Safety implications of concomitant administration of antidepressants and opioid analgesics in surgical patients.

BACKGROUND: Commonly prescribed antidepressants (paroxetine, fluoxetine, duloxetine, bupropion) inhibit bioconversion of several prodrug opioid medications to their active metabolite, potentially decreasing analgesic effect. There is a paucity of studies assessing the risk-benefit of concomitant administration of antidepressants and opioids.

RESEARCH DESIGN AND METHODS: Observational study of adult patients taking antidepressants prior to scheduled surgery using 2017-2019 electronic medical record data to assess perioperative use of opioids and to determine the incidence and risk factors for developing postoperative delirium. We conducted a generalized linear regression with the Gamma log-link to assess the association between use of antidepressants and opioids and a logistic regression to assess the association between antidepressants use and the likelihood of developing postoperative delirium.

RESULTS: After controlling for patient demographic and clinical characteristics, and postoperative pain, use of inhibiting antidepressants was associated with 1.67 times greater use of opioids per hospitalization day (p = 0.00154), a two-fold increase in the risk for developing postoperative delirium (p = 0.0224), and an estimated average of four additional days of hospitalization (p < 0.00001) compared to use of non-inhibiting antidepressants.

CONCLUSIONS: Careful consideration to drug-drug interactions and risk of related adverse events remains critical in the safe and optimal management of postoperative pain in patients taking concomitantly antidepressants.