SynthesisSchizophrenia bulletin2019
Clozapine and Long-Term Mortality Risk in Patients With Schizophrenia: A Systematic Review and Meta-analysis of Studies Lasting 1.1-12.5 Years.
Synthesis in Schizophrenia bulletin, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07120477 (Esketamine Versus Crisis Response Planning Versus Enhanced Treatment as Usual for Suicide Prevention), which is not on this map. Cited by 103 papers, 10 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.
Esketamine Versus Crisis Response Planning Versus Enhanced Treatment as Usual for Suicide Prevention: A Pragmatic Randomized Trial in a Brazilian Municipality (SAVE)
Who cites it
103 citing papers in PubMed, 10 syntheses or guidelines pooled it, 233 citations in OpenAlex.
- Clozapine and Pneumonia: Synthesizing the Link by Reviewing Existing Reports-A Systematic Review and Meta-Analysis.Medicina (Kaunas, Lithuania) · 2024Pooled it
- Clozapine Optimization: A Delphi Consensus Guideline From the Treatment Response and Resistance in Psychosis Working Group.Schizophrenia bulletin · 2023Guideline
- Long-term effects of antipsychotics on mortality in patients with schizophrenia: a systematic review and meta-analysis.Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999) · 2022Pooled it
- Ethnic disparities in clozapine prescription for service-users with schizophrenia-spectrum disorders: a systematic review.Psychological medicine · 2022Pooled it
- A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia.CNS drugs · 2022Guideline
- Leukocytosis Associated with Clozapine Treatment: A Case Series and Systematic Review of the Literature.Medicina (Kaunas, Lithuania) · 2021Pooled it
- Does Switching Antipsychotics Ameliorate Weight Gain in Patients With Severe Mental Illness? A Systematic Review and Meta-analysis.Schizophrenia bulletin · 2021Pooled it
- A systematic review and meta-analysis of the association between clozapine and norclozapine serum levels and peripheral adverse drug reactions.Psychopharmacology · 2021Pooled it
- Heterogeneity and efficacy of antipsychotic treatment for schizophrenia with or without treatment resistance: a meta-analysis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Pooled it
- Pooled it
- Predictors of Mortality Following a Schizophrenia Spectrum Diagnosis: Evidence From the 20-Year Follow-up of the OPUS Randomized Controlled Trial.Schizophrenia bulletin · 2023Trial
- Clozapine and Solid Cancer Risk in Lithuania: A Population-Based Cohort Study.Journal of clinical medicine · 2026Article
- Clozapine Dose Reduction in Remitted Patients With Treatment-Resistant Schizophrenia: A Case Series.Schizophrenia bulletin · 2026Article
- Health, Social and Recidivism Outcomes Among People Who Have Been Incarcerated in New South Wales, Australia: Study Protocol and Cohort Profile for the Prison Outcomes STudy (POST).Drug and alcohol review · 2026Article
- Glutamate change in the anterior cingulate cortex after starting clozapine: evaluating 1H-MRS pilot data.BMC psychiatry · 2026Article
- Real-world comprehensive care of people living with schizophrenia: recommendations across different settings and clinical stages.World psychiatry : official journal of the World Psychiatric Association (WPA) · 2026Article
- "Intranasal clozapine sol-gel formulation induces an antipsychotic effect at a fraction of a comparable oral therapeutic dose".Translational psychiatry · 2026Article
- Identifying Clinical Characteristics of Young People with Treatment-Resistant Schizophrenia Undergoing Community Initiation of Clozapine.Schizophrenia bulletin · 2026Article
- Clozapine-Associated Neutropenia among People on Clozapine in Japan: A Nationally Representative Retrospective Cohort Study.Schizophrenia bulletin · 2026Article
- Adult psychiatrists' views on clozapine prescribing for schizophrenia in Germany-an online survey.Therapeutic advances in psychopharmacology · 2026Article
43 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
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionPatients with schizophrenia have an elevated mortality risk compared to the general population, with cardiovascular-related deaths being the leading cause. The role of clozapine use in the long-term mortality risk is unclear. While clozapine treatment may increase the risk for cardiovascular mortality, it may have protective effects regarding suicidal behavior.
methodsWe systematically searched EMBASE, MEDLINE, and PsycINFO and reviewed studies that used a long-term follow-up (ie, >52 weeks) and reported on mortality in adults diagnosed with schizophrenia-spectrum disorders who had received clozapine treatment.
resultsAltogether, 24 studies reported on 1327 deaths from any causes during 217691 patient years in patients treated with clozapine. The unadjusted mortality rate in 22 unique samples during a follow-up of 1.1-12.5 (median = 5.4) years was 6.7 (95% confidence interval [CI] = 5.4-7.9) per 1000 patient years. Long-term, crude mortality rate ratios were not significantly lower in patients ever treated with clozapine during follow-up, but significantly lower in patients continuously treated with clozapine compared to patients with other antipsychotics (mortality rate ratio = 0.56, 95% CI = 0.36-0.85, P-value = .007). Few studies reported on rates of long-term cause-specific mortality (suicide and ischemic heart disease), which showed no significant difference in patients using clozapine compared to patients using other antipsychotics. Statistical heterogeneity was high in all analyses. DISCUSSION: Continuous clozapine treatment in schizophrenia patients was associated with a significantly lower long-term all-cause mortality rate compared to other antipsychotic use. These findings, combined with the known efficacy of clozapine, give reason to re-evaluate the hesitancy to prescribe clozapine in regular care settings.
trial registrationPROSPERO CRD42017069390.
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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.