Gabapentinoids and Risk for Severe Exacerbation in Chronic Obstructive Pulmonary Disease : A Population-Based Cohort Study

Ann Intern Med. 2024 Feb;177(2):144-154. doi: 10.7326/M23-0849. Epub 2024 Jan 16.


Background: North 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.

Objective: To assess whether gabapentinoid use is associated with severe exacerbation in patients with COPD.

Design: Time-conditional propensity score-matched, new-user cohort study.

Setting: Health insurance databases from the Régie de l'assurance maladie du Québec in Canada.

Patients: Within 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.

Measurements: The 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.

Results: The 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]).

Limitation: Residual confounding, including from lack of smoking information.

Conclusion: In 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 source: Canadian Institutes of Health Research and Canadian Lung Association.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Canada
  • Chronic Pain*
  • Cohort Studies
  • Epilepsy*
  • Humans
  • Neuralgia* / complications
  • Neuralgia* / drug therapy
  • Pulmonary Disease, Chronic Obstructive* / drug therapy