Clozapine, Relapse, and Adverse Events: A 10-Year Electronic Cohort Study in Canada: Commentary, Author Response
Date
2024
Authors
Halayka, Shawn
Balbuena, Lloyd
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Article
Degree Level
Abstract
We agree with Kikuchi that the diversity of diagnoses may have obscured clozapine’s risk-benefit balance in our paper (1). Hence, our findings may have reflected the lower range of the overall benefit of clozapine. Table 1 shows the expected count of rehospitalization events stratified by index diagnosis in adult patients. These were calculated using flexible survival models implemented in the STPM3 Stata package (2).
The above figures show that clozapine had fewer relapse events compared to other drugs in patients with schizophrenia and schizoaffective disorders. In patients with bipolar disorder, the relapse events were the same, but clozapine had higher adverse events. The reverse was true in schizoaffective disorder patients: lower relapse events for clozapine but the same adverse event counts as other drugs. The child and youth cohort could not be stratified by diagnosis because of low numbers.
We agree with Kikuchi that the adverse events analysis was tilted in favor of other antipsychotics. Suicide attempts and deaths were not available in the data, so clozapine’s benefit is probably underestimated (3) while adverse events more specific to other drugs are probably underestimated.
The decision to exclude unmedicated periods was deliberate, since our objective was a head-to-head comparison of medications. In a previous paper (4) we found that over a five-year period, schizophrenia patients, on average, spent 11 months without medication and only 17 days in clozapine. Within-person analysis was considered, but this technique discards the records of people who did not switch from other drugs to clozapine or vice-versa. In our data, these patients made up the majority.
In summary, our register-based study shows that clozapine is an effective medication, with benefits and risks that require balancing.
Description
Commentary and Author Response for "Clozapine, Relapse, and Adverse Events: A 10-Year Electronic Cohort Study in Canada".
Keywords
clozapine, relapse events
Citation
Halayka, S., Balbuena, L. (2024). Clozapine, Relapse, and Adverse Events: A 10-Year Electronic Cohort Study in Canada: Commentary, Author Response