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Population-based study of long-term mortality risk associated with clozapine use among patients with schizophrenia

Published online by Cambridge University Press:  04 July 2025

Huiquan Zhou Open the ORCID record for Huiquan Zhou [Opens in a new window] ,
Hao Luo Open the ORCID record for Hao Luo [Opens in a new window] ,
Jennifer Yee-Man Tang Open the ORCID record for Jennifer Yee-Man Tang [Opens in a new window] ,
William G. Honer ,
Tarun Bastiampillai ,
Jiayi Zhou ,
Heidi Taipale ,
Wing Chung Chang Open the ORCID record for Wing Chung Chang [Opens in a new window] ,
Simon Sai Yu Lui Open the ORCID record for Simon Sai Yu Lui [Opens in a new window]  and
Edwin Ho Ming Lee
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Huiquan Zhou
Affiliation:
Department of Psychiatry, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China
Hao Luo
Affiliation:
School of Public Health Sciences, University of Waterloo, Waterloo, Canada
Jennifer Yee-Man Tang
Affiliation:
Department of Educational Psychology, The Chinese University of Hong Kong, Hong Kong SAR, China
William G. Honer
Affiliation:
Department of Psychiatry, The University of British Columbia, Vancouver, Canada
Tarun Bastiampillai
Affiliation:
Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia Department of Psychiatry, Monash University, Melbourne, Australia
Jiayi Zhou
Affiliation:
Department of Social Work and Social Administration, The University of Hong Kong, Hong Kong SAR, China
Heidi Taipale
Affiliation:
Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
Wing Chung Chang
Affiliation:
Department of Psychiatry, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China
Simon Sai Yu Lui
Affiliation:
Department of Psychiatry, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China
Edwin Ho Ming Lee
Affiliation:
Department of Psychiatry, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China
Sherry Kit Wa Chan*
Affiliation:
Department of Psychiatry, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China
*
Correspondence: Sherry Kit Wa Chan. Email: kwsherry@hku.hk
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Abstract

Background

Patients with schizophrenia have a significantly elevated risk of mortality. Clozapine is effective for treatment-resistant schizophrenia, but its use is limited by side-effects. Understanding its association with mortality risk is crucial.

Aims

To investigate the associations of clozapine with all-cause and cause-specific mortality risk in schizophrenia patients.

Method

In this 18-year population-based cohort study, we retrieved electronic health records of schizophrenia patients from all public hospitals in Hong Kong. Clozapine users (ClozUs) comprised schizophrenia patients who initiated clozapine treatment between 2003 and 2012, with the index date set at clozapine initiation. Comparators were non-clozapine antipsychotic users (Non-ClozUs) with the same diagnosis who had never received a clozapine prescription. They were 1:2 propensity score matched with demographic characteristics and physical and psychiatric comorbidities. ClozUs were further defined according to continuation of clozapine use and co-prescription of other antipsychotics (polypharmacy). Accelerated failure time (AFT) models were used to estimate the risk of all-cause and cause-specific mortality (i.e. suicide, cardiovascular disease, infection and cancer).

Results

This study included 9,456 individuals (mean (s.d.) age at the index date: 39.13 (12.92) years; 50.73% females; median (interquartile range) follow-up time: 12.37 (9.78–15.22) years), with 2020 continuous ClozUs, 1132 discontinuous ClozUs, 4326 continuous non-ClozUs and 1978 discontinuous Non-ClozUs. Results from adjusted AFT models showed that continuous ClozUs had a lower risk of suicide mortality (acceleration factor 3.01; 99% CI: 1.41–6.44) compared with continuous Non-ClozUs. Continuous ClozUs with co-prescription of other antipsychotics exhibited lower risks of suicide mortality (acceleration factor 3.67; 1.41–9.60) and all-cause mortality (acceleration factor 1.42; 1.07–1.88) compared with continuous Non-ClozUs. No associations were found between clozapine and other cause-specific mortalities.

Conclusions

These results add to the existing evidence on the effectiveness of clozapine, particularly its anti-suicide effects, and emphasise the need for continuous clozapine use for suitable patients and the possible benefit of clozapine polypharmacy.

Keywords

Clozapineschizophreniasuicide mortalityall-cause mortalitypopulation-based

Information

Type
Original Article
Information
The British Journal of Psychiatry , First View , pp. 1 - 9
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Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of Royal College of Psychiatrists

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Footnotes

*

These authors contributed equally.

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