Columbus, OH—The safety and effectiveness of the concomitant use of CYP2D6-metabolized opioids and antidepressants among older nursing home residents is not clear, according to a new study that raises concerns about clinical outcomes and opioid-related adverse events (ORAEs).

To better understand the issue, researchers from The Ohio State University and colleagues conducted a retrospective cohort study using a target trial emulation framework. The study used a 100% Medicare nursing home sample linked to Minimum Data Set (MDS) from 2010 to 2021. The results were published in Annals of Internal Medicine.

The participants were 29,435 long-term care residents aged 65 years and older receiving CYP2D6-metabolized opioids with a disease indication for antidepressant use. The focus was on what occurred when CYP2D6-inhibiting versus CYP2D6-neutral antidepressants were initiated that overlapped with use of CYP2D6-metabolized opioids for 1 day or more. Past research has shown that the CYP2D6 enzyme is responsible for the metabolism of hydrocodone,14 codeine,13 and dihydrocodeine to their active metabolites (hydromorphone, morphine, and dihydromorphine, respectively), which then undergo phase II glucuronidation.

In addition, some selective serotonin reuptake inhibitors, including paroxetine, fluoxetine and citalopram, are known to inhibit CYP2D6 activity to a greater or lesser degree.

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

“Use of CYP2D6-metabolized opioids concomitantly with CYP2D6-inhibiting (vs. CYP2D6-neutral) antidepressants was associated with worsening pain and increased risk for most assessed ORAEs among older NH residents,” the authors concluded.

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