Provigil as a Treatment for MS-Related Fatigue

Provigil (modafinil) is a central nervous system stimulant that may be used to treat multiple sclerosis (MS)-related fatigue. While currently only approved by the U.S. Food and Drug Administration (FDA) for excessive daytime sleepiness in people with narcolepsy, shift-work sleep disorder, and sleep apnea, it has been found to improve wakefulness in MS patients as well and may be prescribed for this off-label purpose.

Provigil is just one of several medications used to treat the fatigue of MS, which is often described as a lack of physical and mental energy that doesn't improve with rest. If you experience it, you already know just how much this symptom can impact your quality of life, affecting your ability to work, have a social life, and take part in things you enjoy.

While fatigue can be exacerbated by other MS-related factors—such as medications, underlying sleep disorders, or depression—MS itself is believed to play a role in fatigue.

Scientists don't know exactly how Provigil works, but they suspect it may increase the amount of a neurotransmitter called dopamine that's available for your brain to use. It's thought to do this by slowing reuptake, a mechanism by which neurotransmitters are recycled by the brain.

Dopamine sends chemical messages in the brain and is involved in many important functions, including mental focus, attention, the feeling of reward, movement, and coordination.

So far, research is mixed on how effective Provigil is at treating MS-related fatigue.

At least three reviews and analyses of research on Provigil for fatigue in MS were published in 2017 and 2018. One of these said the limited data available suggest that Provigil is not shown to be effective.

However, another review found that it was promising, stating that further research into drugs for treating MS fatigue ("notably considering the potential of Modafinil") is needed. Another, published in 2018, found that the drug was an effective treatment and that more research was needed to determine optimal dosing.

Other Benefits

Provigil may improve cognition in people with MS, especially working memory, as evidenced by a small 2016 study on 16 patients, which was published in Rehabilitation Psychology. 

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

Larger, randomized studies are needed to substantiate both of these findings.

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

Elderly people may not be able to process Provigil as effectively as younger people, so a lower dosage is suggested.

Some potential side effects of Provigil include:

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

Some of these can mimic or exacerbate MS symptoms, so it can be hard to know where the symptoms are coming from. For example, Provigil can cause insomnia—and poor sleep can worsen your MS-related fatigue, creating a vicious cycle. This is why it's important to take Provigil in the morning; taking a dose later in the day, especially afternoon, can hinder your sleep at night. 

Potential serious side effects of this drug include:

• Heart problems
• Psychiatric problems, such as depression, hallucinations, or mania

Provigil can also cause a serious, potentially life-threatening skin rash or allergic reaction that can affect your liver or blood cells. Contact your doctor if you develop:

• Any skin reaction
• Swelling
• Trouble breathing
• Fever
• Dark urine

As always, once you start a new medication, it's important to schedule a follow-up with your doctor so the effectiveness can be assessed, and so you can address any new side effects or concerns.

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.

Of particular note:

• People taking Provigil and warfarin should get more frequent prothrombin monitoring.
• Provigil may interact negatively with MAOIs. If you're taking one, your doctor will need to weigh the pros and cons of adding Provigil to your treatment regimen.
• Provigil has been shown to decrease the effectiveness of hormonal contraceptives, including birth control pills, patches, rings, implants, injections, and intrauterine devices. Because of this, you should consider other options for preventing unwanted pregnancy, such as condoms, while you take this drug.

Don't take Provigil if you are or are trying to become pregnant. Miscarriage and impaired fetal growth have been reported in connection with this medication.

A Word From Verywell

If you suffer from fatigue, it's important to have a frank discussion with your neurologist. A number of factors can go into this symptom, and it can take a while to figure them all out.

Sometimes, it's an easy fix, such as changing a medication. However, other problems like undiagnosed anemia or thyroid disease can be causing it, instead of your MS. Other times, daily aerobic exercise, treating depression, or cognitive-behavioral therapy can ease fatigue without you having to take another medication.

That being said, Provigil is a sensible option for many people, 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.