Summary: A small study tested the ability of oral modafinil (Provigil) to fight fatigue, a common and potentially disabling symptom of MS:

• 72 people with different forms of MS took two different doses of modafinil and inactive placebo over nine weeks and self-evaluated their own fatigue levels using standard fatigue and sleepiness scales.
• Participants reported feeling least fatigued while taking a lower dose of modafinil, and there was a statistically significant difference in fatigue scores for the lower dose versus placebo.
• Modafinil is currently FDA-approved for the treatment of narcolepsy. It is not clear whether its manufacturer, Cephalon, will use results of this or additional studies to request that the FDA expand the drug's labeling to include the treatment of fatigue in MS.

Details: Fatigue is a common and potentially disabling symptom of MS. A small study led by Kottil Rammohan, MD (Ohio State University; sponsored by Cephalon Inc., West Chester, PA) involving 72 individuals with significant self-reported fatigue and with different forms of multiple sclerosis tested the ability of two different oral doses of modafinil (Provigil) in comparison with inactive placebo to fight fatigue. Modafinil is approved by the U.S. FDA to treat narcolepsy, a disorder that causes excessive daytime sleepiness.

Study Design: All participants received placebo for two weeks, then the lower dose (200 mg/day) of modafinil for two weeks, then the higher dose (400 mg/day) of modafinil for two weeks, then placebo for three final weeks. The participants were not told which type of tablets they were taking during the course of the study. Participants evaluated their own fatigue levels during different phases of the trial using three different self-reporting fatigue scales and one scale that self-reported "sleepiness."

Results: Participants reported feeling least fatigued while taking the lower dose of modafinil, and there was a statistically significant difference in fatigue scores for the lower dose versus placebo. Interestingly, there was no difference in fatigue scores for the higher dose versus placebo although both doses provided a similar degree of relief from self-reported sleepiness compared with placebo. Side effects included headache, weakness and nausea.

Conclusions: In this small study, the 64 patients who completed the study felt that the drug improved their fatigue. It is not clear how modafinil compares to other available medications that are often used to treat MS-related fatigue (such as amantidine or pemoline). Because the drug is FDA-approved for narcolepsy, doctors may prescribe modafinil "off label" for other disorders, including MS fatigue. It is not clear whether Cephalon will use results of this or additional studies to request that the FDA expand the drug's labeling to include the treatment of fatigue in MS.