Understanding Amantadine and Its Role in Treatment
Amantadine is a medication with a unique history. Originally developed as an antiviral agent to treat influenza A, it was coincidentally found to alleviate symptoms of Parkinson's disease (PD) [1.3.6]. Today, it is prescribed to manage motor symptoms associated with PD, such as tremor, stiffness, and sudden, uncontrolled movements known as dyskinesia [1.5.3, 1.2.1]. It can be used as a monotherapy in early-stage PD or, more commonly, as an adjuvant therapy with other medications like levodopa in more advanced stages [1.3.4, 1.2.1]. While its antiviral use has declined due to resistant flu strains, its place in neurology remains significant [1.2.4].
The Pharmacological Action: How Amantadine Works
The precise mechanism of action for amantadine in treating tremors is not fully understood, but it is believed to be multifaceted [1.2.5, 1.2.6]. Its primary effects are thought to involve the brain's dopamine system. Amantadine appears to increase the release of dopamine from nerve endings and may also block its reuptake, making more of this crucial neurotransmitter available in the brain [1.2.2, 1.2.5]. Dopamine is essential for coordinating smooth, controlled muscle movements.
Beyond its dopaminergic action, amantadine also functions as a weak, non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist [1.2.5]. This antiglutamatergic property is believed to contribute to its effectiveness in reducing levodopa-induced dyskinesia, which are involuntary movements that can be a complication of long-term levodopa treatment [1.3.3]. Some research also points to potential anticholinergic and anti-inflammatory effects [1.2.1].
Efficacy for Parkinson's Disease Tremors
Amantadine's effectiveness for the direct treatment of Parkinsonian tremor is modest and subject to debate. Some sources indicate it has a minimal effect on tremor, particularly when compared to other medications [1.2.1, 1.8.1]. One study found that while trihexiphenidyl and carbidopa-levodopa decreased tremor by over 50%, amantadine reduced it by less than 25% [1.8.1]. Parkinson's UK notes there isn't strong evidence to support its use as a first-choice treatment for motor symptoms in early PD [1.3.4].
However, its primary value often emerges in later-stage PD for managing complications. It is particularly effective at reducing levodopa-induced dyskinesias [1.3.3, 1.3.4]. A double-blind, placebo-controlled study showed that amantadine reduced dyskinesia severity by 60% without diminishing the antiparkinsonian effects of levodopa [1.3.3]. By controlling these involuntary movements, it can significantly improve a patient's quality of life and functional ability.
Efficacy for Other Types of Tremors
Essential Tremor (ET): For essential tremor, a common neurological disorder causing involuntary shaking, amantadine has been shown to be ineffective. A randomized, double-blind, placebo-controlled trial concluded that amantadine at a dose of 200 mg per day did not provide any significant benefit [1.4.1, 1.4.2]. In fact, 37.5% of patients in one study reported a worsening of their tremor while taking the medication [1.4.3]. Therefore, it is not recommended for treating ET.
Multiple Sclerosis (MS) Tremor: Amantadine is sometimes used off-label to treat fatigue in patients with Multiple Sclerosis [1.5.2, 1.5.6]. While it is listed as a potential treatment for MS-related fatigue, there is limited high-quality evidence to support its efficacy for this purpose or for MS-related tremor [1.5.4, 1.5.5].
Comparison with Other Tremor Medications
| Medication/Class | Primary Use for Tremor | Mechanism of Action | General Efficacy for PD Tremor | Notes |
|---|---|---|---|---|
| Amantadine | Parkinson's (esp. Levodopa-induced dyskinesia) | Dopamine agonist, NMDA antagonist [1.2.2, 1.2.5] | Mild to Modest [1.8.1] | Often used as an adjuvant therapy [1.3.4]. Ineffective for Essential Tremor [1.4.1]. |
| Levodopa/Carbidopa | Parkinson's Disease | Precursor to dopamine [1.3.2] | High [1.3.2] | The most common and effective drug for PD motor symptoms [1.8.2]. |
| Anticholinergics | Parkinson's Disease | Blocks acetylcholine to rebalance dopamine/acetylcholine | High [1.8.1] | Example: Trihexiphenidyl. Can have significant cognitive side effects. |
| Beta-Blockers | Essential Tremor | Blocks effects of adrenaline (epinephrine) | Not a primary PD treatment | Example: Propranolol. First-line treatment for Essential Tremor [1.4.2]. |
Dosage, Side Effects, and Important Considerations
Dosage for amantadine varies based on the formulation (immediate-release or extended-release) and the condition being treated. For Parkinson's, a typical dose of immediate-release amantadine is 100 mg twice daily [1.7.4]. Extended-release versions like Gocovri and Osmolex ER are taken once daily [1.7.3].
Patients should be aware of potential side effects, which can include [1.6.1, 1.6.2, 1.6.5]:
- Common: Dizziness, insomnia, nausea, dry mouth, constipation, and livedo reticularis (a purplish, net-like skin discoloration).
- Less Common but Serious: Hallucinations, confusion, swelling of the legs (peripheral edema), falls, and orthostatic hypotension (a drop in blood pressure upon standing).
- Rare: Suicidal thoughts, and a serious condition resembling neuroleptic malignant syndrome if the medication is stopped abruptly [1.6.3, 1.6.4].
It is critical not to stop taking amantadine suddenly, as this can lead to a sharp worsening of symptoms. Any dose changes should be managed by a doctor [1.6.6]. Caution is also advised for elderly patients and those with kidney disease, heart failure, or a history of seizures or psychosis [1.6.1].
Conclusion
So, does amantadine help with tremors? The answer is nuanced. While it can provide modest relief for the resting tremor associated with Parkinson's disease, its primary strength lies in managing the levodopa-induced dyskinesias that affect many patients in later stages [1.3.4, 1.3.3]. For other conditions like essential tremor, evidence shows it is not an effective treatment and may even worsen symptoms [1.4.1]. As with any medication, the decision to use amantadine should be made in consultation with a healthcare provider who can weigh its potential benefits against its risks and side effects for the individual patient.
For more information from a leading patient advocacy organization, you can visit the Parkinson's Foundation [1.7.3].
