals have an impact factor greater than 2. CONCLUSION Publications on SGAs in Singapore are still too few to confirm an exponential growth of scientific literature. PMID:24452974

  11. Inflammatory Markers in Schizophrenia: Comparing Antipsychotic Effects in Phase 1 of the CATIE Schizophrenia Trial

    PubMed Central

    Meyer, Jonathan M.; McEvoy, Joseph P.; Davis, Vicki G.; Goff, Donald C.; Nasrallah, Henry A.; Davis, Sonia M.; Hsiao, John K.; Swartz, Marvin S.; Stroup, T. Scott; Lieberman, Jeffrey A.

    2013-01-01

    Background C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin are systemic inflammatory markers (IM) that positively correlate with cardiovascular (CV) risk. Despite the known CV effects of atypical antipsychotics, there is limited prospective data on IM changes during treatment. Methods IM outcomes were compared between antipsychotic treatment groups in the CATIE Schizophrenia Trial phase 1 using subjects with laboratory assessments at baseline and 3 months (n=789). Results There were significant treatment differences in CRP, E-selectin and ICAM-1 at 3 months, with a differential impact of baseline values on the CRP and ICAM-1 results. In overall comparisons, quetiapine and olanzapine had the highest median levels for CRP, and olanzapine for E-selectin and ICAM-1. Olanzapine was significantly different after baseline adjustment than perphenazine (p=0.001) for E-selectin, and, in those with low baseline CRP (< 1 mg/L), olanzapine was significantly different than perphenazine (p<0.001), risperidone (p<0.001) and ziprasidone (p=0.002) for CRP. Perphenazine had the lowest 3-month ICAM-1 levels in subjects with baseline ICAM-1 above the median, but the differences were not statistically significant vs. olanzapine (p=0.010), quetiapine (p=0.010) and risperidone (p=0.006) after controlling for multiple comparisons. The 18-month repeated measures CRP analysis confirmed the significantly higher values for olanzapine in those with low baseline CRP. Conclusions This analysis provides further evidence for differential antipsychotic metabolic liabilities as measured by changes in systemic inflammation. CRP may emerge as a useful target for CV risk outcomes in schizophrenia patients. PMID:19640511

  12. Atypical histiocytosis in the lung

    PubMed Central

    Cao, Weijun; Zhang, Rongxuan; Zhou, Ying; Xu, Jinfu; Garfield, David H.

    2013-01-01

    Objective To report a rare case of atypical histiocytic tumor of the lung with a review of literature. Methods The clinical materials were noted. Literature related to this condition from the past 50 years was reviewed from the group of histiocytic tumors. Results and conclusions Clinical manifestations were non-specific. The imaging characteristics of our case were infiltrative lesions with multiple cysts in both lungs. Pathology showed nodular proliferation of atypical cells. Immunohistochemistry suggested a histiocytic origin of the infiltrating atypical cells. Because the pathological findings did not fall into any particular category of typical histiocytic tumors, the final diagnosis was atypical histiocytic tumor. The presentation of atypical histiocytic tumor of the lungs, only, with infiltrative lesions and multiple air cysts seems very rare, with pathological examination being “gold standard” for the diagnosis. PMID:23991320

  13. Treatment with cimetidine of atypical fasciitis panniculitis syndrome.

    PubMed Central

    Naschitz, J E; Yeshurun, D; Rosner, I; Abrahamson, J E; Misselevitch, I; Boss, J H

    1990-01-01

    Three patients presented with septal fasciitis and panniculitis, associated with clinical and laboratory features which precluded straight-forward classification into eosinophilic fasciitis, localised scleroderma, or lupus erythematosus profundus. Treatment with cimetidine caused the remission of cutaneous manifestations and the extracutaneous abnormalities, such as nailfold capillary disturbances and the presence of antithyroid antibodies, improved. It is concluded that features of eosinophilic fasciitis or localised scleroderma and certain additional atypical elements should be categorised as atypical fasciitis-panniculitis syndrome. Images PMID:2241270

  14. 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

  15. 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

  16. 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

  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. Atypical odontalgia: a review.

    PubMed

    Koratkar, Harish; Pedersen, Jerome

    2008-01-01

    Since persistent and chronic pain is more common in the head and neck region than in any other part of the body, dentists are more likely to encounter these rather complex cases in their practices. This article is a review and update on atypical odontalgia (AO). AO is a persistent neuropathic pain which may be initiated after deafferentiation of trigeminal nerve fibers following root canal treatment, apicectomy, or tooth extraction, or it may be of idiopathic origin. Details concerning its characteristics, pathophysiology, diagnostic criteria, differential diagnosis, and treatment are made. The aim of this article is to help the clinician with the diagnosis and management of AO. The prognosis for AO is most often only fair, and the administration of tricyclic antidepressants often resolves symptoms. Invasive and irreversible treatment attempts are not recommended. PMID:18363287

  19. Dermatofibroma: Atypical Presentations

    PubMed Central

    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

  20. 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

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

    PubMed Central

    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

  2. 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

  3. Atypical ductal hyperplasia: interobserver and intraobserver variability.

    PubMed

    Jain, Rohit K; Mehta, Rutika; Dimitrov, Rosen; Larsson, Lisbeth G; Musto, Paul M; Hodges, Kurt B; Ulbright, Thomas M; Hattab, Eyas M; Agaram, Narasimhan; Idrees, Muhammad T; Badve, Sunil

    2011-07-01

    Interobserver reproducibility in the diagnosis of benign intraductal proliferative lesions has been poor. The aims of the study were to investigate the inter- and intraobserver variability and the impact of the addition of an immunostain for high- and low-molecular weight keratins on the variability. Nine pathologists reviewed 81 cases of breast proliferative lesions in three stages and assigned each of the lesions to one of the following three diagnoses: usual ductal hyperplasia, atypical ductal hyperplasia and ductal carcinoma in situ. Hematoxylin and eosin slides and corresponding slides stained with ADH-5 cocktail (cytokeratins (CK) 5, 14. 7, 18 and p63) by immunohistochemistry were evaluated. Concordance was evaluated at each stage of the study. The interobserver agreement among the nine pathologists for diagnosing the 81 proliferative breast lesions was fair (κ-value=0.34). The intraobserver κ-value ranged from 0.56 to 0.88 (moderate to strong). Complete agreement among nine pathologists was achieved in only nine (11%) cases, at least eight agreed in 20 (25%) cases and seven or more agreed in 38 (47%) cases. Following immunohistochemical stain, a significant improvement in the interobserver concordance (overall κ-value=0.50) was observed (P=0.015). There was a significant reduction in the total number of atypical ductal hyperplasia diagnosis made by nine pathologists after the use of ADH-5 immunostain. Atypical ductal hyperplasia still remains a diagnostic dilemma with wide variation in both inter- and intraobserver reproducibility among pathologists. The addition of an immunohistochemical stain led to a significant improvement in the concordance rate. More importantly, there was an 8% decrease in the number of lesions classified as atypical ductal hyperplasia in favor of usual hyperplasia; in clinical practice, this could lead to a decrease in the number of surgeries carried out for intraductal proliferative lesions. PMID:21532546

  4. QTc prolongation with antipsychotics: is routine ECG monitoring recommended?

    PubMed

    Shah, Asim A; Aftab, Awais; Coverdale, John

    2014-05-01

    Whether or not QTc interval should be routinely monitored in patients receiving antipsychotics is a controversial issue, given logistic and fiscal dilemmas. There is a link between antipsychotic medications and prolongation of QTc interval, which is associated with an increased risk of torsade de pointes (TdP). Our goal is to provide clinically practical guidelines for monitoring QTc intervals in patients being treated with antipsychotics. We provide an overview of the pathophysiology of the QT interval, its relationship to TdP, and a discussion of the QT prolonging effects of antipsychotics. A literature search for articles relevant to the QTc prolonging effects of antipsychotics and TdP was conducted utilizing the databases PubMed and Embase with various combinations of search words. The overall risk of TdP and sudden death associated with antipsychotics has been observed to be low. Medications, genetics, gender, cardiovascular status, pathological conditions, and electrolyte disturbances have been found to be related to prolongation of the QTc interval. We conclude that, while electrocardiogram (ECG) monitoring is useful when administering antipsychotic medications in the presence of co-existing risk factors, it is not mandatory to perform ECG monitoring as a prerequisite in the absence of cardiac risk factors. An ECG should be performed if the initial evaluation suggests increased cardiac risk or if the antipsychotic to be prescribed has been established to have an increased risk of TdP and sudden death. PMID:24847993

  5. Can antipsychotic treatment contribute to drug addiction in schizophrenia?

    PubMed

    Samaha, Anne-Noël

    2014-07-01

    Individuals with schizophrenia are at very high risk for drug abuse and addiction. Patients with a coexisting drug problem fare worse than patients who do not use drugs, and are also more difficult to treat. Current hypotheses cannot adequately account for why patients with schizophrenia so often have a co-morbid drug problem. I present here a complementary hypothesis based on evidence showing that chronic exposure to antipsychotic medications can induce supersensitivity within the brain's dopamine systems, and that this in turn can enhance the rewarding and incentive motivational effects of drugs and reward cues. At the neurobiological level, these effects of antipsychotics are potentially linked to antipsychotic-induced increases in the striatal levels of dopamine D2 receptors and D2 receptors in a high-affinity state for dopamine, particularly at postsynaptic sites. Antipsychotic-induced dopamine supersensitivity and enhanced reward function are not inevitable consequences of prolonged antipsychotic treatment. At least two parameters appear to promote these effects; the use of antipsychotics of the typical class, and continuous rather than intermittent antipsychotic exposure, such that silencing of dopaminergic neurotransmission via D2/3 receptors is unremitting. Thus, by inducing forms of neural plasticity that facilitate the ability of drugs and reward cues to gain control over behaviour, some currently used treatment strategies with typical antipsychotics might contribute to compulsive drug seeking and drug taking behaviours in vulnerable schizophrenia patients. PMID:23793001

  6. Depot antipsychotic drugs. Place in therapy.

    PubMed

    Davis, J M; Matalon, L; Watanabe, M D; Blake, L; Metalon L [corrected to Matalon, L

    1994-05-01

    The pharmacokinetics of depot antipsychotic medications are such that an intramuscular injection given at intervals of from 1 to 4 weeks will produce adequate plasma concentrations that are sufficient to prevent relapse over the dosage interval. Such medication is useful in patients who do not reliably take their oral medication. The pharmacokinetics and clinical actions of various depot formulations of antipsychotic drugs have been extensively studied. Unfortunately, patients who do not reliably take their oral medications are unlikely to volunteer for controlled studies. This is because the same factors that influence a patient to not cooperate with the physician in taking the medication as prescribed will also interfere with their willingness to volunteer for research protocols. Thus, evidence from blinded controlled trials may not necessarily reflect the actual patient population at risk. We feel that particularly important evidence of efficacy of depot vs oral medication comes from mirror-image studies. In these trials, the number of hospitalisations after initiation of depot medication is compared with that observed when the patient was solely taking oral medication. Studies of this type show that depot medication substantially reduces the rate of relapse. There is considerable evidence about how long depot medications should be used. For many patients, depot medication to prevent relapse in schizophrenia should be used for the life of the patient. As the conventional antipsychotic agents are replaced by a new generation of agents, the need for depot formulations will continue, and the knowledge gained about the current formulations should transfer to future generations of drugs. PMID:7520856

  7. 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. PMID:18615139

  8. 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

  9. [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. PMID:25433773

  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. 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. PMID:26421389

  12. Interactions between antiepileptic and antipsychotic drugs.

    PubMed

    Besag, Frank M C; Berry, David

    2006-01-01

    Antiepileptic and antipsychotic drugs are often prescribed together. Interactions between the drugs may affect both efficacy and toxicity. This is a review of human clinical data on the interactions between the antiepileptic drugs carbamazepine, valproic acid (sodium valproate), vigabatrin, lamotrigine, gabapentin, topiramate, tiagabine, oxcarbazepine, levetiracetam, pregabalin, felbamate, zonisamide, phenobarbital and phenytoin with the antipsychotic drugs risperidone, olanzapine, quetiapine, clozapine, amisulpride, sulpiride, ziprasidone, aripiprazole, haloperidol and chlorpromazine; the limited information on interactions between antiepileptic drugs and zuclopenthixol, periciazine, fluphenazine, flupenthixol and pimozide is also presented. Many of the interactions depend on the induction or inhibition of the cytochrome P450 isoenzymes, but other important mechanisms involve the uridine diphosphate glucuronosyltransferase isoenzymes and protein binding. There is some evidence for the following effects. Carbamazepine decreases the plasma concentrations of both risperidone and its active metabolite. It also decreases concentrations of olanzapine, clozapine, ziprasidone, haloperidol, zuclopenthixol, flupenthixol and probably chlorpromazine and fluphenazine. Quetiapine increases the ratio of carbamazepine epoxide to carbamazepine and this may lead to toxicity. The data on valproic acid are conflicting; it may either increase or decrease clozapine concentrations, and it appears to decrease aripiprazole concentrations. Chlorpromazine possibly increases valproic acid concentrations. Lamotrigine possibly increases clozapine concentrations. Phenobarbital decreases clozapine, haloperidol and chlorpromazine concentrations. Phenytoin decreases quetiapine, clozapine, haloperidol and possibly chlorpromazine concentrations. There are major gaps in the data. In many cases there are no published clinical data on interactions that would be predicted on theoretical grounds. PMID

  13. 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. PMID:24897292

  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. 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

  16. Effect of second-generation antipsychotics on cognition: current issues and future challenges

    PubMed Central

    Hill, S Kristian; Bishop, Jeffrey R; Palumbo, Donna; Sweeney, John A.

    2010-01-01

    Generalized cognitive impairments are stable deficits linked to schizophrenia and key factors associated with functional disability in the disorder. Preclinical data suggest that second-generation antipsychotics could potentially reduce cognitive impairments; however, recent large clinical trials indicate only modest cognitive benefits relative to first-generation antipsychotics. This might reflect a limited drug effect in humans, a differential drug effect due to brain alterations associated with schizophrenia, or limited sensitivity of the neuropsychological tests for evaluating cognitive outcomes. New adjunctive procognitive drugs may be needed to achieve robust cognitive and functional improvement. Drug discovery may benefit from greater utilization of translational neurocognitive biomarkers to bridge preclinical and clinical proof-of-concept studies, to optimize assay sensitivity, enhance cost efficiency, and speed progress in drug development. PMID:20021320

  17. The effect of antidepressants and antipsychotics on weight gain in children and adolescents.

    PubMed

    Reekie, J; Hosking, S P M; Prakash, C; Kao, K-T; Juonala, M; Sabin, M A

    2015-07-01

    Psychiatric illness in the paediatric population is increasing and the weight effect of medications for these problems is often unclear. A comprehensive literature search was undertaken to identify studies reporting weight in relation to antipsychotic and antidepressant use in children and adolescents. From 636 articles, 42 were selected for review. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) do not cause weight gain and may lead to improvements in weight status over the short, but not, long term. Antipsychotics were generally associated with weight gain. In drug comparison studies, risperidone had a larger weight gain effect than lithium, divalproex sodium and pimozide. Studies assessing the weight-protective effects of augmentation therapy with metformin or topiramate show less weight gain with addition of these agents. In conclusion, prescribing of SSRIs and SNRIs may be associated with improvements in weight status in children and adolescents but trials assessing their use in obesity, outside of established psychiatric illness, are limited and still experimental. Youth prescribed antipsychotic medication should be monitored for exaggerated weight gain and in those where obesity is a pre-existing concern agents other than olanzapine, clozapine and risperidone may be advantageous. PMID:26016407

  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. Concomitant use of two or more antipsychotic drugs is common in Sweden

    PubMed Central

    Bergendal, Annica; Schiöler, Helena; Wettermark, Björn

    2015-01-01

    Objectives: To assess the prevalence of concomitant use of two or more antipsychotic drugs and other psychotropic drugs in the Swedish population. Methods: Data for this observational cohort study were collected from the Swedish Prescribed Drug Register including all dispensed drugs to the entire Swedish population (9.4 million inhabitants). We identified all individuals with at least one dispensed prescription of antipsychotic drug during January to June 2008. After 12 months, a second exposure period was chosen. Individuals who were dispensed two or more antipsychotic drugs in both periods were considered long-time users of antipsychotic polypharmacy. Results: In 2008, 1.5% of the Swedish population was dispensed antipsychotic drugs, the majority (75%) using only one antipsychotic drug. Out of individuals who were dispensed 2 or more antipsychotic drugs during the first period, 62% also was also dispensed at least 2 antipsychotic drugs during the second period. A total of 665 different unique combinations were used in 2008. Individuals prescribed two or more antipsychotic drugs during both periods were more often dispensed anxiolytics and sedatives than those who were dispensed only one antipsychotic drug. Elderly were dispensed antipsychotic drugs much more often than younger persons. Conclusions: In Sweden, 25% of patients dispensed antipsychotic drugs receive a combination of two or more antipsychotic drugs. Individuals who are dispensed antipsychotic polypharmacy are more often dispensed anxiolytics and sedatives than those prescribed only one antipsychotic drug. Long-term observational studies are needed to assess the efficacy and safety of such combinations. PMID:26301078

  20. Identification of atypical flight patterns

    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 (Inventor)

    2005-01-01

    Method and system for analyzing aircraft data, including multiple selected flight parameters for a selected phase of a selected flight, and for determining when the selected phase of the selected flight is atypical, when compared with corresponding data for the same phase for other similar flights. A flight signature is computed using continuous-valued and discrete-valued flight parameters for the selected flight parameters and is optionally compared with a statistical distribution of other observed flight signatures, yielding atypicality scores for the same phase for other similar flights. A cluster analysis is optionally applied to the flight signatures to define an optimal collection of clusters. A level of atypicality for a selected flight is estimated, based upon an index associated with the cluster analysis.

  1. Prevalence and correlates of antipsychotic polypharmacy in children and adolescents receiving antipsychotic treatment.

    PubMed

    Toteja, Nitin; Gallego, Juan A; Saito, Ema; Gerhard, Tobias; Winterstein, Almut; Olfson, Mark; Correll, Christoph U

    2014-07-01

    Antipsychotic polypharmacy (APP), which is common in adults with psychotic disorders, is of unproven efficacy and raises safety concerns. Although youth are increasingly prescribed antipsychotics, little is known about APP in this population. We performed a systematic PubMed search (last update 26 January 2013) of studies reporting the prevalence of APP in antipsychotic-treated youth. Summary statistics and statistical tests were calculated at the study level and not weighted by sample size. Fifteen studies (n = 58 041, range 68-23 183) reported on APP in youth [mean age = 13.4 ± 1.7 yr, 67.1 ± 10.2% male, 77.9 ± 27.4% treated with second-generation antipsychotics (SGAs)]. Data collected in these studies covered 1993-2008. The most common diagnoses were attention-deficit hyperactivity disorder (ADHD; 39.9 ± 23.5%) and conduct disorder/oppositional defiant disorder (CD/ODD; 33.6 ± 24.8). In studies including predominantly children (mean age = <13 yr, N = 5), the most common diagnosis were ADHD (50.6 ± 25.4%) and CD/ODD (39.5 ± 27.5%); while in studies with predominantly adolescents (mean age = ⩾13 yr, N = 7) the most common diagnoses were schizophrenia-spectrum disorders (28.6 ± 23.8%), anxiety disorders (26.9 ± 14.9%) and bipolar-spectrum disorders (26.6 ± 7.0%), followed closely by CD/ODD (25.8 ± 17.7). The prevalence of APP among antipsychotic-treated youth was 9.6 ± 7.2% (5.9 ± 4.5% in child studies, 12.0 ± 7.9% in adolescent studies, p = 0.15). Higher prevalence of APP was correlated with a bipolar disorder or schizophrenia diagnosis (p = 0.019) and APP involving SGA+SGA combinations (p = 0.0027). No correlation was found with APP definition [⩾1 d (N = 10) vs. >30-⩾90 d (N = 5), p = 0.88]. Despite lacking safety and efficacy data, APP in youth is not uncommon, even in samples predominantly consisting of non-psychotic patients. The duration, clinical motivations and effectiveness of this practice require further study. PMID:23673334

  2. [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

  3. Atypical neurological manifestations of malaria

    PubMed Central

    Singla, Neeraj; Gupta, Monica; Singh, Ram; Kumar, Ashwani

    2014-01-01

    Malaria is known as a great mimic. It can manifest subtly or abruptly, typically or atypically. This aspect of the disease can frequently mislead physicians. We present two patients of malaria with atypical neurological manifestations. The first patient of Plasmodium falciparum malaria presented with fever and altered sensorium; MRI of the brain suggested cerebral venous thrombosis. The second patient of Plasmodium vivax presented with fever, double vision and right eye lateral rectus palsy due to unilateral sixth cranial nerve involvement. Both patients were managed with antimalarials and supportive medical management, and had uneventful recoveries. PMID:25150266

  4. Targeted pharmacogenetic analysis of antipsychotic response in the CATIE study

    PubMed Central

    Liu, Qian; Jamba, Maidar; Patrick, Calvin; Padmanabhan, Saranya; Brennan, Mark D

    2012-01-01

    Aim This study evaluated the impact of 6789 SNPs on treatment response to antipsychotics in Caucasian patients from the CATIE study. Materials & methods An Illumina (CA, USA) BeadChip was designed that targeted genes potentially impacting disease risk, disease presentation or antipsychotic response. SNPs tagged regions of linkage disequilibrium or functional variants not detectable using previous genotypes for CATIE. Change in Positive and Negative Syndrome scale total score was modeled using a mixed model repeated measures method that assumed a 30-day lag period. Genetic association analysis was performed using linear regression. Results Association analysis identified 20 SNPs with p-values of ≤5 × 10−4. Many of these are in genes previously implicated in schizophrenia and other neuropsychiatric diseases. Conclusion The targeted approach identified SNPs possibly influencing response to antipsychotic drugs in Caucasian patients suffering from schizophrenia. The findings support a biological link between disease risk and presentation and antipsychotic response. PMID:22920393

  5. 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

  6. C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications.

    PubMed

    Fernandes, B S; Steiner, J; Bernstein, H-G; Dodd, S; Pasco, J A; Dean, O M; Nardin, P; Gonçalves, C-A; Berk, M

    2016-04-01

    The inflammatory hypothesis of schizophrenia (SZ) posits that inflammatory processes and neural-immune interactions are involved in its pathogenesis, and may underpin some of its neurobiological correlates. SZ is the psychiatric disorder causing the most severe burden of illness, not just owing to its psychiatric impairment, but also owing to its significant medical comorbidity. C-reactive protein (CRP) is a commonly used biomarker of systemic inflammation worldwide. There are some conflicting results regarding the behaviour of CRP in SZ. The aims of this study were to verify whether peripheral CRP levels are indeed increased in SZ, whether different classes of antipsychotics divergently modulate CRP levels and whether its levels are correlated with positive and negative symptomatology. With that in mind, we performed a meta-analysis of all cross-sectional studies of serum and plasma CRP levels in SZ compared to healthy subjects. In addition, we evaluated longitudinal studies on CRP levels before and after antipsychotic use. Our meta-analyses of CRP in SZ included a total of 26 cross-sectional or longitudinal studies comprising 85 000 participants. CRP levels were moderately increased in persons with SZ regardless of the use of antipsychotics and did not change between the first episode of psychosis and with progression of SZ (g=0.66, 95% confidence interval (95% CI) 0.43 to 0.88, P<0.001, 24 between-group comparisons, n=82 962). The extent of the increase in peripheral CRP levels paralleled the increase in severity of positive symptoms, but was unrelated to the severity of negative symptoms. CRP levels were also aligned with an increased body mass index. Conversely, higher age correlated with a smaller difference in CRP levels between persons with SZ and controls. Furthermore, CRP levels did not increase after initiation of antipsychotic medication notwithstanding whether these were typical or atypical antipsychotics (g=0.01, 95% CI -0.20 to 0.22, P=0.803, 8

  7. 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

  8. 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

  9. Antipsychotic prescribing: Do conflict of interest policies make a difference?

    PubMed Central

    Anderson, Timothy S.; Huskamp, Haiden A.; Epstein, Andrew J.; Barry, Colleen L.; Men, Aiju; Berndt, Ernst R.; Horvitz-Lennon, Marcela; Normand, Sharon-Lise; Donohue, Julie M.

    2015-01-01

    Background Academic medical centers (AMCs) have increasingly adopted conflict of interest policies governing physician-industry relationships; it is unclear how policies impact prescribing. Objectives Determine whether nine American Association of Medical Colleges (AAMC)-recommended policies influence psychiatrists’ antipsychotic prescribing and compare prescribing between academic and non-academic psychiatrists. Research Design We measured number of prescriptions for 10 heavily-promoted and 9 newly-introduced/reformulated antipsychotics between 2008 and 2011 among 2,464 academic psychiatrists at 101 AMCs and 11,201 non-academic psychiatrists. We measured AMC compliance with 9 AAMC recommendations. Difference-in-difference analyses compared changes in antipsychotic prescribing between 2008 and 2011 among psychiatrists in AMCs compliant with ≥7/9 recommendations, those whose institutions had lesser compliance, and non-academic psychiatrists. Results Ten centers were AAMC-compliant in 2008, 30 attained compliance by 2011, and 61 were never compliant. Share of prescriptions for heavily promoted antipsychotics was stable and comparable between academic and non-academic psychiatrists (63.0-65.8% in 2008 and 62.7-64.4% in 2011). Psychiatrists in AAMC-compliant centers were slightly less likely to prescribe these antipsychotics compared to those in never compliant centers [Relative Odds Ratio (ROR), 0.95, 95% CI 0.94-0.97, <0.0001]. Share of prescriptions for new/reformulated antipsychotics grew from 5.3% in 2008 to 11.1% in 2011. Psychiatrists in AAMC-compliant centers actually increased prescribing of new/reformulated antipsychotics relative to those in never-compliant centers (ROR 1.39, 95% CI 1.35-1.44, p<0.0001), a relative increase of 1.1% in probability. Conclusions Psychiatrists exposed to strict conflict of interest policies prescribed heavily promoted antipsychotics at rates similar to academic psychiatrists non-academic psychiatrists exposed to less strict

  10. 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

  11. 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

  12. Behavioral Disorders in Dementia: Appropriate Nondrug Interventions and Antipsychotic Use.

    PubMed

    Reese, Tyler R; Thiel, Derrick J; Cocker, Katherine E

    2016-08-15

    Behavioral and psychological symptoms of dementia pose management challenges for caregivers and clinicians. Firstline nonpharmacologic treatments include eliminating physical and emotional stressors, modifying the patient's environment, and establishing daily routines. Family members and caregivers benefit from education about dementia symptoms and reminders that the behaviors are normal and unintentional. Cognitive and emotion-oriented interventions, sensory stimulation interventions, behavior management techniques, and other psychosocial interventions are modestly effective. In refractory cases, physicians may choose to prescribe off-label antipsychotics. Aripiprazole has the most consistent evidence of symptom improvement; however, this improvement is small. Olanzapine, quetiapine, and risperidone have inconsistent evidence of benefit. Physicians should use the smallest effective dose for the shortest possible duration to minimize adverse effects, most notably an increased mortality risk. Other adverse effects include anticholinergic and antidopaminergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, postural hypotension, metabolic syndrome, cardiac arrhythmia, and sedation. Patients should be monitored for these effects while receiving treatment; however, laboratory monitoring may be limited to patients receiving long-term therapy. PMID:27548592

  13. 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

  14. Compliance, persistence, costs and quality of life in young patients treated with antipsychotic drugs: results from the COMETA study

    PubMed Central

    2013-01-01

    Background Little data is available on the real-world socio-economic burden and outcomes in schizophrenia. This study aimed to assess persistence, compliance, costs and Health-Related Quality-of-Life (HRQoL) in young patients undergoing antipsychotic treatment according to clinical practice. Methods A naturalistic, longitudinal, multicentre cohort study was conducted: we involved 637 patients aged 18–40 years, with schizophrenia or schizophreniform disorder diagnosed ≤10 years before, enrolled in 86 Italian Mental Health Centres and followed-up for 1 year. Comparisons were conducted between naïve (i.e., patients visiting the centre for the first time and starting a new treatment regimen) and non naïve patients. Results At enrolment, 84% of patients were taking atypical drugs, 3.7% typical, 10% a combination of the two classes, and 2% were untreated. During follow-up, 23% of patients switched at least once to a different class of treatment, a combination or no treatment. The mean Drug-Attitude-Inventory score was 43.4, with 94.3% of the patients considered compliant by the clinicians. On average, medical costs at baseline were 390.93€/patient-month, mostly for drug treatment (29.5%), psychotherapy (29.2%), and hospitalizations (27.1%). Patients and caregivers lost 3.5 days/patient-month of productivity. During follow-up, attitude toward treatment remained fairly similar, medical costs were generally stable, while productivity, clinical statusand HRQoL significantly improved. While no significantly different overall direct costs trends were found between naïve and non naïve patients, naïve patients showed generally a significant mean higher improvement of clinical outcomes, HRQoL and indirect costs, compared to the others. Conclusions Our results suggest how tailoring the treatment strategy according to the complex and specific patient needs make it possible to achieve benefits and to allocate more efficiently resources. This study can also provide

  15. Atypical cadherin negotiates a turn.

    PubMed

    Shi, Dongbo; Fujimori, Toshihiko; Uemura, Tadashi

    2013-07-15

    Planar cell polarity (PCP) signaling is involved in many polarized cell behaviors. In this issue of Developmental Cell, Tatin et al. (2013) show that the atypical cadherin Celsr1 is transiently localized to cellular protrusions in lymphatic endothelial cells and acts to orient valve-forming cells perpendicular to the vessel axis. PMID:23867224

  16. Atypical Cogan's syndrome mimicking encephalitis.

    PubMed

    Lepur, Dragan; Vranjican, Zoran; Himbele, Josip; Barsić, Bruno; Klinar, Igor

    2004-01-01

    Cogan's syndrome is a rare autoimmune multisystem disease. The main clinical features of typical Cogan's syndrome are vestibuloauditory dysfunction and interstitial keratitis. The authors present a case of atypical Cogan's syndrome with headache, fever, deafness, trigeminal neuralgia and electroencephalographic abnormality which mimicked viral encephalitis. PMID:15307593

  17. Recognition and diagnosis of atypical depression.

    PubMed

    Thase, Michael E

    2007-01-01

    The term atypical depression dates to the first wave of reports describing differential response to monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). In contrast to more TCA-responsive depressions, patients with so-called atypical symptoms (e.g., hypersomnia, interpersonal sensitivity, leaden paralysis, increased appetite and/or weight, and phobic anxiety) were observed to be more responsive to MAOIs. After several decades of controversy and debate, the phrase "with atypical features" was added as an episode specifier in the DSM-IV in 1994. The 1-year prevalence of the defined atypical depression subtype is approximately 1% to 4%; around 15% to 29% of patients with major depressive disorder have atypical depression. Hardly "atypical" in contemporary contexts, atypical depression also is common in dysthymic bipolar II disorders and is notable for its early age at onset, more chronic course, and high rates of comorbidity with social phobia and panic disorder with agoraphobia. The requirement of preserved mood reactivity is arguably the most controversial of the DSM-IV criteria for atypical depression. When compared with melancholia, the neurobiological profiles of patients with atypical depression are relatively normal. The utility of the atypical depression subtype for differential therapeutics diminished substantially when the TCAs were supplanted as first-line antidepressants by the selective serotonin reuptake inhibitors. Although introduction of safer MAOIs has fostered renewed interest in atypical depression, the validity and importance of the DSM-IV definition of atypical depression for the nosology of affective illness remains an open question. PMID:17640153

  18. The predictive value of early treatment response in antipsychotic-naive patients with first-episode psychosis: Haloperidol versus olanzapine.

    PubMed

    Rasmussen, Sean A; Rosebush, Patricia I; Anglin, Rebecca E; Mazurek, Michael F

    2016-07-30

    Early antipsychotic response predicts outcomes for psychotic patients, but recent evidence suggests that this may not be true for patients treated with olanzapine. In this study, we assessed the predictive value of early response to olanzapine or haloperidol in 75 antipsychotic-naive, first-episode psychosis inpatients. Patients were assessed weekly using the Brief Psychiatric Rating Scale (BPRS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Young Mania Rating Scale (YMRS). Regression analyses were used to determine whether improvement at week 2 or week 3 predicted improvement at hospital discharge. The majority of patients in both groups experienced a decrease in symptom severity of ≥50% at week 2. In the haloperidol group, week 2 improvement predicted improvement at discharge for all measures except the HAM-A. In the olanzapine group, week 2 improvement only predicted improvement at discharge for HAM-D scores. However, week 3 improvement in the olanzapine group predicted improvement at discharge for all measures except the HAM-A. Olanzapine non-responders at week 3 (but not week 2) benefited from having olanzapine switched to another antipsychotic. These results suggest that a 2 week trial of haloperidol is sufficient to predict treatment outcomes, while a 3 week trial is required for olanzapine. PMID:27156027

  19. Antipsychotics, Other Psychotropics, and the Risk of Death in Patients With Dementia

    PubMed Central

    Maust, Donovan T.; Kim, Hyungjin Myra; Seyfried, Lisa S.; Chiang, Claire; Kavanagh, Janet; Schneider, Lon S.; Kales, Helen C.

    2015-01-01

    (95% CI, 21–312); and quetiapine, 2.0% (95% CI, 0.7%–3.3%; P < .01) with an NNH of 50 (95% CI, 30–150). Compared with antidepressant users, mortality risk ranged from 12.3% (95% CI, 8.6%–16.0%; P < .01) with an NNH of 8 (95% CI, 6–12) for haloperidol users to 3.2% (95% CI, 1.6%–4.9%; P < .01) with an NNH of 31 (95% CI, 21–62) for quetiapine users. As a group, the atypical antipsychotics (olanzapine, quetiapine, and risperidone) showed a dose-response increase in mortality risk, with 3.5% greater mortality (95% CI, 0.5%–6.5%; P = .02) in the high-dose subgroup relative to the low-dose group. When compared directly with quetiapine, dose-adjusted mortality risk was increased with both risperidone (1.7%; 95% CI, 0.6%–2.8%; P = .003) and olanzapine (1.5%; 95% CI, 0.02%–3.0%; P = .047). CONCLUSIONS AND RELEVANCE The absolute effect of antipsychotics on mortality in elderly patients with dementia may be higher than previously reported and increases with dose. PMID:25786075

  20. 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

  1. 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

  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. 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

  4. [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. PMID:25853834

  5. 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

  6. Conventional versus novel antipsychotics: changing concepts and clinical implications.

    PubMed Central

    Remington, G; Chong, S A

    1999-01-01

    Novel antipsychotics represent a significant advance in the treatment of schizophrenia after many years of few developments. The conventional antipsychotics are potent D2 antagonists, but fail to achieve a response in about 30% of cases. They are also associated with a high rate of extrapyramidal side effects. The greater and broader spectrum of efficacy combined with the reduced short- and long-term side effects of the new drugs such as quetiapine, risperidone, olanzapine and ziprasidone, contribute to a fresh optimism for the pharmacotherapy of schizophrenia. These novel agents are now driving further advances in schizophrenia research through a growing understanding of their pharmacological and clinical profiles. Clozapine, the first novel antipsychotic, has relatively low activity at D2 receptors, a high affinity for D4 receptors and a greater 5-HT2 (serotonin) than D2 antagonism. Hence, clozapine and other novel antipsychotics can be classified as such by this latter characteristic. However, some of these drugs have D2 occupancy greater than 60% (the clinical response threshold), while others have a lower D2 occupancy. The novel antipsychotics according have also been classified according to their activity on different neurotransmitter systems. While more effective, novel antipsychotics are not a panacea; they have limitations and side effects. In clinical practice, the American Psychiatric Association recommends either a conventional or novel antipsychotic for initial treatment of schizophrenia, whereas Canadian guidelines recommend novel agents. These agents should also be considered for treatment of refractory schizophrenia. Patients whose schizophrenia does not respond to one of these agents may respond to another. Future research should involve longer clinical trials, given the long periods needed to establish efficacy, and should address many remaining questions about the novel agents. PMID:10586534

  7. Fracture Risk among Nursing Home Residents Initiating Antipsychotic Medications

    PubMed Central

    Rigler, Sally K.; Shireman, Theresa I.; Cook-Wiens, Galen J.; Ellerbeck, Edward F.; Whittle, Jeffrey C.; Mehr, David R.; Mahnken, Jonathan D.

    2013-01-01

    Objectives to determine whether antipsychotic medication initiation is associated with subsequent fracture in nursing home residents, whether fracture rates differ between first-generation versus second-generation antipsychotic use, and whether fracture rates differ among users of haloperidol, risperidone, olanzapine, and quetiapine. Design time-to-event analyses were conducted in a retrospective cohort using linked Medicaid, Medicare, Minimum Data Set and Online Survey, Certification and Reporting data sets. Setting and Participants nursing home residents aged ≥ 65 years in CA, FL, MO, NJ and PA. Measurements fracture outcomes (any fracture; hip fracture) in first-versus second-generation antipsychotic users, and specifically among users of haloperidol, risperidone, olanzapine and quetiapine. Comparisons incorporated propensity scores that included patient-level variables (demographics, comorbidity, diagnoses, weight, fall history, concomitant medications, cognitive performance, physical function, aggressivebehavior) and facility-level variables (nursing home size, ownership factors, staffing levels). Results Among 8,262 subjects (within 4,131 pairs), 4.3% suffered any fracture during observation with 1% having a hip fracture during an average follow up period of 93 ± 71 days; range 1 to 293 days). Antipsychotic initiation was associated with any fracture (hazard ratio (HR) 1.39, p=0.004) and with hip fracture (HR 1.76, p=0.024). The highest risk was found for hip fracture when antipsychotic use was adjusted for dose(HR=2.96; p=0.008). However, no differences in time-to-fracture were found in first-versus second-generation agents or across competing individual drugs. Conclusion Antipsychotic initiation is associated with fracture in nursing home residents, but risk does not differ across commonly used antipsychotics. PMID:23590366

  8. 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

  9. 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

  10. Integrative role for serotonergic and glutamatergic receptor mechanisms in the action of NMDA antagonists: potential relationships to antipsychotic drug actions on NMDA antagonist responsiveness.

    PubMed

    Breese, George R; Knapp, Darin J; Moy, Sheryl S

    2002-06-01

    NMDA receptor antagonists worsen symptoms in schizophrenia and induce schizophrenic-like symptoms in normal individuals. In animals, NMDA antagonist-induced behavioral responses include increased activity, head weaving, deficits in paired pulse inhibition and social interaction, and increased forced swim immobility. Repeated exposure to NMDA antagonists in animals results in behavioral sensitization-a phenomenon accentuated in rats with dopaminergic neurons lesioned during development. In keeping with an involvement of serotonin and glutamate release in NMDA antagonist action, selected behaviors induced by NMDA antagonists are minimized by 5-HT(2A) receptor antagonists and mGLU2 receptor agonists. These observations provide promising new approaches for treating acute NMDA antagonist-induced psychosis. Further, acute atypical antipsychotic drugs also minimize NMDA antagonist actions to a greater degree than typical antipsychotics. However, because knowledge concerning acute versus chronic effectiveness of various antipsychotic drugs against NMDA antagonist neuropathology is limited, future studies to define more fully the basis of their differences in efficacy after chronic treatment could provide an understanding of their actions on neural mechanisms responsible for the core pathogenesis of schizophrenia. PMID:12204191

  11. Feasibility study of an optimised person-centred intervention to improve mental health and reduce antipsychotics amongst people with dementia in care homes: study protocol for a randomised controlled trial

    PubMed Central

    2013-01-01

    Background People living in care homes often have complex mental and physical health problems, disabilities and social needs which are compounded by the use of psychiatric and other drugs. In the UK dementia care is a national priority with a vast impact on services. WHELD combines the most effective elements of existing approaches to develop a comprehensive but practical intervention. This will be achieved by training care staff to provide care that is focused on an understanding of the individual and their needs; and by using additional components such as exercise, activities and social interaction to improve mental health and quality of life (QoL) and reduce the use of sedative drugs. Design Work Package 3 (WP3) is the pilot randomised trial and qualitative evaluation to help develop a future definitive randomised controlled clinical trial. The study design is a cluster randomised 2x2x2 factorial design with two replications in 16 care homes. Each care home is randomized to receive one of the eight possible permutations of the four key interventions, with each possible combination delivered in two of the 16 homes. Each cluster includes a minimum of 12 participants (depending upon size of the care home, the number of people with dementia and the number consenting). Discussion The overarching goal of the programme is to provide an effective, simple and practical intervention which improves the mental health of, and reduces sedative drug use in, people with dementia in care homes and which can be implemented nationally in all UK care homes as an NHS intervention. Trial Registration Current controlled trials ISRCTN40313497 PMID:23305152

  12. 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

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

    PubMed Central

    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

  14. Proton magnetic resonance spectroscopy changes after antipsychotic treatment.

    PubMed

    Szulc, Agata; Galinska-Skok, Beata; Waszkiewicz, Napoleon; Bibulowicz, Daniel; Konarzewska, Beata; Tarasow, Eugeniusz

    2013-01-01

    Proton magnetic resonance spectroscopy ((1)H MRS) enables the observation of brain function in vivo. Several brain metabolites can be measured by the means of (1)H MRS: N-acetylaspartate (NAA), choline containing compounds (Cho), myo-inositol (mI) and glutamate (Glu), glutamine (Gln) and GABA (together as Glx complex or separately). (1)H MRS measures have been found to be abnormal in psychotic disorders such as schizophrenia. Here we specifically review the influence exerted by antipsychotic drugs on brain metabolism, as detected by (1)H MRS. We systematically reviewed the available literature and uncovered 27 studies, 16 before-after treatment and 11 cross-sectional. Most of them addressed the effects of antipsychotics in schizophrenia and mainly focusing on NAA alterations. Follow up studies indicated antipsychotic drugs may act by increasing NAA levels in selected brain areas (the frontal lobe and thalamus), especially during the short-time observation. This phenomenon seems to vanish after longer observation. Other studies indicated that glutamate measures are decreasing along with the duration of the disease, suggesting both a neurodegenerative process present in schizophrenic brain as well as an influence of antipsychotics. The above results were reviewed according to the most recent theories in the field accounting for the impact of antipsychotics (1)HMRS measures. PMID:23157634

  15. The pharmacokinetics of long-acting antipsychotic medications.

    PubMed

    Spanarello, Stefano; La Ferla, Teresa

    2014-01-01

    The depot antipsychotics are synthesized by esterification of the active drug to a long chain fatty acid and the resultant compound is then dissolved in a vegetable oil, with the exception of some molecules of new generation characterized by microcrystalline technologies. The absorption rate constant is slower than the elimination rate constant and therefore, the depot antipsychotics exhibit 'flip-flop' kinetics where the time to steady-state is a function of the absorption rate, and the concentration at steady-state is a function of the elimination rate. The pharmacokinetics of depot antipsychotic medications are such that an intramuscular injection given at intervals from 1 to 4 weeks will produce adequate plasma concentrations that are sufficient to prevent relapse over the dosage interval. Such medication is useful in patients who do not reliably take their oral medication. The pharmacokinetics and clinical actions of various depot formulations of antipsychotic drugs have been extensively studied. The clinical pharmacokinetics of the depot antipsychotics for which plasma level studies are available (i.e. fluphenazine enanthate and decanoate, haloperidol decanoate, bromperidol decanoate, clopenthixol decanoate, flupenthixol decanoate, perphenazine onanthat, pipotiazine undecylenate, pipotiazine palmitate, fluspirilene, long-acting injectable risperidone, olanzapine pamoate, paliperidone palmitate, long-acting iloperidone, long-acting injectable aripiprazole) are reviewed. The proper study of these agents has been handicapped until recently by the necessity of accurately measuring subnanomolar concentrations in plasma. Their kinetic properties, the relationship of plasma concentrations to clinical effects, and conversion from oral to injectable therapy are discussed. PMID:23343447

  16. 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

  17. 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

  18. 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

  19. Cardiogenic shock from atypical Takotsubo cardiomyopathy attributed to acute disseminated encephalomyelitis lesion involving the medulla.

    PubMed

    Venkatraman, A; Bajaj, N S; Khawaja, A; Meador, W

    2016-04-01

    We present here a case of atypical Takotsubo cardiomyopathy arising as a result of a lesion in the medulla oblongata. The patient was diagnosed with acute disseminated encephalomyelitis, and had improvement with intravenous steroids. PMID:26868678

  20. 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

  1. 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. PMID:25785228

  2. Adverse Drug Reactions Associated with Antipsychotics, Antidepressants, Mood Stabilizers, and Stimulants.

    PubMed

    Givens, Courtney J

    2016-06-01

    The advent of psychotropic medications in the 1950s greatly impacted the practice of psychiatry. Since then, efforts have been made to produce effective medications with few side effects (SEs) or adverse drug reactions (ADRs). Newer psychotropics have been developed but are not without risk. ADRs and SEs can lead to medication noncompliance, morbidity, and mortality. In many cases, ADRs can be prevented and common SEs relieved through proper interventions. Nursing interventions are vital to improving patient safety and outcomes in mental health populations. This article discusses ADRs and SEs of antipsychotics, antidepressants, mood stabilizers, and stimulants. PMID:27229284

  3. Some adverse effects of antipsychotics: prevention and treatment.

    PubMed

    Lader, M

    1999-01-01

    Antipsychotic medication causes a wide range of adverse effects, which can be serious and may further imperil both the physical and psychological health of schizophrenic patients. The range of side effects patients commonly encounter includes weight gain, endocrine disturbances, sedation, anticholinergic effects, hypotension, seizures, and extrapyramidal symptoms. Less common and unpredictable reactions are blood dyscrasias, cardiotoxicity, sudden death, and the neuroleptic malignant syndrome. Antipsychotic drugs differ significantly regarding their propensity to cause these reactions. Patients should undergo comprehensive health checks before an antipsychotic is prescribed, and drug therapy should be individualized to take account of any preexisting symptoms. Side effects and the wider implications of drug treatment, such as effects on occupational and social functioning, should be discussed with the patient before initiating therapy. Patients should be regularly monitored for side effects during treatment and switched to alternative therapy if side effects are serious and/or persistent. PMID:10372605

  4. 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

  5. Zebrafish behavioral profiling identifies multitarget antipsychotic-like compounds.

    PubMed

    Bruni, Giancarlo; Rennekamp, Andrew J; Velenich, Andrea; McCarroll, Matthew; Gendelev, Leo; Fertsch, Ethan; Taylor, Jack; Lakhani, Parth; Lensen, Dennis; Evron, Tama; Lorello, Paul J; Huang, Xi-Ping; Kolczewski, Sabine; Carey, Galen; Caldarone, Barbara J; Prinssen, Eric; Roth, Bryan L; Keiser, Michael J; Peterson, Randall T; Kokel, David

    2016-07-01

    Many psychiatric drugs act on multiple targets and therefore require screening assays that encompass a wide target space. With sufficiently rich phenotyping and a large sampling of compounds, it should be possible to identify compounds with desired mechanisms of action on the basis of behavioral profiles alone. Although zebrafish (Danio rerio) behavior has been used to rapidly identify neuroactive compounds, it is not clear what types of behavioral assays would be necessary to identify multitarget compounds such as antipsychotics. Here we developed a battery of behavioral assays in larval zebrafish to determine whether behavioral profiles can provide sufficient phenotypic resolution to identify and classify psychiatric drugs. Using the antipsychotic drug haloperidol as a test case, we found that behavioral profiles of haloperidol-treated zebrafish could be used to identify previously uncharacterized compounds with desired antipsychotic-like activities and multitarget mechanisms of action. PMID:27239787

  6. 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…

  7. 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. PMID:23835329

  8. 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

  9. Aberrant Hippocampal Connectivity in Unmedicated Patients With Schizophrenia and Effects of Antipsychotic Medication: A Longitudinal Resting State Functional MRI Study.

    PubMed

    Kraguljac, Nina Vanessa; White, David Matthew; Hadley, Nathan; Hadley, Jennifer Ann; Ver Hoef, Lawrence; Davis, Ebony; Lahti, Adrienne Carol

    2016-07-01

    To better characterize hippocampal pathophysiology in schizophrenia, we conducted a longitudinal study evaluating hippocampal functional connectivity during resting state, using seeds prescribed in its anterior and posterior regions. We enrolled 34 unmedicated patients with schizophrenia or schizoaffective disorder (SZ) and 34 matched healthy controls. SZ were scanned while off medication, then were treated with risperidone for 6 weeks and re-scanned (n = 22). Group differences in connectivity, as well as changes in connectivity over time, were assessed on the group's participant level functional connectivity maps. We found significant dysconnectivity with anterior and posterior hippocampal seeds in unmedicated SZ. Baseline connectivity between the hippocampus and anterior cingulate cortex, caudate nucleus, auditory cortex and calcarine sulcus in SZ predicted subsequent response to antipsychotic medications. These same regions demonstrated changes over the 6-week treatment trial that were correlated with symptomatic improvement. Our findings implicate several neural networks relevant to clinical improvement with antipsychotic medications. PMID:26873890

  10. Developing a policy for second-generation antipsychotic drugs.

    PubMed

    Rosenheck, Robert A; Sernyak, Michael J

    2009-01-01

    Second-generation antipsychotics (SGAs) have replaced older drugs in the treatment of schizophrenia; their costs in the United States have reached $13 billion a year. Recent research, however, shows that their net risk/benefit profiles are no better than some older, cheaper drugs. Stepped therapy, allowing exceptions with prior authorization and giving preference to generic drugs with low risk of both neurologic and metabolic side effects, could increase the cost-effectiveness and safety of antipsychotic drugs. Educational preparation and monitoring of adverse events would foster better acceptance of such procedures among providers, patients, and families. Research to evaluate these interventions would ideally precede their widespread implementation. PMID:19622538

  11. Atypical inflammatory demyelinating syndromes of the CNS.

    PubMed

    Hardy, Todd A; Reddel, Stephen W; Barnett, Michael H; Palace, Jacqueline; Lucchinetti, Claudia F; Weinshenker, Brian G

    2016-08-01

    Atypical inflammatory demyelinating syndromes are rare disorders that differ from multiple sclerosis owing to unusual clinical or MRI findings or poor response to treatments used for multiple sclerosis. These syndromes include neuromyelitis optica spectrum disorder, acute disseminated encephalomyelitis, tumefactive demyelination, Baló's concentric sclerosis, Schilder's disease, and Marburg's multiple sclerosis. The overlapping features of these syndromes with multiple sclerosis and with each other complicate diagnosis and their categorisation as distinct or related conditions. Recognition of these syndromes is crucial because they differ from multiple sclerosis and other demyelinating and non-demyelinating conditions in their prognosis and treatment. Advances in MRI, pathology, and immunobiology are needed to increase understanding of these syndromes, including the extent to which some of them represent distinct entities, and to assist with improvements in their diagnosis and management. PMID:27478954

  12. 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

  13. 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.

  14. Antipsychotic, antidepressant, and cognitive-impairment properties of antipsychotics: rat profile and implications for behavioral and psychological symptoms of dementia.

    PubMed

    Kołaczkowski, Marcin; Mierzejewski, Paweł; Bienkowski, Przemyslaw; Wesołowska, Anna; Newman-Tancredi, Adrian

    2014-06-01

    Many dementia patients exhibit behavioral and psychological symptoms (BPSD), including psychosis and depression. Although antipsychotics are frequently prescribed off-label, they can have marked side effects. In addition, comparative preclinical studies of their effects are surprisingly scarce, and strategies for discovery of novel pharmacotherapeutics are lacking. We therefore compared eight antipsychotics in rat behavioral tests of psychosis, antidepressant-like activity, and cognitive impairment as a basis for preclinical evaluation of new drug candidates. The methods used in this study include inhibition of MK-801-induced hyperactivity, forced swim test (FST), passive avoidance (PA), spontaneous locomotor activity, and catalepsy. The drugs exhibited antipsychotic-like activity in the MK-801 test but with diverse profiles in the other models. Risperidone impaired PA performance, but with some dose separation versus its actions in the MK-801 test. In contrast, clozapine, olanzapine, lurasidone, and asenapine showed little or no dose separation in these tests. Aripiprazole did not impair PA performance but was poorly active in the MK-801 test. Diverse effects were also observed in the FST: chlorpromazine was inactive and most other drugs reduced immobility over narrow dose ranges, whereas clozapine reduced immobility over a wider dose range, overlapping with antipsychotic activity. Although the propensity of second-generation antipsychotics to produce catalepsy was lower, they all elicited pronounced sedation. Consistent with clinical data, most currently available second-generation antipsychotics induced cognitive and motor side effects with little separation from therapeutic-like doses. This study provides a uniform in vivo comparative basis on which to evaluate future early-stage drug candidates intended for potential pharmacotherapy of BPSD. PMID:24599316

  15. 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

  16. Atypical presentation of infective endocarditis.

    PubMed

    Arunachalam, Karuppiah

    2016-01-01

    The HACEK group of organisms are one of the infrequent causes of infective endocarditis. Infective endocarditis should be recognized and treated promptly to prevent excessive morbidity and mortality associated with the disease. Sometimes the diagnosis is delayed due to vague and subtle presentation. Through this case report, risk factors of Cardiobacterium hominis endocarditis and its atypical presentation is illustrated to increase the recognition of infective endocarditis as one of the differential diagnosis. [Full article available at http://rimed.org/rimedicaljournal-2016-07.asp, free with no login]. PMID:27379355

  17. Atypical parkinsonism: diagnosis and treatment.

    PubMed

    Stamelou, Maria; Bhatia, Kailash P

    2015-02-01

    Atypical parkinsonism comprises typically progressive supranuclear palsy, corticobasal degeneration, and mutilple system atrophy, which are distinct pathologic entities; despite ongoing research, their cause and pathophysiology are still unknown, and there are no biomarkers or effective treatments available. The expanding phenotypic spectrum of these disorders as well as the expanding pathologic spectrum of their classic phenotypes makes the early differential diagnosis challenging for the clinician. Here, clinical features and investigations that may help to diagnose these conditions and the existing limited treatment options are discussed. PMID:25432722

  18. Atypical odontalgia: a case report.

    PubMed

    Koratkar, Harish; Koratkar, Sonal

    2008-01-01

    Diagnosis and treatment of orofacial pain is not uncommon; however, reaching a definitive diagnosis in these cases can be a complex challenge. Dentists are most likely to face this situation, because persistent and chronic pain is more common in the head and neck region than in any other part of the body. However, the complexities and diagnostic challenges mean that misdiagnosing neuropathic pain is common. This article presents a case of atypical odontalgia and illustrates the complexities involved when diagnosing the condition. PMID:19284197

  19. 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…

  20. Antipsychotics can induce pre-shock in very elderly patients: a report of two cases.

    PubMed

    Ueda, Satoshi; Omori, Ataru; Shioya, Touko; Okubo, Yoshiro

    2016-01-01

    Antipsychotics have often been administered to treat delirium and intractable insomnia in elderly patients with or without dementia. However, antipsychotics sometimes cause severe adverse effects. We report two cases of very elderly patients who developed pre-shock after the administration of antipsychotics in a clinical consultation-liaison setting. These cases suggest that antipsychotics can induce fatal adverse events in very elderly patients. Although there has been little evidence regarding the most appropriate kind of drug and dosage for such patients, psychiatrists should exercise great caution in the use of antipsychotics for the very elderly, including deciding to prescribe the lowest dose or not prescribing them at all. PMID:25914062

  1. Detecting and Managing Adverse Effects of Antipsychotic Medications: Current State of Play.

    PubMed

    Ames, Donna; Carr-Lopez, Sian M; Gutierrez, Mary A; Pierre, Joseph M; Rosen, Jennifer A; Shakib, Susan; Yudofsky, Lynn M

    2016-06-01

    Antipsychotics are some of the most frequently prescribed medications not only for psychotic disorders and symptoms but also for a wide range of on-label and off-label indications. Because second-generation antipsychotics have largely replaced first-generation antipsychotics as first-line options due to their substantially decreased risk of extrapyramidal side effects, attention has shifted to other clinically concerning adverse events associated with antipsychotic therapy. The focus of this article is to update the nonextrapyramidal side effects associated with second-generation antipsychotics. Issues surrounding diagnosis and monitoring as well as clinical management are addressed. PMID:27216904

  2. Antipsychotics-Associated Serious Adverse Events in Children: An Analysis of the FAERS Database

    PubMed Central

    Kimura, Goji; Kadoyama, Kaori; Brown, J.B.; Nakamura, Tsutomu; Miki, Ikuya; Nisiguchi, Kohshi; Sakaeda, Toshiyuki; Okuno, Yasushi

    2015-01-01

    Objective: The reports submitted to the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from 1997 to 2011 were reviewed to assess serious adverse events induced by the administration of antipsychotics to children. Methods: Following pre-processing of FAERS data by elimination of duplicated records as well as adjustments to standardize drug names, reports involving haloperidol, olanzapine, quetiapine, clozapine, ziprasidone, risperidone, and aripiprazole were analyzed in children (age 0-12). Signals in the data that signified a drug-associated adverse event were detected via quantitative data mining algorithms. The algorithms applied to this study include the empirical Bayes geometric mean, the reporting odds ratio, the proportional reporting ratio, and the information component of a Bayesian confidence propagation neural network. Neuroleptic malignant syndrome (NMS), QT prolongation, leukopenia, and suicide attempt were focused on as serious adverse events. Results: In regard to NMS, the signal scores for haloperidol and aripiprazole were greater than for other antipsychotics. Significant signals of the QT prolongation adverse event were detected only for ziprasidone and risperidone. With respect to leukopenia, the association with clozapine was noteworthy. In the case of suicide attempt, signals for haloperidol, olanzapine, quetiapine, risperidone, and aripiprazole were detected. Conclusions: It was suggested that there is a level of diversity in the strength of the association between various first- and second-generation antipsychotics with associated serious adverse events, which possibly lead to fatal outcomes. We recommend that research be continued in order to gather a large variety and quantity of related information, and that both available and newly reported data be placed in the context of multiple medical viewpoints in order to lead to improved levels of care. PMID:25589889

  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. 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…

  5. Antipsychotic-like effects of zolpidem in Wistar rats.

    PubMed

    Mierzejewski, Pawel; Kolaczkowski, Marcin; Marcinkowska, Monika; Wesolowska, Anna; Samochowiec, Jerzy; Pawlowski, Maciej; Bienkowski, Przemyslaw

    2016-02-15

    Aside from their use in the treatment of anxiety disorders and insomnia, benzodiazepines and other GABAA receptor positive modulators are widely used as add-on treatments in schizophrenic and non-schizophrenic psychoses. However, there is relatively little direct clinical or pre-clinical evidence for antipsychotic effects of GABAergic medications. Previous studies have indicated that zolpidem, a GABAergic drug acting preferentially at α1-containing GABAA receptors, may produce catalepsy through interactions with dopaminergic neurotransmission. The aim of the present study was to investigate effects of zolpidem in experimental models of antipsychotic activity and extrapyramidal side effects in Wistar rats. Effects of zolpidem were compared with that of a classic benzodiazepine drug, diazepam and a second-generation antipsychotic medication, risperidone. High doses of risperidone (10.0mg/kg, i.p.) and zolpidem (10.0mg/kg, i.p.), but not diazepam, induced relatively short-lasting cataleptic responses in the bar test. Zolpidem and risperidone, but not diazepam, produced some antipsychotic-like effects at doses, which produced no catalepsy and did not inhibit spontaneous locomotor activity and apomorphine-induced stereotypies. The present results tend to indicate that zolpidem exerts some neuroleptic-like effects at doses, which do not produce motor side effects. Our findings may provide further rationale for the development of new subtype-selective GABAA receptor modulators for the treatment of psychotic symptoms. PMID:26825544

  6. A Case Report: Anti-Psychotic Agents Related Ocular Toxicity.

    PubMed

    Choy, Bonnie Nga Kwan; Ng, Alex Lap Ki; Shum, Jennifer Wei Huen; Fan, Michelle Ching Yim; Lai, Jimmy Shiu Ming

    2016-04-01

    Chlorpromazine is known to cause ocular pigmentary deposits. However, delayed presentation after cessation of chlorpromazine has not been reported. There are also no reports on whether newer generation of anti-psychotic agents contribute to ocular toxicity. We describe a case of ocular toxicity related to anti-psychotic agents. To the best of our knowledge, this is the first reported case of anterior segment pigmentary deposits associated with olanzapine use, 2 years after the cessation of chlorpromazine.We report a case of ocular toxicity in a patient with history of chlorpromazine usage of 100 mg per day for 13 years and subsequently switched to olanzapine 5 mg for 2 years. There were no signs of ocular toxicity while the patient was on chlorpromazine. However, when the patient switched to olanzapine, she developed the ocular side effect as described for chlorpromazine-induced ocular toxicity, with pigmentary depositions on both corneas and the anterior lens surface and decrease in vision.Olanzapine, a newer anti-psychotic agent, may play a role in the ocular pigmentary deposition, either directly causing pigmentary deposition itself or accentuating the effect of chlorpromazine as the 2 drugs act on the same receptors, although further studies are required to support this hypothesis. As patients with psychiatric conditions may not voluntarily complain of visual symptoms, ocular screening could be considered in these patients receiving chronic anti-psychotic treatment, so that any ocular toxicity could be diagnosed in a timely manner. PMID:27082594

  7. 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…

  8. Antipsychotic treatment modulates glutamate transport and NMDA receptor expression.

    PubMed

    Zink, Mathias; Englisch, Susanne; Schmitt, Andrea

    2014-11-01

    Schizophrenia patients often suffer from treatment-resistant cognitive and negative symptoms, both of which are influenced by glutamate neurotransmission. Innovative therapeutic strategies such as agonists at metabotropic glutamate receptors or glycin reuptake inhibitors try to modulate the brain's glutamate network. Interactions of amino acids with monoamines have been described on several levels, and first- and second-generation antipsychotic agents (FGAs, SGAs) are known to exert modulatory effects on the glutamatergic system. This review summarizes the current knowledge on effects of FGAs and SGAs on glutamate transport and receptor expression derived from pharmacological studies. Such studies serve as a control for molecular findings in schizophrenia brain tissue and are clinically relevant. Moreover, they may validate animal models for psychosis, foster basic research on antipsychotic substances and finally lead to a better understanding of how monoaminergic and amino acid neurotransmissions are intertwined. In the light of these results, important differences dependent on antipsychotic substances, dosage and duration of treatment became obvious. While some post-mortem findings might be confounded with multifold drug effects, others are unlikely to be influenced by antipsychotic treatment and could represent important markers of schizophrenia pathophysiology. In similarity to the convergence of toxic and psychotomimetic effects of dopaminergic, serotonergic and anti-glutamatergic substances, the therapeutic mechanisms of SGAs might merge on a yet to be defined molecular level. In particular, serotonergic effects of SGAs, such as an agonism at 5HT1A receptors, represent important targets for further clinical research. PMID:25214389

  9. Antipsychotic Therapy During Early and Late Pregnancy. A Systematic Review

    PubMed Central

    Gentile, Salvatore

    2010-01-01

    Objective: Both first- (FGAs) and second-generation antipsychotics (SGAs) are routinely used in treating severe and persistent psychiatric disorders. However, until now no articles have analyzed systematically the safety of both classes of psychotropics during pregnancy. Data sources and search strategy: Medical literature information published in any language since 1950 was identified using MEDLINE/PubMed, TOXNET, EMBASE, and The Cochrane Library. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from companies developing drugs. Search terms were pregnancy, psychotropic drugs, (a)typical-first-second-generation antipsychotics, and neuroleptics. A separate search was also conducted to complete the safety profile of each reviewed medication. Searches were last updated on July 2008. Data selection: All articles reporting primary data on the outcome of pregnancies exposed to antipsychotics were acquired, without methodological limitations. Conclusions: Reviewed information was too limited to draw definite conclusions on structural teratogenicity of FGAs and SGAs. Both classes of drugs seem to be associated with an increased risk of neonatal complications. However, most SGAs appear to increase risk of gestational metabolic complications and babies large for gestational age and with mean birth weight significantly heavier as compared with those exposed to FGAs. These risks have been reported rarely with FGAs. Hence, the choice of the less harmful option in pregnancy should be limited to FGAs in drug-naive patients. When pregnancy occurs during antipsychotic treatment, the choice to continue the previous therapy should be preferred. PMID:18787227

  10. 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

  11. 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

  12. Pregnancy-Associated Atypical Hemolytic-Uremic Syndrome

    PubMed Central

    Saad, Antonio F.; Roman, Jorge; Wyble, Aaron; Pacheco, Luis D.

    2016-01-01

    Précis Introduction Early diagnosis of atypical uremic–hemolytic syndrome may be challenging during the puerperium period. Correct diagnosis and timely management are crucial to improve outcomes. Background Pregnancy-associated atypical hemolytic-uremic syndrome (p-aHUS) is a rare condition characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Triggered by pregnancy, genetically predisposed women develop the syndrome, leading to a disastrous hemolytic disease characterized by diffuse endothelial damage and platelet consumption. This disease is a life-threatening condition that requires prompt diagnosis and therapy. Case A 19-year-old G1P1 Caucasian female with suspicion of HELLP syndrome was treated at our facility for severe thrombocytopenia and acute kidney injury. A diagnosis of atypical uremic–hemolytic syndrome was later confirmed. The patient's condition improved with normalization of platelets and improvement in kidney function after 14 days of plasmapheresis. She was subsequently treated with eculizumab, a monoclonal antibody against C5. The patient tolerated well the therapy and is currently in remission. Conclusion Diagnosis of p-aHUS is challenging, as it can mimic various diseases found during pregnancy and the postpartum. Plasma exchange should be promptly initiated within 24 hours of diagnosis. Eculizumab has risen to become an important tool to improve long-term comorbidities and mortality in this group population. PMID:26989566

  13. Pregnancy-Associated Atypical Hemolytic-Uremic Syndrome.

    PubMed

    Saad, Antonio F; Roman, Jorge; Wyble, Aaron; Pacheco, Luis D

    2016-03-01

    Introduction Early diagnosis of atypical uremic-hemolytic syndrome may be challenging during the puerperium period. Correct diagnosis and timely management are crucial to improve outcomes. Background Pregnancy-associated atypical hemolytic-uremic syndrome (p-aHUS) is a rare condition characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Triggered by pregnancy, genetically predisposed women develop the syndrome, leading to a disastrous hemolytic disease characterized by diffuse endothelial damage and platelet consumption. This disease is a life-threatening condition that requires prompt diagnosis and therapy. Case A 19-year-old G1P1 Caucasian female with suspicion of HELLP syndrome was treated at our facility for severe thrombocytopenia and acute kidney injury. A diagnosis of atypical uremic-hemolytic syndrome was later confirmed. The patient's condition improved with normalization of platelets and improvement in kidney function after 14 days of plasmapheresis. She was subsequently treated with eculizumab, a monoclonal antibody against C5. The patient tolerated well the therapy and is currently in remission. Conclusion Diagnosis of p-aHUS is challenging, as it can mimic various diseases found during pregnancy and the postpartum. Plasma exchange should be promptly initiated within 24 hours of diagnosis. Eculizumab has risen to become an important tool to improve long-term comorbidities and mortality in this group population. PMID:26989566

  14. Association of a bovine prion gene haplotype with atypical BSE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Atypical bovine spongiform encephalopathies (BSEs) are recently recognized prion diseases of cattle. Atypical BSEs are rare; approximately 30 cases have been identified worldwide. We tested prion gene (PRNP) haplotypes for an association with atypical BSE. Methodology/Principal Findin...

  15. Defining and Assessing Adherence to Oral Antipsychotics: A Review of the Literature

    PubMed Central

    Velligan, Dawn I.; Lam, Yui-Wing Francis; Glahn, David C.; Barrett, Jennifer A.; Maples, Natalie J.; Ereshefsky, Larry; Miller, Alexander L.

    2006-01-01

    The definition and assessment of adherence vary considerably across studies. Increasing consensus regarding these issues is necessary to improve our understanding of adherence and the development of more effective treatments. We review the adherence literature over the past 3 decades to explore the definitions and assessment of adherence to oral antipsychotics in schizophrenia patients. A total of 161 articles were identified through MEDLINE and PsycINFO searches. The most common method used to assess adherence was the report of the patient. Subjective and indirect methods including self-report, provider report, significant other report, and chart review were the only methods used to assess adherence in over 77% (124/161) of studies reviewed. Direct or objective measures including pill count, blood or urine analysis, electronic monitoring, and electronic refill records were used in less than 23% (37/161) of studies. Even in studies utilizing the same methodology to assess adherence, definitions of an adherent subject varied broadly from agreeing to take any medication to taking at least 90% of medication as prescribed. We make suggestions for consensus development, including the use of recommended terminology for different subject samples, the increased use of objective or direct measures, and the inclusion in all studies of an estimate of the percentage of medication taken as prescribed in an effort to increase comparability among studies. The suggestions are designed to advance the field with respect to both understanding predictors of adherence and developing interventions to improve adherence to oral antipsychotic medications. PMID:16707778

  16. Course and treatment of atypical depression.

    PubMed

    Nierenberg, A A; Alpert, J E; Pava, J; Rosenbaum, J F; Fava, M

    1998-01-01

    Atypical depression is the most common form of depression in outpatients, but compared with melancholia, little is known about its comorbidity, course, and treatment. Beyond the well-characterized constellation of symptoms that define atypical depression (mood reactivity, hypersomnia, leaden paralysis, hyperphagia, and rejection sensitivity), specific Axis I and II comorbid conditions may differentiate atypical from other depressed patients. Similarly, age at onset, duration of episodes, frequency of relapses and recurrences, and frequency of complete remission in atypical depression may be different. It has not even been established if atypical depression is a stable subtype or if it is just one of several forms of depression that an individual may express during a lifetime of recurrent depressions. Monoamine oxidase inhibitors (MAOIs) are superior to tricyclic antidepressants (TCAs) for the treatment of atypical depression, but few studies have compared MAOIs to the newer generation of antidepressants (SSRIs, bupropion, venlafaxine, nefazodone, and mirtazapine). Because of the favorable benefit/risk ratio, clinicians tend to use these newer antidepressants for all outpatients, including those with atypical depression, even though the literature is limited. A review and critique of the relevant literature on atypical depression will be presented. PMID:9840192

  17. Higher Education and the Black Atypical Student.

    ERIC Educational Resources Information Center

    Hull, W. Frank, IV

    The black atypical student, defined as that black student who would be excluded from most colleges and universities in America by traditional admission policy, is beginning to find entrance into institutions of higher education. There is no indication reported of these institutions admitting large numbers of black atypical students. In the…

  18. Successful withdrawal from antipsychotic treatment in elderly male inpatients with schizophrenia--description of four cases and review of the literature.

    PubMed

    Suzuki, Takefumi; Uchida, Hiroyuki

    2014-12-15

    We describe four elderly male inpatients with chronic schizophrenia successfully withdrawn from long-lasting antipsychotic treatment. Then we review studies in which antipsychotics were discontinued in patients 65 y.o. (or at least 50 on the average) or older using PubMed (last search; August 2014). The average (±S.D.) age, duration of illness and total duration of hospitalization of the patients were 77.0±8.6 y.o., 46.0±26.9 years, and 41.0±27.3 years, respectively. Illness severity as assessed with the Clinical Global Impression (CGI)-Severity was five for three patients and six for the other. After withdrawal from antipsychotic treatment for 28.3±11.4 weeks, none showed appreciable changes in psychopathology, functioning as well as adverse effects and the resultant CGI-Improvement was four for all patients. Compared with those who needed continuous antipsychotic treatment in the same unit (n=51; mean±S.D. age: 56.0±12.1 y.o.), they were significantly older and treated with a fewer number of total psychotropics at baseline (1.50±1.00 versus 4.94±1.93 agents). A literature search failed to find any studies in which antipsychotics were discontinued exclusively in patients with schizophrenia 65 years or older and underscored a clear paucity of data on this important topic. Cessation of chronic antipsychotic treatment could be a viable option at least in some patients with geriatric schizophrenia although more systematic studies are necessary. PMID:25200762

  19. Reversal of evoked gamma oscillation deficits is predictive of antipsychotic activity with a unique profile for clozapine

    PubMed Central

    Hudson, M R; Rind, G; O'Brien, T J; Jones, N C

    2016-01-01

    Recent heuristic models of schizophrenia propose that abnormalities in the gamma frequency cerebral oscillations may be closely tied to the pathophysiology of the disorder, with hypofunction of N-methyl-d-aspartate receptors (NMDAr) implicated as having a crucial role. Prepulse inhibition (PPI) is a behavioural measure of sensorimotor gating that is disrupted in schizophrenia. We tested the ability for antipsychotic drugs with diverse pharmacological actions to (1) ameliorate NMDAr antagonist-induced disruptions to gamma oscillations and (2) attenuate NMDAr antagonist-induced disruptions to PPI. We hypothesized that antipsychotic-mediated improvement of PPI deficits would be accompanied by a normalization of gamma oscillatory activity. Wistar rats were implanted with extradural electrodes to facilitate recording of electroencephalogram during PPI behavioural testing. In each session, the rats were administered haloperidol (0.25 mg kg−1), clozapine (5 mg kg−1), olanzapine (5 mg kg−1), LY379268 (3 mg kg−1), NFPS (sarcosine, 1 mg kg−1), d-serine (1800 mg kg−1) or vehicle, followed by the NMDAr antagonists MK-801(0.16 mg kg−1), ketamine (5 mg kg−1) or vehicle. Outcome measures were auditory-evoked, as well as ongoing, gamma oscillations and PPI. Although treatment with all the clinically validated antipsychotic drugs reduced ongoing gamma oscillations, clozapine was the only compound that prevented the sensory-evoked gamma deficit produced by ketamine and MK-801. In addition, clozapine was also the only antipsychotic that attenuated the disruption to PPI produced by the NMDAr antagonists. We conclude that disruptions to evoked, but not ongoing, gamma oscillations caused by NMDAr antagonists are functionally relevant, and suggest that compounds, which restore sensory-evoked gamma oscillations may improve sensory processing in patients with schizophrenia. PMID:27093066

  20. Reversal of evoked gamma oscillation deficits is predictive of antipsychotic activity with a unique profile for clozapine.

    PubMed

    Hudson, M R; Rind, G; O'Brien, T J; Jones, N C

    2016-01-01

    Recent heuristic models of schizophrenia propose that abnormalities in the gamma frequency cerebral oscillations may be closely tied to the pathophysiology of the disorder, with hypofunction of N-methyl-d-aspartate receptors (NMDAr) implicated as having a crucial role. Prepulse inhibition (PPI) is a behavioural measure of sensorimotor gating that is disrupted in schizophrenia. We tested the ability for antipsychotic drugs with diverse pharmacological actions to (1) ameliorate NMDAr antagonist-induced disruptions to gamma oscillations and (2) attenuate NMDAr antagonist-induced disruptions to PPI. We hypothesized that antipsychotic-mediated improvement of PPI deficits would be accompanied by a normalization of gamma oscillatory activity. Wistar rats were implanted with extradural electrodes to facilitate recording of electroencephalogram during PPI behavioural testing. In each session, the rats were administered haloperidol (0.25 mg kg(-1)), clozapine (5 mg kg(-1)), olanzapine (5 mg kg(-1)), LY379268 (3 mg kg(-1)), NFPS (sarcosine, 1 mg kg(-1)), d-serine (1800 mg kg(-1)) or vehicle, followed by the NMDAr antagonists MK-801(0.16 mg kg(-1)), ketamine (5 mg kg(-1)) or vehicle. Outcome measures were auditory-evoked, as well as ongoing, gamma oscillations and PPI. Although treatment with all the clinically validated antipsychotic drugs reduced ongoing gamma oscillations, clozapine was the only compound that prevented the sensory-evoked gamma deficit produced by ketamine and MK-801. In addition, clozapine was also the only antipsychotic that attenuated the disruption to PPI produced by the NMDAr antagonists. We conclude that disruptions to evoked, but not ongoing, gamma oscillations caused by NMDAr antagonists are functionally relevant, and suggest that compounds, which restore sensory-evoked gamma oscillations may improve sensory processing in patients with schizophrenia. PMID:27093066

  1. 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. PMID:21208484

  2. [Apropos of atypical melancholia with Sustiva (efavirenz)].

    PubMed

    Lang, J P; Halleguen, O; Picard, A; Lang, J M; Danion, J M

    2001-01-01

    The treatment of HIV infection has changed dramatically in recent years as a result of the development of new drugs which allows a variety of multitherapy combinations more adapted to patients' needs and thereby improving compliance. Efavirenz is a non-nucleoside reverse transcriptase inhibitor. In addition to a potent antiretroviral activity, efavirenz is an easy-to-take drug with once-daily dosing and is usually well tolerated. Efavirenz, however, may induce psychic alterations which are variable and atypical in both their clinical presentation and severity. As early as the first days of treatment, efavirenz may provoke surprising phenomena such as nightmares, vivid dreams, hallucinations or illusions, and twilight states. Depersonalization and derealization episodes, personality alterations, stream of thought troubles and unusual thought contents, atypical depression and cognitive disorders have also been observed. These phenomena may occur either early or later on treatment. The prevalence of severe psychic disorders is less than 5%, but they are often responsible for harmful treatment discontinuations. Psychiatric side effects are heterogeneous and probably not related to pre-existing psychologic weakness. We do not have enough data to evaluate these side effects and their etiopathogeny. The drug could act directly on the central nervous system since it crosses the blood-brain barrier, on the serotoninergic and dopaminergic systems. Some authors have compared efavirenz-induced psychic effects to those associated with LSD and found structural similarities between the two molecules. However, the heterogeneity and low prevalence of the psychiatric side effects of efavirenz suggest and individual sensitivity. In order to improve patient care, a better clinical approach, neuropsychological evaluation, and functional brain imagery should be used to progress in the analysis and comprehension of these disorders. We discuss in this paper the case of Mister H. This HIV

  3. Concurrent Oral Antipsychotic Drug Use Among Schizophrenia Patients Initiated on Long-Acting Injectable Antipsychotics Post-Hospital Discharge.

    PubMed

    Doshi, Jalpa A; Pettit, Amy R; Stoddard, Jeffrey J; Zummo, Jacqueline; Marcus, Steven C

    2015-08-01

    Pharmacological treatment is central to effective management of schizophrenia. Prescribing clinicians have an increasing array of options from which to choose, and oral antipsychotic polypharmacy is common in routine clinical practice. Practice guidelines recommend long-acting injectable (LAI) formulations, typically viewed as monotherapeutic alternatives, for patients with established nonadherence. Yet there are limited data on the prevalence and nature of concurrent oral antipsychotic prescriptions in patients receiving LAIs. Our observational, claims-based study examined the frequency and duration of concurrent oral prescriptions in 340 Medicaid patients receiving LAI therapy. Specifically, we examined patients with a recent history of nonadherence and hospitalization for schizophrenia and included both first-generation antipsychotic depot medications (fluphenazine decanoate, haloperidol decanoate) and more recently available second-generation injectables (LAI risperidone, paliperidone palmitate). Of all patients initiated on LAIs, 75.9% had a concurrent oral antipsychotic prescription in the 6 months post-hospital discharge. Patients receiving concurrent prescriptions were frequently prescribed an oral formulation of their LAI agent, but many first-generation LAI users received a concurrent second-generation oral medication. The lowest rate of concurrent prescribing (58.8%) was found with paliperidone palmitate, whereas the highest rate was with LAI risperidone (88.9%). Overlap in oral and LAI prescriptions typically occurred for a substantial period of time (ie, >30 days) and for a notable percentage of the days covered by LAIs (often 50% or more). Our findings highlight the need to further examine such prescribing patterns, to probe the reasons for them, and to clarify the optimal roles of different antipsychotic treatments in clinical practice. PMID:26075492

  4. An Atypical Case of Hemoptysis.

    PubMed

    Wang'ondu, Ruth W; Long, Theodore

    2016-03-01

    Hemoptysis, a common sign of diffuse alveolar hemorrhage, can be caused by multiple factors, both infectious and noninfectious. A 45-year-old male with hypertension, obstructive sleep apnea, and stage IV pulmonary sarcoidosis with cardiac involvement, presented with a two-month history of cough and acute nonmassive hemoptysis with hypoxia. A chest CT showed ground glass consolidation and interlobular septal thickening, concerning for diffuse alveolar hemorrhage. Flexible bronchoscopy confirmed diffuse alveolar hemorrhage; microbiological analyses of bronchoalveolar washings did not reveal a causative organism. Mycoplasma pneumoniae-specific IgM in serum studies was consistent with mycoplasma pneumonia as the most likely etiology of this patient's diffuse alveolar hemorrhage and resultant hemoptysis. This report points to the need to consider atypical mycoplasma pneumonia as a possible etiology of hemoptysis in patients with underlying sarcoidosis. PMID:27169298

  5. [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

  6. Atypical combinations and scientific impact.

    PubMed

    Uzzi, Brian; Mukherjee, Satyam; Stringer, Michael; Jones, Ben

    2013-10-25

    Novelty is an essential feature of creative ideas, yet the building blocks of new ideas are often embodied in existing knowledge. From this perspective, balancing atypical knowledge with conventional knowledge may be critical to the link between innovativeness and impact. Our analysis of 17.9 million papers spanning all scientific fields suggests that science follows a nearly universal pattern: The highest-impact science is primarily grounded in exceptionally conventional combinations of prior work yet simultaneously features an intrusion of unusual combinations. Papers of this type were twice as likely to be highly cited works. Novel combinations of prior work are rare, yet teams are 37.7% more likely than solo authors to insert novel combinations into familiar knowledge domains. PMID:24159044

  7. 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

  8. 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

  9. Antipsychotic-induced sensitization and tolerance: Behavioral characteristics, developmental impacts, and neurobiological mechanisms.

    PubMed

    Li, Ming

    2016-08-01

    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

  10. 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

  11. Recognition of patients who would benefit from LAI antipsychotic treatment: how to assess adherence.

    PubMed

    Correll, Christoph U

    2014-11-01

    Many patients with schizophrenia have problems adhering to their medication regimen. Numerous factors affect patients' adherence, such as patient and illness characteristics; medication efficacy, tolerability and formulations; provider and system characteristics; and patients' support networks. To compound this problem, accurately measuring adherence is challenging. Data suggest that clinicians should use multiple methods to assess patients' adherence, including supplementing their own clinical judgment and patient reports with more objective measures. Patients with poor social support, substance abuse disorders, or a history of florid psychosis and those in the earlier phases of their illness may be at risk for nonadherence. Assessing patients for nonadherence is a key step in determining their optimal form of treatment and avoiding frequent switching or deterioration. Doing so, clinicians can identify patients who would potentially benefit from a long-acting injectable (LAI) antipsychotic, which can be a valuable treatment option. Because lack of adherence increases the risk of hospitalization and does not help prevent suicide attempts, clinicians should address barriers to adherence, provide psychoeducation about medication-taking behaviors, and offer a wide range of antipsychotic treatment options, including LAIs, to improve patient outcomes. PMID:25470105

  12. Nonadherence to antipsychotics: the role of positive attitudes towards positive symptoms.

    PubMed

    Moritz, Steffen; Hünsche, Alexandra; Lincoln, Tania M

    2014-11-01

    Approximately 50-75% of all patients do not take their antipsychotic medication as prescribed. The current study examined reasons why patients continue versus discontinue antipsychotic medication. We were particularly interested to which extent positive attitudes towards psychotic symptoms foster medication nonadherence. An anonymous online questionnaire was set up to decrease response biases. After a strict selection process, 91 participants with schizophrenia spectrum disorders were retained for the final analyses. On average, 6.2 different reasons for nonadherence were reported. Side-effects (71.4%), sudden subjective symptom improvement (52.4%) and forgetfulness (33.3%) emerged as the most frequent reasons for drug discontinuation. Approximately one fourth of all participants (27.3%) reported at least one positive aspect of psychosis as a reason for nonadherence. In contrast, patients reported on average 3.5 different reasons for adherence (e.g., want to live a normal life (74.6%) and fear of psychotic symptoms (49.3%)). The belief that paranoia represents a survival strategy (subscale derived from the Beliefs about Paranoia Scale) was significantly associated with nonadherence. Patients' attitudes toward medication and the individual illness model need to be carefully considered when prescribing medication. In particular for patients who are likely to discontinue psychopharmacological treatment complementary or alternative psychological treatment should be sought because of a largely increased risk of relapse in the case of sudden drug discontinuation. PMID:25444234

  13. 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

  14. Repeated effects of the neurotensin receptor agonist PD149163 in three animal tests of antipsychotic activity: assessing for tolerance and cross-tolerance to clozapine

    PubMed Central

    Chou, Shinnyi; Davis, Collin; Jones, Sean; Li, Ming

    2014-01-01

    Neurotensin is an endogenous neuropeptide closely associated with the mesolimbic dopaminergic system and shown to possess antipsychotic-like effects. In particular, acute neurotensin receptor activation can inhibit conditioned avoidance response (CAR), attenuate phencyclidine (PCP)-induced prepulse inhibition (PPI) disruptions, and reverse PCP-induced hyperlocomotion. However, few studies have examined the long term effects of repeated neurotensin receptor activation and results are inconsistent. Since clinical administration of antipsychotic therapy often requires a prolonged treatment schedule, here we assessed the effects of repeated activation of neurotensin receptors using an NTS1 receptor selective agonist, PD149163, in 3 behavioral tests of antipsychotic activity. We also investigated whether reactivity to the atypical antipsychotic clozapine was altered following prior PD149163 treatment. Using both normal and prenatally immune activated rats generated through maternal immune activation with polyinosinic:polycytidilic acid, we tested PD149163 in CAR, PCP (1.5 mg/kg)-induced PPI disruption, and PCP (3.2 mg/kg)-induced hyperlocomotion. For each paradigm, rats were first repeatedly tested with vehicle or PD149163 (1.0, 4.0, 8.0 mg/kg, sc) along with vehicle or PCP for PPI and hyperlocomotion tests, then challenged with PD149163 after 2 drug-free days. All rats were then challenged with clozapine (5.0 mg/kg, sc). During the repeated test period, PD149163 exhibited antipsychotic-like effects in all three models. On the PD149163 challenge day, prior drug treatment only caused a tolerance effect in CAR. This tolerance in CAR was transferrable to clozapine, as it enhanced clozapine tolerance in the same group of animals. Although no tolerance effect was seen in the PD149163 challenge for the PCP-induced hyperlocomotion test, the clozapine challenge showed increased sensitivity in groups previously exposed to repeated PD149163 treatment. Our findings suggest

  15. 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. PMID:26075840

  16. Olanzapine Activates Hepatic Mammalian Target of Rapamycin: New Mechanistic Insight into Metabolic Dysregulation with Atypical Antipsychotic Drugs

    PubMed Central

    Schmidt, Robin H.; Jokinen, Jenny D.; Massey, Veronica L.; Falkner, K. Cameron; Shi, Xue; Yin, Xinmin; Zhang, Xiang; Beier, Juliane I.

    2013-01-01

    Olanzapine (OLZ), an effective treatment of schizophrenia and other disorders, causes weight gain and metabolic syndrome. Most studies to date have focused on the potential effects of OLZ on the central nervous system’s mediation of weight; however, peripheral changes in liver or other key metabolic organs may also play a role in the systemic effects of OLZ. Thus, the purpose of this study was to investigate the effects of OLZ on hepatic metabolism in a mouse model of OLZ exposure. Female C57Bl/6J mice were administered OLZ (8 mg/kg per day) or vehicle subcutaneously by osmotic minipumps for 28 days. Liver and plasma were taken at sacrifice for biochemical analyses and for comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry metabolomics analysis. OLZ increased body weight, fat pad mass, and liver-to-body weight ratio without commensurate increase in food consumption, indicating that OLZ altered energy expenditure. Expression and biochemical analyses indicated that OLZ induced anaerobic glycolysis and caused a pseudo-fasted state, which depleted hepatic glycogen reserves. OLZ caused similar effects in cultured HepG2 cells, as determined by Seahorse analysis. Metabolomic analysis indicated that OLZ increased hepatic concentrations of amino acids that can alter metabolism via the mTOR pathway; indeed, hepatic mTOR signaling was robustly increased by OLZ. Interestingly, OLZ concomitantly activated AMP-activated protein kinase (AMPK) signaling. Taken together, these data suggest that disturbances in glucose and lipid metabolism caused by OLZ in liver may be mediated, at least in part, via simultaneous activation of both catabolic (AMPK) and anabolic (mammalian target of rapamycin) pathways, which yields new insight into the metabolic side effects of this drug. PMID:23926289

  17. Imaging appearances of atypical hydatid cysts

    PubMed Central

    Malik, Amita; Chandra, Ranjan; Prasad, Rajni; Khanna, Geetika; Thukral, Brij B

    2016-01-01

    Hydatid disease continues to be a significant health problem in many parts of the world. It can occur in any part of the body, but liver is the commonest site of involvement. The disease may remain asymptomatic for years. Symptoms occur due to compression of local structures or complications like rupture and infection. The diagnosis is clear when typical radiological appearance is observed at the common sites of involvement. Complications give rise to atypical appearances. These coupled with unusual localizations pose diagnostic difficulty. The aim of this pictorial essay is to demonstrate the atypical manifestations of hydatid cysts – atypical either due to complications or the unusual site. PMID:27081221

  18. Intramuscular long-acting paliperidone palmitate in acute patients with schizophrenia unsuccessfully treated with oral antipsychotics.

    PubMed

    Hargarter, Ludger; Cherubin, Pierre; Bergmans, Paul; Keim, Sofia; Rancans, Elmars; Bez, Yasin; Parellada, Eduard; Carpiniello, Bernardo; Vidailhet, Pierre; Schreiner, Andreas

    2015-04-01

    In this prospective multicentre, open-label, 6-month study (Paliperidone Palmitate Flexible Dosing in Schizophrenia [PALMFlexS]), tolerability, safety and treatment response with paliperidone palmitate (PP) were explored in patients with acute symptoms of schizophrenia following switching from previously unsuccessful treatment with oral antipsychotics. This pragmatic study was conducted in a large, more representative sample of the general schizophrenia population compared to randomized controlled pivotal trials, to specifically mimic real-world clinical situations. After initiation on Day 1 and Day 8, patients received PP once monthly at flexible doses (50-150mgeq.) intramuscularly. The primary efficacy outcome was defined as the percentage of patients achieving ≥30% improvement in PANSS total score from baseline (BL) to last-observation-carried-forward (LOCF) endpoint (EP). Safety and tolerability assessments included Extrapyramidal Symptom Rating Scale (ESRS) total score and treatment-emergent adverse events (TEAEs). Overall, 212 patients received PP at least once after switching from oral antipsychotics, primarily due to lack of efficacy (45.8%). Significant improvements from BL in mean (SD) PANSS total score were observed from Day 8 onwards (BL to LOCF EP: -31.0 [29.0]; p<0.0001). At endpoint, two-thirds (66.7%) and 43.5% of patients achieved a ≥30% and ≥50% improvement in mean PANSS total score, respectively. PP was associated with significant improvements across secondary measures of symptom severity, subjective well-being, medication satisfaction, illness-related disorders of activity and participation, and patient functioning (p<0.0001; BL to LOCF EP). PP was generally well tolerated, with significant reductions in ESRS total score (p<0.0001) and mainly mild-to-moderate TEAEs. TEAEs reported in ≥5% of patients were injection-site pain (13.7%), insomnia (10.8%), psychotic disorder (10.4%), headache and anxiety (both 6.1%). The PALMFlexS study

  19. 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

  20. 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

  1. Antipsychotic-like effect of minocycline in a rat model

    PubMed Central

    Dokuyucu, Recep; Kokacya, Hanifi; Inanir, Sema; Copoglu, Umit Sertan; Erbas, Oytun

    2014-01-01

    Objectives: Tetracycline antibiotic drug minocycline has strongly neuroprotective and anti-inflammatory effects. Minocycline has also remarkable brain tissue penetration, is clinically entirely tolerated and properly absorbed when taken orally. In our study, we class with the effects of minocycline and chlorpromazine, a conventional antipsychotic drug, by evaluating the novelty-induced rearing, apomorphine-induced stereotypic behavior, and brain MDA levels in rats. Materials and Methods: Four groups of rat (n = 7) were applied with minocycline (50 and 100 mg/kg, i.p.), chlorpromazine (1 mg/kg, i.p.), or isotonic saline (1 mL/kg, i.p.). One hour later, apomorphine (2 mg/kg, s.c.) was applied to each rat. Result: Our results showed that both doses of minocycline significantly decreased the rearing behavior in rats, whereas the decrease with chlorpromazine was higher. Minocycline also decreased the stereotypy scores in a dose-dependent manner. Conclusion: We concluded that minocycline has beneficial effects on rearing behavior and stereotypy, which are accepted to be indicators of antipsychotic effect. Taken together, minocycline, as an anti-oxidant and cytoprotective agent, can be useful in neuroprotection especially on early stages of psychosis or prepsychotic patients with insignificant symptoms. Minocycline is worthy of being investigated for its anti-psychotic effects as a primary or an adjunctive drug. PMID:25419368

  2. First-generation antipsychotics: not gone but forgotten.

    PubMed

    Dibben, Claire R M; Khandaker, Golam M; Underwood, Benjamin R; O'Loughlin, Christopher; Keep, Catherine; Mann, Louisa; Jones, Peter B

    2016-04-01

    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

  3. Adjunctive metformin for antipsychotic-induced hyperprolactinemia: A systematic review.

    PubMed

    Bo, Qi-Jing; Wang, Zhi-Min; Li, Xian-Bin; Ma, Xin; Wang, Chuan-Yue; de Leon, Jose

    2016-03-30

    This systematic review examines adjunctive metformin therapy for the treatment of antipsychotic-induced hyperprolactinemia. A computerized search of databases in Chinese and the international databases in English provided three trials with a total of 325 patients including one randomized clinical trial (RCT) and two observational studies (single-group, before-after design). A meta-analysis could not be conducted. The quality of evidence ranged from "very low" to "moderate". Metformin patients had a significant decrease in serum prolactin level with a mean of 54.6μg/l in the three trials. In the RCT, menstruation restarted in 67% of those with menstrual disturbances versus 5% in placebo. In one observational study, 91% of patients no longer had signs or symptoms of galactorrhea. In the RCT, adverse drug reactions (ADRs) occurred at similar incidence rates among metformin and placebo patients, except that no significant increases in nausea, insomnia and agitation occurred which were not associated with discontinuations. Our systematic review indicated that adjunctive metformin significantly lowered prolactin level and relieved prolactin-related symptoms in patients with antipsychotic-induced hyperprolactinemia. Future higher quality RCTs need to verify the currently available limited evidence based on three trials which suggest that adjunctive metformin may be used effectively and safely for antipsychotic-induced hyperprolactinemia. PMID:26822064

  4. Pharmacological treatment of antipsychotic-induced dyslipidemia and hypertension.

    PubMed

    Tse, Lurdes; Procyshyn, Ric M; Fredrikson, Diane H; Boyda, Heidi N; Honer, William G; Barr, Alasdair M

    2014-05-01

    Second-generation antipsychotics (SGAs) are associated with significant comorbid metabolic abnormalities. Adjunct medications may be prescribed to treat these metabolic side effects, but the evidence supporting this practice (especially for the management of antipsychotic-associated dyslipidemia and hypertension) is limited. The purpose of this review was to evaluate the effects of adjunct medications on triglyceride, total cholesterol, low-density lipoprotein, high-density lipoprotein, and blood pressure levels in participants taking SGAs for psychosis. Studies were systematically searched and evaluated. Studies were included for review if participants were taking SGAs and if lipid and/or blood pressure levels were included as outcome measures. Statins, conventional lipid-lowering agents, fluvoxamine, ramelteon, topiramate, valsartan, telmisartan, omega-3 fatty acids, metformin (including both immediate-release and extended-release formulations), and a combination of metformin-sibutramine seemed to have beneficial effects on lipid levels. Valsartan, telmisartan, and topiramate appeared to be effective for controlling increases in blood pressure. The literature on adjunct medications for the treatment of antipsychotic-associated dyslipidemia and hypertension is not exhaustive, and long-term randomized-controlled trials would offer valuable results. PMID:24169026

  5. 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

  6. Experiencing antipsychotic discontinuation: results from a survey of Australian consumers.

    PubMed

    Salomon, C; Hamilton, B; Elsom, S

    2014-12-01

    Despite high reported rates of antipsychotic non-adherence, little is known about consumer experiences during discontinuation. This study was designed to increase understanding of antipsychotic discontinuation from consumer perspectives. In 2011-2012, 98 Australian consumers involved with participating organizations completed an anonymous survey detailing past antipsychotic discontinuation attempts. Of the 88 participants who reported at least one discontinuation attempt, over half (n = 47, 54.7%) reported stopping without clinician knowledge or support. This group was 35% (confidence interval 15.4-54.6%) more likely to stop abruptly than those (n = 41, 45.3%) stopping with clinician support (P = 0.002). Only 10 participants (23.3%) recalled being given information about discontinuation symptoms other than relapse; however, 68 participants (78.2%) reported experiencing a range of discontinuation symptoms including physical, cognitive, emotional, psychotic or sleep-related disturbances. Findings cannot be readily generalized because of sampling constraints. However, the significant number of participants who reported discontinuation symptoms, in addition to psychosis, is consistent with previous research. This study provides new insight into consumer motivations for discontinuation and possible problems in clinical communication that may contribute to frequent non-collaborative discontinuation attempts. Mental health nurses, who play a pivotal role in medication communication events, may benefit from increased awareness of consumer perspectives on this topic. PMID:25298092

  7. 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

  8. Altered heart rate dynamics associated with antipsychotic-induced subjective restlessness in patients with schizophrenia

    PubMed Central

    Kim, Jong-Hoon; Ann, Jun-Hyung; Lee, Jinyoung; Kim, Mee-Hee; Han, Ah-Young

    2013-01-01

    Background Antipsychotic-induced subjective inner restlessness is one of the common and distressing adverse effects associated with antipsychotics; however, its underlying neurobiological basis is not well understood. We examined the relationship between antipsychotic-induced subjective inner restlessness and autonomic neurocardiac function. Methods Twenty-two schizophrenia patients with antipsychotic-induced subjective restlessness, 28 schizophrenia patients without antipsychotic-induced subjective restlessness, and 28 matched healthy control subjects were evaluated. Assessments of the linear and nonlinear complexity measures of heart rate dynamics were performed. Multivariate analysis of variance and correlation analysis were conducted. Results The mean interbeat (RR) interval value was significantly higher in control subjects than in patients with and without antipsychotic-induced subjective restlessness (P < 0.05). The low frequency/high frequency ratio was significantly higher in patients with antipsychotic-induced subjective restlessness than in control subjects and in patients without antipsychotic-induced subjective restlessness (P < 0.05), while the approximate entropy value was significantly lower in patients with antipsychotic-induced subjective restlessness than in control subjects and in patients without antipsychotic-induced subjective restlessness (P < 0.05). Correlation analyses controlling for psychotic symptom severity showed that the degree of antipsychotic-induced restlessness had a significant negative correlation with the value of approximate entropy (P < 0.05). Conclusion The results indicate that antipsychotic-induced subjective restlessness is associated with altered heart rate dynamics parameters, particularly the nonlinear complexity measure, suggesting that it might adversely affect autonomic neurocardiac integrity. Further prospective research is necessary to elucidate the precise interrelationships and causality. PMID:23986638

  9. 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

  10. The inhibitory effect of the antipsychotic drug haloperidol on HERG potassium channels expressed in Xenopus oocytes

    PubMed Central

    Suessbrich, H; Schönherr, R; Heinemann, S H; Attali, B; Lang, F; Busch, A E

    1997-01-01

    The antipsychotic drug haloperidol can induce a marked QT prolongation and polymorphic ventricular arrhythmias. In this study, we expressed several cloned cardiac K+ channels, including the human ether-a-go-go related gene (HERG) channels, in Xenopus oocytes and tested them for their haloperidol sensitivity.Haloperidol had only little effects on the delayed rectifier channels Kv1.1, Kv1.2, Kv1.5 and IsK, the A-type channel Kv1.4 and the inward rectifier channel Kir2.1 (inhibition <6% at 3 μM haloperidol).In contrast, haloperidol blocked HERG channels potently with an IC50 value of approximately 1 μM. Reduced haloperidol, the primary metabolite of haloperidol, produced a block with an IC50 value of 2.6 μM.Haloperidol block was use- and voltage-dependent, suggesting that it binds preferentially to either open or inactivated HERG channels. As haloperidol increased the degree and rate of HERG inactivation, binding to inactivated HERG channels is suggested.The channel mutant HERG S631A has been shown to exhibit greatly reduced C-type inactivation which occurs only at potentials greater than 0 mV. Haloperidol block of HERG S631A at 0 mV was four fold weaker than for HERG wild-type channels. Haloperidol affinity for HERG S631A was increased four fold at +40 mV compared to 0 mV.In summary, the data suggest that HERG channel blockade is involved in the arrhythmogenic side effects of haloperidol. The mechanism of haloperidol block involves binding to inactivated HERG channels. PMID:9138706

  11. The tyrosine phosphatase STEP: implications in schizophrenia and the molecular mechanism underlying antipsychotic medications.

    PubMed

    Carty, N C; Xu, J; Kurup, P; Brouillette, J; Goebel-Goody, S M; Austin, D R; Yuan, P; Chen, G; Correa, P R; Haroutunian, V; Pittenger, C; Lombroso, P J

    2012-01-01

    Glutamatergic signaling through N-methyl-D-aspartate receptors (NMDARs) is required for synaptic plasticity. Disruptions in glutamatergic signaling are proposed to contribute to the behavioral and cognitive deficits observed in schizophrenia (SZ). One possible source of compromised glutamatergic function in SZ is decreased surface expression of GluN2B-containing NMDARs. STEP(61) is a brain-enriched protein tyrosine phosphatase that dephosphorylates a regulatory tyrosine on GluN2B, thereby promoting its internalization. Here, we report that STEP(61) levels are significantly higher in the postmortem anterior cingulate cortex and dorsolateral prefrontal cortex of SZ patients, as well as in mice treated with the psychotomimetics MK-801 and phencyclidine (PCP). Accumulation of STEP(61) after MK-801 treatment is due to a disruption in the ubiquitin proteasome system that normally degrades STEP(61). STEP knockout mice are less sensitive to both the locomotor and cognitive effects of acute and chronic administration of PCP, supporting the functional relevance of increased STEP(61) levels in SZ. In addition, chronic treatment of mice with both typical and atypical antipsychotic medications results in a protein kinase A-mediated phosphorylation and inactivation of STEP(61) and, consequently, increased surface expression of GluN1/GluN2B receptors. Taken together, our findings suggest that STEP(61) accumulation may contribute to the pathophysiology of SZ. Moreover, we show a mechanistic link between neuroleptic treatment, STEP(61) inactivation and increased surface expression of NMDARs, consistent with the glutamate hypothesis of SZ. PMID:22781170

  12. The tyrosine phosphatase STEP: implications in schizophrenia and the molecular mechanism underlying antipsychotic medications

    PubMed Central

    Carty, N C; Xu, J; Kurup, P; Brouillette, J; Goebel-Goody, S M; Austin, D R; Yuan, P; Chen, G; Correa, P R; Haroutunian, V; Pittenger, C; Lombroso, P J

    2012-01-01

    Glutamatergic signaling through N-methyl-D-aspartate receptors (NMDARs) is required for synaptic plasticity. Disruptions in glutamatergic signaling are proposed to contribute to the behavioral and cognitive deficits observed in schizophrenia (SZ). One possible source of compromised glutamatergic function in SZ is decreased surface expression of GluN2B-containing NMDARs. STEP61 is a brain-enriched protein tyrosine phosphatase that dephosphorylates a regulatory tyrosine on GluN2B, thereby promoting its internalization. Here, we report that STEP61 levels are significantly higher in the postmortem anterior cingulate cortex and dorsolateral prefrontal cortex of SZ patients, as well as in mice treated with the psychotomimetics MK-801 and phencyclidine (PCP). Accumulation of STEP61 after MK-801 treatment is due to a disruption in the ubiquitin proteasome system that normally degrades STEP61. STEP knockout mice are less sensitive to both the locomotor and cognitive effects of acute and chronic administration of PCP, supporting the functional relevance of increased STEP61 levels in SZ. In addition, chronic treatment of mice with both typical and atypical antipsychotic medications results in a protein kinase A-mediated phosphorylation and inactivation of STEP61 and, consequently, increased surface expression of GluN1/GluN2B receptors. Taken together, our findings suggest that STEP61 accumulation may contribute to the pathophysiology of SZ. Moreover, we show a mechanistic link between neuroleptic treatment, STEP61 inactivation and increased surface expression of NMDARs, consistent with the glutamate hypothesis of SZ. PMID:22781170

  13. Autophagy inhibition uncovers the neurotoxic action of the antipsychotic drug olanzapine.

    PubMed

    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

    2014-01-01

    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. Interstellar A-type methanol masers

    NASA Astrophysics Data System (ADS)

    Zeng, Q.; Lou, G. F.

    1990-02-01

    The formation conditions for A-type methanol masers are discussed. The correlation between A-type masers and external radiation fields is determined, with emphasis on the energy levels of A-type methanol and brightness temperature. Radiative transfer equations and statistical equilibrium are solved using a large velocity gradient model and the escape probability model. It is demonstrated that the 9(2)-10(1)A+ emission in W3(OH) and 7(0)-6(1)A in SgrB2 are masers, as discovered previously. The formation of the first type of masers requires pumping from an external radiation field, while the second type might be excited in the absence of an external radiation field. It is also pointed out that according to calculations there are A-type maser series similar to E-type methanol maser series of J2-J1E.

  15. Surgical Options for Atypical Facial Pain Syndromes.

    PubMed

    Rahimpour, Shervin; Lad, Shivanand P

    2016-07-01

    Atypical neuropathic facial pain is a syndrome of intractable and unremitting facial pain that is secondary to nociceptive signaling in the trigeminal system. These syndromes are often recalcitrant to pharmacotherapy and other common interventions, including microvascular decompression and percutaneous procedures. Herein, the authors present two other viable approaches (nucleus caudalis dorsal root entry zone lesioning and motor cortex stimulation), their indications, and finally a possible treatment algorithm to consider when assessing patients with atypical facial pain. PMID:27325003

  16. Results of barbiturate antiepileptic drug discontinuation on antipsychotic medication dose in individuals with intellectual disability.

    PubMed

    Hanzel, T E; Bauernfeind, J D; Kalachnik, J E; Harder, S R

    2000-04-01

    Five individuals with intellectual disability prescribed both a barbiturate antiepileptic drug (AED) and an antipsychotic medication were identified in a public residential facility. It was hypothesized that antipsychotic medication was prescribed at doses higher than necessary as a result of inadvertent barbiturate AED behavioural side-effects thought to be part of the underlying psychiatric or behavioural condition. To test this hypothesis, barbiturate AEDs were gradually reduced, and replaced with either carbamazepine or valproic acid, and antipsychotic medication was gradually reduced as well. Challenging behaviours, such as physical aggression, self-injurious behaviour and property destruction, were measured with a frequency count or partial interval recording, and retrospectively analysed for time periods of approximately 60 days before phenobarbital reduction, after phenobarbital discontinuation and after the lowest antipsychotic medication dose. Challenging behaviour collectively decreased by 81.5% after barbiturate discontinuation, mean antipsychotic medication dose significantly decreased from 146 mg day(-1) (SD = 98) to 106 mg day(-1) (SD = 88) chlorpromazine equivalence, and antipsychotic medication was discontinued in the cases of two individuals. Compared to the prebarbiturate AED reduction period, challenging behaviour collectively decreased by 96.3% after the lowest antipsychotic medication dose, which confirmed that reduced antipsychotic medication was not achieved at the expense of behaviour deterioration. The data supported the hypothesis that discontinuation of barbiturate AEDs results in decreased challenging behaviour and less antipsychotic medication. PMID:10898379

  17. 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

  18. Biopsychosocial aspects of atypical odontalgia.

    PubMed

    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 A β , A δ , and C trigeminal fiber pain perception threshold when compared to a pain-free control group. Resentment was determined to be inversely related to A β (rho: 0.62, P < 0.05), A δ (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

  19. 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

  20. 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

  1. 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

  2. Effects of antipsychotics on insight in schizophrenia: results from independent samples of first-episode and acutely relapsed patients.

    PubMed

    Misiak, Błażej; Frydecka, Dorota; Beszłej, Jan A; Moustafa, Ahmed A; Tybura, Piotr; Kucharska-Mazur, Jolanta; Samochowiec, Agnieszka; Bieńkowski, Przemysław; Samochowiec, Jerzy

    2016-07-01

    We aimed to investigate whether antipsychotics differentially impact insight and whether these effects appear because of improvement in psychopathological manifestation in 132 first-episode schizophrenia patients and 201 acutely relapsed schizophrenic patients, who were followed up for 12 weeks. Olanzapine and risperidone were administered to first-episode schizophrenia patients, whereas acutely relapsed schizophrenic patients were treated with olanzapine, perazine and ziprasidone. The Positive And Negative Syndrome Scale (PANSS) was used to assess psychopathology. Insight was assessed using the G12 item of PANSS. Unadjusted mixed-model regression analysis indicated a significant improvement in the PANSS G12 item score in both groups. There were no significant differences between distinct treatment subgroups of patients in terms of improvement in the PANSS G12 item score. After adjustment for the trajectories of changes in symptom dimensions, a decrease in the PANSS G12 item score was because of an improvement in positive, negative and excitement symptoms. A decrease in the PANSS G12 item score was also related to an increase in the severity of depressive symptomatology. Our results indicate that antipsychotics exert similar effects on insight in acute psychosis. These effects are likely because of an improvement in psychopathological manifestation. The improvement in insight might be related to the development of depressive symptoms. PMID:26836264

  3. 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

  4. 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

  5. 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

  6. 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

  7. Antipsychotic withdrawal-induced relapse predicts future relapses in institutionalized adults with severe intellectual disability.

    PubMed

    Janowsky, David S; Barnhill, L Jarrett; Khalid, Abdul S; Davis, John M

    2008-08-01

    Severe intellectual and developmental disabilities are frequently associated with aggression toward self and others, destruction of property, and disruption. Antipsychotic medications are a mainstay of treatment of such behaviors. National and state guidelines suggest stopping these medications or decreasing their dosages when possible if patients have maintained stability. The current study evaluated the likelihood of future antipsychotic drug withdrawal-induced relapses in those individuals where such a relapse had occurred previously. Subjects were 57 institutionalized adults with severe or profound intellectual disability. Between 1990 and 2000, each had experienced an initial activation of maladaptive aggressive behaviors after an attempt at antipsychotic drug withdrawal and/or termination. Quarterly behavioral reports were evaluated to determine whether subsequent antipsychotic drug withdrawal attempts were also associated with future relapses. Initial relapse was followed by subsequent antipsychotic drug withdrawal attempts in 49 of the 57 individuals. Between 1990 and 2005, 28.6% of these 49 subjects had experienced 1, 38.7% had 2, 20.4% had 3, and 8.2% had 4 additional relapses. Two (4.1%) had not relapsed. Eight individuals remained on antipsychotic agents without a subsequent withdrawal attempt. By the end of 2005, only 4 (7%) of the 57 individuals had become antipsychotic drug free, 22.8% were receiving first-generation antipsychotic agents alone, 45.6% were receiving second-generation antipsychotic agents alone, and 24.6% were receiving a combination of first- and second-generation antipsychotic agents. Thus, if relapse occurs after an antipsychotic drug withdrawal attempt, subsequent attempts at withdrawal are also very likely to lead to further relapses. PMID:18626266

  8. Approaches to improve adherence to pharmacotherapy in patients with schizophrenia

    PubMed Central

    Shuler, Kimberly M

    2014-01-01

    Purpose In patients with schizophrenia, nonadherence to prescribed medications increases the risk of patient relapse and hospitalization, key contributors to the costs associated with treatment. The objectives of this review were to evaluate the impact of nonadherence to pharmacotherapy in patients with schizophrenia as it relates to health care professionals, particularly social workers, and to identify effective team approaches to supporting patients based on studies assessing implementation of assertive community treatment teams. Materials and methods A systematic review of the medical literature was conducted by searching the Scopus database to identify articles associated with treatment adherence in patients with schizophrenia. Articles included were published from January 1, 2003, through July 15, 2013, were written in English, and reported findings concerning any and all aspects of nonadherence to prescribed treatment in patients with schizophrenia. Results Of 92 unique articles identified and formally screened, 47 met the inclusion criteria for the systematic review. The burden of nonadherence in schizophrenia is significant. Factors with the potential to affect adherence include antipsychotic drug class and formulation, patient-specific factors, and family/social support system. There is inconclusive evidence suggesting superior adherence with an atypical versus typical antipsychotic or with a long-acting injectable versus an oral formulation. Patient-specific factors that contribute to adherence include awareness/denial of illness, cognitive issues, stigma associated with taking medication, substance abuse, access to health care, employment/poverty, and insurance status. Lack of social or family support may adversely affect adherence, necessitating the assistance of health care professionals, such as social workers. Evidence supports the concept that an enhanced team-oriented approach to managing patients with schizophrenia improves adherence and supports

  9. Activity in A-type Stars

    NASA Astrophysics Data System (ADS)

    Balona, L. A.

    2013-12-01

    Kepler photometry shows that most A-type stars have low frequency variations which can be understood in terms of rotational modulation. Indeed, the distribution of equatorial velocities derived from the photometric periods agrees with the distribution of equatorial velocities of A-type stars in the general field. The amplitude of the rotational frequency varies by 20-30 percent as might be expected of star spots. From the light amplitudes we estimate that most spots are considerably larger than typical sunspots but generally smaller than the largest sunspots. The rotation peaks in the periodograms of a significant fraction of A-type stars have a peculiar structure which is not understood. Although peaks corresponding to the rotation frequency can be identified in many δ Scuti stars, the low frequency peaks in these stars are too numerous to be caused by rotational modulation. It thus appears that while the variability of non-pulsating A stars can be explained by rotation, the low-frequency variability in A-type δ Sct stars requires a new pulsation mechanism. We also find several γ Dor stars much hotter than the theoretical hot edge of the instability strip. We find 13 new A-type flare stars, which means that about 1.5 percent of A stars flare. Less dramatic flares may be common in all A-type stars. We show that these superflares cannot be attributed to normal flares on a cool companion. We conclude that A-type stars are active and, like cooler stars, have starspots and flares. Surprisingly, there does not seem to be a drop in activity as the granulation boundary is crossed.

  10. Pharmacological Strategies to Counteract Antipsychotic-Induced Weight Gain and Metabolic Adverse Effects in Schizophrenia: A Systematic Review and Meta-analysis

    PubMed Central

    Mizuno, Yuya; Suzuki, Takefumi; Nakagawa, Atsuo; Yoshida, Kazunari; Mimura, Masaru; Fleischhacker, Walter Wolfgang; Uchida, Hiroyuki

    2014-01-01

    Background: Antipsychotic-induced metabolic adversities are often difficult to manage. Using concomitant medications to counteract these adversities may be a rational option. Objective: To systematically determine the effectiveness of medications to counteract antipsychotic-induced metabolic adversities in patients with schizophrenia. Data Sources: Published articles until November 2013 were searched using 5 electronic databases. Clinical trial registries were searched for unpublished trials. Study Selection: Double-blind randomized placebo-controlled trials focusing on patients with schizophrenia were included if they evaluated the effects of concomitant medications on antipsychotic-induced metabolic adversities as a primary outcome. Data Extraction: Variables relating to participants, interventions, comparisons, outcomes, and study design were extracted. The primary outcome was change in body weight. Secondary outcomes included clinically relevant weight change, fasting glucose, hemoglobin A1c, fasting insulin, insulin resistance, cholesterol, and triglycerides. Data Synthesis: Forty trials representing 19 unique interventions were included in this meta-analysis. Metformin was the most extensively studied drug in regard to body weight, the mean difference amounting to −3.17 kg (95% CI: −4.44 to −1.90 kg) compared to placebo. Pooled effects for topiramate, sibutramine, aripiprazole, and reboxetine were also different from placebo. Furthermore, metformin and rosiglitazone improved insulin resistance, while aripiprazole, metformin, and sibutramine decreased blood lipids. Conclusion: When nonpharmacological strategies alone are insufficient, and switching antipsychotics to relatively weight-neutral agents is not feasible, the literature supports the use of concomitant metformin as first choice among pharmacological interventions to counteract antipsychotic-induced weight gain and other metabolic adversities in schizophrenia. PMID:24636967

  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. 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…

  13. 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…

  14. 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…

  15. A Systemic Review and Experts' Consensus for Long-acting Injectable Antipsychotics in Bipolar Disorder.

    PubMed

    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

    2015-08-31

    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

  16. Representation of People with Intellectual Disabilities in Randomised Controlled Trials on Antipsychotic Treatment for Behavioural Problems

    ERIC Educational Resources Information Center

    Scheifes, A.; Stolker, J. J.; Egberts, A. C. G.; Nijman, H. L. I.; Heerdink, E. R.

    2011-01-01

    Background: Behavioural problems are common in people with intellectual disability (ID) and are often treated with antipsychotics. Aim: To establish the frequency and characteristics of people with ID included in randomised controlled trials (RCTs) on antipsychotic treatment for behavioural problems, and to investigate the quality of these RCTs.…

  17. 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

  18. Regional variation and clinical indicators of antipsychotic use in residential treatment: a four-state comparison.

    PubMed

    Rawal, Purva H; Lyons, John S; MacIntyre, James C; Hunter, John C

    2004-01-01

    The last decade saw an increase in psychotropic use with pediatric populations. Antipsychotic prescriptions are used frequently in residential treatment settings, with many youth receiving antipsychotics for off-label indications. Residential treatment data from 4 states were examined to determine if regional variation exists in off-label prescription and what clinicalfactors predict use. The study used clinical and pharmacological data collected via retrospective chart reviews (N = 732). The Child and Adolescent Needs and Strengths Assessment-Mental Health Version was used to measure symptom and risk severity. Of youth receiving antipsychotics, 42.9% had no history of or current psychosis. Statistical analyses resulted in significant regional variation in use across states and yielded attention deficit/impulsivity, physical aggression, elopement, sexually abusive behavior, and criminal behavior as factors associated with antipsychotic prescription in nonpsychotic youth. Antipsychotic prescription is inconsistent across states. Off-label prescription is frequent and likelihood of use increases with behavior problems. PMID:15255225

  19. Abnormalities in the fatty acid composition of the postmortem orbitofrontal cortex of schizophrenic patients: gender differences and partial normalization with antipsychotic medications.

    PubMed

    McNamara, Robert K; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Hahn, Chang-Gyu; Richtand, Neil M; Stanford, Kevin E

    2007-03-01

    Previous studies have observed significant abnormalities in the fatty acid composition of peripheral tissues from drug-naïve first-episode schizophrenic (SZ) patients relative to normal controls, including deficits in omega-3 and omega-6 polyunsaturated fatty acids, which are partially normalized following chronic antipsychotic treatment. We hypothesized that postmortem cortical tissue from patients with SZ would also exhibit deficits in cortical docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA; 20:4n-6) relative to normal controls, and that these deficits would be greater in drug-free SZ patients. We determined the total fatty acid composition of postmortem orbitofrontal cortex (OFC) (Brodmann area 10) from drug-free and antipsychotic-treated SZ patients (n=21) and age-matched normal controls (n=26) by gas chromatography. After correction for multiple comparisons, significantly lower DHA (-20%) concentrations, and significantly greater vaccenic acid (VA) (+12.5) concentrations, were found in the OFC of SZ patients relative to normal controls. Relative to age-matched same-gender controls, OFC DHA deficits, and elevated AA:DHA, oleic acid:DHA and docosapentaenoic acid (22:5n-6):DHA ratios, were found in male but not female SZ patients. SZ patients that died of cardiovascular-related disease exhibited lower DHA (-31%) and AA (-19%) concentrations, and greater OA (+20%) and VA (+17%) concentrations, relative to normal controls that also died of cardiovascular-related disease. OFC DHA and AA deficits, and elevations in oleic acid and vaccenic acid, were numerically greater in drug-free SZ patients and were partially normalized in SZ patients treated with antipsychotic medications (atypical>typical). Fatty acid abnormalities could not be wholly attributed to lifestyle or postmortem tissue variables. These findings add to a growing body of evidence implicating omega-3 fatty acid deficiency as well as the OFC in the pathoaetiology of SZ, and suggest that

  20. Sulfotransferase 4A1 Haplotype 1 (SULT4A1-1) Is Associated With Decreased Hospitalization Events in Antipsychotic-Treated Patients With Schizophrenia

    PubMed Central

    Liu, Qian; Ramsey, Timothy L.; Meltzer, Herbert Y.; Massey, Bill W.; Padmanabhan, Saranya

    2012-01-01

    Objective: To evaluate a common genetic variant, sulfotransferase 4A1 haplotype 1 (SULT4A1-1), as a predictor of hospitalization events due to the exacerbation of schizophrenia for patients treated with antipsychotic medications. Haplotypes were determined using single nucleotide polymorphism data. Method: The study included 417 white subjects from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study with a DSM-IV diagnosis of schizophrenia. Patients were assigned to 1 of 4 atypical antipsychotics (olanzapine, quetiapine, risperidone, or ziprasidone) or to the first-generation antipsychotic perphenazine. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to measure if haplotype status impacted hospitalization events for these 5 treatments. Haplotype status was evaluated for its relationship to hospitalization events regardless of treatment and for the individual treatments, with or without previous exacerbation. Data for the CATIE study were collected from January 2001 to December 2004. The current post hoc analysis was performed between May 2011 and August 2011. Results: In phase 1 of the trial, considering only the first hospitalization events, the haplotype had a significant impact on hospitalization events, with a hazard ratio for SULT4A1-1(−) versus SULT4A1-1(+) of 2.54 (P = .048). When prior exacerbation was included in the model for phase 1, the hazard ratio was 2.34 (P = .072) considering only the first hospitalization event and 2.71 (P = .039) considering all hospitalization events in the phase. When data for all phases were evaluated, SULT4A1-1(−) status was associated with increased hospitalization risk for subjects treated with olanzapine, with a hazard ratio of 8.26 (P = .041), and possibly for subjects treated with quetiapine, with a hazard ratio of 6.80 (P = .070). Conclusions: The SULT4A1-1 haplotype may be an important predictor of risk of hospitalization. SULT4A1-1(+) status was

  1. 'The worm that got away': parainfectious atypical optic neuritis associated with schistosomiasis infection.

    PubMed

    Osman, Chinar; Hannigan, Sally; Ditchfield, Adam; Harden, Stephen; Marshall, Ben; Pinto, Ashwin Arnold

    2016-06-01

    Although optic neuritis is commonly associated with multiple sclerosis, patients with atypical optic neuritis require further investigations to exclude other associated conditions. We report a woman presenting with cough, fatigue, atypical optic neuritis with chiasmitis. She responded partially to corticosteroids and we subsequently found she had a ground-glass lung nodule. Follow-up CT scan of thorax at 12 months showed new parenchymal lung lesions that suggested schistosomiasis. Further questioning by a respiratory physician identified, in retrospect, a previous exposure history; serological testing confirmed schistosoma infection. She was treated with praziquantel and slowly improved clinically, with radiological improvement in the optic chiasm, regression of the parenchymal lung lesions but with the ground glass nodule unchanged. We diagnosed parainfectious optic neuritis associated with schistosomiasis, based upon exposure history, serological confirmation and radiological features, together with the response to treatment, and having excluded other causes of an atypical optic neuritis. PMID:26888797

  2. Skin Self-Examinations and Visual Identification of Atypical Nevi: Comparing Individual and Crowdsourcing Approaches

    PubMed Central

    King, Andy J.; Gehl, Robert; Grossman, Douglas; Jensen, Jakob D.

    2013-01-01

    Purpose Skin self-examination (SSE) is one method for identifying atypical nevi among members of the general public. Unfortunately, past research has shown that SSE has low sensitivity in detecting atypical nevi. The current study investigates whether crowdsourcing (collective effort) can improve SSE identification accuracy. Collective effort is potentially useful for improving people’s visual identification of atypical nevi during SSE because, even when a single person has low reliability at a task, the pattern of the group can overcome the limitations of each individual. Methods Adults (N = 500) were recruited from a shopping mall in the Midwest. Participants viewed educational pamphlets about SSE and then completed a mole identification task. For the task, participants were asked to circle mole images that appeared atypical. Forty nevi images were provided; nine of the images were of nevi that were later diagnosed as melanoma. Results Consistent with past research, individual effort exhibited modest sensitivity (.58) for identifying atypical nevi in the mole identification task. As predicted, collective effort overcame the limitations of individual effort. Specifically, a 19% collective effort identification threshold exhibited superior sensitivity (.90). Conclusions The results of the current study suggest that limitations of SSE can be countered by collective effort, a finding that supports the pursuit of interventions promoting early melanoma detection that contain crowdsourcing visual identification components. PMID:24075797

  3. 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

  4. 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

  5. Atypical arthritis revisited: Acute rheumatic fever

    PubMed Central

    Shankar, Binoy; Bhutia, Euden; Kumar, Dinesh

    2016-01-01

    A 13-year-old boy presented with vague musculoskeletal pain and involvement of multiple small and large joints along with axial skeleton for the last 3 years, poorly responsive to aspirin. However, on account of presence of carditis and fulfilment of Jones criteria, a diagnosis of acute rheumatic fever (ARF) with atypical arthritis was made. We report this case to break the myth and sensitize pediatricians and rheumatologists to keep the possibility of atypical articular presentations, as in our case, in patients with ARF and prevent delayed diagnosis and treatment. PMID:27212853

  6. Association between atypical parathyroid adenoma and neurofibromatosis.

    PubMed

    Favere, Aline Mesquita Ferreira de; Tsukumo, Daniela Miti; Matos, Patrícia Sabino de; Santos, Sérgio Luiz Marques dos; Lalli, Cristina Alba

    2015-10-01

    Primary hyperparathyroidism is a disease characterized by excessive production of parathyroid hormone (PTH), which is due to a parathyroid adenoma in 85% of cases. An atypical parathyroid adenoma, with some histopathological features of parathyroid carcinoma, may be found in some of the cases, although it may not fulfill all the criteria for this diagnosis. Neurofibromatosis type 1 (NF1) is an autosomal dominant systemic disease that may be associated with hyperparathyroidism. We report here the rare combination of a patient with NF1 and clinical manifestations of hyperparathyroidism due to an atypical parathyroid adenoma. PMID:26421674

  7. 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

  8. Beyond Dopamine: Glutamate as a Target for Future Antipsychotics

    PubMed Central

    Sendt, Kyra-Verena; Giaroli, Giovanni; Tracy, Derek K.

    2012-01-01

    The dopamine hypothesis of schizophrenia remains the primary theoretical framework for the pharmacological treatment of the disorder. Despite various lines of evidence of dopaminergic abnormalities and reasonable efficacy of current antipsychotic medication, a significant proportion of patients show suboptimal treatment responses, poor tolerability, and a subsequent lack of treatment concordance. In recent decades, intriguing evidence for the critical involvement of other neurotransmitter systems in the pathophysiology of schizophrenia has emerged, most notably of dysfunctions within the glutamate pathways. Consequently, the glutamate synapse has arisen as a promising target for urgently needed novel antipsychotic compounds—particularly in regards to debilitating negative and cognitive symptoms poorly controlled by currently available drugs. In this paper, recent findings integrating glutamatergic and dopaminergic abnormalities in schizophrenia and their implications for novel pharmacological targets are discussed. An overview of compounds in various stages of development is given: drugs enhancing NMDA receptor function as well as metabotropic glutamate receptor (mGluR) agonist and positive allosteric modulators (PAMs) are emphasised. Together with other agents more indirectly affecting glutamatergic neurotransmission, their potential future role in the pharmacotherapy of schizophrenia is critically evaluated. PMID:22830044

  9. 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

  10. 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

  11. Antipsychotic-Like Effect of Trimetazidine in a Rodent Model

    PubMed Central

    Erbaş, Oytun; Akseki, Hüseyin Serdar; Eliküçük, Betül; Taşkıran, Dilek

    2013-01-01

    Trimetazidine (TMZ) has been used as an anti-ischemic agent for angina pectoris, chorioretinal disturbances, and vertigo. Also, it can induce extrapyramidal type adverse reaction such as parkinsonism, gait disorder, and tremor via blockade of D2 receptors. In the present study, we evaluated the effect of TMZ on novelty-induced rearing behavior and apomorphine-induced stereotypy behavior in male rats. Four groups of rat (n = 7) were administrated with TMZ (10 and 20 mg/kg, i.p.), chlorpromazine (1 mg/kg, i.p.), or isotonic saline. One hour later, apomorphine (2 mg/kg, s.c.) was administrated to each rat. Our results showed that both doses of TMZ significantly decreased the rearing behavior in rats, whereas the decrease with chlorpromazine was higher. TMZ also decreased the stereotypy scores in a dose-dependent manner. We concluded that TMZ has beneficial effects on rearing behavior and stereotypy, which are accepted to be indicators of antipsychotic effect. Taken together, with its antioxidative and cytoprotective properties, TMZ is worthy of being investigated for its anti-psychotic effects as a primary or an adjunctive drug. PMID:24250273

  12. 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

  13. 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

  14. Pipotiazine palmitate: an evaluation of a new long acting intramuscular antipsychotic agent in severely ill schizophrenic patients.

    PubMed

    Gallant, D M; Mielke, D; Bishop, G; Oelsner, T; Guerrero-Figueroa, R

    1975-04-01

    Findings in this study support earlier investigations in attesting to the antipsychotic efficacy and relatively low toxicity of pipotiazine palmitate. Results with all efficacy measures utilized were consistent in indicating a high level of efficacy for this investigational compound. Pipotiazine palmitate apparently has an average duration of action that extends beyond 4 weeks in severely ill schizophrenic patients. This particular long acting IM antipsychotic preparation appears to have an even longer duration of activity than some of the other available standard long acting agents. The optimal dosage range for severely ill schizophrenic patients appears to be between 100 and 600 mg once monthly. While this type of drug (as is the case with many antipsychotic drugs) does reduce the psychotic symptomatology and improves the thought associations sufficient to enable the patient to leave the hospital, it should be re-emphasized that socioeconomic and guidance counseling services are necessary to maintain the patient in the community. The availability of this type of long acting preparation is not only economical in terms of nursing care and hospital cost but it should also increase the efficacy of psychopharmacologic treatment of schizophrenics by reducing both patient errors and staff errors in administration of medication. In addition, this IM preparation should prove to be of invaluable help in maintaining the schizophrenic patient in his community by reducing the relapse and the rehospitalization rates. It should be noted that there are schizophrenic patients who either absorb compounds from the gastrointestinal tract in a very poor manner or too rapidly metabolize the antipsychotic agents with resultant suboptimal blood levels and these subjects may be called "drug refractory." This type of long acting medication is an ideal preparation for the schizophrenic patient who has these types of absorption or metabolic problems since the "circulatory pass" through the

  15. 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…

  16. Atypical Pyoderma Gangrenosum Mimicking an Infectious Process

    PubMed Central

    To, Derek; Wong, Aaron; Montessori, Valentina

    2014-01-01

    We present a patient with atypical pyoderma gangrenosum (APG), which involved the patient's arm and hand. Hemorrhagic bullae and progressive ulcerations were initially thought to be secondary to an infectious process, but a biopsy revealed PG. Awareness of APG by infectious disease services may prevent unnecessary use of broad-spectrum antibiotics. PMID:25024856

  17. Atypical pyoderma gangrenosum mimicking an infectious process.

    PubMed

    To, Derek; Wong, Aaron; Montessori, Valentina