GABAPENTINOIDS were linked to higher asthma exacerbation risk among adults with asthma and chronic or neuropathic pain.
Gabapentinoids and Asthma Exacerbation Risk
A nationwide retrospective cohort study has found that gabapentinoids may increase the risk of asthma exacerbations in adults with asthma who are being treated for neuropathic or chronic pain.
Using Japan’s National Database of Health Insurance Claims and Specific Health Check-ups, researchers compared new users of gabapentinoids with patients initiating tricyclic antidepressants or serotonin norepinephrine reuptake inhibitors. These active comparators were selected because they are also used in the management of neuropathic or chronic pain. The study population was limited to adults aged 40 years and older with asthma and a history of neuropathic or chronic pain.
The primary outcome was the first asthma exacerbation requiring systemic corticosteroids. Hospitalization for asthma was assessed as a secondary outcome. Overlap propensity score weighting was used to account for potential confounders, including demographics, comorbidities, treatment history, smoking status, asthma-related variables, and health-related factors.
Higher Risk Seen Versus Pain Comparators
In the tricyclic antidepressant cohort, 171,393 gabapentinoid users were compared with 5,916 tricyclic antidepressant users. Gabapentinoids were associated with a higher incidence of corticosteroid-requiring asthma exacerbations, at 59.4 versus 33.7 per 100 person-years, with a hazard ratio of 1.46. Hospitalization-requiring exacerbations were also more common, at 0.91 versus 0.42 per 100 person-years, with a hazard ratio of 2.02.
In the serotonin norepinephrine reuptake inhibitor cohort, 189,055 gabapentinoid users were compared with 19,800 serotonin norepinephrine reuptake inhibitor users. Gabapentinoids were again associated with a higher incidence of corticosteroid-requiring exacerbations, at 63.5 versus 42.8 per 100 person-years, with a hazard ratio of 1.24. The difference in hospitalization-requiring exacerbations did not reach statistical significance in this comparison.
Pregabalin and Mirogabalin Drive Signal
Subgroup analyses found that pregabalin and mirogabalin were each associated with increased asthma exacerbation risk in both comparator cohorts, while gabapentin was not. Exploratory analyses also suggested higher hazard ratios in medium and high dosage groups compared with low dosage groups.
The findings support greater vigilance when gabapentinoids are initiated in patients with asthma, particularly when alternative treatments for neuropathic or chronic pain may be appropriate. Potential mechanisms include sedation, hypoventilation, cough suppression leading to mucus impaction, respiratory infection, and possible heart failure being misclassified as asthma exacerbation.
As an observational study, residual confounding remains possible. The relatively short follow-up period, exclusion of adults younger than 40 years, and Japan-based population also limit generalizability. Even so, the consistent findings across sensitivity analyses suggest that clinicians should approach gabapentinoid prescribing with caution in patients with asthma.
Reference
Kimura Y et al. Gabapentinoids and risk for asthma exacerbations: a nationwide retrospective cohort study. Thorax. 2026;81(2):121-130.
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