Ann Intern Med

CYP2D6-inhibitor antidepressants + CYP2D6-metabolized opioids: A potentially dangerous mix in seniors

July 24, 2024

Among older nursing home residents, the use of opioids metabolized by CYP2D6* concomitantly with CYP2D6-inhibiting antidepressants** (vs. CYP2D6-neutral agents) was associated with more severe pain and higher risk of opioid-related adverse effects.

This retrospective cohort study used a target trial emulation framework and included 29,435 long-term residents ≥65 years of age receiving CYP2D6-metabolized opioids and who also had an indication for antidepressant use. Researchers compared individuals initiating CYP2D6-inhibiting vs. CYP2D6-neutral antidepressants that overlapped with use of CYP2D6-metabolized opioids for ≥1 day.

Concomitant use of CYP2D6-metabolized opioids with CYP2D6-inhibiting (vs. CYP2D6-neutral) antidepressants was associated with a higher adjusted rate ratio of worsening pain (1.13; 95% CI, 1.09 to 1.17) and higher adjusted incidence rate ratios of pain-related hospitalization (1.37; CI, 1.19 to 1.59), pain-related ED visit (1.49; CI, 1.24 to 1.80), and opioid use disorder (1.93; CI, 1.37 to 2.73), with no difference in physical function, depression, and opioid OD.

*Selected CYP2D6-metabolized opioids:

• codeine
• hydrocodone
• oxycodone
• methadone
• tramadol

**Selected CYP2D6-inhibiting antidepressants:

• bupropion hydrochloride
• fluoxetine
• paroxetine
• duloxetine
• citalopram
• escitalopram
• fluvoxamine
• venlafaxine

Source:

Wei YJ, at al. (2024, July 23). Ann Intern Med. Clinical and Adverse Outcomes Associated With Concomitant Use of CYP2D6-Metabolized Opioids With Antidepressants in Older Nursing Home Residents : A Target Trial Emulation Study. https://pubmed.ncbi.nlm.nih.gov/39038293/