The Role of Amantadine in Parkinson's Treatment
Originally developed as an antiviral medication, amantadine was serendipitously discovered to have benefits for Parkinson's disease over 50 years ago [1.9.4]. Its primary role today is not as a standalone initial therapy but as an important adjunctive treatment, especially for patients experiencing complications from long-term levodopa use [1.9.2]. Levodopa is the most effective drug for Parkinson's symptoms, but its long-term use can lead to debilitating motor fluctuations, including dyskinesia (involuntary, erratic movements) and "OFF" periods, where the medication's effects wear off and symptoms return [1.8.4, 1.11.3]. Studies show that after 10 years of levodopa treatment, dyskinesias can affect nearly 60% of patients [1.11.1].
Amantadine is uniquely positioned to address these issues. It is particularly valued for its proven ability to reduce the severity of levodopa-induced dyskinesia, with some studies showing a reduction of up to 60% without worsening the underlying parkinsonian symptoms [1.5.1]. This makes it a critical tool for improving the quality of life for patients with advanced Parkinson's disease [1.5.2].
How Does Amantadine Work?
The precise mechanism of amantadine in Parkinson's disease is complex and not fully understood, but it is known to act on multiple neurotransmitter systems [1.3.2, 1.9.4]. Its primary proposed mechanisms include:
- NMDA Receptor Antagonism: Amantadine blocks N-methyl-D-aspartate (NMDA) receptors, which are linked to the neurotransmitter glutamate [1.3.2, 1.3.5]. Overactivity in the glutamatergic system is believed to contribute to the development of dyskinesia, so by blocking these receptors, amantadine helps to calm these excessive signals [1.5.1].
- Dopaminergic Action: It is thought to increase the release of dopamine from nerve endings and may also inhibit its reuptake, making more dopamine available in the brain [1.3.1, 1.3.3]. This helps to alleviate some of the core motor symptoms of Parkinson's like rigidity and bradykinesia (slowness of movement) [1.3.2].
- Anticholinergic Effects: Amantadine also has mild anticholinergic properties, which can contribute to its effectiveness against tremor and rigidity [1.3.2].
This multi-faceted action accounts for its dual effect on both parkinsonian symptoms and the complications arising from their primary treatment [1.9.4].
Comparing Amantadine Formulations: Immediate vs. Extended-Release
Amantadine is available in different formulations, which have significant implications for its use and effectiveness.
| Feature | Immediate-Release (IR) Amantadine | Extended-Release (ER) Amantadine (e.g., Gocovri, Osmolex ER) |
|---|---|---|
| Primary Use | Used off-label to manage dyskinesia and sometimes motor symptoms [1.6.1]. | FDA-approved specifically for treating dyskinesia and "OFF" time in Parkinson's patients [1.6.3, 1.6.5]. |
| Dosing | Typically taken two or more times a day [1.7.1]. | Taken once daily, usually at bedtime [1.6.1, 1.6.5]. |
| Effectiveness | Can be effective for dyskinesia, but benefits may be inconsistent or wane over time. Not shown to improve "OFF" time [1.6.3, 1.6.4]. | Provides higher, more stable plasma concentrations, leading to a robust and sustained reduction in both dyskinesia and "OFF" time [1.6.2, 1.6.5]. |
| Side Effects | Tolerability can be a concern, limiting the ability to use higher, more effective doses [1.6.4]. | The pharmacokinetic profile is designed to improve tolerability while maximizing efficacy [1.6.1, 1.6.4]. |
Clinical data suggests that switching from amantadine IR to an ER formulation can lead to an incremental reduction in motor complications [1.6.1]. Studies on the ER formulation Gocovri have shown it reduces "OFF" time by about 1 hour per day and increases "ON" time without troublesome dyskinesia by 2.4 hours [1.2.2, 1.6.3].
Potential Side Effects and Risks
While beneficial, amantadine is associated with a range of potential side effects. It's crucial for patients and caregivers to be aware of these risks. Common side effects include nausea, dizziness, insomnia, dry mouth, and confusion [1.4.1, 1.4.4]. A distinctive but generally harmless side effect is livedo reticularis, a purplish, net-like discoloration of the skin [1.4.2].
More serious potential side effects can include:
- Hallucinations and Psychosis: Seeing or hearing things that are not there can occur, particularly at higher doses or in patients with cognitive impairment [1.4.2, 1.4.3].
- Impulse Control Disorders: Amantadine can cause or worsen issues like compulsive gambling, spending, or eating [1.4.4, 1.10.4].
- Cardiovascular Effects: Swelling of the ankles (peripheral edema) and orthostatic hypotension (dizziness upon standing) are possible [1.4.3].
- Sudden Withdrawal Issues: Abruptly stopping amantadine can lead to a severe worsening of Parkinson's symptoms or a state resembling neuroleptic malignant syndrome, a life-threatening condition [1.9.1, 1.10.1]. Therefore, the dosage should always be tapered down under a doctor's supervision [1.4.2].
Due to these risks, amantadine must be used cautiously, especially in the elderly and in patients with a history of seizures, kidney disease, or psychiatric disorders [1.7.2, 1.4.4].
Conclusion
So, is amantadine good for Parkinson's? The answer is a qualified yes. While not a primary therapy for early-stage disease, it serves as a valuable and effective adjunctive treatment for managing the challenging motor complications that arise in later stages [1.9.4]. Its proven efficacy in reducing levodopa-induced dyskinesia can significantly improve a patient's quality of life [1.5.1, 1.5.3]. The development of extended-release formulations has further enhanced its utility by providing more consistent symptom control and improving its tolerability profile [1.6.1, 1.6.2]. As with any medication, the benefits must be weighed against the potential side effects, and its use should be carefully managed by a neurologist specializing in movement disorders.
For more information, you can visit the The Michael J. Fox Foundation for Parkinson's Research.
