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Schizophr Bull. 2019 Mar 7;45(2):315-329. doi: 10.1093/schbul/sby052.

Clozapine and Long-Term Mortality Risk in Patients With Schizophrenia: A Systematic Review and Meta-analysis of Studies Lasting 1.1-12.5 Years.

Author information

1
Department of Psychiatry, Academic Medical Center, University of Amsterdam, Meibergdreef, AZ Amsterdam, The Netherlands.
2
Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY.
3
Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY.
4
Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany.

Abstract

INTRODUCTION:

Patients 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.

METHODS:

We 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.

RESULTS:

Altogether, 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 REGISTRATION:

PROSPERO CRD42017069390.

KEYWORDS:

antipsychotics; clozapine; mortality; schizophrenia

PMID:
29697804
PMCID:
PMC6403051
[Available on 2020-03-01]
DOI:
10.1093/schbul/sby052

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