Fatigue is a common challenge for people living with multiple sclerosis (MS). Up to 80 percent of people with MS report this symptom, and for many, sleep doesn’t restore their energy. This ongoing tiredness can make daily tasks more difficult, but certain medications may help. One option is modafinil — a wakefulness-promoting drug first developed to treat sleep disorders.

What Is Modafinil?

Modafinil (Provigil) is a prescription drug approved by the U.S. Food and Drug Administration (FDA) for treating excessive daytime sleepiness from narcolepsy, shift work sleep disorder, and obstructive sleep apnea. It’s a stimulant that works by changing the levels of chemicals in the brain that control wakefulness and sleep to help you feel more alert.

Modafinil is a tablet that you take by mouth once a day. When used for MS fatigue, you’ll take modafinil in the morning so it helps you feel awake during the day.

Why Is Modafinil Used for MS Fatigue?

Modafinil isn’t FDA-approved for treating MS-related fatigue, but doctors can prescribe it off-label. This means it’s being used for a condition it wasn’t originally approved to treat.

Before trying modafinil, your doctor will see if exercising and eating a healthy diet help relieve your fatigue. You also might try physical or occupational therapy. If these don’t work, your provider might have you try amantadine since it’s often the first drug prescribed for MS fatigue. Doctors may recommend modafinil when fatigue doesn’t get better with these options.

Does Modafinil Actually Help?

Many studies have looked at the potential of modafinil in improving MS fatigue. Let’s see what the research shows.

Study Findings

Some studies suggest that modafinil helps to ease MS fatigue, but the results are inconsistent. While some people find it helpful, others do not.

One review from the journal Brain and Behavior looked at multiple clinical trials to see how well modafinil works for MS fatigue. This analysis found that modafinil helped some people feel less tired. It also showed that people with MS taking modafinil had a better quality of life.

Another study by the Patient-Centered Outcomes Research Institute compared modafinil with amantadine and methylphenidate (Concerta). Both amantadine and methylphenidate are also used to reduce fatigue. The researchers found that people in all groups, including the placebo group (people who took a pill with no active ingredients), reported feeling less tired. This means that modafinil may not always work better than other options for the treatment of MS fatigue.

One study explored whether cognitive behavioral therapy (CBT) could improve the effect of modafinil in people with MS. CBT is a type of talk therapy that helps people change unhelpful thinking and behaviors. This study from The Lancet Neurology found that modafinil, CBT, and the combination of both led to similar improvements in MS fatigue. While CBT’s benefits may fade over time, some people report that modafinil offers more consistent relief than other options.

Why Results Are Mixed

Results in studies often vary because MS fatigue can have many causes, such as poor sleep, depression, or side effects from other medications. One review in Practical Neurology noted that sleep problems are common in MS and can make fatigue symptoms worse. Modafinil helps with certain causes of fatigue, like daytime sleepiness. However, it doesn’t treat every possible source, which can be why it works well for some people but not for others.

Fatigue is often measured using questionnaires like the Modified Fatigue Impact Scale (MFIS) or the Fatigue Severity Scale (FSS). The Epworth Sleepiness Scale (ESS) can also be used to test daytime sleepiness in people with MS. These tools help doctors understand how fatigue affects your daily life and can help keep track of how treatments are working. How researchers measure fatigue in studies may not reflect daily life, which can make treatments like modafinil look more or less effective than they really are.

MyMSTeam Members Share Their Experiences

Not everyone feels the same after taking modafinil for MS fatigue. MyMSTeam members have expressed both positive and negative experiences after trying this medicine.

Positive Experiences

Many MyMSTeam members have discussed how modafinil affects them. Some say it makes a big difference and improves their quality of life. They’ve shared the following:

• “Modafinil has allowed me to live a fuller, happier, and richer life. Don’t get me wrong, there are other parts of my body that MS has gotten to, but being able to think rationally, make better choices for myself, and talk to people without slurring or falling asleep has been a game changer.”
• “I have been on modafinil almost since diagnosis. I can tell you it kept me working in my profession for 29 years.”
• “Modafinil was an effective therapy for me. It allows me to get things done, and does not seem to interfere with my sleep.“

Negative Experiences or Mixed Reviews

Some people stopped taking modafinil because it didn’t relieve their fatigue. Others talked about the unpleasant side effects. Below are some negative comments members have said about their experiences with modafinil:

• “I previously tried modafinil, but it didn’t help much. It just made me jittery all over, so I stopped it.“
• “I’m on modafinil. I believe it helps my fatigue, but it makes my headaches worse and gives me anxiety sometimes.”
• ”I have tried modafinil; however, it did nothing for me.”

Possible Side Effects of Modafinil

Modafinil can cause side effects. Some are mild, but others are more serious. The most common side effects of modafinil include:

• Headache
• Runny or stuffy nose
• Dizziness
• Upset stomach
• Diarrhea
• Difficulty having a bowel movement
• Nausea or vomiting
• Heartburn
• Decreased appetite
• Burning or tingling skin
• Dry mouth or skin
• Indigestion
• Back pain
• Belching
• Mouth sores
• Nervousness or anxiety

Modafinil may also cause more serious side effects. Some people may have an allergic reaction to modafinil. If you have signs of an allergic reaction, like itching, fever, or difficulty breathing, stop taking modafinil and seek medical attention.

Other severe side effects that require medical attention include mental health symptoms. Stop taking modafinil and immediately call your doctor if you have any mental health changes, including depression, hallucinations (seeing or hearing things that aren’t there), or suicidal thoughts.

Some people who have been taking modafinil for a long time can become dependent on it. Signs of dependence may include:

• Feeling a strong need to keep taking modafinil
• Needing a higher dose to feel the effects
• Having withdrawal symptoms when you stop

If you notice any of these signs, discuss them with your doctor to make sure it’s safe to keep taking modafinil.

Who Should Avoid Modafinil?

Modafinil isn’t right for everyone. People with the following health concerns should talk with their doctor to see if modafinil is right for them:

• Heart problems
• Kidney disease
• Liver issues
• A history of mental health concerns

Modafinil can interact with birth control. Use another form of protection while taking it and for at least one month after your last dose.

Doctors usually don’t recommend taking modafinil during pregnancy. There aren’t enough studies to understand if modafinil can be taken while breastfeeding, so talk with your doctor before breastfeeding while taking this medicine. You should also avoid drinking alcohol while taking modafinil.

Modafinil can interact with omeprazole (Prilosec), so be sure to tell your doctor if you’re taking this medication before starting modafinil.

Talk to Your Doctor

Modafinil can help some people with MS fatigue feel more awake. If MS fatigue is affecting you, talk with a healthcare professional about ways to manage it. A doctor can help you weigh the benefits and risks to see if modafinil is right for you.

Find Your Team

On MyMSTeam, the social network for people living with multiple sclerosis and their loved ones, members come together to ask questions, give advice, and share their stories with others who understand life with MS.

Do you take modafinil to help with MS fatigue? Does it work well for you? Share your experience in the comments below, or start a conversation by posting on your Activities page.