Do CYP2D6-Inhibiting Antidepressants Worsen Pain for Patients on CYP2D6-Metabolized Opioids?

Opioids and antidepressants often are coprescribed. However, some antidepressants (e.g., fluoxetine) inhibit CYP2D6, an enzyme involved in metabolism of several prescription opioids (e.g., codeine). This drug–drug interaction has been linked to opioid toxicity and worsened pain control, possibly caused by attenuated conversion of these opioids to active forms (NEJM JW Psych Apr 1 2019 and PLoS One 2019; 14:e0210575).

In this retrospective cohort study, researchers identified 29,000 U.S. nursing home residents (age, ≥65) who were prescribed CYP2D6-metabolized opioids (i.e., codeine, hydrocodone, oxycodone, or tramadol) plus antidepressants. During 1 year of follow-up after antidepressant initiation, residents who received CYP2D6-inhibiting an…