Causes of death in clozapine-treated patients in a catchment area: a 10-year retrospective case-control study.

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Rose, Emily 
Turrion, Concha 
Jenkins, Christopher 
Cardinal, Rudolf N 

Uncertainty regarding the excess of mortality in patients treated with clozapine persists. A decrease in all-cause mortality, and perhaps also in suicide, after clozapine initiation has been reported, but there are no studies in which preventable causes were ascertained in those taking medication in the long term. Here, we aimed to assess a decade of causes of deaths in a catchment area in patients with schizophrenia chronically treated with clozapine and compared them to a clozapine-treated control cohort. Causes of deaths were classified as suicide, expected (e.g. cancer), and unexpected deaths (encompassing causes of death potentially due to clozapine side effects, and unexplained sudden death). We used descriptive statistics for comparing socio-demographic and clinical factors between the three groups. Logistic regression models were used to examine risk factors associated with unexpected death compared to the control group. We found that the overall mortality was similar to that in previous studies (at 0.8% yearly on average) with unexpected deaths accounting for 52% of total deaths. The unexpected deaths group was on average treated with higher clozapine doses (mean 460 mg/day). A small but significant peak of unexpected deaths was found during the 2018 summer heat wave, which might have exacerbated dose-dependent side effects of clozapine. We suggest increased monitoring for those on higher doses of clozapine as one potential intervention to decrease mortality in this population.

Antipsychotics, Clozapine, Heat-wave, Mortality, Suicide, Adult, Aged, Antipsychotic Agents, Case-Control Studies, Catchment Area, Health, Cause of Death, Clozapine, Cohort Studies, England, Female, Humans, Male, Middle Aged, National Health Programs, Retrospective Studies, Schizophrenia, Suicide
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Eur Neuropsychopharmacol
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Elsevier BV
Medical Research Council (MC_PC_17213)
This work is not directly funded by any organization. The work uses information for the CPFT Research Database, which was supported by the UK National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC); the views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. SC’s and RNC’s research was supported by the Medical Research Council (grant MC_PC_17213 to RNC).