What is the role of Amantadine (generic name) in treating axonal (nerve fiber) injury?

From the Guidelines

Amantadine may be considered for promoting consciousness recovery in patients with severe acute brain injuries, including axonal injury, based on its potential neurostimulant effects, as suggested by a 2023 guideline from the American Heart Association/American Stroke Association 1. When considering the use of amantadine for axonal injury, it's essential to weigh the potential benefits against the lack of robust evidence specifically targeting axonal injury treatment. The medication has been studied more extensively in the context of traumatic brain injury and aneurysmal subarachnoid hemorrhage, where its safety and possible efficacy in promoting consciousness recovery have been noted 1. Key points to consider include:

• The dose of amantadine can range from 100-400 mg daily, often initiated at 100 mg twice daily and adjusted based on patient response and tolerability.
• Treatment duration can vary significantly, from several weeks to months, depending on the clinical response and the patient's condition.
• Amantadine's mechanism of action as an NMDA receptor antagonist and its potential to enhance dopaminergic transmission may contribute to reducing excitotoxicity and promoting neural recovery after injury.
• Potential side effects include nausea, dizziness, insomnia, hallucinations, and livedo reticularis, necessitating close medical supervision and regular assessment of benefits versus side effects.
• Patients with renal impairment require dose adjustment, and amantadine is contraindicated in severe renal disease. Given the information from the 2023 guideline 1, while amantadine is not universally recommended for axonal injury treatment due to the heterogeneity of studies and the lack of pooled analysis, its use can be considered on a case-by-case basis, particularly in the subacute period of brain injury, under close medical supervision.

From the Research

Role of Amantadine in Treating Axonal Injury

• Amantadine has been studied for its potential role in improving cognitive function and outcomes in patients with traumatic brain injury (TBI) and diffuse axonal injury (DAI) 2, 3, 4, 5, 6.
• Research suggests that amantadine may have a positive effect on cognitive function, particularly when started early after injury 3, 4, 5.
• A meta-analysis found that amantadine significantly enhanced cognitive function in patients with TBI, with the greatest effect seen when started in the first week after injury 3.
• Studies have also shown that amantadine may improve outcomes such as Glasgow Coma Scale (GCS) scores, Glasgow Outcome Scale (GOS) scores, and Disability Rating Scale (DRS) scores 2, 4, 5.
• The exact mechanism of amantadine's effect on axonal injury is not fully understood, but it is thought to involve its effects on dopamine and N-methyl-D-aspartate (NMDA) channels 5.

Key Findings

• Amantadine may improve cognitive function in patients with TBI and DAI, particularly when started early after injury 3, 4, 5.
• Amantadine has been shown to improve outcomes such as GCS, GOS, and DRS scores in patients with TBI and DAI 2, 4, 5.
• The optimal timing and duration of amantadine treatment for axonal injury are not yet established, but research suggests that starting treatment early and continuing for several weeks may be beneficial 3, 5.

Study Results

• A randomized controlled trial found that amantadine improved GCS and GOS scores in patients with acute severe TBI and DAI, although the difference was not statistically significant 2.
• A meta-analysis found that amantadine significantly enhanced cognitive function in patients with TBI, with a mean difference of 0.50 (95% CI, 0.33-0.66) 3.
• A pilot study found that amantadine use in the acute post-injury period was associated with improved cognitive disability and discharge to TBI rehabilitation 4.
• A double-blind randomized trial found that amantadine improved MMSE, DRS, GOS, and FIM-cog scores in patients with TBI and DAI 5.