Neurostimulant Use and Cognitive Outcomes in Patients with Acute, Severe Traumatic Brain Injury

Background: We sought to examine the use of neurostimulants (NS) in the acute setting among patients with severe traumatic brain injury (TBI) and assess their impact on cognitive outcomes. Methods: We performed a retrospective analysis of prospectively collected data from patients aged ≥ 18 years with a severe (Glasgow Coma Scale score ≤ 8), blunt TBI at eight US trauma centers from 2020 to 2023. Patients were grouped according to whether they received NS. Our primary outcome was cognitive disability at 28 days or discharge (whichever occurred first), measured by the Disability Rating Scale (DRS). A DRS score < 12 was considered a favorable outcome. Results: The cohort comprised 405 patients: 29.9% (n = 121) received NS and 70.1% (n = 284) did not. The most common NS was amantadine (97.5%, n = 118). The median time to NS initiation was 8.0 days (5.0–13.5), and the median treatment duration was 12.0 days (5.5–17.0). NS patients had worse injury severity scores (29 vs. 26, p = 0.02), had more neurosurgical interventions (64.4% vs. 33.2%, p < 0.0001), and were less likely to have a favorable outcome (30.8% vs. 67.1%, p < 0.0001). In a subgroup analysis of only NS patients, individuals receiving NS within 7 days of admission were three times as likely to have a favorable outcome compared to those receiving NS > 7 days after admission (odds ratio 3.01, 95% confidence interval 1.11–8.18, p = 0.03). Conclusions: Nearly a third of patients with severe TBI received NS. Patients receiving NS were more injured and had worse disability at discharge compared to non-NS patients. However, among patients who received NS, treatment within 7 days was associated with an increased odds of a favorable outcome.