SSRI Antidepressant Drugs Interfere With Opioid Pain Relief

Researchers examined whether SSRI antidepressants diminish the pain reduction effects of certain opioids.

Selective serotonin reuptake inhibitor (SSRI) antidepressants diminish the pain reduction effects of prodrug opioids according to a new study published in PLOS One.1

Researchers at Stanford University hypothesized that patients taking SSRI antidepressants who are prescribed a prodrug opioid will have greater postoperative pain. They used a machine learning approach to examine the effects of SSRI use on opioid types both before and after surgery.

The investigators identified 4306 patients who had been diagnosed with depression and undergone a major surgical procedure from 2009 to 2016. Of those patients, 14.1% had been prescribed an SSRI and prodrug opioid, 29.4% had been prescribed an SSRI and nonprodrug opioid, 18.6% had been prescribed a prodrug opioid but no SSRI, and 37.5% had been prescribed a nonprodrug opioid but no SSRI.

The researchers found that patients who had been prescribed an SSRI antidepressant and a prodrug opioid had greater pain levels after surgery than patients in the other 3 groups. The investigators recommended that clinicians consider alternative pain management strategies for patients taking SSRIs.

Related Articles

“There was theoretical evidence that suggested SSRIs might block prodrug opioids, but we didn’t know if it actually affected patient outcomes” noted Tina Hernandez-Boussard, PhD, a computational biologist and co-author of the study.2

Dr Hernandez-Boussard is hopeful these findings could lead to better pain management and fewer opioid prescriptions. The hope is that clinicians will tailor pain treatment toward more vulnerable groups. “More work needs to be done, but this is a good first step.”


  1. Parthipan A, Banerjee I, Humphreys K, et al. Predicting inadequate postoperative pain management in depressed patients: a machine learning approach. PLoS One. 2019;14(2):e0210575.
  2. Lambert J. Antidepressants can interfere with pain relief of common opioids. NPR. February 6, 2019. Accessed February 13, 2019.