Improved insomnia is one pathway underlying the anti-suicidal properties of clozapine.

Background: Insomnia is common in schizophrenia and associated with suicide. Clozapine has anti-suicidal properties and beneficial effects on sleep. Whether effects on insomnia mediate the anti-suicidal properties of clozapine remains unclear.

Methods: In n = 76 patients from the Clinical Antipsychotic Trials of intervention effectiveness schizophrenia trial using a within-subjects design, we investigated whether improvement in terminal insomnia was associated with improvement in suicidal ideation (SI) after treatment with non-clozapine antipsychotics, and then after treatment with clozapine, using binary logistic regression. Terminal insomnia and SI over the past 2 weeks were assessed before and after both non-clozapine antipsychotic and clozapine treatment with the Calgary Depression Scale for Schizophrenia.

Results: There was no association between improved terminal insomnia and resolution of SI after treatment with non-clozapine antipsychotics (OR = 0.2, 95% CI 0.0-9.0, p = 0.41). In the same patients, improved terminal insomnia was associated with resolution of SI after clozapine treatment (OR = 14.6, 95% CI 1.7-129.2, p = 0.02).

Conclusions: Improved terminal insomnia is associated with improved SI following clozapine treatment. Findings warrant replication in a larger sample with standard instruments in the assessment of insomnia and suicide, but suggest beneficial effects on sleep as a mediator of the anti-suicidal properties of clozapine. Future mechanistic studies are also needed.