Amantadine (Symmetrel)

Class

Dopaminergic agent / NMDA receptor antagonist

Mechanism

Enhances dopamine release and blocks NMDA glutamate receptors, which may improve motor symptoms and reduce excitotoxicity

FDA-Approved Use

Parkinson’s disease (PD), drug-induced extrapyramidal symptom

Off-Label Use

Fatigue in multiple sclerosis (MS), post-stroke apathy, post-stroke fatigue, agitation and aggression in traumatic brain injury (TBI), fatigue in TBI, catatonia (second-line)

Formulation

Immediate-release tablets, extended-release capsules

Titration

Start 100 mg p.o. daily, titrate up to 100–300 mg/day as tolerated

Dose Range

100–300 mg/day

Kinetics

Half-life approximately 10–14 hours; renally excreted unchanged

Common AEs

Insomnia, nausea, dry mouth, dizziness, hallucinations, livedo reticularis

Serious/Rare AEs

Psychosis, seizures (rare)

Monitoring

Monitor renal function, neuropsychiatric symptoms, and skin changes

Black Box Warning

None

Considerations

Amantadine should be used cautiously in elderly patients and those with cognitive impairment due to risk of confusion and hallucinations. In TBI or post-stroke populations, it may improve apathy, fatigue, or aggression, though monitoring for behavioral disinhibition is warranted. Dose reductions are necessary in renal impairment.