Clozapine and all-cause mortality in treatment-resistant schizophrenia: a historical cohort study

Jaelim Cho, Richard D. Hayes, Amelia Jewell, Giouliana Kadra, Hitesh Shetty, James H. MacCabe, Johnny Downs

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Objective: Large-scale epidemiological studies have demonstrated a protective effect of clozapine on mortality in people with schizophrenia. Clozapine is reserved for use in patients with treatment-resistant schizophrenia (TRS), but evidence of clozapine’s effect on mortality exclusively within TRS samples is inconclusive. Hence, we aimed to investigate the effect of clozapine use on all-cause mortality in TRS patients.

Methods: A historical patient cohort sample of 2,837 patients, who met criteria for TRS between 1st Jan 2008 and 1st Jan 2016, were selected from the South London and Maudsley NHS Foundation Trust (SLAM) electronic health records (EHR). The ZTAS mandatory monitoring system linked to the SLAM EHR was used to distinguish which patients were initiated on clozapine (n=1,025). Cox proportional hazard models were used, adjusting for socio-demographics, clinical monitoring, mental and physical illness severity and functional status.

Results: After controlling for potential confounders, the protective effect of clozapine on all-cause mortality was significant (adjusted hazard ratio 0.61; 95% confidence interval 0.38–0.97; p=0.04).

Conclusions: Clozapine reduces the risk of mortality in patients who meet criteria for TRS. We provide further evidence that improving access to clozapine in TRS is likely to reduce the mortality gap in schizophrenia.
Original languageEnglish
Pages (from-to)237-247
Number of pages11
JournalActa Psychiatrica Scandinavica
Issue number3
Early online date26 Nov 2018
Publication statusPublished - 27 Feb 2019


  • clozapine
  • mortality
  • schizophrenia
  • treatment-resistant


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