Adverse respiratory events during treatment with gabapentin and opioids among older adults with spine-related conditions: a propensity-matched cohort study in the US Medicare population.

Background context: Recent work indicates no increased mortality risk with concurrent gabapentin and opioid use when using an active comparator control design. However, concurrent gabapentin and opioid prescriptions have been associated with greater risk of respiratory depression in some studies.

Purpose: To compare the risk of respiratory events among Medicare enrollees with histories of spine-related diagnoses treated with gabapentin+opioids versus those treated with tricyclic antidepressants (TCA) or duloxetine+opioids. We hypothesized that enrollees treated with gabapentin+opioids would have increased risk of adverse respiratory events compared to those treated with an active control+opioids.

Study design/setting: Propensity score-matched cohort study with an incident user, active comparator (TCA/duloxetine) control design. The primary analysis included those who concurrently (within 30 days) filled ≥1 incident gabapentin+≥1 opioid or ≥1 incident TCA/duloxetine+≥1 opioid prescription.

Patient sample: U.S. Medicare beneficiaries with histories of spine-related diagnoses 2017 to 2019. People treated with gabapentin+opioids (n=66,860) were matched on demographic and clinical factors to people treated with TCAs/duloxetine+opioids (n=66,860).

Outcome measures: Time to a composite respiratory outcome consisting of mechanical ventilation, intubation, respiratory failure, pneumonia, or acute respiratory distress syndrome.

Methods: Cox proportional hazard regression was used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs).

Results: Among 133,720 Medicare enrollees (median age 73.3 years; 66.9% female), 6277 (4.7%) experienced respiratory events before the end of follow-up. A total of 3,469 (5.2%) of people who were treated with gabapentin+opioids (median initial dose/day of gabapentin was 300 mg) had respiratory events compared to 2808 (4.2%) of those treated with an active control+opioids. The increased risk in those treated with gabapentin+opioids was statistically significant after adjustment (HR 1.19; 95% CI 1.13, 1.25; p<.0001). The most common respiratory events were pneumonia (3.7% of people in the gabapentin+opioids group versus 3.0% of people in the TCA/duloxetine+opioids group) and respiratory failure (2.3% in the gabapentin+opioids group versus 1.8% in the TCA/duloxetine+opioids group). Results were similar in analyses (a) restricted to ≤30-day follow-up and (b) that required ≥2 fills of each prescription.

Conclusions: While recent work indicates no increased mortality risk with concurrent gabapentin and opioid use in this population, the current findings suggest clinicians should exercise caution in prescribing gabapentin to older adults with spine conditions who are using opioids, due to possible impacts on respiratory events. However, we cannot be certain that unmeasured confounding may explain these results and replication is needed.