Gabapentinoids and Risk for Exacerbation of Chronic Obstructive Pulmonary Disease

Rationale Data on the effect of gabapentinoids on patients with chronic obstructive pulmonary disease (COPD) are sparse, although the U.S. Food and Drug Administration has issued a safety warning for these medications, particularly in individuals with respiratory risk factors. Objectives To investigate whether gabapentinoid use is associated with increased COPD exacerbations requiring systemic corticosteroids. Methods Using a nationwide administrative claims database, we conducted a retrospective cohort study using an active-comparator new-user design. We identified patients with COPD and neuropathic or chronic pain who initiated gabapentinoid treatment between 2015 and 2022. Two active-comparator new-user cohorts were created: one with tricyclic antidepressants and the other with serotonin–noradrenaline reuptake inhibitors. Patient backgrounds were balanced using overlapping propensity score weighting. Results The primary outcome was the initial occurrence of COPD exacerbations requiring systemic corticosteroids. Hazard ratios (HRs) associated with gabapentinoids were assessed using a weighted Cox proportional hazards model. In the tricyclic antidepressant cohort (37,098 patients), gabapentinoids were associated with a higher incidence of the primary outcome (67.8 vs. 46.7 per 100 person-years; HR, 1.21 [95% confidence interval, 1.03–1.42]). In the serotonin–noradrenaline reuptake inhibitor cohort (48,480 patients), gabapentinoids were also linked to a higher incidence of the primary outcome (68.8 vs. 51.4 per 100 person-years; HR, 1.18 [95% confidence interval, 1.10–1.28]). Conclusions Gabapentinoids may increase the risk of COPD exacerbations compared with other central nervous system–active medications at the same treatment stage for neuropathic or chronic pain, suggesting that their use should be limited to clearly beneficial cases.