Amantadine is a complex medication with varied pharmacological actions, primarily used today for its neurological benefits rather than its original antiviral properties. While it was once a standard treatment for influenza A, widespread viral resistance means it is no longer recommended for this purpose. Instead, its modern applications focus on managing symptoms associated with certain movement disorders and fatigue.
Amantadine for Parkinson's Disease
The most prominent and modern use of amantadine is in the treatment of Parkinson's disease (PD). It is often prescribed to manage specific motor symptoms that are not well-controlled by other medications, such as levodopa.
Targeting Dyskinesia
One of the main reasons for taking amantadine in the context of Parkinson's is to reduce dyskinesia. Dyskinesia refers to the involuntary, erratic, and writhing movements that can develop after long-term use of levodopa. The extended-release formulation of amantadine, available under brand names like Gocovri, is specifically approved for this purpose. It helps control these troublesome movements, improving the patient's quality of life.
Addressing 'Off' Episodes
Amantadine can also help with "off" episodes in people with PD. These are periods when the effects of other medications, like levodopa, wear off, and Parkinson's symptoms (difficulty moving, walking, and speaking) return. By increasing dopamine levels in the brain, amantadine helps to smooth out these fluctuations and extend the "on" time.
Management of Early-Stage Symptoms
In the early stages of PD, before more powerful drugs are needed, amantadine can be used as a monotherapy to help reduce stiffness (rigidity), slowness of movement (akinesia), and tremor. However, its effectiveness for these primary symptoms is generally considered mild compared to other medications.
Treatment for Drug-Induced Movement Disorders
Beyond Parkinson's disease, amantadine is effective in managing extrapyramidal symptoms (EPS) caused by certain antipsychotic medications. These side effects can include drug-induced parkinsonism, characterized by stiffness, tremors, and slow movements. Evidence suggests that amantadine is a reliable treatment for this condition and may have a more favorable side effect profile than anticholinergic alternatives.
Managing Fatigue in Neurological Conditions
Amantadine has shown potential for reducing fatigue in various neurological disorders. Clinical trials have explored its use for fatigue associated with conditions like multiple sclerosis (MS) and, more recently, post-COVID-19 syndrome.
- Multiple Sclerosis (MS) Fatigue: While the mechanism is unclear, amantadine has been used to alleviate fatigue in some MS patients. However, some studies have shown mixed or inconclusive results, and its efficacy is considered poorly documented by some reviews.
- Post-COVID-19 Fatigue: A clinical trial found that a two-week course of amantadine significantly reduced fatigue in patients with persistent post-COVID-19 symptoms compared to a control group. The study authors suggest amantadine's effects on dopamine and NMDA receptors may play a role. It is important to note this was an open-label trial, and further research is needed.
Mechanism of Action and Side Effects
The dual nature of amantadine is key to understanding its effects. It acts as both a weak dopaminergic agent and an N-methyl-D-aspartate (NMDA) receptor antagonist.
- Dopaminergic effects: It enhances the release and inhibits the re-uptake of dopamine in the brain, helping to restore the balance of neurotransmitters that is disrupted in Parkinson's disease.
- NMDA receptor antagonism: By blocking the NMDA receptor, amantadine helps reduce the glutamatergic over-activity associated with dyskinesia.
Notable side effects
As with any medication, amantadine can cause side effects. Common ones include dizziness, nausea, dry mouth, and insomnia. More serious, though less frequent, side effects can include hallucinations, confusion, and peripheral edema. Patients should also be monitored for impulse control behaviors, such as gambling or excessive spending. Livedo reticularis, a purplish, web-like discoloration of the skin, is another potential side effect.
Comparison of Amantadine with Other Parkinson's Medications
To understand amantadine's place in therapy, it is useful to compare it with other common treatments for Parkinson's disease.
| Feature | Amantadine | Levodopa | Anticholinergics (e.g., trihexyphenidyl) |
|---|---|---|---|
| Primary Use in PD | Dyskinesia, 'off' episodes, early symptoms | Mainstay for motor symptoms (tremor, rigidity, bradykinesia) | Tremor, rigidity |
| Effectiveness | Mild effect on primary symptoms; effective for dyskinesia | Strongest and most effective for primary motor symptoms | Moderate effect, primarily on tremor |
| Role in Therapy | Add-on for dyskinesia and 'off' time; some use in early PD | Cornerstone treatment for most PD patients | Early use, though less common due to side effects |
| Mechanism | Dopaminergic and NMDA antagonist | Converts to dopamine in the brain | Blocks acetylcholine |
| Key Side Effects | Dizziness, nausea, insomnia, confusion, hallucinations, livedo reticularis | Nausea, vomiting, dyskinesia | Dry mouth, blurred vision, urinary retention, confusion |
| Renal Function | Requires dose adjustment in patients with renal impairment | Not as dependent on renal function | Use with caution in some patients |
Important Considerations for Taking Amantadine
- Renal Function: Amantadine is primarily cleared by the kidneys. Patients with renal impairment require a lower dose to avoid toxicity.
- Sudden Discontinuation: Stopping amantadine abruptly can lead to serious withdrawal symptoms, such as fever, confusion, and changes in mental state, resembling neuroleptic malignant syndrome. Any changes to the medication should be done under a doctor's supervision.
- Cognitive and Behavioral Changes: The medication can cause confusion, anxiety, and in rare cases, psychosis or compulsive behaviors. Caregivers should monitor for any unusual changes.
- Interaction with Alcohol: Alcohol can worsen some of amantadine's side effects, such as dizziness and confusion, and should be avoided.
- Formulations: Amantadine is available in immediate-release (IR) and extended-release (ER) forms, which have different dosing schedules. The ER formulation (Gocovri) is often used for dyskinesia and taken at bedtime.
Conclusion
Why does someone take amantadine? The reasons have evolved significantly over time. While it is no longer an effective antiviral for influenza A, it remains a valuable tool in modern neurology for managing movement disorders. Its ability to reduce dyskinesia and manage 'off' episodes in Parkinson's disease, treat drug-induced parkinsonism, and potentially alleviate certain types of chronic fatigue makes it a versatile medication. However, its use requires careful consideration of potential side effects, dosage, and interactions. Patients should always consult their healthcare provider to determine if amantadine is the right choice for their specific condition. For more detailed information on amantadine, you can visit the National Institutes of Health's NCBI Bookshelf.
