• Alvi A Rahman, Sophie Dell'Aniello, MoodieErica E MEEM0000-0002-7225-3977Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada (E.E.M.M.)., Madeleine Durand, Janie Coulombe, Jean-François Boivin, Samy Suissa, Pierre Ernst, and Christel Renoux.
• Department of Epidemiology, Biostatistics and Occupational Health, McGill University, and Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada (A.A.R., J.-F.B.).
• Ann. Intern. Med. 2024 Feb 1; 177 (2): 144154144-154.

BackgroundNorth American and European health agencies recently warned of severe breathing problems associated with gabapentinoids, including in patients with chronic obstructive pulmonary disease (COPD), although supporting evidence is limited.ObjectiveTo assess whether gabapentinoid use is associated with severe exacerbation in patients with COPD.DesignTime-conditional propensity score-matched, new-user cohort study.SettingHealth insurance databases from the Régie de l'assurance maladie du Québec in Canada.PatientsWithin a base cohort of patients with COPD between 1994 and 2015, patients initiating gabapentinoid therapy with an indication (epilepsy, neuropathic pain, or other chronic pain) were matched 1:1 with nonusers on COPD duration, indication for gabapentinoids, age, sex, calendar year, and time-conditional propensity score.MeasurementsThe primary outcome was severe COPD exacerbation requiring hospitalization. Hazard ratios (HRs) associated with gabapentinoid use were estimated in subcohorts according to gabapentinoid indication and in the overall cohort.ResultsThe cohort included 356 gabapentinoid users with epilepsy, 9411 with neuropathic pain, and 3737 with other chronic pain, matched 1:1 to nonusers. Compared with nonuse, gabapentinoid use was associated with increased risk for severe COPD exacerbation across the indications of epilepsy (HR, 1.58 [95% CI, 1.08 to 2.30]), neuropathic pain (HR, 1.35 [CI, 1.24 to 1.48]), and other chronic pain (HR, 1.49 [CI, 1.27 to 1.73]) and overall (HR, 1.39 [CI, 1.29 to 1.50]).LimitationResidual confounding, including from lack of smoking information.ConclusionIn patients with COPD, gabapentinoid use was associated with increased risk for severe exacerbation. This study supports the warnings from regulatory agencies and highlights the importance of considering this potential risk when prescribing gabapentin and pregabalin to patients with COPD.Primary Funding SourceCanadian Institutes of Health Research and Canadian Lung Association.

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