High-Dose Opioids, Depression Increase Risk for Overdose

This retrospective cohort study examined the complex interactions between opioid medications prescribed for chronic non-cancer pain (CNCP), mental health disorders, polypharmacy, and overdose risk. Researchers examined enrollment data for 206,869 patients 18–64 years with CNCP who filled ≥ 2 prescriptions for opioid analgesics 2009–2012. Medications, clinical conditions, and utilization were examined in 6-month intervals after the first opioid prescription up to a maximum of 42 months.

• Over 3.5 years, 1385 (0.67%) of the cohort experienced a drug overdose, for an incidence rate of 421 per 100,000 person-years. The highest rates of overdose were seen in women (64%) and patients with depression (55%), followed by those with large joint arthritis (53%) or back pain (52%), and those residing in the South (47%).
• Higher opioid dose conferred higher risk, but the highest risk for overdose was seen among patients with depression receiving high-dose opioids (> 100 mg morphine equivalent, adjusted odds ratio, 7.06).
• In each 6-month interval, 19–24% of the patients filled ≥ 1 antidepressant prescription; short-term (1–30 day) receipt of antidepressants conferred higher risk of overdose.
• In each 6-month interval, 15–25% filled ≥ 1 benzodiazepine prescription; longer duration of receipt of benzodiazepines conferred higher overdose risk.

Comments:

This article suggests that short-term antidepressant receipt is associated with higher risk of overdose in patients with CNCP, even among those without depression. This finding might implicate overdose as a means of suicide among acutely depressed patients, or it might be an artifact of confounding by indication. Since antidepressants are commonly used as first-line agents for CNCP, short-term use (i.e., early discontinuation) might be a marker for opioid-seeking patients, or for CNCP patients whose pain is severe and unresponsive to non-opioid modalities. Either type of patient might seek higher opioid doses, including illicit opioids or self-escalations of prescribed opioids, both of which increase overdose risk. This study conversely suggests that longer-term antidepressant use might be protective against overdose. Long-term receipt of antidepressants could be a marker for more adherent patients or those whose pain responded to non-opioid modalities and can be controlled with lower, less risky opioid doses.

Peter D. Friedmann, MD

Reference:

Turner BJ, Liang Y. Drug overdose in a retrospective cohort with non-cancer pain treatment with opioids, antidepressants, and/or sedative-hypnotics: interactions with mental health disorders. J Gen Intern Med. 2015;30(8):1081–1096.