Can Medications Reduce MS Fatigue?

For many people with MS, living with an overwhelming feeling of fatigue is the hardest symptom to cope with, and it’s an all-too-common one. Up to four out of five people with multiple sclerosis experience fatigue, according to the National Multiple Sclerosis Society, and we still don’t really know what causes it.

“If you ask MS patients what’s the number one most disabling symptom they have, it’s fatigue,” says neurologist Ari Green, M.D., the medical director of the UCSF Multiple Sclerosis and Neuroinflammation Center in San Francisco, CA. “In part it’s because it’s a hidden symptom. It’s really hard to see if someone has fatigue issues. It impacts their work, and it impacts their family life. It’s really a major symptom.”

Fatigue can be tough to manage. For some people, medications may ease certain symptoms and thereby restore energy levels as part of their MS treatment plan. For many others, natural remedies and lifestyle changes play a bigger part in fighting fatigue.

There are no drugs specifically approved by the Food and Drug Administration (FDA) to treat fatigue resulting from multiple sclerosis, per the National MS Society—but there are a few common medications that doctors can prescribe to try to provide relief. However, doctors caution these meds work better for some people than others. “The response to symptomatic treatment of fatigue is very individual,” says neurologist Irena Dujmovic Basuroski, M.D., Ph.D., the multiple sclerosis/neuroimmunology division chief in the department of neurology at UNC School of Medicine in Chapel Hill, NC. “About 30% of patients who are treated with fatigue medications for MS report some benefit to taking the medications.”

Yet for many, medications may not work any better for MS fatigue than a placebo. In one small study published in the journal Lancet Neurology, researchers investigated the effectiveness of three of the most commonly prescribed drugs for MS fatigue: amantadine, modafinil, and methylphenidate, all of which help induce sleep. They proved no more effective than a placebo, and had the potential to cause adverse effects.

That research has led neurologist Tyler Smith, M.D., a clinical assistant professor in NYU Langone Health’s Multiple Sclerosis Comprehensive Care Center in New York City, to be cautious about prescribing these medications to his MS patients. “However, I do recognize that some patients experience significant benefit from these and other medications, so on a case-by-case basis I will recommend one of these,” he adds.

Another concern: Drugs for MS fatigue can have significant side effects. Not everyone can take them safely. For example, some stimulants can raise your blood pressure or heart rate. That may be dangerous for someone with heart disease or high blood pressure, says Dr. Dujmovic Basuroski, or for people who have had or are risk for stroke. They also can cause or worsen insomnia.

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It’s also possible that you don’t need these drugs because something other than MS explains your fatigue. “I rule out other causes of fatigue, such as sleep apnea and hypothyroidism, before reaching for prescription treatments for fatigue,” Dr. Smith says.

No drug has been FDA-approved specifically to treat fatigue in multiple sclerosis. Rather, certain drugs that were developed for other health conditions are prescribed by doctors to be used “off-label,” or for purposes other than their initial approval. If you are talking with your provider about possible medications to help with MS fatigue, these are a few options you may discuss.

Symmetrel (Amantadine)

This antiviral medication was initially developed to treat influenza A, a type of flu, and it’s also used to treat Parkinson’s disease. Experts don’t know exactly how it helps with fatigue, but it may be tied to the drug’s stimulant effect on the dopaminergic system, the part of the brain responsible for mood, emotions, cognition, and other functions.

Dose: For MS fatigue, it’s typically prescribed in either once or twice daily doses of 100 milligrams (mg), per the Cleveland Clinic.

Possible side effects include:

• Confusion

• Dizziness

• Hallucinations

• Hypotension (low blood pressure)

• Insomnia

• Leg discoloration (called livedo reticularis)

• Nausea

• Paranoia

• Urinary retention

Provigil (Modafinil)

Developed to treat narcolepsy, a neurological disorder which causes overwhelming daytime sleepiness, this stimulant drug promotes wakefulness by activating the hypothalamus, the part of the brain the controls sleep. A similar drug, Nuvigil (armodafinil), is also prescribed for MS fatigue, but less commonly than modafinil, per the Multiple Sclerosis Association of America (MSAA).

Dose: For MS fatigue, a common starting daily dose of modafinil is 100 mg once per day, which may be increased up to 400 mg, per the Cleveland Clinic. The average once-daily dose is 200 mg.

Possible side effects include:

• Anxiety

• Headache

• Irritability

• Nausea

• Nervousness

Ritalin (Methylphenidate)

Although it may be best known as a drug used to treat attention deficit/hyperactivity disorder, methylphenidate is a stimulant drug that affects dopamine as well as another neurotransmitter called norepinephrine, and is sometimes used off-label to treat MS-related fatigue.

Dose: Your doctor likely will start you on Ritalin at a dose of 5 mg once or twice a day. Your dose can be increased up to a maximum of 40 mg per day.

Possible side effects: The most side effects are insomnia and nervousness. Other common side effects include:

• Delayed growth in children who take the drug long term

• Dizziness

• Dry mouth

• Fast, fluttering, or pounding heartbeat, called palpitations

• Headaches

• Nausea and vomiting

• Reduced appetite

• Restlessness or trouble staying still

• Tics

• Weight loss

While Symmetrel, Provigil, and Ritalin are the most commonly prescribed drugs for MS fatigue, they may not be for everyone, in which case your doctor may instead opt for another medication. These can include:

Adderall (Dextroamphetamine/Amphetamine)

Another stimulant medication commonly used to treat ADHD, Adderall is also sometimes prescribed for MS fatigue. The dosing and common side effects are similar to Ritalin.

Antidepressants

Two classes of these medications are less commonly used and are usually prescribed to treat depression and anxiety. However, in some cases they may help relieve MS fatigue, according to the MSAA, due to their stimulant effect.

• Selective serotonin reuptake inhibitors (SSRIs), such as Prozac (fluoxetine), Paxil (paroxetine), and Zoloft (sertraline).

• Wellbutrin (bupropion), a norepinephrine-dopamine reuptake inhibitor (NDRI).

Concerns about medication side effects and the ineffectiveness for many people with MS fatigue make drugs a less-appealing treatment option, agree Dr. Smith and Dr. Dujmovic Basuroski. Instead, many people living with multiple sclerosis opt for natural approaches to fighting fatigue.

Role of Diet

What you eat may help relieve fatigue, says Dr. Dujmovic Basuroski, while boosting your overall health. “There is some data to suggest that following a Mediterranean-style diet, which includes a reduced consumption of red meat, saturated fatty acids, and sweets, and increased fish consumption, could potentially reduce MS fatigue severity,” she explains.

The Mediterranean diet also encourages loading your plate with vegetables, fruit, whole grains, and other good-for-you foods. Two 2023 studies, one in the journal Nutrients and the other in the journal Nutritional Neuroscience, both report some improvement in fatigue when following the Mediterranean diet.

Supplements

While there’s no magic pill (pharmacological or natural) that will take away fatigue, there is evidence that certain supplements may help reduce some symptoms. One small study in Nutritional Neuroscience found the dietary supplement coenzyme Q10 (CoQ10) helped reduce fatigue and depression when 500 mg were taken once a day for 12 weeks. “However, those results need to be confirmed in a larger trial,” says Dr. Dujmovic Basuroski.

She also generally recommends vitamin D supplements for her patients who have a proven vitamin D deficiency. However, she adds, “there is not enough data to justify the general use of multivitamins in MS."

Remember that you should not take anything, even over-the-counter dietary supplements, without first talking with your doctor, adds Dr. Smith.

Other Lifestyle Changes

Both Dr. Smith and Dr. Dujmovic Basuroski encourage their patients to try the following to reduce fatigue:

• Conserving energy, such as planning rest periods and minimizing trips up and down the stairs

• Exercising regularly

• Getting good sleep, with your doctor’s help if necessary

• Keeping cool if you are sensitive to heat (and most people with MS are)

It’s important to talk your doctor before starting any new medication, especially if you have multiple sclerosis. This includes asking the following questions.

• Is it MS or something else that’s causing my fatigue?

• What side effects can I expect from this medication?

• Will this drug interact with my MS medications?

• What lifestyle changes help with fatigue?

Fatigue is very common in MS, and it can be debilitating. Medication may help relieve fatigue, but many people with MS do not benefit from it. Treating MS fatigue typically requires a broad approach that usually starts with lifestyle changes, like regular exercise, getting good sleep, and following a healthy diet. Talk to your doctor about what options might work best for you.