Concurrent Insomnia and Suicidal Ideation and Behavior as Psychiatric Adverse Effects of Clozapine Versus Other Atypical Antipsychotics.

Abstract

Background: Clozapine is associated with decreased insomnia and suicidal ideation and behavior (SIB), both of which are prevalent in psychiatric disorders. Aims: To consider effects on insomnia underlying the antisuicidal properties of clozapine, we investigated the reported odds of suicidal ideation, suicide attempt and/or suicide death with and without concurrent insomnia as spontaneously reported psychiatric adverse drug reactions (ADRs) in adults using clozapine compared to other second-generation antipsychotics (SGAs) for schizophrenia or schizoaffective disorder. Methods: We searched the US FDA Adverse Event Reporting System from inception through September 2024 for which an SGA used for schizophrenia or schizoaffective disorder was the suspected agent of a psychiatric ADR. Results: Compared to clozapine, the unadjusted reported odds of concurrent insomnia and suicidal ideation (rORs = 1.39-3.44) were significantly increased for all other SGAs. Similarly, compared to clozapine, the unadjusted reported odds of concurrent insomnia and suicide attempt/death (rORs = 2.32-4.76) were significantly increased for all other SGAs. Controlling for age and sex did not change the pattern of findings. Our findings are consistent with existing evidence for decreased insomnia and SIB in individuals taking clozapine for schizophrenia or schizoaffective disorder. Limitations: Rigorous longitudinal studies with established measures of sleep and suicide are warranted to investigate this mechanism. Conclusion: Compared to clozapine, all other SGAs were associated with increased reported odds of concurrent insomnia SIB. Findings provide additional evidence for improved sleep as a potential pathway underlying the antisuicidal properties of clozapine.