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Provigil as Treatment for MS Fatigue


Updated April 11, 2009

Provigil (modafinil) is in a class of drugs called central nervous system stimulants and is most often prescribed for people with narcolepsy or other sleep disorders (such as sleep apnea) which cause excessive daytime sleepiness. Although it clearly shows benefit and is widely-prescribed for MS-related fatigue, Provigil is not specifically approved by the FDA for this application.

Note: Before going any further, read this Provigil Warning!!! that was issued in 2007, linking Provigil to fatal skin rashes and psychiatric adverse effects.

How It Works

The exact mechanism by which Provigil increases wakefulness is not known.

Usual Dosage

Provigil is taken in pill form and the usual dose for MS-related fatigue is between 100 to 200 mg.

Side Effects

The most common side effects of Provigil are headache and nausea. Other side effects, while rarer, are important to watch for, as they can mimic or exacerbate other MS symptoms. These include:
  • Insomnia, especially if not taken early in the day (This is important to report to your doctor if it does not improve, as sleep problems can themselves be one of the causes of fatigue.)
  • Diarrhea
  • Anxiety
  • Dizziness

In 2007, the FDA issued a warning that Provigil was linked to deadly skin rashes and psychiatric effects. Anyone who is taking Provigil and experiences a rash or other skin reaction should contact their doctor immediately. Provigil should be used with extreme caution in anyone with a history of psychosis, depression, or mania.

Potential Interactions and Warnings

Provigil may interact with the following medications: anticoagulants (blood thinners) such as warfarin (Coumadin); certain antidepressants such as clomipramine (Anafranil) and desipramine (Norpramin); cyclosporine (Neoral, Sandimmune); cyclophosphamide (Cytoxan, Neosar); diazepam (Valium); certain medications for seizures such as carbamazepine (Tegretol), phenobarbital (Luminal, Solfoton), and phenytoin (Dilantin); monoamine oxidase (MAO) inhibitors, including isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl), and tranylcypromine (Parnate); primidone (Mysoline); propranolol (Inderal); certain proton pump inhibitors such as lansoprazole (Prevacid), omeprazole (Prilosec), and pantoprazole (Protonix); selective serotonin reuptake inhibitors (SSRIs) such as as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft); rifampin (Rifadin, Rimactane); and triazolam (Halcion).

In addition, Provigil has been shown to decrease the effectiveness of hormonal contraceptives, including birth control pills, patches, rings, implants, injections, and intrauterine devices. Use another form of birth control while taking Provigil and for one month after you stop taking it. Talk to your doctor about types of birth control that will work for you while you are taking Provigil.

You should not eat grapefruit or drink grapefruit juice while taking Provigil.

Mention any cardiac problems to your doctor, especially mitral valve prolapse and left ventricular hypertrophy.

Other Uses in MS

Provigil is occasionally used to treat depression related to fatigue (and fatigue due to depression), which are two MS symptoms that often appear together and can exacerbate each other so that both the fatigue and depression become worse if both are not treated.

Just recently, Provigil was shown to improve nocturnal enuresis (which is the involuntary discharge of urine during sleep at night) in people with MS.


Turkington, Carol. The A to Z of Multiple Sclerosis. New York: Checkmark Books. 2005.

National Library of Medicine. National Institutes of Health. Medline Plus: Modafinil.

Carrieri PB, de Leva MF, Carrieri M, Buongiorno M. Modafinil improves primary nocturnal enuresis in multiple sclerosis. European Journal of Neurology. 2007 Mar;14(3).

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