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Current Psychiatry Reports Jul 2016Clozapine is exceptionally effective in psychotic disorders and can reduce suicidal risk. Nevertheless, its use is limited due to potentially life-threatening adverse... (Review)
Review
Clozapine is exceptionally effective in psychotic disorders and can reduce suicidal risk. Nevertheless, its use is limited due to potentially life-threatening adverse effects, including myocarditis and cardiomyopathy. Given their clinical importance, we systematically reviewed research on adverse cardiac effects of clozapine, aiming to improve estimates of their incidence, summarize features supporting their diagnosis, and evaluate proposed monitoring procedures. Incidence of early (≤2 months) myocarditis ranges from <0.1 to 1.0 % and later (3-12 months) cardiomyopathy about 10 times less. Diagnosis rests on relatively nonspecific symptoms, ECG changes, elevated indices of myocardial damage, cardiac MRI findings, and importantly, echocardiographic evidence of developing ventricular failure. Treatment involves stopping clozapine and empirical applications of steroids, diuretics, beta-blockers, and antiangiotensin agents. Mortality averages approximately 25 %. Safety of clozapine reuse remains uncertain. Systematic studies are needed to improve knowledge of the epidemiology, avoidance, early identification, and treatment of these adverse effects, with effective and practicable monitoring protocols.
Topics: Adverse Drug Reaction Reporting Systems; Antipsychotic Agents; Cardiomyopathies; Cardiotoxicity; Clozapine; Drug Monitoring; Humans; Psychotic Disorders
PubMed: 27222142
DOI: 10.1007/s11920-016-0704-3 -
Der Nervenarzt May 2021The benefits and risks of treatment with antipsychotics during pregnancy must be weighed up carefully and individually because antipsychotics can penetrate the placental... (Review)
Review
BACKGROUND
The benefits and risks of treatment with antipsychotics during pregnancy must be weighed up carefully and individually because antipsychotics can penetrate the placental barrier and prescription is off-label.
OBJECTIVE
Evaluation of the risks and benefits of administering antipsychotics during pregnancy or for women who wish to become pregnant regarding teratogenic effects, risk of fetal death and stillbirths, perinatal complications, persisting postnatal impairments or disorders and gestational diabetes.
METHODS
A systematic review of the literature is provided to aid the selection of psychotropic drugs during pregnancy and in determining whether to begin, continue or switch an antipsychotic treatment during pregnancy.
RESULTS
Large, well-designed and controlled studies are missing; however, most studies suggest that the group of antipsychotics seem to be safe in terms of teratogenicity during pregnancy, at least in monotherapy.
CONCLUSION
Treating mental illnesses during pregnancy requires an individual assessment of the benefits and risks. The risk of an untreated mental illness versus the benefit of a suitable treatment with antipsychotics and the potential harm to the infant must be evaluated. If certain rules are observed and a suitable antipsychotic is selected the risk to the newborn child and/or mother during pregnancy can be minimized, however, a decision about subsequent medication can only be indirectly made from the results of this study.
Topics: Antipsychotic Agents; Female; Humans; Infant, Newborn; Mental Disorders; Pregnancy; Pregnancy Complications; Psychotropic Drugs
PubMed: 33000289
DOI: 10.1007/s00115-020-01006-8 -
Human Psychopharmacology Mar 2017The association between long-term antipsychotic treatment and changes in brain structure in schizophrenia is unclear. Our aim was to conduct a systematic review and a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The association between long-term antipsychotic treatment and changes in brain structure in schizophrenia is unclear. Our aim was to conduct a systematic review and a meta-analysis on long-term antipsychotic effects on brain structures in schizophrenia focusing on studies with at least 2 years of follow-up between MRI scans.
DESIGN
Studies were systematically collected using 4 databases, and we also contacted authors for unpublished data. We calculated correlations between antipsychotic dose and/or type and brain volumetric changes and used random effect meta-analysis to study correlations by brain area.
RESULTS
Thirty-one publications from 16 samples fulfilled our inclusion criteria. In meta-analysis, higher antipsychotic exposure associated statistically significantly with parietal lobe decrease (studies, n = 4; r = -.14, p = .013) and with basal ganglia increase (n = 4; r = .10, p = .044). Most of the reported correlations in the original studies were statistically nonsignificant. There were no clear differences between typical and atypical exposure and brain volume change. The studies were often small and highly heterogeneous in their methods and seldom focused on antipsychotic medication and brain changes as the main subject.
CONCLUSIONS
Antipsychotic medication may associate with brain structure changes. More long-term follow-up studies taking into account illness severity measures are needed to make definitive conclusions.
Topics: Antipsychotic Agents; Brain; Dose-Response Relationship, Drug; Humans; Magnetic Resonance Imaging; Schizophrenia
PubMed: 28370309
DOI: 10.1002/hup.2574 -
The Cochrane Database of Systematic... Nov 2015Schizophrenia is a highly prevalent and chronic disorder that comprises a wide range of symptomatology. Asenapine is a recently developed atypical antipsychotic that is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Schizophrenia is a highly prevalent and chronic disorder that comprises a wide range of symptomatology. Asenapine is a recently developed atypical antipsychotic that is approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia.
OBJECTIVES
To determine the clinical effects of asenapine for adults with schizophrenia or other schizophrenia-like disorders by comparing it with placebo.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Trials Register (July 04, 2014) which is based on regular searches of MEDLINE, EMBASE, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and registries of clinical trials. There are no language, date, document type, or publication status limitation for inclusion of records into the register. We inspected references of all included studies for further relevant studies.
SELECTION CRITERIA
Our review includes randomised controlled trials (RCTs) comparing asenapine with placebo in adults (however defined) with schizophrenia or related disorders, including schizophreniform disorder, schizoaffective disorder and delusional disorder, again, by any means of diagnosis.
DATA COLLECTION AND ANALYSIS
We inspected citations from the searches and identified relevant abstracts, and extracted data from all included studies. For binary data we calculated risk ratio (RR) with 95% confidence intervals (CI), and for continuous data we calculated mean differences (MD). We used the GRADE approach to produce a 'Summary of findings' table which included our outcomes of interest, where possible. We used a fixed-effect model for our analyses.
MAIN RESULTS
We obtained and scrutinised 41 potentially relevant records, and from these we could include only six trials (n = 1835). Five of the six trials had high risk of attrition bias and all trials were sponsored by pharmaceutical companies. Results showed a clinically important change in global state (1 RCT, n = 336, RR 0.81, 95% CI 0.68 to 0.97, low-quality evidence) and mental state (1 RCT, n = 336, RR 0.72, 95% CI 0.59 to 0.86, very low-quality evidence) at short-term amongst people receiving asenapine. People receiving asenapine demonstrated significant reductions in negative symptoms (1 RCT, n = 336, MD -1.10, 95% CI -2.29 to 0.09, very low-quality evidence) at short-term. Individuals receiving asenapine demonstrated significantly fewer incidents of serious adverse effects (1 RCT, n = 386, RR 0.29, 95% CI 0.14 to 0.63, very low-quality evidence) at medium-term. There was no clear difference in people discontinuing the study for any reason between asenapine and placebo at short-term (5 RCTs, n = 1046, RR 0.91, 95% CI 0.80 to 1.04, very low-quality evidence). No trial reported data for extrapyramidal symptoms or costs.
AUTHORS' CONCLUSIONS
There is some, albeit preliminary, evidence that asenapine provides an improvement in positive, negative, and depressive symptoms, whilst minimising the risk of adverse effects. However due to the low-quality and limited quantity of evidence, it remains difficult to recommend the use of asenapine for people with schizophrenia. We identify a need for large-scale, longer-term, better-designed and conducted randomised controlled trials investigating the clinical effects and safety of asenapine.
Topics: Adult; Antipsychotic Agents; Dibenzocycloheptenes; Heterocyclic Compounds, 4 or More Rings; Humans; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome
PubMed: 26599405
DOI: 10.1002/14651858.CD011458.pub2 -
Journal of Affective Disorders Oct 2023Antipsychotic medications are increasingly used for difficult-to-treat depression in young people. However, the evidence-base for this is unclear. Our aim was to assess... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic medications are increasingly used for difficult-to-treat depression in young people. However, the evidence-base for this is unclear. Our aim was to assess the evidence for the efficacy of atypical antipsychotics in treating unipolar and bipolar depression in adolescents and young adults.
METHOD
We conducted a comprehensive systematic review and meta-analysis of randomized-control-trial studies (RCTs) of antipsychotic medications for 10- to 25-year-olds with unipolar and bipolar depression. The primary outcome of interest was change in depressive symptoms from baseline to trial endpoint.
RESULTS
No studies were identified that evaluated the use of antipsychotics in the treatment of unipolar depression. However, we identified four studies, of quetiapine, lurasidone and olanzapine/fluoxetine combination, comprising a total of 866 randomized patients, that evaluated treatment of bipolar depression. All studies used the Children's Depression Rating Scale-Revised (CDRS-R). Our meta-analysis revealed the weighted mean difference (WMD) was -4.58 (95 % CI, -6.59 to -2.57) between antipsychotic and placebo-treated groups. Response and remission rates were also significantly in favor of antipsychotic treatment.
LIMITATIONS
There were few studies, several did not address risk-of-bias domains and there was a lack of non-industry sponsored studies.
CONCLUSION
There is an absence of evidence for the use of antipsychotic medications in treatment of youth unipolar depression, and no recommendations can be made. There is some evidence for the efficacy of antipsychotics, specifically lurasidone and olanzapine/fluoxetine combination, in the treatment of young people with bipolar depression. However, this evidence is limited and more studies investigating the use of these medications in young people are needed.
Topics: Child; Adolescent; Young Adult; Humans; Antipsychotic Agents; Bipolar Disorder; Fluoxetine; Olanzapine; Lurasidone Hydrochloride
PubMed: 37467794
DOI: 10.1016/j.jad.2023.07.082 -
Schizophrenia Research Nov 2023Antipsychotic drug-induced myocarditis is a serious and potentially fatal adverse drug reaction characterized by inflammation of the heart muscle (myocardium) that... (Review)
Review
Antipsychotic drug-induced myocarditis is a serious and potentially fatal adverse drug reaction characterized by inflammation of the heart muscle (myocardium) that typically develops within the first month after commencing an antipsychotic drug. Although the precise mechanism of this severe adverse drug reaction is unknown, multiple theories have been proposed with varying levels of support from cellular or animal studies. We conducted a systematic review, in accordance with PRISMA guidelines, of published preclinical and clinical studies investigating the cellular mechanism by which antipsychotic drugs induce myocarditis. A literature search including all studies available before December 10, 2022, yielded 15 studies that met our inclusion criteria. Antipsychotics examined in the included studies included clozapine (n = 13), ziprasidone (n = 1), amisulpride (n = 1), haloperidol (n = 1), levomepromazine (n = 1), olanzapine (n = 1), and sertindole (n = 1). The evidence suggests several overlapping mechanistic cascades involving: (1) increased levels of catecholamines, (2) increased proinflammatory cytokines, (3) increased reactive oxygen species (ROS), (4) reduced antioxidant levels and activity, and (5) mitochondrial damage. Notable limitations such as, a focus on clozapine, sample heterogeneity, and use of supratherapeutic doses will need to be addressed in future studies. Discovery of the mechanism by which antipsychotic drugs induce myocarditis will allow the development of clinically-useful biomarkers to identify those patients at increased risk prior to drug exposure. The development or repurposing of therapeutics to prevent or treat drug-induced myocarditis will also be possible and this will enable increased and safe use of antipsychotics for those patients in need.
Topics: Animals; Humans; Antipsychotic Agents; Clozapine; Myocarditis; Schizophrenia; Drug-Related Side Effects and Adverse Reactions
PubMed: 37797362
DOI: 10.1016/j.schres.2023.09.039 -
Schizophrenia Research Feb 2021The aim of this systematic review and meta-analysis was to characterize ultra-treatment-resistant Schizophrenia also known as clozapine-resistant schizophrenia (CRS)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The aim of this systematic review and meta-analysis was to characterize ultra-treatment-resistant Schizophrenia also known as clozapine-resistant schizophrenia (CRS) patients across clozapine combination and augmentation trials through demographic and clinical baseline data. Furthermore, we investigated the variability and consistency in CRS definitions between studies.
METHODS
Systematic searches of articles indexed in PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and PsycINFO were conducted in March 2020. 1541 randomized and non-randomized clinical trials investigating pharmacological and non-pharmacological clozapine add-on strategies were screened and a total of 71 studies were included. The primary outcome was the overall symptom score at baseline, measured with Positive and Negative Syndrome Scale (PANSS) total or Brief Psychiatric Rating Scale (BPRS) total scores.
RESULTS
Data from 2731 patients were extracted. Patients were overall moderately ill with a mean PANSS total score at baseline of 79.16 (±7.52), a mean duration of illness of 14.64 (±4.14) years with a mean clozapine dose of 436.94 (±87.47) mg/day. Illness severity data were relatively homogenous among patients independently of the augmentation strategy involved, although stark geographical differences were found. Overall, studies showed a large heterogeneity of CRS definitions and insufficient guidelines implementation.
CONCLUSIONS
This first meta-analysis characterizing CRS patients and comparing CRS definitions revealed a lack of consistent implementation of a CRS definition from guidelines into clinical trials, compromising the replicability of the results and their applicability in clinical practice. We offer a new score modeled on a best practice definition to help future trials increase their reliability.
Topics: Antipsychotic Agents; Clozapine; Drug Resistance; Humans; Reproducibility of Results; Schizophrenia
PubMed: 33454644
DOI: 10.1016/j.schres.2020.12.002 -
The Cochrane Database of Systematic... Sep 2017The efficacy of chlorpromazine, a benchmark antipsychotic, has not been fully assessed in direct comparison with different individual antipsychotics. Penfluridol is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The efficacy of chlorpromazine, a benchmark antipsychotic, has not been fully assessed in direct comparison with different individual antipsychotics. Penfluridol is another old antipsychotic with a long half-life so one oral dose may last up to one week. This could confer advantage.
OBJECTIVES
To assess the clinical effects of chlorpromazine compared with penfluridol for adults with schizophrenia.
SEARCH METHODS
On 31 March 2017, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There are no language, date, document type, or publication status limitations for inclusion of records in the register.
SELECTION CRITERIA
We included all randomised clinical trials focusing on chlorpromazine versus penfluridol for adults with schizophrenia or related disorders. Outcomes of interest were death, service utilisation, global state, mental state, adverse effects and leaving the study early. We included trials meeting our selection criteria and reporting useable data.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we planned to estimate the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
The review includes three studies with a total of 130 participants. Short-term results for hospital admissions showed no clear difference between chlorpromazine and penfluridol (1 RCT, n = 29, RR 0.19, 95% CI 0.01 to 3.60, low-quality evidence). No clear difference in the incidence of akathisia was found at medium term (2 RCTs, n = 85, RR 0.19, 95% CI 0.04 to 1.06, low-quality evidence), and similar numbers of participants - nearly half - from each treatment group left the study early (3 RCTs, n = 130, RR 1.21, 95% CI 0.83 to 1.77, low-quality evidence). The risk of needing additional antiparkinsonian medication was less in the chlorpromazine group (2 RCTs, n = 74, RR 0.70, 95% CI 0.51 to 0.95). No useable data reported clinically important change in global or mental state. No data were reported for relapse. No deaths were reported by the trials.
AUTHORS' CONCLUSIONS
Only three small studies provided data and the quality of reporting and evidence is low. Limited data indicate the efficacy and adverse effects profiles of chlorpromazine and penfluridol are generally similar. Penfluridol, however, may confer advantage by needing to be given only once per week. Firm conclusions are not possible without good-quality trials, and where these treatments are used, such trials are justified.
Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Chlorpromazine; Humans; Length of Stay; Penfluridol; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 28940256
DOI: 10.1002/14651858.CD011831.pub2 -
The Journal of Dermatological Treatment Mar 2022Delusional infestation (DI) is a rare delusional disorder in which individuals have a false belief that they are infested with bugs, parasites, or insects, despite the... (Review)
Review
BACKGROUND
Delusional infestation (DI) is a rare delusional disorder in which individuals have a false belief that they are infested with bugs, parasites, or insects, despite the lack of medical evidence that such an infestation exists. Data on the effectiveness of antipsychotics for DI are limited.
METHODS
We conducted a systematic review using EMBASE, MEDLINE, PsycINFO, and Cochrane Central Register of Controlled Trials from inception of the databases up until July 20, 2018. Studies examining typical or atypical antipsychotics for primary DI were included.
RESULTS
A total of 51 relevant articles were identified, primarily case reports/series. Overall response was favorable for both typical and atypical antipsychotics, but there was no strong evidence to suggest that any one antipsychotic agent was preferable to other agents. Pimozide (1-16 mg/day) and risperidone (0.5-8 mg/day) were the most commonly studied typical and atypical antipsychotics, respectively. Inconsistent reporting of treatment outcomes and variability in study designs limited the overall evaluation of the data.
CONCLUSIONS
There remains a lack of sound data supporting the effectiveness of antipsychotic treatment for primary DI. Further research is required to establish more definitive conclusions about the relative clinical utility of antipsychotic agents for DI.
Topics: Antipsychotic Agents; Humans; Risperidone; Treatment Outcome
PubMed: 32658556
DOI: 10.1080/09546634.2020.1795061 -
Annals of Clinical Psychiatry :... Nov 2016Nonadherence to medication is a major problem for patients with schizophrenia. To counter this problem, pharmaceutical companies began developing depot antipsychotics.... (Review)
Review
BACKGROUND
Nonadherence to medication is a major problem for patients with schizophrenia. To counter this problem, pharmaceutical companies began developing depot antipsychotics. Although there are currently 5 first-generation and 6 second-generation depot antipsychotics available worldwide, many physicians are still reluctant to use this category of drug initially. This review provides the latest information about the use of depot antipsychotics in schizophrenia treatment as well as several studies in support of depot antipsychotic use as first-line treatment for patients with schizophrenia.
METHODS
A systematic review of 4 milestone schizophrenia studies was performed to provide an aggregate analysis of the history and use of depot antipsychotics. Results and findings from several clinical trials--the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), European First Episode Schizophrenia Trial (EUFEST), A Comparison of Long-Acting Injectable Medications for Schizophrenia (ACLAIMS), and Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE)--were summarized to provide more information on the development and evolution of depot antipsychotics, common factors that contribute to nonadherence, and guidelines for each long-acting injectable currently available.
RESULTS
The CATIE schizophrenia study revealed a 74% rate of discontinuation of oral antipsychotics within 6 months of use. Similar findings from the EUFEST study indicated that 42% of participants discontinued oral medications after 12 months of use. The ACLAIMS study reported no statistically significant difference in efficacy failure rate between haloperidol decanoate and paliperidone palmitate. The PRIDE study found that first hospitalization or arrest was 43% higher among patients in the oral antipsychotic group vs the depot group during the study.
CONCLUSIONS
This review provides clinical evidence to support the use of depot formulations as first-line treatment for patients with schizophrenia, which may improve adherence and thereby lower risk of relapse, suicide, rehospitalization, and incarceration.
Topics: Antipsychotic Agents; Haloperidol; Hospitalization; Humans; Medication Adherence; Paliperidone Palmitate; Schizophrenia
PubMed: 27901520
DOI: No ID Found