Dual Neurostimulant Therapy May Optimize Acute Neurorecovery for Severe Traumatic Brain Injuries

Background: Neurostimulants (NS) can be used to treat patients with a traumatic brain injury (TBI) with altered levels of consciousness. We sought to determine if amantadine alone (monotherapy) versus amantadine + methylphenidate (dual therapy) would correlate with better neurorecovery (NR) among acutely hospitalized patients with a severe TBI. Methods: We performed a retrospective review of adult patients admitted to our level I trauma center from 2016-2019 with a severe TBI. NR was calculated by dividing the difference between admission and discharge Glasgow Coma Scale (GCS) scores by 12. Resulting ratios were used to divide the cohort into two groups: excellent NR (1) and non–excellent NR (<1). Results: A total of 76 patients comprised the cohort; 19.7% (n = 15) had excellent NR. The excellent NR group had a larger proportion of patients receiving dual therapy compared to the non–excellent group (86.7% versus 59%, P = 0.04). In monotherapy (n = 27), amantadine was initiated 13 (8-20) d following injury and treatment lasted 7 (2-16) d. In dual therapy (n = 49), amantadine was initiated 12 (6-19) d following injury and continued for 9 (4-25.5) d. Methylphenidate was initiated 15 (7-20.5) d following injury and continued for 5 (2-13.5) d. After adjusting for confounders, dual versus monotherapy predicted excellent NR (OR 5.4, 95% CI 1.2 - 38.9, P = 0.03). Conclusions: During the acute hospitalization for a severe TBI, dual NS therapy compared to monotherapy is associated with an increased likelihood of excellent NR. Larger prospective trials are warranted to validate these findings.