amantadine

General Information

Amantadine (brand Symmetrel; generics) is an antiparkinson medication (and historically an antiviral) with a labeled indication for drug-induced extrapyramidal reactions, including antipsychotic-induced Parkinsonism (label).

It is not an anticholinergic and may be considered when anticholinergic cognitive burden is a concern, balancing potential benefit against neuropsychiatric adverse effects (insomnia, hallucinations) and renal dose constraints (label/clinical).

Because it is primarily renally cleared, dosing and safety are highly dependent on kidney function and age; dose reductions are common in older adults and renal impairment (label).

Trials comparing amantadine with anticholinergics support it as a symptomatic option for neuroleptic-induced parkinsonism (Kelly 1974; AJP 1976).

The amantadine compare view, evidence feed, and print page support EPS counseling and monitoring.

In psychiatric care, amantadine is most often used for antipsychotic- induced parkinsonism when anticholinergic therapy is poorly tolerated or undesirable. Neuropsychiatric adverse effects and renal dosing are the main constraints (clinical).

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Antiparkinson activity is often framed as dopaminergic (increased presynaptic dopamine release and reduced reuptake) with additional NMDA receptor antagonism (mechanism/class).

The activating profile can worsen insomnia or agitation in susceptible patients (clinical).

• Dopaminergic / NMDA-modulating antiparkinson agent (not anticholinergic).

Metabolism and Pharmacokinetics

• Amantadine is well absorbed orally and is primarily excreted unchanged in urine via glomerular filtration and tubular secretion (label).
• In healthy adults, half-life averages ~17 ± 4 hours (range ~10–25 hours); half-life increases in older adults and markedly increases in renal impairment (label).
• Urine pH can influence excretion: acidic urine increases elimination (label).

Dosing and Administration

• Drug-induced extrapyramidal reactions: labeling commonly describes 100 mg twice daily, with some patients using 100 mg once daily depending on response and tolerability (label).
• Renal impairment reduces clearance and requires dose adjustment; dosing is often reduced substantially when creatinine clearance is low (label).
• When insomnia is problematic, earlier dosing and slower titration are common adjustment levers (clinical).

Monitoring & Labs

• Renal function and renal-dose appropriateness, especially in older adults and after intercurrent illness (label/clinical).
• Neuropsychiatric monitoring (sleep, agitation, hallucinations/confusion), particularly in patients with psychosis risk (label/clinical).
• Edema/skin monitoring (livedo reticularis) during longer courses (label/clinical).

When amantadine is used for antipsychotic-induced parkinsonism, periodic reassessment of the antipsychotic regimen and ongoing need can help reduce long-term adverse effects and unnecessary exposure (clinical).

Adverse Effects

Interactions

• Medications that alter urine pH can change amantadine clearance; urine acidifiers can increase elimination and alkalinizers can increase exposure (label/clinical).
• Other dopaminergic or activating agents can worsen insomnia or agitation; regimen review focuses on total activating burden (clinical).
• Co-use with anticholinergics may increase confusion and other adverse effects; caution is typical in older adults (clinical).

Other Useful Information

• Randomized comparisons with benztropine and trihexyphenidyl support amantadine as a symptomatic option for neuroleptic-induced parkinsonism, with a different adverse-effect profile than anticholinergics (Kelly 1974; AJP 1976).
• For antipsychotic-induced parkinsonism, reviews emphasize addressing the antipsychotic driver (dose reduction or switching when feasible) alongside symptomatic medications (Wisidagama 2021/clinical).
• If psychosis or mania risk is high, clinicians often weigh amantadine’s activating profile against anticholinergic risks and consider non- pharmacologic or antipsychotic-adjustment approaches first (clinical).

References

1. Amantadine hydrochloride capsules prescribing information — DailyMed (2024)
2. A Double Blind Study OF Amantadine Hydrochloride Versus Benztropine Mesylate IN Drug Induced Parkinsonism — European Neurology (1974)
3. Amantadine Versus Trihexyphenidyl IN THE Treatment OF Neuroleptic Induced Parkinsonism — American Journal of Psychiatry (1976)
4. Recognition AND Management OF Antipsychotic Induced Parkinsonism IN Older Adults A Narrative Review — Medicines (2021)
5. AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology — Pharmacopsychiatry (2018)