Antipsychotics and other risk factors for mortality among people with schizophrenia during an extreme heat event: a population-based case-control study

Schizophrenia is associated with increased mortality during extreme heat events (EHEs), including the unprecedented 2021 Western North America EHE in British Columbia, Canada. We sought to examine the association between mortality during the 2021 EHE and multiple risk factors among people with schizophrenia, with a focus on antipsychotic medications. We identified all individuals with schizophrenia in British Columbia using an administrative chronic disease registry and linked them with antipsychotic dispensations for the 30 days prior to the EHE. We compared 137 individuals who died during the EHE with 57,394 who survived using multiple logistic regression. Analyses also included age, sex, income assistance, comorbidities, and indicators of schizophrenia severity. Dispensation of any antipsychotic was associated with increased EHE mortality [OR 2.43, 95% CI 1.52, 4.01], which was driven by haloperidol, clozapine, and zuclopenthixol. The risk was increased for dispensation of two or more antipsychotics in combination [OR 4.05, 95% CI 2.41, 6.98]. Other variables associated with EHE mortality included being on income assistance, age, sex, having a mental health-related emergency department visit, and time since disease registry entry. Being dispensed an antipsychotic prior to the EHE was associated with increased odds of mortality among people with schizophrenia. Some antipsychotics had larger effects, and risk increased with combination therapy. There were also significant non-pharmaceutical risk factors. People with schizophrenia are at-risk during EHEs due to multiple overlapping factors, including antipsychotic medications.