¹University College Dublin, Department of Psychiatry, Dublin, Ireland, ²St John of God’s, Psychiatry, Celbridge, Co Kildare, Ireland

Background: Clozapine is the only licensed medication for treatment resistant schizophrenia (TRS). Understanding reasons for clozapine discontinuation is important, as once clozapine is stopped, treatment options are limited.

Aims & Objectives: We conducted a systematic review and proportional meta-analysis of observational studies to identify the prevalence of clozapine discontinuation and to identify reasons for clozapine discontinuation.

Method: We systematically searched PubMed and Scopus databases, until September 2024. We included English language observational studies which reported on clozapine treated cases and reasons for clozapine discontinuation.

Results: Thirty-seven studies met inclusion criteria. The pooled proportion of clozapine discontinuation was 38% (95% CI: 32–45%, n=5496, 25 studies (n=14978), I2=98.4%). The pooled proportion of discontinuation in the total population due to non-adherence (all reasons) was 13% (95% CI: 9-19%, n=1148, 28 studies, I2=97%); side effects 10% (95% CI: 8-14%, n=2840, 32 studies, I2=96.3%); and ineffectiveness, 7% (95% CI: 5-10%, n=1143, 26 studies, I2=96.6%).

Discussion & Conclusions: The most common reasons for clozapine discontinuation are non-adherence and side effects. By identifying and addressing these issues, clozapine continuation and thus clinical outcomes can be optimised. Lack of consistency in reporting reasons for discontinuation may indicate incomplete representation of reasons and could affect the findings of our study.