Brain & Nervous System Multiple Sclerosis Treatment Provigil as a Treatment for MS-Related Fatigue Dosage, Benefits, and Side Effects By Julie Stachowiak, PhD facebook Julie Stachowiak, PhD, is the author of the Multiple Sclerosis Manifesto, the winner of the 2009 ForeWord Book of the Year Award, Health Category. Learn about our editorial process Julie Stachowiak, PhD Medically reviewed by Medically reviewed by Claudia Chaves, MD on April 22, 2019 Claudia Chaves, MD, is board-certified in cerebrovascular disease and neurology with a subspecialty certification in vascular neurology. She is an associate professor of neurology at Tufts Medical School and medical director of the Lahey Clinic Multiple Sclerosis Center in Lexington, Massachusetts. Learn about our Medical Review Board Claudia Chaves, MD Updated on June 24, 2019 Print Table of Contents View All How It Works Efficacy Dosage Side Effects Interactions Contraindications 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. Tetra Images / Getty Images 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. Fatigue is present in about 80 percent of people with MS and is considered the most debilitating symptom in about half of people with the disease. How It Works 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. Efficacy 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. The takeaway is that this drug may well help relieve fatigue in some people with MS. As with all treatments, though, it probably doesn't work for everyone. 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. Dosage 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. Side Effects Some potential side effects of Provigil include: Stuffy noseBack painDiarrheaNausea or vomitingAnxiety DizzinessInsomnia 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 problemsPsychiatric 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 reactionSwellingTrouble breathingFeverDark 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. Interactions 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. Contraindications 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. Was this page helpful? Thanks for your feedback! Get tips and advice on how you can live a full and happy life with MS. Sign Up You're in! Thank you, {{form.email}}, for signing up. There was an error. Please try again. What are your concerns? Other Inaccurate Hard to Understand Submit Article Sources Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy. NDA 20-717 PROVIGIL (modafinil) Tablets. FDA Approved Labeling dated August 17, 2007. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/020717s020s013s018lbl.pdf Brown JN, Howard CA, Kemp DW. Modafinil for the treatment of multiple sclerosis-related fatigue. Ann Pharmacother. 2010 Jun;44(6):1098-103. doi: 10.1345/aph.1M705. 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. doi: 10.1111/j.1468-1331.2007.01163.x. FDA. (2015). Medication Guide: Provigil. https://www.fda.gov/downloads/Drugs/DrugSafety/UCM231722.pdf Ford-Johnson L, et al. Cognitive effects of modafinil in patients with multiple sclerosis: A clinical trial. Rehab Psychol. 2016 Feb;61(1):82-91. doi: 10.1037/a0039919. Miller P, Soundy A. The pharmacological and non-pharmacological interventions for the management of fatigue related multiple sclerosis. J Neurol Sci. 2017 Oct 15;381:41-54. doi: 10.1016/j.jns.2017.08.012. National Institutes of Health U.S. National Library of Medicine. DailyMed. Label: Provigil-modafinil tablet 2018. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e16c26ad-7bc2-d155-3a5d-da83ad6492c8 Shangyan H, Kuiqing L, Yumin X, Jie C, Weixiong L. Meta-analysis of the efficacy of modafinil versus placebo in the treatment of multiple sclerosis fatigue. Mult Scler Relat Discord. 2018 Jan;19:85-89. doi: 10.1016/j.msard.2017.10.011 Yang TT, Wang L, Deng XY, Yu G. Pharmacological treatments for fatigue in patients with multiple sclerosis: A systematic review and meta-analysis. 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