For older nursing home (NH) residents, use of CYP2D6-metabolized opioids concomitantly with CYP2D6-inhibiting antidepressants is associated with worsening pain and increased risk of opioid-related adverse events (ORAEs), according to a study published online July 23 in the Annals of Internal Medicine.

Yu-Jung Jenny Wei, Ph.D., from the College of Pharmacy at The Ohio State University in Columbus, and colleagues examined the associations of concomitant use of CYP2D6-metabolized opioids and antidepressants with clinical outcomes and ORAEs in a retrospective cohort study using a target trial emulation framework. Data were included for 29,435 long-term residents aged 65 years and older receiving CYP2D6-metabolized opioids with a disease indication for antidepressant use who initiated CYP2D6-inhibiting versus CYP2D6-neutral antidepressants.

The researchers found that use of CYP2D6-metabolized opioids concomitantly with CYP2D6-inhibiting antidepressants was associated with increased adjusted rate ratio of worsening pain compared with CYP2D6-neutral antidepressants (1.13). In addition, CYP2D6-inhibiting antidepressants were associated with higher adjusted incidence rate ratios of pain-related hospitalization, pain-related emergency department visits, and opioid use disorder (1.37, 1.49, and 1.93, respectively); no differences were seen in physical function, depression, and opioid overdose.

“When co-use of CYP2D6-metabolizing opioids and antidepressants is clinically needed, selecting CYP2D6-neutral antidepressants, rather than CYP2D6-inhibiting antidepressants, may provide better or equal clinical and adverse outcomes,” the authors write.

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