- More than half (54.0%) of deaths in clozapine-treated patients were non-intentional and unexpected.
- Malignancy was the commonest cause (24.1%), followed by cardiovascular (14.9%) and respiratory or infective causes (10.3%).
- Unexpected decedents were older and more likely to smoke than a 2019 clozapine-treated cohort, supporting physical health monitoring and smoking cessation.
BJPsych Open. 2026 Aug 10;12(5):e213. doi: 10.1192/bjo.2026.12069.
ABSTRACT
BACKGROUND: Clozapine reduces overall mortality and suicide risk in schizophrenia, but the specific causes and clinical contexts of death among clozapine-treated patients remain less well characterised.
AIMS: We aimed to characterise causes of death in clozapine-treated patients within a defined UK catchment area over 17 years (2009-2025); compare features across predefined mortality clusters (suicide, expected, unexpected); compare unexpected death cases with a clozapine-treated comparison cohort alive in 2019 and examine temporal mortality patterns.
METHOD: We conducted a retrospective, descriptive cohort study of all deaths among clozapine-treated patients within a UK mental health National Health Service Trust between 1 January 2009 and 31 December 2025. Deaths were classified into suicide, expected and non-intentional unexpected, using a previously established framework. Variables were compared across clusters and between unexpected death cases and a clozapine-treated comparison cohort alive in 2019.
RESULTS: Of 87 deaths, 11 (12.6%) were suicides, 29 (33.3%) were expected and 47 (54.0%) were non-intentional unexpected. Malignancy was the most common cause (21/87, 24.1%), followed by cardiovascular (13/87, 14.9%) and respiratory or infective causes (9/87, 10.3%). Age differed across clusters (p = 0.005), with suicides at younger ages. Compared with the 2019 cohort, patients who died unexpectedly were older (55.0 v. 48.6 years, p = 0.006) and more likely to smoke (75.0 v. 34.6%, p < 0.001). Annual mortality peaked in 2021 and was not fully explained by direct COVID-19 deaths.
CONCLUSIONS: Mortality in clozapine-treated patients arises across diverse clinical contexts, with more than half classified as non-intentional unexpected. Findings support sustained physical health monitoring, closer attention to smoking and other modifiable risks, and continuity of care.
PMID:42572271 | DOI:10.1192/bjo.2026.12069
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