Long-term Psychoactive Medications, Polypharmacy, and Risk of Suicide and Unintended Overdose Death Among Midlife and Older Women Veterans

BACKGROUND: Rates of suicide and unintended overdose death are high among midlife and older women, yet there is paucity of data identifying women at greatest risk. Psychoactive medications, commonly prescribed and co-prescribed in this population, may serve as salient indicators of risk for these outcomes. OBJECTIVE: To determine whether long-term psychoactive medications and psychoactive polypharmacy predict risk of suicide and unintended overdose death among midlife and older women Veterans above and beyond other recognized factors. DESIGN: Longitudinal cohort study PARTICIPANTS: Women Veterans aged ≥ 50 with at least one Veterans Health Administration (VHA) clinical encounter in FY2012–2013. MAIN MEASURES: Long-term psychoactive medications (opioids, benzodiazepines, sedative-hypnotics, antidepressants, antipsychotics, and antiepileptics, prescribed for ≥ 90/180 days) and psychoactive polypharmacy (overlapping for ≥ 1 day) from VHA pharmacy records; suicide and unintended overdose death through December 31, 2018. KEY RESULTS: In this national sample of 154,558 midlife and older women Veterans (mean age 63.4, SD 9.3 years), 130 died by suicide and 175 died from unintentional overdose over an average of 5.6 years. In fully adjusted models, long-term opioids (hazard ratio (HR) 2.01, 95% CI 1.21–3.35) and benzodiazepines (HR 2.99, 95% CI 1.82–4.91) were associated with death by suicide; opioids (HR 3.62, 95% CI 2.46–5.34), benzodiazepines (HR 2.77, 95% CI 1.73–4.42), sedative-hypnotics (HR 1.87, 95% CI 1.06–3.29), antidepressants (HR 1.47, 95% CI 1.03–2.12), antipsychotics (HR 1.81, 95% CI 1.02–3.22), and antiepileptics (HR 2.17, 95% CI 1.48–3.19) were associated with unintended overdose death. Women who were co-prescribed ≥ 3 psychoactive medications had over 2-fold increased risk of suicide (HR 2.83, 95% CI 1.65–4.84) and unintended overdose death (HR 2.60, 95% CI 1.72–3.94). CONCLUSIONS: Long-term psychoactive medications and psychoactive medication polypharmacy were important indicators of risk for death by suicide and death by unintended overdose among midlife and older women Veterans, even after accounting for psychiatric and substance use disorders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-022-07592-4.