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Prodrug opioids less effective for pain control in patients on SSRIs
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Using a machine learning approach, researchers found that patients on selective serotonin reuptake inhibitors who were prescribed prodrug opioids had more pain after leaving the hospital than those prescribed active form opioids.
Most surgical patients receive opioids regardless of whether they have comorbidities, like depression, that impact post-operative pain management, Tina Hernandez-Boussard, PhD, MPH, associate professor of medicine at Stanford University, and colleagues explained in PLOS One.
“The interaction between SSRIs and prodrug opioids has been theorized for many years but its effect on pain management was previously unknown,” Hernandez-Boussard told Healio Psychiatry. “Given that both SSRIs and prodrug opioids are commonly prescribed in the U.S. population, we wanted to provide direct clinical evidence that this theory is real and actually affects pain. This is a step to understanding how we can better manage pain in vulnerable populations.”
With machine learning, researchers identified patients prescribed a combination of SSRIs and prodrug opioids post-operatively and evaluated how this combination affected pain control.
The investigators developed and validated natural language processing algorithms to extract data on depression diagnosis, SSRI use and symptoms in 4,306 patients who received surgery over a 9-year period. They measured the difference between pre- and post-operative pain at discharge, after 3 weeks and after 8 weeks. The computational models were used to predict the change in pain after surgery across the three time points by using patient’s electronic health record data (eg, medications, vitals and demographics) taken before surgery.
Overall, 14.1% of patients were prescribed both an SSRI and a prodrug opioid, 29.4% were prescribed an SSRI and a nonprodrug opioid, 18.6% were prescribed a prodrug opioid but were not on SSRIs and 37.5% were prescribed a nonprodrug opioid but were not on SSRIs.
The natural language processing algorithm achieved precision of 0.92 and identified depression with a F1 score of 0.95 when being compared against 300 manually annotated clinical notes, according to the results.
The results revealed that patients on SSRIs who were prescribed prodrug opioids experienced significantly worse pain control at discharge, 3- and 8-week follow-up (P < .01) compared with those on SSRIs who received a nonprodrug opioid. However, in patients who were not on SSRIs, the researchers found that those who received nonprodrug opioids had better pain outcomes compared with those who received prodrug opioids.
The machine learning algorithm was able to predict the increase or decrease of the discharge, 3-week and 8-week follow-up pain scores when compared with the preoperative pain score, the researchers wrote. The strongest predictors of post-operative pain control were pre-operative pain, surgery type and opioid tolerance.
“Every opioid has a side effect and there is not one opioid that is better than another — if properly dosed,” Hernandez-Boussard said. “However, our research suggests that for patients taking a common SSRI antidepressant, morphine or oxycodone might be a better choice, as these opioids do not require activation by the liver enzyme inhibited by SSRIs.” – by Savannah Demko
Disclosure: The authors report no relevant financial disclosures.
Perspective
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Lawrence Greenblatt, MD, FACP
Individuals undergoing surgery typically need postoperative systemic analgesic therapy regardless of their medial background and current medical therapy. Many people in the United States are treated with antidepressant therapy, particularly SSRIs.
Based on the concern that SSRIs can inhibit CYP-2D6, an enzyme required to convert prodrug opioids such as codeine or hydrocodone to active compounds, Parthipan et al, studied whether concomitant treatment with these two classes of drugs might lead to worse pain outcomes. Fully 14% of all patients included in the 7-year study were prescribed both an SSRI and a prodrug opioid. As hypothesized, these individuals had worse pain at discharge. Surprising to me, they also had worst pain outcomes at 3 weeks and 8 weeks after follow-up. This is likely well after the vast majority of patients included were no longer taking opioids. This finding suggests me that the patient’s poor postoperative pain control may have affected their perception of pain long after the procedure.
These data allow one to speculate that perhaps the reason for the increased risk of chronic postsurgical pain in individuals treated for depression may be that certain antidepressants might interfere with achieving effective pain control in the acute setting.
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