Oral Caffeine vs Amantadine for Neurostimulation in Traumatic Brain Injury and Acute Ischemic Stroke

Introduction: Brain injuries such as acute ischemic stroke (AIS) and traumatic brain injury (TBI) can lead to many deficits including cognitive deficits, sensory losses, behavior changes, and physical disabilities. Neurostimulant medications may accelerate the recovery of patient’s neurologic function following these events. An agent commonly used at the University of Missouri Health Care for neurostimulation is caffeine, which may have positive effects on neurostimulation for patients, however, there are adverse effects such as tachycardia, arrythmias, worsening ischemia, and exacerbation of pre-existing cardiovascular disease states. The purpose of this study is to compare the effectiveness and safety of caffeine versus amantadine for neurostimulation in patients with AIS and TBI.


Methods: This was a single-center observational retrospective cohort study. We evaluated patients with TBI or AIS between January 2015 to December 2023 at The University of Missouri Health Care University Hospital. The primary outcome of this study was the difference in Glasgow Coma Score (GCS) from the start of study medication to discharge. Secondary outcomes included hospital length of stay, intensive care unit length of stay, duration of mechanical ventilation, incidence of tachycardia, arrythmia, or agitation, and need for an additional neurostimulation agent.


Results: The primary outcome in the change of GCS from start of study medication to discharge was similar between the two groups (1 (IQR 0-2) vs 1 (IQR 0-2). p=0.551). Tachycardia occurred in 20 patients (56%) in the amantadine group vs 16 (44%) in the caffeine group (p=0.346). Arrhythmias occurred in 4 patients (11%) in the amantadine group vs 10 patients (28%) in the caffeine group (p=0.073). Agitation was more common in the amantadine group, occurring in 16 patients (44%) vs 12 patients (33%) in the caffeine group (p=0.334).


Conclusions: These results suggest that caffeine and amantadine have similar efficacy for neurostimulation in AIS and TBI. Amantadine may be associated with tachycardia and agitation, while caffeine may be associated with tachycardia and cardiac arrhythmias. Due to the single-center retrospective design of this trial, further studies need to be conducted to confirm these findings.