Clozapine, relapse, and adverse events: a 10-year electronic cohort study in Canada
Date
2024-09
Authors
Balbuena, Lloyd
Halayka, Shawn
Lee, Andrew
AHMED, AG
Hinz, Tamara
Kolla, Nathan
Pylypow, Jenna
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The British Journal of Psychiatry
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Article
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Abstract
Background
Clozapine is the most effective medication for treatment-resistant psychoses, but the balance of benefits and risks is understudied in real-world settings.
Aims
To examine the relative re-hospitalisation rates for mental health relapse and adverse events associated with clozapine and other antipsychotics in adult and child/youth cohorts.
Method
Data were obtained from the Canadian Institute of Health Information for adults (n = 45 616) and children/youth (n = 1476) initially hospitalised for mental health conditions in British Columbia, Manitoba and Saskatchewan from 2008 to 2018. Patient demographics and hospitalisations were linked with antipsychotic prescriptions dispensed following the initial visit. Recurrent events survival analysis for relapse and adverse events were created and compared between clozapine and other antipsychotics.
Results
In adults, clozapine was associated with a 14% lower relapse rate versus other drugs (adjusted hazard ratio: 0.86, 95% CI: 0.83–0.90) over the 10-year follow-up. In the first 21 months, the relapse rate was higher for clozapine but then reversed. Over 1000 person-months, clozapine-treated adults could be expected to have 38 relapse hospitalisations compared with 45 for other drugs. In children/youth, clozapine had a 38% lower relapse rate compared with other antipsychotic medications (adjusted hazard ratio: 0.62, 95% CI: 0.49–0.78) over the follow-up period. This equates to 29 hospitalisations for clozapine and 48 for other drugs over 1000 person-months. In adults, clozapine had a higher risk for adverse events (hazard ratio: 1.34, 95% CI: 1.18–1.54) over the entire follow-up compared with other antipsychotics. This equates to 1.77 and 1.30 hospitalisations over 1000 person-months for clozapine and other drugs, respectively.
Conclusions
Clozapine was associated with lower relapse overall, but this was accompanied by higher adverse events for adults. For children/youth, clozapine was associated with lower relapse all throughout and had no difference in adverse events compared with other antipsychotics.
Description
Keywords
Psychotic disorders/schizophrenia, register-based study, antipsychotics, drug or substance interactions and side effects
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DOI
https://doi.org/10.1192/bjp.2024.140