A National Retrospective Study of Antidepressants' Effects on Overdose and Self-Harm Among Adults Treated With Opioid Analgesics

Published in: Psychiatric Services, Articles in Advance (2022). doi: 10.1176/appi.ps.20220070

Posted on RAND.org on October 19, 2022

by Tisamarie B. Sherry, Thuy D. Nguyen, Andrew W. Dick, Ashley C. Bradford, Kosali Ilayperuma Simon, Bradley D. Stein

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Because individuals with a history of depression who are receiving opioids are at higher risk for adverse events, the authors examined whether antidepressant treatment reduces risk for overdose and self-harm among individuals with a history of depression who receive opioids.


Commercial insurance claims of individuals with a history of depression receiving opioids from 2007 to 2017 were used to quantify the association between antidepressant fills and adverse events among individuals after initiation of opioid treatment; the authors accounted for selection into treatment and used discrete-time, proportional hazards survival models.


Among 283,374 adults with a history of depression treatment, 8,203 experienced 47,486 adverse events from 2007 to 2017 in the 12 months after initiation of opioid treatment. Approximately half (N=144,052, 50.8%) filled an antidepressant prescription at least once in the 12 months after the opioid episode began. Individuals receiving antidepressants for at least 6 weeks had a reduced risk for any adverse event (adjusted odds ratio [AOR]=0.79, 95% confidence interval [CI]=0.65–0.97) as well as a reduced risk for opioid overdoses (AOR=0.78, 95% CI=0.64–0.96), overdoses from nonopioid controlled substances (AOR=0.76, 95% CI=0.62–0.94), overdoses from other substances (AOR=0.79, 95% CI=0.65–0.97), and other self-harm events (AOR=0.82, 95% CI=0.67–1.00).


Individuals with a history of depression who received opioid analgesics had a significantly lower risk for overdose and self-harm after they had been taking antidepressants for at least 6 weeks. Universal screening for mood disorders among individuals receiving opioids, and promptly providing evidence-based depression treatment when appropriate, may reduce adverse events.

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