Clinical and Demographic Predictors of Early Clozapine Discontinuation Across Mood and Psychotic Disorders

Mete Ercis; Kristin C Cole; Ross A Dierkhising; Aysegul Ozerdem; Matej Markota; Balwinder Singh; Susan L McElroy; Mark A Frye; Jonathan G Leung

doi:10.1097/JCP.0000000000001951

Clinical and Demographic Predictors of Early Clozapine Discontinuation Across Mood and Psychotic Disorders

J Clin Psychopharmacol. 2025 Jan 14. doi: 10.1097/JCP.0000000000001951. Online ahead of print.

Authors

Mete Ercis¹, Kristin C Cole², Ross A Dierkhising², Aysegul Ozerdem¹, Matej Markota¹, Balwinder Singh¹, Susan L McElroy, Mark A Frye¹, Jonathan G Leung³

Affiliations

¹ From the Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN.
² Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN.
³ Department of Pharmacy, Mayo Clinic, Rochester, MN.

PMID: 39804782
DOI: 10.1097/JCP.0000000000001951

Abstract

Background: Clozapine is effective for treatment-resistant schizophrenia and bipolar disorder but is often discontinued due to adverse effects. This study compared early clozapine discontinuation rates and reasons in patients with mood and psychotic disorders.

Methods: Data from all individuals with mood or psychotic disorders who initiated clozapine for the first time at the inpatient psychiatric unit of Mayo Clinic, Rochester, Minnesota, between 2014 and 2022 were retrospectively analyzed. Early clozapine discontinuation, defined as discontinuation within 90 days of initiation, was the primary outcome. Cox proportional hazards regression was used to assess factors associated with discontinuation.

Results: Of 83 patients (mood group n = 37, psychosis group n = 46), those in the mood group were older (P = 0.022) and more likely to be nonsmokers (P = 0.034). The overall 90-day clozapine discontinuation rate was 45.7%. Early discontinuation was significantly higher in the mood group than in the psychosis group (hazard ratio = 2.41, 95% confidence interval = 1.26-4.64, P = 0.008). Other factors associated with early discontinuation were female sex (P = 0.033), older age (P = 0.026), and nonsmoking (P = 0.001). In multivariable analysis, smoking status was the only factor significantly inversely associated with early clozapine discontinuation (hazard ratio = 0.47, 95% confidence interval = 0.22-0.99, P = 0.048), while diagnostic group, sex, and age did not show significant associations (all P > 0.05). Discontinuations were primarily due to adverse drug reactions in both groups.

Conclusions: Nearly half of the patients discontinued clozapine early, with higher rates in the mood group. Studies should further explore potential pharmacodynamic and pharmacokinetic factors associated with discontinuation, including the influence of smoking. Careful monitoring and personalized management of side effects are crucial for optimizing clozapine therapy and improving treatment outcomes.