Provigil as a Treatment for MS-Related Fatigue

Dosage, Benefits, and Side Effects

Woman looking tired sitting on sofa
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Fatigue is present in about 80 percent of people with multiple sclerosis (MS) and is considered the most debilitating symptom in about half of people with multiple sclerosis. Provigil (modafinil) is a medication that is sometimes prescribed to patients with MS-related fatigue.

Provigil is a central nervous system stimulant that is currently FDA-approved for treating people with narcolepsy, shift-work sleep disorder, and sleep apnea that is associated with excessive daytime sleepiness. The precise mechanism of this medication is unclear, but it has been found to improve wakefulness. 

Why Treating Fatigue Is Important

Fatigue can significantly impact a person's quality of life, affecting their ability to work, engage in social relationships, and participate in pleasurable activities. While fatigue can be exacerbated by other MS-related factors like medications, underlying sleep disorders, or depression, MS itself is believed to play a role in a person's fatigue — often described as a lack of physical and mental energy that does not improve with rest.


Provigil is taken in pill form, and the usual dose for MS-related fatigue is 200 mg daily. Higher doses, like 400mg daily, have not been found to be more effective.

Side Effects

It's tricky because some side effects of Provigil can mimic or exacerbate MS symptoms. For example, one potential side effect is insomnia — and difficulty sleeping at night can worsen your MS-related fatigue, creating a vicious cycle. This is why it's important to take Provigil in the morning, as taking a dose later in the day, especially afternoon, can hinder your sleep at night. 

Other potential side effects include:

  • Stuffy nose
  • Back pain
  • Diarrhea
  • Nausea or vomiting
  • Anxiety 
  • Dizziness

It's important to note too that Provigil can cause a serious, potentially life-threatening, skin rash or allergic reaction that can affect your liver or blood cells. It's important to contact your doctor if you develop any skin reaction, swelling, trouble breathing, fever, dark urine, or yellowing of your eyes when taking Provigil. Other potential serious side effects include heart problems or psychiatric problems like depression, hallucinations, or mania.

As always, once you start a new medication, it's important to schedule a follow-up with your doctor so he can assess how you are doing on it, and you can address any new side effects or worries.

What to Tell Your Doctor

In addition to your medical history, be sure to tell your doctor all the medications you are taking. This includes any over-the-counter medications, supplements, or vitamins, as they may interact with Provigil. For instance, Provigil has been shown to decrease the effectiveness of hormonal contraceptives, including birth control pills, patches, rings, implants, injections, and intrauterine devices. This may increase your chance of becoming pregnant on Provigil. 

Other Benefits

Provigil may improve cognition in people with MS, especially working memory, as evidenced by a small 2015 study on 16 patients in Rehabilitation Psychology

Also, in a very small 2007 study in the European Journal of Neurology, two patients with MS and primary nocturnal enuresis — the involuntary discharge of urine during sleep at night — had improvement in their nighttime urination episodes after taking Provigil.

Of course, larger, randomized studies are needed to substantiate both of these findings.

What This Means for You

If you suffer from MS-related fatigue, it's important to have a frank and open discussion with your neurologist. There are a number of factors related to fatigue in MS, and your neurologist will want to tease these out. There may be an easy fix, like a medication side effect. Sometimes, undiagnosed anemia or thyroid disease ends up being the culprit of what you thought was MS-related fatigue. Other times, daily aerobic exercise, treatment of your depression, or cognitive-behavioral therapy can ease your fatigue without you having to take another medication.

That being said, Provigil is a sensible option for treating MS-related fatigue based on the scientific data available. If you are prescribed Provigil, please remember to continue taking care of yourself, which means getting adequate sleep. In other words, while Provigil improves wakefulness, this doesn't mean you don't need sleep.

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Article Sources
  • Brown JN, Howard CA, & Kemp DW. Modafinil for the treatment of multiple sclerosis-related fatigue. Ann Pharmacother. 2010 Jun;44(6):1098-103.

  • Carrieri PB, de Leva MF, Carrieri M & Buongiorno M. Modafinil improves primary nocturnal enuresis in multiple sclerosis. Eur J Neurol. 2007 Mar;14(3):e1.
  • FDA. (2015). Medication Guide: Provigil.

  • Ford-Johnson L et al. Cognitive effects of modafinil in patients with multiple sclerosis: A clinical trial. Rehab Psychol. 2015 Dec 14. [Epub ahead of print].
  • Turkington, Carol. The A to Z of Multiple Sclerosis. New York: Checkmark Books. 2005.