Amantadine use during acute hospitalization for neurological recovery after stroke: a systematic review

Disorders of consciousness and impaired neurological recovery are common during acute hospitalization for stroke, yet evidence-based pharmacologic strategies to enhance neurorecovery remain limited. Amantadine is frequently used off-label in this setting based on data from traumatic brain injury; however, evidence supporting its use in stroke is unclear.

To systematically review the available literature evaluating the use of amantadine during acute hospitalization in adult patients with stroke.

This systematic review was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420251273897). PubMed/MEDLINE, Embase, and Cochrane CENTRAL were searched for studies that included adults with stroke who received amantadine during acute hospitalization compared to standard care without amantadine, placebo, or within-cohort comparisons among amantadine-treated patients. Outcomes of interest included recovery of consciousness, neurological and functional outcomes, in-hospital mortality, and adverse events. Due to heterogeneity in study design, patient populations, and outcome measures, a quantitative meta-analysis was not performed.

Seven studies involving a total of 929 patients were included, the majority with stroke, although one mixed non-traumatic brain injury cohort also included patients with status epilepticus (n = 29) and bacterial meningitis (n = 11). Amantadine was initiated during acute hospitalization, mostly in the intensive care unit, at doses of 100-200 mg twice daily. Across observational cohorts, 50-65% of patients responded to amantadine, defined as improvement in arousal or recovery of consciousness, with higher response rates observed in smaller cohorts. Amantadine exposure was also associated with earlier improvement in consciousness compared with no treatment. However, no consistent long-term functional effect or reduction in mortality was reported. Amantadine was generally well tolerated; reported adverse events included seizures (5-13%), agitation (6-14%), QTc prolongation (up to 8%), and sleep disruption (16%). No consistent safety signal attributable to amantadine was identified, although comparative safety data were limited. Risk of bias ranged from low to moderate across the included studies.

The evidence supporting amantadine use during acute hospitalization for stroke is limited and heterogeneous. While amantadine is commonly used to promote arousal in patients with impaired consciousness after stroke, available data do not allow firm conclusions regarding efficacy for functional recovery or mortality, and safety conclusions remain limited by inconsistent adverse-event reporting. Prospective, stroke-specific studies conducted in the acute hospital setting are needed to clarify the efficacy, optimal timing, and safety of amantadine in this population.