Amantadine as Treatment for MS Fatigue

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Amantadine is an antiviral drug used to treat Parkinson’s disease that is often prescribed to treat fatigue in people with multiple sclerosis (MS). Its use for this symptom, however, is off-label, as it has not yet been approved by the U.S. Food and Drug Administration for this purpose.

Its anti-fatigue effects were first discovered when people with MS were treated for Asian flu and found that their energy levels were suddenly and significantly improved. However, due to widespread amantadine resistance, this drug has been phased out as an influenza treatment.

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How Amantadine Works

Amantadine acts directly on the central nervous system and helps stimulate the production of dopamine, a neurotransmitting chemical similar to adrenaline. Dopamine affects a structures in the brain collectively known as the basal ganglia, which help regulate movement, emotional response, and the ability to experience pleasure and pain.

The mechanism of action in terms of how it specifically improves MS fatigue is still not entirely understood.


Amantadine is FDA-approved for use in dyskinesias in Parkinson's disease, and appears to offer mild-to-moderate relief in people with MS-related fatigue. In fact, it appears to work well enough for MS-related fatigue that a lot of healthcare providers consider amantadine the first-line choice for treating this frustrating and often debilitating condition.

One study conducted in 2014 evaluated the effectiveness of the drug based on the Modified Fatigue Impact Scale (MFIS), which measures fatigue on a scale of 0 to 84. After one month of use, people taking it had a 34 percent decrease in the severity of their MS fatigue.

While that's significant, when compared to other treatments such as aspirin or acetyl-L-carnitine (a popular dietary supplement), amantadine was not shown to be any more or less effective.

Dosage and Formulation

Amantadine comes as an orange round pill or in capsules (red or yellow). It is also available as a syrup.

For managing the fatigue of MS, the usual dosage is 100 milligrams (mg) to 200 mg daily. It's best to take the medication early in the day so that it doesn’t interfere with sleep.

Side Effects

The side effects of amantadine are typically considered minor. The most common ones are:

  • Jitteriness
  • Dry mouth

Though uncommon, other side effects of amantadine include:

  • Insomnia, especially if taken later in the day
  • Blurred vision, particularly in people with MS-associated optic neuritis
  • Constipation
  • Dizziness
  • Urinary hesitation

Some side effects, such as insomnia and bladder dysfunction, are also common MS symptoms. If you start taking this medication, be sure to watch for worsening, reappearance, or changes in these symptoms so you know whether it's from the drug or an MS relapse.

High-Dose Side Effect

Doses of amantadine at or above 300 milligrams can sometimes cause livedo reticularis, a skin condition characterized by purple blotches on the legs.

Considerations and Contraindications

Amantadine can cause adverse events in people with certain conditions, or exacerbate those conditions. These include:

  • Seizure disorder
  • Heart problems
  • Kidney dysfunction
  • Clinical depression

People with schizophrenia or other psychotic disorders should use caution if taking amantadine, as it can sometimes worsen psychiatric symptoms.

Due to a lack of research, amantadine is not recommended during pregnancy as it is unknown whether the drug can harm the fetus. It should also be avoided during breastfeeding and in women who are planning to conceive.

A Word From Verywell

Fatigue is a symptom that can impact every area of your life. Treating it isn't easy, but you have a lot of options, and amantadine and other prescription drugs are likely to come up in conversations with your healthcare provider.

The important thing to remember is that some of these treatments may not work for you, but others might. Keep the lines of communication with your healthcare team open while you consider and try different treatments so that you can make good decisions and get feeling better.

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