Fatigue is a common symptom of multiple sclerosis (MS) that is not always related to any underlying disability but can still significantly impact patient quality of life. The cause of fatigue in MS is unknown and must be distinguished from other causes. Treatment options include exercise, energy budgeting, and the off-label use of stimulant medications.

MS patient care includes treatment with disease-modifying therapies and the treatment of a patient’s residual symptoms, which can occur anywhere along the disease course and can impact quality of life. Fatigue is an important MS symptom because it is common and tends to be unrelated to the underlying disability. So, individuals who have very little-to-no impairment from their MS may have considerable fatigue, and, accordingly, there is a disconnect between the 2. Fatigue in MS is variable, it can fluctuate over time, and it is difficult to treat.

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We do not know the cause of MS-associated fatigue, although we have seen similar fatigue in patients with other autoimmune diseases. It is important to distinguish it from sleepiness, but sometimes it is difficult to determine which (ie, fatigue or sleepiness) is the problem. We may have to address sleep hygiene and fatigue to eliminate sleepiness as a potential cause of the fatigue. Finally, depression also needs to be excluded as a cause of fatigue, and this may involve a psychiatric referral.

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One strategy to help with fatigue is graded exercise therapy. Although it may sound counterintuitive, exercise can help increase energy as long as it is not done to exhaustion. Another helpful tool is energy budgeting, where people do the things that are most important earlier in the day, when they have the most energy.

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With respect to medication-related treatment strategies for fatigue, agents such as amantadine, modafinil, and methylphenidate have been used off-label for this indication, although the data on their use are not particularly strong. However, because the treatment of fatigue is symptomatic, you can try any of these agents and see if they help improve the patient’s fatigue. They may work in an individual patient even if they did not work in a clinical trial. If one medication does not work, you can stop it and try another. One of the potential side effects of these agents is insomnia, so they should be taken earlier in the day, and you should confirm with the patient that they are not interfering with their sleep. Right now, it is hard to say if any of the disease-modifying therapies for MS have any impact on patient fatigue because more data from high-quality studies are needed.