Abstract
Background: In the United States, clozapine was first approved for treatment-resistant schizophrenia and then for suicidality in schizophrenia psychoses. Systematic reviews support clozapine’s anti-suicidal effect, but the forensic literature stresses its lethality during overdoses. Research design and methods: Clozapine reports to the international pharmacovigilance database (VigiBase) were analyzed for suicidal ideation, suicide attempts, intentional overdose, and completed suicides from introduction to 1 January 2024. VigiBase uses the information component (IC) as a disproportionality analysis. Results: The clozapine ICs (range: other antipsychotics) were: 1) suicidal ideation IC = 0.570 with IC025 = 0.454 to IC975 = 0.680 (IC = 3.568 for aripiprazole and 1.729 for risperidone), 2) suicide attempt IC = 1.428 with IC025 = 1.323 to IC975 = 1.529 (IC = 4.150 for quetiapine and 2.968 for risperidone), 3) intentional overdose: IC = 0.995 with IC025 = 0.864 to IC975 = 1.120 (IC = 4.080 for quetiapine and 1.957 for aripiprazole), and 4) completed suicide IC = 1.133 with IC025 = 1.026 to IC975 = 1.235 (IC = 4.648 for quetiapine and 2.160 for risperidone). In summary, all clozapine ICs were significantly lower. We found 2391 clozapine-treated patients on the suicidality spectrum (627 cases with suicidal ideation, 752 with suicide attempt, 488 with intentional overdose, and 731 with completed suicide) but many were taking other antipsychotics. The most frequent reporting countries were the United States, the United Kingdom, and Croatia. Conclusion: This pharmacovigilance study, with all its inherent limitations, provides independent proof, not overlapping with prior literature, that clozapine may have specific strong anti-suicidal effects that do not appear to be present in other antipsychotics. Further VigiBase studies are needed to compare the lethality of an intentional overdose of clozapine (14.3%) with other antipsychotics.
| Original language | English |
|---|---|
| Pages (from-to) | 1301-1311 |
| Number of pages | 11 |
| Journal | Expert Opinion on Drug Safety |
| Volume | 24 |
| Issue number | 11 |
| DOIs | |
| State | Published - 2025 |
Bibliographical note
Publisher Copyright:© 2024 Informa UK Limited, trading as Taylor & Francis Group.
Funding
This paper was not funded. The authors acknowledge Lorraine Maw, M.A., from the University of Kentucky Mental Health Research Center at Eastern State Hospital, who helped in editing the article. The authors are indebted to the national centers that make up the World Health Organization (WHO) Program for International Drug Monitoring and contribute reports to VigiBase at the Uppsala Monitoring Centre. The information comes from a variety of sources, and the probability that the suspected adverse effect is drug-related is not the same in all cases. However, the opinions and conclusions of this study are not necessarily those of the various centers nor of the WHO.
| Funders | Funder number |
|---|---|
| Lorraine Maw | |
| University of Kentucky | |
| national centers that make up the World Health Organization | |
| PAHO/WHO |
Keywords
- Antipsychotic agents
- clozapine
- drug overdose
- drug-related side effects and adverse reactions
- pharmacovigilance
- suicidal ideation
- suicide, attempted
- suicide, completed
ASJC Scopus subject areas
- Pharmacology (medical)
