Clozapine and Suicide in VigiBase: Most Important Fatal Outcome in Young Males and Differences Between Attempted and...

In the United States, clozapine is the only antipsychotic approved for preventing suicide in schizophrenia. Using the worldwide pharmacovigilance database (VigiBase), 2 studies explore fatal outcomes during suicide and other adverse drug reactions (ADRs) in adults treated with clozapine.

The first study (from inception until January 15, 2023) focused on 17,624 fatal outcomes in 6 groups after stratification by sex and age group (young, 18 to 44 y; middle-aged, 45 to 64 y; and geriatric, above 64 y). Fatal ADR outcomes were ranked by frequency; overrepresentation/underrepresentation was determined by univariate odds ratios (OR), 95% CIs, and adjusted ORs. The second study (from inception until January 1, 2024) tested differences between 752 completed suicides (cases) and 692 nonfatal suicide attempts (controls) using logistic regression.

In young males, the prevalence of completed suicide within fatal outcome labels was 9.2% (299/3223), second only after the unspecific label, "death"; it was significantly overrepresented when compared with females (adjusted OR=1.5 (CI 1.1-1.9; P=0.004). In the comparison of completed versus attempted suicides, the adjusted ORs were (1) 2.1 (CI: 1.7-2.7) for male sex, (2) 1.5 (CI: 1.2-2.0) for the middle-aged and 3.2 (CI: 1.6-6.3) for the geriatric groups, and (3) 7.5 (CI: 5.2-10.9) for the United States.

The literature and this new data indicate that, for saving the lives of young males treated with clozapine, the most important focus should be on preventing completed suicide and avoiding clozapine nonadherence. In VigiBase, the proportion of fatal outcomes during US suicide attempts was 70% (261/375); other studies are needed.