Efficacy and safety of amantadine for functional recovery in adults with traumatic brain injuries: A comprehensive systematic review and meta-analysis

Background

Amantadine is a dopaminergic agonist with neuroprotective and neurostimulant properties. Growing evidence about amantadine’s potential role for functional recovery in patients with Traumatic Brain Injury (TBI) was delivered by experimental and observational studies. Hence, this meta-analysis aimed to assess the efficacy and safety of amantadine in adults who suffered a TBI.

Methods

We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science until June 2024. The outcomes were Glasgow Coma Scale (GCS), Disability Rating Scale (DRS), total mortality, seizures, and gastrointestinal adverse events. We performed statistical analysis through R software (version 4.4.0). I² was used to assess heterogeneity.

Results

Our analyses included 10 studies, accounting for a total of 1182 patients. The doses ranged from 87.5 to 400 mg/day, and the phase when amantadine was administered varied from the acute phase to 6 months after the TBI. Amantadine showed no significant advantage in the pooled analysis for functional recovery [SMD −0.07; 95 % CI (−0.45, 0.31); p = 0.720; I² = 77.9 %]. The analysis of the RCTs subgroup found no difference between groups [SMD −0.37; 95 % CI (−0.82, 0.08); p = 0.107; I² = 67 %]. In a sensitivity analysis of the RCTs that assessed amantadine's effects in the first 6 weeks of treatment, a significant difference was found favoring amantadine [SMD −0.52; 95 % CI (−0.91, −0.13); p = 0.009; I² = 55 %]. Safety analysis showed no difference for total mortality [RR 0.77; 95 % CI (0.28, 2.17); p = 0.627; I² = 53 %].

Conclusions

Amantadine might be an adjuvant to standard care for adults with TBI, but further randomized research is required regarding its effects in the short and long-term periods.