When to Use Amantadine in Parkinson's? A Guide to Its Role

October 10, 2025 •

4 min read

Originally developed as an antiviral medication for influenza, amantadine was later discovered to possess antiparkinsonian properties. Knowing when to use amantadine in Parkinson's disease is crucial for managing specific symptoms, most notably involuntary movements caused by other treatments, though its role has evolved over time.

Quick Summary

Amantadine is typically used in Parkinson's patients to treat levodopa-induced dyskinesia, motor fluctuations, and mild symptoms in early stages. It is often an adjunctive therapy, with various formulations available for different patient needs.

Key Points

Primary Use: Managing levodopa-induced dyskinesia is amantadine's most well-established role in later-stage Parkinson's disease.
Extended-Release Formulations: The extended-release capsule (Gocovri®) was specifically developed and approved by the FDA for the treatment of dyskinesia and 'off' episodes.
Mechanism of Action: Amantadine works through a dual mechanism, acting as an NMDA receptor antagonist and influencing dopamine pathways to control movement problems.
Early-Stage Use: While once used for initial motor symptoms, amantadine's use in early PD is limited due to questionable long-term efficacy and the availability of more effective alternatives.
Important Safety Precautions: Abruptly stopping amantadine is dangerous and can lead to severe complications. Patients should also be monitored for side effects like hallucinations and impulse control disorders.
Kidney Function and Dosing: Dosage must be carefully adjusted based on a patient's kidney function to prevent drug toxicity, and it is contraindicated in end-stage renal disease.

The Evolving Role of Amantadine in Parkinson's Disease

Amantadine is a medication with a unique history in the treatment of Parkinson's disease (PD). While once used more broadly for early motor symptoms, its primary indications have become more specific over time. It is now recognized as a valuable tool for managing a complex challenge in PD: the involuntary movements known as dyskinesia that can result from long-term levodopa therapy. This guide details when amantadine is most appropriately used, its mechanisms, and considerations for its use.

Amantadine for Levodopa-Induced Dyskinesia

For many patients with advanced Parkinson's, the long-term use of levodopa leads to dyskinesia—uncontrollable, jerky, or writhing movements. This is the strongest and most evidence-supported indication for amantadine's use in PD. The U.S. Food and Drug Administration (FDA) has approved an extended-release formulation (Gocovri®) specifically for this purpose.

How it helps:

Reduces severity: Clinical trials have shown that amantadine can significantly reduce the severity of dyskinesia.
Increases 'on' time: By controlling dyskinesia, amantadine helps increase the amount of time patients experience their best motor control ('on' time).
Without worsening parkinsonian symptoms: It can improve dyskinesia without compromising the antiparkinsonian effect of levodopa, which is crucial for maintaining mobility.

Amantadine for Motor Fluctuations and 'Off' Episodes

Patients taking levodopa often experience motor fluctuations, cycling between periods of good motor control ('on' time) and periods when medication effects wear off, leading to a return of symptoms ('off' episodes). Extended-release amantadine can be used as an adjunct to levodopa to help manage these fluctuations, including the 'off' periods.

Amantadine in Early-Stage Parkinson's

Historically, immediate-release amantadine was used as a monotherapy for mild motor symptoms like tremor, stiffness, and slowness in early PD. However, this is no longer the standard of care.

Limited efficacy: National guidelines suggest there is not enough evidence to support amantadine as a first-choice treatment in early PD.
Transient effect: Many patients experience a loss of effectiveness after a few months of treatment, though some may regain benefit by temporarily stopping and restarting the medication.

The Mechanism Behind Amantadine's Actions

Amantadine's effectiveness in PD is attributed to a dual mechanism, primarily its interaction with two key neurotransmitter systems in the brain:

NMDA Receptor Antagonism: Amantadine acts as a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. Excess glutamate activity is thought to contribute to levodopa-induced dyskinesia, and by blocking NMDA receptors, amantadine helps regulate this pathway.
Dopaminergic Effects: The drug also has effects on the dopaminergic system, increasing dopamine release from nerve endings and blocking its reuptake. This helps boost dopamine availability, which is beneficial for managing Parkinson's symptoms.

Comparison of Amantadine and Other Parkinson's Medications


Feature	Amantadine	Levodopa	Dopamine Agonists (e.g., pramipexole)
Primary Role	Adjunctive therapy, primarily for dyskinesia and motor fluctuations.	First-line, most potent treatment for motor symptoms.	Adjunctive or monotherapy for motor symptoms, sometimes used earlier than levodopa.
Mechanism	NMDA antagonism, enhanced dopamine release.	Replenishes dopamine supply in the brain.	Mimic dopamine by directly stimulating dopamine receptors.
Onset of Action	Can show benefits for dyskinesia within a few weeks.	Very rapid and effective for improving motor symptoms.	Variable; can be slower than levodopa.
Effect on Dyskinesia	Reduces severity of dyskinesia.	Can cause or worsen dyskinesia with long-term use.	Can also contribute to dyskinesia, though less commonly than levodopa.
Side Effects	Hallucinations, dizziness, confusion, constipation, livedo reticularis.	Nausea, fatigue, orthostatic hypotension, dyskinesia.	Nausea, sleepiness, impulse control disorders.

Important Safety Considerations

Potential Side Effects

Common side effects associated with amantadine include:

Dizziness, lightheadedness, or confusion
Insomnia or vivid dreams
Nausea and constipation
Swelling in the ankles and feet
A purplish, lace-like skin discoloration called livedo reticularis
Hallucinations or other psychiatric symptoms

Abrupt Discontinuation

It is crucial not to stop amantadine suddenly without consulting a doctor. Abrupt withdrawal can lead to a marked worsening of PD symptoms and can trigger a syndrome resembling neuroleptic malignant syndrome, characterized by high fever, severe muscle stiffness, and mental status changes.

Renal Impairment

Since amantadine is primarily cleared by the kidneys, patients with kidney disease require significant dose adjustments to prevent drug accumulation and toxicity. For patients with severe renal impairment, lower doses are necessary, and amantadine is contraindicated in those with end-stage renal disease.

Impulse Control Disorders

Similar to other dopaminergic medications, amantadine can be associated with impulse control disorders, such as pathological gambling, hypersexuality, or binge eating. Patients and their families should be aware of this risk.

Dosing and Administration

Amantadine is available in immediate-release (IR) and extended-release (ER) forms, which have different dosing schedules and uses.

IR amantadine: Typically taken twice or three times daily, with an initial lower dose that can be increased gradually.
ER amantadine (e.g., Gocovri®): Taken once daily at bedtime to provide sustained benefit, particularly for nocturnal and morning symptoms.

It is important to follow the prescribing physician's instructions carefully, as the IR and ER formulations are not interchangeable. The optimal dose and schedule will depend on the patient's symptoms, overall medication regimen, and kidney function.

Conclusion

Amantadine's place in Parkinson's treatment is highly specific, particularly in the later stages of the disease. While its efficacy for early-stage symptoms is limited and often temporary, it remains a frontline therapy for managing levodopa-induced dyskinesia and motor fluctuations. The decision to use amantadine should be made in consultation with a neurologist, weighing its potential benefits against the risks of side effects, especially in patients with pre-existing psychiatric or renal issues. For more information, refer to the Parkinson's Foundation website.

Frequently Asked Questions

The primary reason to prescribe amantadine for Parkinson's disease is to manage levodopa-induced dyskinesia, the involuntary, uncontrolled movements that can develop after long-term levodopa therapy.

No, amantadine is not typically a first-line treatment for early Parkinson's disease. Its use for initial motor symptoms is limited and often temporary, as more effective medications are available.

Extended-release amantadine (Gocovri®) is specifically approved to treat levodopa-induced dyskinesia and reduce 'off' episodes in Parkinson's disease. It is taken once daily at bedtime for sustained effect.

Common side effects include dizziness, confusion, nausea, constipation, insomnia, hallucinations, and swelling of the ankles and feet. A doctor should be consulted for proper management.

No, you should never stop taking amantadine suddenly. Abrupt discontinuation can lead to severe worsening of Parkinson's symptoms and serious complications. Any dose reduction must be done under a doctor's supervision.

Amantadine is often used in combination with other Parkinson's medications, like levodopa. However, combinations and dosages must be carefully managed by a physician to maximize benefits and minimize side effects.

Yes, amantadine dosing needs to be adjusted for patients with impaired kidney function, as the drug is cleared by the kidneys. Lower doses or less frequent administration may be necessary.