ReviewTranslational psychiatry2021
Efficacy and safety of clozapine in psychotic disorders-a systematic quantitative meta-review.
Review in Translational psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 8 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
88 citing papers in PubMed, 8 syntheses or guidelines pooled it.
- Is Aripiprazole an Effective Adjunct to Reduce Metabolic Adverse Effects Caused by Clozapine in Patients With Schizophrenia-A Systematic Review.Neuropsychopharmacology reports · 2026Pooled it
- Clozapine prescribing in treatment-resistant schizophrenia - an updated systematic literature review of barriers and facilitators among clinicians.European journal of clinical pharmacology · 2026Pooled it
- Saliva Based Clozapine Therapeutic Drug Monitoring: A Systematic Review.Pharmacology research & perspectives · 2025Pooled it
- Clozapine and Pneumonia: Synthesizing the Link by Reviewing Existing Reports-A Systematic Review and Meta-Analysis.Medicina (Kaunas, Lithuania) · 2024Pooled it
- Diagnostics and treatment of impulse control disorders, psychosis and delirium: systemic review-based recommendations - guideline "Parkinson's disease" of the German Society of Neurology.Journal of neurology · 2024Guideline
- Pharmacological interventions for antipsychotic-related sialorrhea: a systematic review and network meta-analysis of randomized trials.Molecular psychiatry · 2023Pooled it
- Clozapine Optimization: A Delphi Consensus Guideline From the Treatment Response and Resistance in Psychosis Working Group.Schizophrenia bulletin · 2023Guideline
- A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia.CNS drugs · 2022Guideline
- Cardiometabolic screening, elevated results and clinical follow-up actions in Māori and non-Māori with psychosis in Canterbury, Aotearoa New Zealand.The Australian and New Zealand journal of psychiatry · 2026Article
- Off-target effects of DREADD ligands revealed by an anesthesia emergence paradigm in mice.Cell reports methods · 2026Article
- Schizophrenia: Converging Neurobiological Mechanisms and Emerging Therapeutic Strategies.Biomolecules · 2026Review
- Revisiting clozapine-induced mania: When a case report informs clinical decisions.Dusunen adam : Bakirkoy Ruh ve Sinir Hastaliklari Hastanesi yayin organi · 2026Article
- A Case Report: Successful Management of Mixed Tardive Syndrome With Combination Pharmacotherapy in a 19-Year-Old Female With Schizophrenia.Clinical case reports · 2026Article
- Effectiveness of amisulpride augmentation versus other antipsychotics in clozapine-treated adolescents: a real-world retrospective study.BMC psychiatry · 2026Article
- Prevalence and frequency of haematological testing in patients initiating clozapine in the USA.BMJ mental health · 2026Article
- Genetic overlap between treatment-resistant schizophrenia and smoking initiation.The international journal of neuropsychopharmacology · 2026Article
- Clozapine-induced Myocarditis in Korea: Analysis of a Nationwide Database and Comparison to Other Countries.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026Article
- Clozapine prescribing in Germany: temporal trends and regional variations, 2012-2022.Schizophrenia (Heidelberg, Germany) · 2026Article
- Repurposing FDA-approved drugs as multi-target neuroprotective agents for Alzheimer's disease via computational screening and experimental validation.Scientific reports · 2026Article
- Why Is Clozapine Uniquely Effective in Treatment-Resistant Schizophrenia? A Review and Proposal.Biological psychiatry · 2026Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A recent increase in the literature regarding the evidence base for clozapine has made it increasingly difficult for clinicians to judge "best evidence" for clozapine use. As such, we aimed at elucidating the state-of-the-art for clozapine with regard to efficacy, effectiveness, tolerability, and management of clozapine and clozapine-related adverse events in neuropsychiatric disorders. We conducted a systematic PRISMA-conforming quantitative meta-review of available meta-analytic evidence regarding clozapine use. Primary outcome effect sizes were extracted and transformed into relative risk ratios (RR) and standardized mean differences (SMD). The methodological quality of meta-analyses was assessed using the AMSTAR-2 checklist. Of the 112 meta-analyses included in our review, 61 (54.5%) had an overall high methodological quality according to AMSTAR-2. Clozapine appears to have superior effects on positive, negative, and overall symptoms and relapse rates in schizophrenia (treatment-resistant and non-treatment-resistant subpopulations) compared to first-generation antipsychotics (FGAs) and to pooled FGAs/second-generation antipsychotics (SGAs) in treatment-resistant schizophrenia (TRS). Despite an unfavorable metabolic and hematological adverse-event profile compared to other antipsychotics, hospitalization, mortality and all-cause discontinuation (ACD) rates of clozapine surprisingly show a pattern of superiority. Our meta-review outlines the superior overall efficacy of clozapine compared to FGAs and most other SGAs in schizophrenia and suggests beneficial efficacy outcomes in bipolar disorder and Parkinson's disease psychosis (PDP). More clinical studies and subsequent meta-analyses are needed beyond the application of clozapine in schizophrenia-spectrum disorders and future studies should be directed into multidimensional clozapine side-effect management to foster evidence and to inform future guidelines.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.