Gabapentin Use in COPD Patients: Significant Risk of Severe Exacerbations
Gabapentin and other gabapentinoids should be used with extreme caution or avoided in patients with COPD due to consistent evidence showing a 35-58% increased risk of severe exacerbations requiring hospitalization or systemic corticosteroids. 1, 2, 3
Evidence of Harm
The most recent and highest quality evidence demonstrates clear respiratory risks:
A 2025 UK population-based cohort study of 29,882 gabapentinoid users with COPD found a 43% increased risk of severe exacerbation (HR 1.43; 95% CI: 1.35-1.52) compared to non-users. 1 This risk was consistent across all indications: epilepsy (HR 1.39), neuropathic pain (HR 1.43), and other chronic pain (HR 1.45). 1
A 2024 Canadian study of 13,504 COPD patients showed a 39% increased risk of severe exacerbation requiring hospitalization (HR 1.39; 95% CI: 1.29-1.50) with gabapentinoid use. 2 The risk was elevated across epilepsy (HR 1.58), neuropathic pain (HR 1.35), and other chronic pain (HR 1.49) indications. 2
A 2025 Japanese nationwide study of 85,578 patients demonstrated an 18-21% increased risk of COPD exacerbations requiring systemic corticosteroids when comparing gabapentinoids to alternative medications (TCAs: HR 1.21; SNRIs: HR 1.18). 3
Regulatory Context
These findings support warnings from North American and European health agencies regarding severe breathing problems associated with gabapentinoids, particularly in patients with respiratory conditions like COPD. 2
Clinical Implications
When Gabapentinoids Are Being Considered:
For neuropathic pain in COPD patients, prioritize alternative agents such as tricyclic antidepressants or serotonin-noradrenaline reuptake inhibitors over gabapentinoids. 3
If gabapentinoids must be used, patients require intensive monitoring for signs of respiratory deterioration, including increased dyspnea, increased sputum volume or purulence, and worsening breathlessness. 4
The risk appears consistent regardless of the indication (epilepsy, neuropathic pain, or chronic pain), meaning no specific patient subgroup is exempt from this concern. 1, 2
For Patients Already on Gabapentinoids:
Reassess the necessity of continued gabapentinoid therapy and consider transitioning to safer alternatives when clinically appropriate. 3
Educate patients about warning signs of COPD exacerbation and ensure they have an action plan for acute worsening. 4
Important Caveats
The evidence comes from observational studies, which may have residual confounding, particularly from lack of smoking information. 2 However, the consistency across three large, independent cohorts from different countries strengthens the causal inference.
The mechanism of respiratory harm is not fully elucidated but likely relates to central nervous system depression affecting respiratory drive. 2
This risk exists in addition to COPD's baseline exacerbation risk and standard management with bronchodilators, corticosteroids, and other guideline-directed therapies remains essential. 5, 4