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Clinical Drug Investigation Apr 2021Second-generation antipsychotics (SGAs) for schizophrenia show different risk profiles, whose evidence has been evaluated through comparative reviews on randomized... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Second-generation antipsychotics (SGAs) for schizophrenia show different risk profiles, whose evidence has been evaluated through comparative reviews on randomized controlled trials (RCTs) and observational studies.
METHODS
We performed a systematic review and meta-analysis of weight gains, metabolic and cardiovascular side effects of SGAs, relying on both RCTs and observational studies, by comparing variations between the start of treatment and the end of follow-up. The systematic review refers to papers published from June 2009 to November 2020. PRISMA criteria were followed. No restrictions on heterogeneity level have been considered for meta-analysis. A test for the summary effect measure and heterogeneity (I metric) was used.
RESULTS
Seventy-nine papers were selected from 3076 studies (61% RCTs, 39% observational studies). Olanzapine and risperidone reported the greatest weight gain and olanzapine the largest BMI increase. Paliperidone showed the highest increase in total cholesterol, but is the only drug reporting an increase in the HDL cholesterol. Quetiapine XR showed the highest decrease in fasting glucose. Lurasidone showed the lowest increase in body weight and a reduction in BMI and was also the only treatment reporting a decrease in total cholesterol and triglycerides. The highest increase in systolic and diastolic blood pressure was reported by quetiapine XR.
CONCLUSIONS
Despite some limitations (differences in the mean dosages per patient and other side effects not included) this paper provides the first complete meta-analysis on SGAs in variations on metabolic risk profile between start of treatment and end of follow-up, with useful results for clinical practice and possibly for future economic evaluation studies.
Topics: Antipsychotic Agents; Humans; Randomized Controlled Trials as Topic; Schizophrenia; Weight Gain
PubMed: 33686614
DOI: 10.1007/s40261-021-01000-1 -
Schizophrenia Bulletin Jun 2022In treatment-resistant schizophrenia (TRS), Clozapine is only approved treatment with undesirable side-effects, warranting better alternatives. Our hypothesis is acute... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of Acute Followed by Maintenance ECT vs Clozapine on Psychopathology and Regional Cerebral Blood Flow in Treatment-Resistant Schizophrenia: A Randomized Controlled Trial.
BACKGROUND AND HYPOTHESIS
In treatment-resistant schizophrenia (TRS), Clozapine is only approved treatment with undesirable side-effects, warranting better alternatives. Our hypothesis is acute followed by maintenance Electroconvulsive Therapy (M-ECT) will be comparable in efficacy and safety to Clozapine in TRS.
STUDY DESIGN
In this open-label trial, 60 TRS patients were randomized equally to M-ECT (following an acute-course) or Clozapine. Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Schizophrenia Scale (CGI-SCH), Montreal Cognitive Assessment (MoCA), and Global assessment of functioning (GAF) were measured and compared within and between the groups at baseline, 6 weeks, 12 weeks, and 24 weeks. SPECT-CT brain was done at baseline and 24 weeks to compare the changes in regional cerebral perfusion between the groups and correlate with the changes in the outcome-measures.
STUDY RESULTS
The PANSS-T scores changes from baseline over the observation-points were significant in both M-ECT and clozapine groups (P < .001), with comparatively better reduction with M-ECT (P < .001). Similar trends were observed in PANSS subscales, CGI-SCH and GAF in both groups, with significantly better improvement with M-ECT over the study-period. After 24 weeks, there was significantly better perfusion with M-ECT in bilateral prefrontal and temporal cortices (P < .05). With M-ECT, a positive correlation was found between changes in PANSS-P scores and left-lateral Temporal cortical perfusion (r = .465, P = .017).
CONCLUSIONS
Acute followed by M-ECT was more effective than clozapine over 6 months in reducing the positive and negative symptoms, general psychopathology, illness-severity, and improving the global functionality in TRS [clinicaltrials.gov: NCT03807882].
Topics: Antipsychotic Agents; Cerebrovascular Circulation; Clozapine; Electroconvulsive Therapy; Humans; Schizophrenia; Schizophrenia, Treatment-Resistant; Treatment Outcome
PubMed: 35556138
DOI: 10.1093/schbul/sbac027 -
JAMA Psychiatry Nov 2021The doses of antipsychotic drugs needed for relapse prevention in schizophrenia is a debated issue. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The doses of antipsychotic drugs needed for relapse prevention in schizophrenia is a debated issue.
OBJECTIVE
To examine dose-response findings in a meta-analysis of randomized clinical trials.
DATA SOURCES
Studies were identified through the Cochrane Schizophrenia Group's Study-Based Register of Trials (March 9, 2020), PubMed (January 1, 2021), and previous reviews. First authors and/or pharmaceutical companies were contacted for additional information.
STUDY SELECTION
Two reviewers independently selected randomized clinical trials that compared fixed doses of a second-generation antipsychotic, haloperidol, or fluphenazine for relapse prevention in patients with stable schizophrenia.
DATA EXTRACTION AND SYNTHESIS
Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline, all parameters in duplicate were extracted and frequentist dose-response random-effects meta-analyses were conducted.
MAIN OUTCOMES AND MEASURES
Study-defined relapse (primary outcome), rehospitalization, Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale total score reduction from baseline, all-cause discontinuation, and dropouts due to adverse events.
RESULTS
Evidence from 72 dose arms from 26 studies with 4776 participants was analyzed. The efficacy-related dose-response curves had a hyperbolic shape meaning that the probability to relapse decreased rapidly with doses of up to 5-mg/d risperidone equivalent (relative relapse risk, 0.43; 95% CI, 0.31-0.57; standardized mean difference for Positive and Negative Syndrome Scale total score reduction, -0.55; 95% CI, -0.68 to -0.41), but flattened thereafter. In contrast, dropouts due to adverse events continued to increase beyond this dose (relative risk at 5 mg/d, 1.38; 95% CI, 0.87-2.55; relative risk at 15 mg/d, 2.68; 95% CI, 1.49-4.62). In a subgroup analysis of patients in remission, a plateau was reached earlier, at approximately 2.5-mg/d risperidone equivalent.
CONCLUSIONS AND RELEVANCE
The findings of this meta-analysis suggest that doses higher than approximately 5-mg/d risperidone equivalent may provide limited additional benefit for relapse prevention but more adverse events. For patients in remission or who are receiving high-potency first-generation antipsychotics, doses as low as 2.5-mg/d risperidone equivalent may be sufficient. However, caution is needed at this low dose end when further decreases of dose may be accompanied by a disproportionally higher relapse risk. Moreover, the observations are averages, and factors such as slow or rapid metabolism, age, illness stage, comorbidities, and drug-drug interactions suggest that individual patients will often need higher or lower doses.
Topics: Antipsychotic Agents; Humans; Outcome Assessment, Health Care; Schizophrenia; Secondary Prevention
PubMed: 34406325
DOI: 10.1001/jamapsychiatry.2021.2130 -
Tijdschrift Voor Psychiatrie 2022
Topics: Antipsychotic Agents; Humans; Schizophrenia
PubMed: 35420139
DOI: No ID Found -
Neuropharmacology Jun 2023Schizophrenia is a severe brain disorder that usually produces a lifetime of disability. First generation or typical antipsychotics such as haloperidol and second... (Review)
Review
Schizophrenia is a severe brain disorder that usually produces a lifetime of disability. First generation or typical antipsychotics such as haloperidol and second generation or atypical antipsychotics such as clozapine and risperidone remain the current standard for schizophrenia treatment. In some patients with schizophrenia, antipsychotics produce complete remission of positive symptoms, such as hallucinations and delusions. However, antipsychotic drugs are ineffective against cognitive deficits and indeed treated schizophrenia patients have small improvements or even deterioration in several cognitive domains. This underlines the need for novel and more efficient therapeutic targets for schizophrenia treatment. Serotonin and glutamate have been identified as key parts of two neurotransmitter systems involved in fundamental brain processes. Serotonin (or 5-hydroxytryptamine) 5-HT receptor (5-HTR) and metabotropic glutamate 2 receptor (mGluR2) are G protein-coupled receptors (GPCRs) that interact at epigenetic and functional levels. These two receptors can form GPCR heteromeric complexes through which their pharmacology, function and trafficking becomes affected. Here we review past and current research on the 5-HTR-mGluR2 heterocomplex and its potential implication in schizophrenia and antipsychotic drug action. This article is part of the Special Issue on "The receptor-receptor interaction as a new target for therapy".
Topics: Humans; Schizophrenia; Antipsychotic Agents; Serotonin; Glutamates; Receptor, Serotonin, 5-HT2A
PubMed: 36889432
DOI: 10.1016/j.neuropharm.2023.109489 -
Psychiatry and Clinical Neurosciences Jul 2019The primary aim of this study was to analyze the impact of schizophrenic disorders on pregnancy outcomes. The secondary aim was to briefly analyze the potential role of...
The primary aim of this study was to analyze the impact of schizophrenic disorders on pregnancy outcomes. The secondary aim was to briefly analyze the potential role of antipsychotic treatment on influencing pregnancy outcomes in expectant mothers with schizophrenia. We searched the MEDLINE, PsycINFO, and Science.gov databases for articles published in English from January 1980 to January 2019. We used the following search terms: 'schizophrenia', 'motherhood', 'pregnancy/foetal/neonatal outcomes', and 'birth defects'. The reference lists of retrieved articles were also consulted to find additional pertinent studies missed in the electronic search and/or those published before 1980. Data were extracted from articles that provided primary data on the impact of maternal schizophrenia spectrum disorders on obstetrical and perinatal outcomes. After excluding duplicates, 35 articles were identified. Systematic reviews were searched on the same databases to briefly assess the effects of antipsychotics on pregnancy outcomes. The reviewed studies showed several limitations. They were published during a time range from the early 1970s to 2019. During this period, there were significant changes in the diagnostic criteria for schizophrenia. Moreover, such studies showed no homogeneity in the investigation of potential confounders. Most importantly, no research has differentiated the effects of maternal illness on pregnancy, fetal, and neonatal outcomes from those associated with antipsychotic treatments. Thus, it is not surprising that such studies show conflicting results. Despite such limitations, in managing pregnant women with schizophrenia clinicians should consider an integrated approach that includes: antipsychotic treatment, psychological treatment, optimal dietary approaches for prevention of excessive weight gain and gestational diabetes, meticulous gynecologic and obstetric surveillance, and social and occupational support.
Topics: Abnormalities, Drug-Induced; Antipsychotic Agents; Female; Humans; Obstetric Labor Complications; Pregnancy; Prenatal Exposure Delayed Effects; Schizophrenia
PubMed: 31026107
DOI: 10.1111/pcn.12856 -
BMJ Case Reports May 2017Aripiprazole is an atypical antipsychotic agent commonly used in the management of schizophrenia. Aripiprazole has not been reported to have an association with...
Aripiprazole is an atypical antipsychotic agent commonly used in the management of schizophrenia. Aripiprazole has not been reported to have an association with interstitial lung disease. We describe a case of a 36-year-old woman who began to experience respiratory issues shortly after starting aripiprazole and presented to us 4 years later with progressive exertional shortness of breath. High-resolution CT of the chest showed a bilateral ground glass pattern. Video-assisted thoracoscopy with biopsy revealed alveolar septal thickening and an inflammatory infiltrate composed mainly of lymphocytes, suggestive of chronic hypersensitivity pneumonitis. After discontinuing aripiprazole and initiating prednisolone therapy, the patient's pulmonary symptoms improved. This case highlights that aripiprazole can cause hypersensitivity pneumonitis in susceptible individuals.
Topics: Adult; Alveolitis, Extrinsic Allergic; Antipsychotic Agents; Aripiprazole; Diagnosis, Differential; Female; Humans; Lung Diseases, Interstitial; Schizophrenia; Tomography, X-Ray Computed
PubMed: 28487307
DOI: 10.1136/bcr-2017-219929 -
The Primary Care Companion For CNS... Feb 2019
Topics: Adult; Antipsychotic Agents; Fever; Humans; Male; Olanzapine; Schizophrenia, Paranoid
PubMed: 30817864
DOI: 10.4088/PCC.18l02332 -
Ugeskrift For Laeger May 2024Long-acting injectable antipsychotics (LAI) is a frequently used treatment modality which has advantages over oral antipsychotics regarding hospitalization or relapse... (Review)
Review
Long-acting injectable antipsychotics (LAI) is a frequently used treatment modality which has advantages over oral antipsychotics regarding hospitalization or relapse prevention. However, the pharmacokinetic properties of LAI greatly differ from oral antipsychotics. This necessitates an increased knowledge about LAI among clinicians, especially when commencing treatment, changing doses and discontinuing treatment. In this review, we summarize an array of clinically important characteristics of LAI and give a conceptual framework for understanding the pharmacokinetics of LAI.
Topics: Humans; Antipsychotic Agents; Delayed-Action Preparations; Injections; Injections, Intramuscular
PubMed: 38808759
DOI: 10.61409/V12230776 -
Tidsskrift For Den Norske Laegeforening... Sep 2018
Topics: Antipsychotic Agents; Drug Prescriptions; Drug Utilization; Humans; Quetiapine Fumarate
PubMed: 30180497
DOI: 10.4045/tidsskr.18.0535