Importance Given the negative impact of opioid use on population health, prescriptions for alternative pain-relieving medications, including gabapentin, have increased. Concurrent gabapentin and opioid prescriptions are commonly reported in retrospective studies of opioid-related overdose deaths.

Objective To determine whether people who filled gabapentin and opioid prescriptions concurrently (“gabapentin + opioids”) had greater mortality than those who filled an active control medication (tricyclic antidepressants [TCAs] or duloxetine) and opioids concurrently (“TCAs/duloxetine + opioids”). We hypothesized that people treated with gabapentin + opioids would have higher mortality rates compared to people treated with TCAs/duloxetine + opioids.

Design Propensity score-matched cohort study with an incident user, active control design. The median (maximum) follow-up was 45 (1093) days.

Setting Population-based.

Participants Medicare beneficiaries with spine-related diagnoses 2017-2019. The primary analysis included those who concurrently (within 30 days) filled ≥1 incident gabapentin + ≥1 opioid or ≥1 incident TCA/duloxetine + ≥1 opioid.

Exposures People treated with gabapentin + opioids (n=67,133) were matched on demographic and clinical factors in a 1:1 ratio to people treated with TCAs/duloxetine + opioids (n=67,133).

Main Outcomes and Measures The primary outcome was mortality at any time. A secondary outcome was occurrence of a major medical complication at any time.

Results Among 134,266 participants (median age 73.4 years; 66.7% female), 2360 died before the end of follow-up. No difference in mortality was observed between groups (adjusted hazard ratio (HR) and 95% confidence interval (CI) for gabapentin + opioids was 0.98 (0.90, 1.06); p=0.63). However, people treated with gabapentin + opioids were at slightly increased risk of a major medical complication (1.02 (1.00, 1.04); p=0.03) compared to those treated with TCAs/duloxetine + opioids. Results were similar in analyses (a) restricted to ≤30-day follow-up and (b) that required ≥2 fills of each prescription.

Conclusions and Relevance When treating pain in older adults taking opioids, the addition of gabapentin did not increase mortality risk relative to addition of TCAs or duloxetine. However, providers should be cognizant of a small increased risk of major medical complications among opioid users initiating gabapentin compared to those initiating TCAs or duloxetine.

The authors have declared no competing interest.

https://osf.io/9u6re/

This study was funded by the University of Washington Clinical Learning, Evidence, And Research (CLEAR) Center for Musculoskeletal Disorders, Administrative, Methodologic and Resource Cores and NIAMS/NIH grant P30AR072572. The funding source had no role in the study design, collection, analysis and interpretation of the data, writing of the report, or the decision to submit this article for publication.

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The Institutional Review Board at the University of Washington waived ethical approval for this work.

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Funding: This work was supported by the University of Washington Clinical Learning, Evidence, And Research (CLEAR) Center for Musculoskeletal Disorders, Administrative, Methodologic and Resource Cores and NIAMS/NIH grant P30AR072572. The funding source had no role in the study design, collection, analysis and interpretation of the data, writing of the report, or the decision to submit this article for publication.

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