Safety of Gabapentin Prescribed for Any Indication in a Large Clinical Cohort of 571,718 US Veterans with and without Alcohol Use Disorder

BACKGROUND: Gabapentin is prescribed for seizures and pain and has efficacy for treating alcohol use disorder (AUD) starting at doses of 900 milligrams per day (mg/d). Recent evidence suggests safety concerns associated with gabapentin including adverse neurologic effects. Individuals with hepatitis C (HCV), HIV, or AUD may be at increased risk due to comorbidities and potential medication interactions. METHODS: We identified patients prescribed gabapentin for ≥ 60 days for any indication between 2002 and 2015. We propensity‐score matched each gabapentin‐exposed patient with up to 5 gabapentin‐unexposed patients. We followed patients for 2 years or until diagnosed with (i) falls or fractures, or (ii) altered mental status using validated ICD‐9 diagnostic codes. We used Poisson regression to estimate incidence rates and relative risk (RR) of these adverse events in association with gabapentin exposure overall and stratified by age, race/ethnicity, sex, HCV, HIV, AUD, and dose. RESULTS: Incidence of falls or fractures was 1.81 per 100 person‐years (PY) among 140,310 gabapentin‐exposed and 1.34/100 PY among 431,408 gabapentin‐unexposed patients (RR 1.35, 95% confidence interval [CI] 1.28 to 1.44). Incidence of altered mental status was 1.08/100 PY among exposed and 0.97/100 PY among unexposed patients, RR of 1.12 (95% CI 1.04 to 1.20). Excess risk of falls or fractures associated with gabapentin exposure was observed in all subgroups except patients with HCV, HIV, or AUD; however, these groups had elevated incidence regardless of exposure. There was a clear dose–response relationship for falls or fractures with highest risk observed among those prescribed ≥ 2,400 mg/d (RR 1.90, 95% CI 1.50 to 2.40). Patients were at increased risk for altered mental status at doses 600 to 2,399 mg/d; however, low number of events in the highest dose category limited power to detect a statistically significant association ≥ 2,400 mg/d. CONCLUSIONS: Gabapentin is associated with falls or fractures and altered mental status. Clinicians should be monitoring gabapentin safety, especially at doses ≥ 600 mg/d, in patients with and without AUD.