Drug Overdose in a Retrospective Cohort with Non-Cancer Pain Treated with Opioids, Antidepressants, and/or Sedative-Hypnotics: Interactions with Mental Health Disorders

Background: Opioid analgesics and other psychoactive drugs may pose an even greater risk for drug overdose in persons with mental health disorders. Objective: The purpose of this study was to examine interactions of filled prescriptions for opioids, benzodiazepines, antidepressants, and zolpidem with mental health disorders in regard to drug overdose. Design: The study was a retrospective cohort review. Subjects: Subjects were national HMO beneficiaries aged 18–64 years, enrolled at least 1 year (01/2009 to 07/2012), who filled at least two prescriptions for Schedule II or III opioids for non-cancer pain. Main Measures: The outcome was the first inpatient or outpatient drug overdose after the first filled opioid prescription. Predictors were calculated in 6-month intervals and exactly 6 months before a drug overdose: opioid use (mean daily morphine-equivalent dose), benzodiazepine use (days’ supply), antidepressant use (days’ supply), zolpidem use (days’ supply), mental health disorders (depression, anxiety/PTSD, psychosis), pain-related conditions, and substance use disorders (alcohol, other drug). Key Results: A total of 1,385 (0.67 %) subjects experienced a drug overdose (incidence rate 421/100,000 person-years). The adjusted odds ratios (AOR) for overdose among all subjects rose monotonically with daily opioid dose, but highest (AOR = 7.06) for persons with depression and a high opioid dose (≥100 mg) versus no depression or opioid use. Longer-term antidepressants (91–180 days) were protective for persons with depression, with 20 % lower AORs for overdose versus short-term (1–30 days) or none. For persons without depression, the AORs of overdose were increased for antidepressant use, but greatest (AOR = 1.98) for short-term use versus none. The AORs of overdose increased with the duration of benzodiazepine therapy among all subjects, with over 2.5-fold higher AORs for 91–180 days versus none. Conclusions: Opioids and longer-duration benzodiazepines were associated with drug overdose among all subjects, but opioid risk was greatest for persons with depression. Antidepressant use > 90 days reduced the odds of overdose for persons with depression, but all antidepressant use increased the risk for persons without depression.