From the Guidelines
Amantadine is an effective medication for treating Parkinson's disease that works by increasing dopamine release and blocking glutamate receptors in the brain. It is typically prescribed at doses of 100 mg once or twice daily, with a maximum of 400 mg per day, usually taken in the morning and early afternoon to avoid sleep disturbances. Amantadine helps reduce tremors, rigidity, and bradykinesia (slowness of movement) in Parkinson's patients, and is particularly useful for managing levodopa-induced dyskinesias (involuntary movements) that develop in advanced disease. The medication can be used as monotherapy in early Parkinson's disease or as an adjunct to levodopa therapy in more advanced stages. Common side effects include ankle swelling, livedo reticularis (mottled skin discoloration), dry mouth, constipation, and occasionally hallucinations or confusion, particularly in elderly patients. Amantadine should be used cautiously in patients with kidney disease, as dose adjustments may be necessary 1. The medication's effectiveness may diminish over time for some patients, typically after several months of continuous use, though many patients continue to benefit long-term. Some key points to consider when prescribing amantadine include:
- Monitoring for side effects, particularly in elderly patients
- Adjusting doses in patients with kidney disease
- Considering alternative treatments if amantadine is not effective or if side effects are severe
- Educating patients about the potential benefits and risks of amantadine treatment. It's also worth noting that amantadine has anticholinergic effects and might cause mydriasis, so it should not be used among patients with untreated angle closure glaucoma 1. Additionally, amantadine can be used to treat drug-induced Parkinsonism syndrome, which is often caused by antipsychotic medications 1. Overall, amantadine is a valuable treatment option for Parkinson's disease, and its use should be tailored to the individual patient's needs and medical history.
From the FDA Drug Label
Amantadine hydrochloride is indicated in the treatment of idiopathic Parkinson's disease (Paralysis Agitans), postencephalitic parkinsonism, and symptomatic parkinsonism which may follow injury to the nervous system by carbon monoxide intoxication. The mechanism of action of amantadine in the treatment of Parkinson's disease is not explicitly stated in the drug label.
- The label only mentions that amantadine hydrochloride is indicated for the treatment of Parkinson's disease, but it does not provide information on how it works.
- It also states that amantadine hydrochloride is less effective than levodopa in the treatment of Parkinson's disease, but it does not explain the mechanism of action 2.
From the Research
Mechanism of Action of Amantadine in Parkinson's Disease
The mechanism of action of amantadine in the treatment of Parkinson's disease is complex and involves several pathways.
- Amantadine has demonstrated significant antidyskinetic effects in animal PD models and in randomized double-blind placebo-controlled trials (RCTs) in patients with PD, which are thought to be related to the blockade of NMDA receptors modulating cortico-striatal glutamatergic-dopaminergic interactions involved in the genesis of LIDs 3.
- The blockade of NMDA receptors by amantadine reduces the severity and duration of dyskinesia during the day, reduces OFF time and increases ON time without troublesome dyskinesia 4.
- Amantadine has also been shown to have possible effects on other PD symptoms such as apathy or fatigue, although the exact mechanism of action for these effects is not well understood 3.
Role of Amantadine in Treating Parkinson's Disease
Amantadine plays a significant role in the treatment of Parkinson's disease, particularly in the management of L-DOPA-induced dyskinesia.
- Amantadine has been shown to be effective in reducing the severity and duration of dyskinesia in PD patients, with extended-release formulations providing consistent and long-lasting reductions in LIDs 3, 4.
- Amantadine has also been proposed as a potential initial treatment for Parkinson's disease, due to its efficacy and safety profile, as well as its lack of association with impulse control disorder 5.
- However, the evidence for the efficacy and safety of amantadine in the treatment of idiopathic Parkinson's disease is not conclusive, with some studies suggesting that the current evidence is insufficient to support its use as a monotherapy or adjuvant therapy 6.