Insomnia and suicide as reported adverse effects of second-generation antipsychotics and mood stabilizers

Study Objectives: Insomnia and suicide ideation/behavior/death (SIB) are common in psychiatric disorders. There is evidence that clozapine and lithium have antisuicidal properties and beneficial effects on sleep. We investigated the reported odds of spontaneously reported psychiatric adverse drug reactions of insomnia and SIB in adults for second-generation antipsychotics (SGAs) and mood stabilizers compared to clozapine and lithium, respectively. Methods: We searched the U.S. Food & Drug Administration Adverse Event Reporting System from inception through February 2021 for which an SGA or mood stabilizer was the suspected agent of a psychiatric adverse drug reaction. Results: We investigated 10 SGAs and 5 mood stabilizers. Compared to clozapine, other SGAs were associated with a significantly increased reported odds of insomnia (reported odds ratio [rOR] = 2.41-9.70) and SIB (rOR = 1.18-2.72). Compared to lithium, there was a significantly increased reported odds of SIB (rOR = 1.17-1.70) for other mood stabilizers and odds of insomnia (rOR = 1.66) for lamotrigine. The insomnia and SIB rORs for SGAs and mood stabilizers were positively correlated. Conclusions: Our results are consistent with evidence for antisuicidal properties of clozapine and lithium. Findings also raise the possibility of beneficial effects on sleep as one potential pathway underlying the antisuicidal properties for these agents. Future studies are needed to identify underlying biological mechanisms that contribute to these associations.

Automated summary

This study investigated the association between second-generation antipsychotics (SGAs) and mood stabilizers compared to clozapine and lithium, respectively, in terms of insomnia and suicide ideation/behavior/death (SIB). The results showed that other SGAs and mood stabilizers were significantly associated with increased reported odds of insomnia and SIB compared to clozapine and lithium. The findings support the antisuicidal properties of clozapine and lithium and suggest that beneficial effects on sleep may be one potential pathway underlying these properties.