March 2024
Gabapentin and pregabalin are associated with severe COPD exacerbations

A study suggests yet another potential adverse effect of gabapentinoid drugs.

In 2019, the US Food and Drug Administration issued a warning related to nearly 50 case reports of breathing difficulties following use of gabapentinoids (i.e. gabapentin and pregabalin) that were reported between 2012 and 2017; however, such warnings are not reflected in current pain management guidelines. To explore this issue further, Canadian investigators retrospectively studied a cohort of patients with chronic obstructive pulmonary disease (COPD): 14,000 new users of gabapentinoids were propensity matched with 14,000 nonusers, based on duration of COPD, age, sex and gabapentinoid indication.

Gabapentinoid use was associated with significantly higher risk for severe COPD exacerbations requiring hospitalisation (15.1% vs 8.3% annually; adjusted hazard ratio [aHR], 1.4). New users of gabapentinoids also had significantly higher risks for respiratory failure (5.7% vs 3.6% annually; aHR, 1.3) and moderate-to-severe COPD exacerbations (53% vs 29% annually; aHR, 1.1). Gabapentin did not differ from pregabalin in risk for severe COPD exacerbations.

Comment: Although this study has typical limitations of a retrospective cohort design, it affirms reported cases of respiratory problems related to these medications and parallels anaesthesia-setting cohort studies that have suggested respiratory depression associated with gabapentinoid use. Clinicians should have informed risk-benefit discussions with their patients who have COPD prior to initiating these medications; these discussions should reflect not only the adverse effects of gabapentinoids but also that evidence of their effectiveness for many painful conditions is limited (NEJM JW Gen Med May 1 2019 and JAMA Intern Med 2019; 179: 695-701).

Daniel D. Dressler, MD, MSc, MHM, FACP, Professor of Medicine, Emory University School of Medicine, Atlanta, USA.

Rahman AA, et al. Gabapentinoids and risk for severe exacerbation in chronic obstructive pulmonary disease: a population-based cohort study. Ann Intern Med 2024 Jan 16; e-pub (https://

This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine, Hospital Medicine.

Ann Intern Med