Concurrent Gabapentin and Opioid Use and Risk of Mortality in Medicare Recipients with Non-Cancer Pain.

Gabapentin is prescribed for pain and is perceived as safe generally. However, gabapentin can cause respiratory depression, exacerbated by concomitant central nervous system depressants (e.g., opioids), a concern for vulnerable populations. We compared mortality rates among new users of either gabapentin or duloxetine with or without concurrent opioids in the 20% Medicare sample. We conducted a new-user design retrospective cohort study, in Medicare enrollees ages 65-89 with non-cancer chronic pain and no severe illness who filled prescriptions between 2015-2018 for gabapentin (n=233,060) or duloxetine (n=34,009). Daily opioid doses, estimated in morphine milligram equivalents (MME), were classified into none, low (0< MME< 50), and high (≥50 MME), based on Centers for Disease Control and Prevention (CDC) recommendations. The outcomes were all-cause mortality (primary) and out-of-hospital mortality (secondary). We used inverse probability of treatment weighting to adjust for differences between gabapentin and duloxetine users. During 116,707 person-years of follow-up, 1,379 patients died. All-cause mortality rate in gabapentin users was 12.16/1,000 person-years versus 9.94/1,000 in duloxetine users. Risks were similar for users with no concurrent opioids (aHR=1.03, 95%CI: 0.80, 1.31) or low-dose daily opioids (aHR=1.06, 95%CI: 0.63, 1.76). However, gabapentin users receiving concurrent high-dose daily opioids had an increased rate of all-cause mortality compared to duloxetine users on high-dose opioids (aHR=2.03, 95%CI: 1.19, 3.46). Out-of-hospital mortality yielded similar results. In this retrospective cohort study of Medicare beneficiaries, concurrent use of high-dose opioids and gabapentin was associated with a higher all-cause mortality risk than that for concurrent use of high-dose opioids and duloxetine.