Provigil® Among Recommendations in Treatment of MS Fatigue
A Working Group of neurologists has recommended the wake-promoting agent Provigil® (generic name: modafinil), as the first line of treatment for moderate to severe MS fatigue. Provigil was initially approved in the US in 1998 for the treatment of excessive daytime sleepiness and narcolepsy.
The neurologists presented their conclusions at a symposium of the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC) in June 2002. MS fatigue is reported by more than 95 percent of people with MS, and is considered to be the worst symptom in as much as 50 percent of individuals with MS.
The recommendation is based on a study examining the efficacy and safety of Provigil. Led by Kottil W. Rammohan, MD, of Ohio State University, and Jay H. Rosenberg, MD of Kaiser Permanente, the results of this nine-week, two-center, phase II study were recently reported in The Journal of Neurology, Neurosurgery, and Psychiatry (2002, vol. 72, pp. 179-183).
During the single-blinded study, all 72 individuals with MS were given a placebo, 200 mg/day of Provigil, or 400 mg/day of Provigil, in two-week increments. The data suggested that 200 mg/day of Provigil significantly improves MS fatigue and is well tolerated. The 400-mg/day dose did not differ in efficacy from the placebo in certain outcome measures. No drug interactions were observed with Provigil in conjunction with long-term immunologic therapies, and no serious adverse events occurred at either dose. Side effects were usually mild and included headache and sleeplessness in some patients. The Working Group recommended starting Provigil at a lower dose and increasing the dose to 200 mg/day.
Additionally, the Working Group found self-assessment scales to be the most efficient means of measuring MS fatigue, and also recommended amantadine (Symmetrel®) as a first-line treatment for mild MS fatigue (although this is shown to be effective in only 20 to 40 percent of patients). Pemoline (Cylert®) is no longer recommended as a first-line option due to safety concerns and limited effectiveness. Other agents, such as aminopyridines and SSRIs (selective serotonin reuptake inhibitors such as Prozac®), have yet to be approved for treating MS fatigue, although they may be useful for some individuals.
More studies are needed to determine the long-term safety and efficacy of Provigil. The FDA has yet to approve MS fatigue as an indication for prescribing Provigil, and more research into the cause of MS fatigue and its relationship to other MS symptoms is necessary. Fatigue therapies must be individualized, as responses to any therapy can vary from one person to another.
