From the Guidelines
Amantadine is not recommended for the treatment of axonal injury due to the lack of clinical evidence supporting its effectiveness in this specific context. While amantadine is sometimes used in traumatic brain injury rehabilitation, particularly for disorders of consciousness and to enhance cognitive recovery, its role in treating axonal injury is not well-established. The current understanding of traumatic axonal injury, as discussed in a 2018 study published in JCI Insight 1, highlights the complexity of the condition, involving secondary axotomy and Wallerian degeneration, which can lead to further damage through demyelination.
Key Considerations
- The standard of care for patients with diffuse axonal injury remains supportive treatment, focusing on preventing secondary injury through management of intracranial pressure, maintaining cerebral perfusion, and preventing complications like seizures and infections.
- If pharmacological intervention is needed for neurobehavioral symptoms following axonal injury, a neurologist or rehabilitation specialist should determine appropriate medications based on specific symptoms.
- Amantadine's mechanism of action, which includes enhancing dopaminergic transmission and NMDA receptor antagonist properties, theoretically could support neural recovery, but there is no strong clinical evidence to support its use specifically for axonal repair.
Clinical Approach
- Any consideration of amantadine should be part of a comprehensive neurorehabilitation program and not used as a standalone treatment for axonal injury.
- The decision to use amantadine or any other pharmacological agent should be based on a thorough assessment of the patient's symptoms and needs, rather than its potential effects on axonal injury alone.
- Given the lack of direct evidence from studies like the one published in JCI Insight 1 supporting the use of amantadine for axonal injury, a cautious approach is warranted, prioritizing established supportive care and individualized treatment plans.
From the Research
Role of Amantadine in Treating Axonal Injury
- Amantadine has been studied for its potential role in treating axonal injury, particularly in patients with traumatic brain injury (TBI) and diffuse axonal injury (DAI) 2, 3, 4.
- The results of these studies suggest that amantadine may have a beneficial effect on the neurological outcomes of patients with DAI, including improved Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS) scores 2, 4.
- However, the evidence is not consistent, and some studies have found no significant difference in outcomes between patients treated with amantadine and those receiving placebo 3.
- The mechanism of action of amantadine in TBI is thought to involve its effects on dopamine and N-methyl-D-aspartate (NMDA) channels, which may help to protect injured axons or stimulate axonal regeneration 4, 5.
- Further research is needed to fully understand the role of amantadine in treating axonal injury and to determine its potential benefits and limitations in this context 3, 6, 5.
Key Findings
- 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 double-blind clinical trial found no significant difference in neurological outcomes between patients with DAI treated with amantadine and those receiving placebo 3.
- A pilot double-blind randomized trial found that amantadine improved MMSE, DRS, GOS, and FIM-cog scores in patients with TBI and DAI 4.
- A review of the literature highlights the need for further research on the diagnosis and treatment of DAI, including the potential role of amantadine 6, 5.