Gabapentin and cognitive impairment after traumatic brain injury: A multinational cohort of 49,925 patients

Traumatic brain injury (TBI) is a major cause of morbidity and mortality, and cognitive impairment can be devastating among survivors. The objective was to assess an association between gabapentin and cognitive impairment after TBI. This retrospective cohort study used the multinational TriNetX Research Network (>150 million patients). Adults (≥18 years) with a first TBI and Glasgow Coma Scale (GCS) score recorded on the day of injury were included. Patients with known cognitive impairment or gabapentin exposure were excluded. The cohort (n = 49,925) was stratified into mild (GCS 13-15; n = 34,376), moderate (9-12; n = 4035), and severe (3-8; n = 12,845) TBI. The risk of cognitive impairment and mortality were assessed using Cox proportional hazard models adjusted for known predictors. Secondary analyses examined levetiracetam use (as seizure prophylaxis) and long-term medical and functional outcomes. Among 49,925 included patients w, 3.5% received gabapentin on the day of TBI. After adjustment, gabapentin was associated with a 22% lower risk of cognitive impairment in mild TBI (HR = 0.78; 95% CI, 0.62-0.98; P = .03) and a 46% lower risk of mortality in severe TBI (HR = 0.54; 95% CI, 0.40-0.72; P < .001). Levetiracetam showed no protective association with cognition. Long-term follow-up associated gabapentin use with lower mortality but higher rates of psychiatric/sleep diagnoses, reduced mobility, atrial fibrillation, and pulmonary embolism. Although causality cannot be inferred, these findings suggest gabapentin warrant prospective investigation as a candidate neuroprotective therapy.