Associations between insomnia medications and risk of death by suicide

Purpose: Insomnia is a modifiable risk factor for suicide often treated with medications. However, little is known about the associations between insomnia medications and risk of death by suicide. The purpose of this study is to model the comparative risk of suicide by each insomnia medication compared to zolpidem, a sedative-hypnotic approved for insomnia. Methods: First prescription fills of medications commonly used to treat insomnia were identified in electronic medical records. Date and cause of death were identified in death certificates. Cox proportional hazards models were used to analyze time from insomnia prescription to suicide. Results: More than 2 million patients filled a new insomnia prescription between 2005 and 2015, and 518 of them died by suicide within 12 months. Compared to zolpidem, the tricyclic antidepressants (amitriptyline, doxepin) were associated with a 64% lower risk of suicide (HR 0.36 (95% CI 0.22–0.66) and the sedating antihistamines (hydroxyzine, diphenhydramine) a 40% lower risk of suicide (HR 0.60 (0.41–0.89)). In contrast, the tetracyclic antidepressant (mirtazapine) was associated with a 62% higher risk of suicide (HR 1.62 (95% CI 1.10–2.38) compared to zolpidem. Conclusion: Insomnia is a modifiable risk factor for suicide, yet many medications used to treat insomnia have never been tested for the indication in clinical trials. To define efficacy in the prevention of suicide, trials are warranted.