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.