Polypharmacy in clozapine-treated patients: A retrospective analysis of 667 patients in Ottawa, Canada

Abstract

Background: Clozapine is the gold standard for treatment-resistant schizophrenia (TRS), yet only 40 % of patients respond. Clinicians often add other psychotropics despite limited evidence and possible harms. Canadian data on this practice remains sparse.

Methods: We retrospectively reviewed charts of 667 adults prescribed clozapine between 2017-2020 in Ottawa, Canada. Clozapine augmentation was defined as prescription of ≥1 other psychotropic medication. Descriptive statistics summarized medication class frequences; X² or Wilcoxon tests assessed associations with demographic and clinical variables.

Results: After excluding four charts without medication data, 550/663 patients (83 %) received at least one add-on class (median 2 classes, IQR 1-3). Anti-psychotics were the commonest add-ons with 354 patients (53.4 % of all; 64.4 % of the augmented group) receiving clozapine plus another antipsychotic, most often aripiprazole (n=83). Valproate/divalproex was the commonest add-on (n=115). Clozapine with Paliperidone was the most frequent two-drug combination (n=29). Augmentation was more frequent in schizoaffective disorder than schizophrenia (91 vs. 81 %, p=0.010), in older adults (median 46 vs. 38 yrs, p<0.001), in females (88 vs. 81 %, p=0.028), and in patients with respiratory disease (p=0.015) or diabetes (p=0.019). Residence in supported or inpatient housing was also associated with augmentation (p<0.001). Recent hospitalization, current smoking, and self-reported ethnicity showed no association with augmentation (p≥0.33).

Conclusions: Clozapine polypharmacy is common in patients treated at this Canadian psychiatric hospital, with more than half of clozapine-treated patients receiving an additional antipsychotic. This high prevalence highlights a need for evidence-based guidelines and integrated monitoring to balance symptomatic benefit against additive pharmacologic risk in TRS.

Keywords: Clozapine; Schizophrenia-spectrum disorders; polypharmacy.