Medications to Treat Multiple Sclerosis-Related Fatigue

Medically Reviewed by Carmelita Swiner, MD on March 02, 2023
4 min read

If you have multiple sclerosis (MS), you might feel very fatigued from time to time. It’s different than normal tiredness, and it doesn’t get better with sleep.

The best way to ease fatigue is to treat what’s causing it. That’s hard to do when you have MS. But you don’t need to manage your symptoms alone. Your doctor can help you figure out what triggers your fatigue. They’ll suggest some lifestyle changes that may help. You might need to treat other issues like sleep problems or depression.

If that’s not enough to ease your fatigue, medication can be an option.

There isn’t an FDA-approved drug to treat MS-related fatigue. But your doctor can give you certain kinds of medicine if they think they’ll help. That’s called an “off-label” use.

Some common options used for MS include:

Amantadine (Gocovri, Symmetrel). This is an antiviral drug used to treat Parkinson's disease. It’s not clear how it treats MS-related fatigue. It might change how your immune system works. Some experts think amantadine helps because it affects your body’s levels of something called dopamine. That’s a brain chemical that controls how you move and think. 

Armodafinil (Nuvigil) or modafinil (Provigil). These drugs may help you stay awake if you tend to doze off during the day. They’re approved to promote wakefulness in people with narcolepsy, obstructive sleep apnea (OSA), or shift work disorder (SWD).

Stimulants. These drugs work on your central nervous system. They’re used to treat attention deficit hyperactive disorder (ADHD) and narcolepsy. But if you have MS, your doctor might give them to you to help with “brain fog.” That’s when you can’t think very clearly or focus on a task.

Common stimulants include:

  • Methylphenidate
  • Amphetamine/dextroamphetamine (Dexedrine)

There’s conflicting evidence about which drugs, if any, ease MS-related fatigue. Some studies show that amantadine may have a moderate effect for some people. Other research found that modafinil or methylphenidate could improve wakefulness in people with excessive daytime sleepiness (EDS).

Some people with MS say drugs don’t get rid of their fatigue. But medicine can keep them awake and make their tiredness easier to handle.

Even if a drug helps you, it may not work as well over time. Tell your doctor if that happens. You may need to take a “drug holiday.” That means you’ll quit for a weekend or a few weeks. Your doctor will let you know when you can start your treatment back up again.

Like all medications, drugs for fatigue may cause some unwanted symptoms. Your doctor can go over the pros and cons of each drug with you.

Insomnia is one of the most common symptoms of these treatments. You may have less trouble sleeping if you take your fatigue medicine when you first wake up in the morning.

Other mild side effects include:

  • Headache
  • Dizziness
  • Nausea
  • Nervousness

Stimulants may also cause:

  • Fast heart rate
  • Extra sweating

Some of these symptoms may go away on their own, but it may take a few weeks. Tell your doctor about anything that really bothers you. They may need to lower your dose or switch you to a different medicine.

Also let them know if you notice any new rashes, ulcers, or mouth sores. Rarely, drugs like modafinil or armodafinil can cause a life-threatening skin reaction. If you have it, you’ll need to stop taking these medicines to get better.

Some drugs for fatigue may change your mental outlook. Get help right away if you feel really confused or you think about hurting yourself.

Aspirin. This isn’t normally used for MS-related tiredness. But studies found that fatigue went down in people who took 325 milligrams of aspirin twice a day or 500 milligrams once a day. This drug is cheap and easily available without a prescription. But you should still ask your doctor if it’s safe for you. It can cause stomach problems like ulcers in some people.

Antidepressants. These may help your fatigue if you also have depression. Some antidepressants also help with MS-related nerve pain. You may need to try several medicines to find one that works for you. But some common options used with MS include:

  • Bupropion (Wellbutrin) 
  • Citalopram (Celexa)
  • Duloxetine (Cymbalta)
  • Fluoxetine (Prozac)
  • Venlafaxine (Effexor XR)

Ask your doctor if these medicines can affect other parts of your body. Go over anything that might cause or make kidney, heart, or vision problems worse.

Make sure to tell them about any other drugs you’re taking. That includes vitamins and supplements. And always take all medicine exactly as prescribed. It can be dangerous if you take too much.

Don’t stop your treatment suddenly. Talk to your doctor first. You may need to lower your dose slowly over time.