TY - JOUR
T1 - Clozapine and Long-Term Mortality Risk in Patients With Schizophrenia
T2 - A Systematic Review and Meta-analysis of Studies Lasting 1.1-12.5 Years
AU - Vermeulen, Jentien M
AU - van Rooijen, Geeske
AU - van de Kerkhof, Marita P J
AU - Sutterland, Arjen L
AU - Correll, Christoph U
AU - de Haan, Lieuwe
N1 - © The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: [email protected].
PY - 2019/3/7
Y1 - 2019/3/7
N2 - 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.
AB - 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.
U2 - https://doi.org/10.1093/schbul/sby052
DO - https://doi.org/10.1093/schbul/sby052
M3 - Article
C2 - 29697804
SN - 0586-7614
VL - 45
SP - 315
EP - 329
JO - Schizophrenia Bulletin
JF - Schizophrenia Bulletin
IS - 2
ER -