Meds generally ineffective for MS fatigue

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Fatigue is considered to be the most common symptom of multiple sclerosis, reported by about 75% of people living with MS (Krupp L. Mult Scler 2006;12:367-368). MS fatigue is unlike garden-variety fatigue. The crushing lack of physical and mental energy can make it difficult to hold a job or do the usual chores and activities of daily life.

Why MS causes fatigue is not very well understood. Various theories have been floated – lesions in the brain, the immune system on overdrive – but no well-established cause has been determined. This does not mean that MS fatigue does not exist – the symptom is real. But it does mean that targeting fatigue with medications is difficult if the drug target is unknown.

Doctors often prescribe a variety of medications to ease MS fatigue. All are “off-label”, meaning that they have not been specifically approved as a treatment for fatigue (doctors can still prescribe them at their discretion). Among the most common are Alertec (modafinil), used to treated narcolepsy and obstructive sleep apnea; Ritalin (methylphenidate), used to treat attention deficit-hyperactivity disorder (ADHD); and Symmetrel, an antiviral drug used to treat the flu.

Unfortunately, a recent trial has found that none of these drugs provides much benefit for MS fatigue (Nourbakhsh and colleagues. Lancet Neurol 2021;20:38-48). In the TRIUMPHANT-MS study, 136 people with MS fatigue received Alertec, Ritalin, Symmetrel and placebo in various sequences. Each drug was taken for six weeks; after a two-week break, the next drug in the sequence was tried. Fatigue was calculated using a questionnaire called the Modified Fatigue Impact Scale (MFIS) (to see the questionnaire go to

At the end of the treatment sequence, the researchers found that people did no better taking one of the drugs compared with a placebo. No benefit was seen in various subgroups, such as people with relapsing-remitting or progressive MS, with or without depression, people with varying levels of disability or people taking or not taking a disease-modifying therapy (DMT) for their MS. The only positive finding was a slight improvement on psychosocial items with Ritalin. (The psychosocial items are two questions about a person’s motivation to participate in social activities, and ability to do things away from home.)

One problem with these medications is that they act as stimulants, which is helpful for people with excessive daytime sleepiness. However, MS fatigue is not the same as sleepiness. People may feel the need to rest but they do not necessarily feel the need to sleep. But an interesting finding was that in the subgroup of people who did have excessive daytime sleepiness, there was a small boost with Alertec and Ritalin, a benefit that was not seen in people without excessive sleepiness.

A second consideration is that these medications can cause serious side effects and are not advised for people with psychiatric symptoms such depression or anxiety.

Medications may be a help to some people but managing MS fatigue usually requires a range of strategies. A neurologist or MS nurse can offer some useful tips on managing fatigue. A doctor can also determine if there are other factors contributing to fatigue, such as another medical condition (e.g. anemia, a thyroid disorder, sleep disorder) or a psychological problem (e.g. anxiety or depression).

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