Coadministration of antidepressants, certain opioids linked to adverse events in nursing home patients
Older nursing home patients who received both CYP2D6-metabolized opioids and CYP2D6-inhibiting antidepressants were at higher risk for worsening pain, pain-related hospitalization, pain-related ED visits, and opioid use disorder in a recent study.
Use of CYP2D6-metabolized opioids with CYP2D6-inhibiting antidepressants was associated with worsening pain and increased risk for opioid-related adverse events in older nursing home patients, a recent study found.
Researchers used a target trial emulation framework to perform a retrospective cohort study examining the associations between concomitant use of CYP2D6-metabolized opioids (i.e., hydrocodone, codeine, tramadol, and oxycodone) and antidepressants and clinical outcomes as well as opioid-related adverse events. The study was based on 2010-2021 Medicare data on long-term nursing home residents ages 65 years and older who were receiving CYP2D6-metabolized opioids and had an indication for use of antidepressants. The intervention was defined as initiation of CYP2D6-inhibiting versus CYP2D6-neutral antidepressants that overlapped with use of CYP2D6-metabolized opioids for at least one day. Worsening pain, physical function, and depression were the primary clinical outcomes, while opioid-related adverse events outcomes included pain-related hospitalizations and ED visits, opioid use disorder (OUD), and opioid overdose. The results were published July 23 by Annals of Internal Medicine.
The study included 29,435 older nursing home residents who received CYP2D6-metabolized opioids along with antidepressants for at least one day, equating to 30,156 resident observations from January 2011 to December 2021. Mean age was 84.9 years. Within this sample, there were 28,613 patient episodes available for analysis. Of the 30,156 observations with concomitant opioid-antidepressant use, 5,293 residents (17.6%) received CYP2D6-metabolized opioids with CYP2D6-inhibiting antidepressants (study group) and 24,863 residents (82.4%) received CYP2D6-metabolized opioids with CYP2D6-neutral antidepressants (comparison group).
The researchers found that concomitant use of CYP2D6-metabolized opioids and CYP2D6-inhibiting 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 hospitalizations (1.37; 95% CI, 1.19 to 1.59), pain-related ED visits (1.49; 95% CI, 1.24 to 1.80), and OUD (1.93; 95% CI, 1.37 to 2.73). No difference was seen in physical function, depression, or opioid overdose, with adjusted incidence rate ratios of 0.99 (95% CI, 0.97 to 1.01), 1.03 (95% CI, 0.99 to 1.07), and 0.88 (95% CI, 0.57 to 1.37), respectively.
The study applies only to nursing home patients, results could have been affected by self-reporting of clinical outcomes, and Medicare data did not provide details on drug consumption or administration, among other limitations, the authors noted. "In conclusion, among older [nursing home] residents, those who used CYP2D6-metabolized opioids concomitantly with CYP2D6-inhibiting (vs. CYP-neutral) antidepressants were more likely to experience worsening pain and have increased risk for pain-related hospital and ED visits, and OUD, with no difference in physical function, depressive symptoms, and [opioid overdose]," they wrote. "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."