Power surge?

Real Living with Multiple Sclerosis, Jun 2000 by Hinson-Smith, Vicki

Provigil may reduce MS fatigue.

Persons experiencing fatigue associated with multiple sclerosis (MS) may benefit from a relatively new drug originally prescribed to promote wakefulness and treat the excessive daytime sleepiness of narcolepsy.

Data from a 72-patient, placebo-controlled MS fatigue study showed that 200 mg daily of Provigil (modafinil) reduced fatigue in persons with the disease, when measured by several validated fatigue rating scales. About 80% of the 250,000 to 350,000 people with MS in the United States experience fatigue. Cephalon Inc., the pharmaceutical company that makes Provigil, plans additional MS fatigue studies later this year.

Paul Glovinsky, PhD, clinical director of the Capitol Region SleepWake Disorders Center in Albany, N.Y., wasn't really surprised by the news about Provigil. "Instead of a polysomnographic test for sleep, it was a test for fatigue subjectively rated," he explained. And he said Provigil helped the latter. Dr. Glovinsky, who has patients with MS, said, "In the United States, we knew modafinil was coming, but it was a long wait-a couple of years-while in Europe, there were all these good reports." He said Provigil would be welcomed here because of its favorable side effect profile.

"With a good [side effect] profile," said Dr. Glovinsky, "we can begin to think about where else we can reasonably use medications-this is what motivated the research, not only with MS fatigue, but in other conditions where fatigue is a factor." He said that, with all the "pitfalls" of traditional stimulants, the benefits do not always outweigh the drawbacks. Due to reports of liver failure associated with the use of Cylert (pemoline), for example, an agent sometimes used to treat fatigue in persons with MS, a warning was issued by the U.S. Food and Drug Administration last year recommending liver function tests every 2 weeks. The National Multiple Sclerosis Society recommends a baseline test when Cylert is first begun, then "periodically" thereafter.

"Fatigue is [a major] pathway for many [health] problems such as MS," said Dr. Glovinsky. "Anything like this that causes an intrusion of electroencephalogram activity into a person's sleep-one that actually belongs in wakefulness-will cause fatigue during the day." He called fatigue "a place to intervene with a drug like modafinil. When someone has a chronic condition such as MS, there is a breakdown of the circadian sleep-wake cycle." When that happens, he said, alertness is "not as alert," and sleepiness is "not as sleepy." When either is improved, he said, the amplitude of that circadian cycle is rebuilt over the course of a few weeks.

Provigil is the first nonaddicting drug available for people with narcolepsy. A study published in Neurology (2000; 54:1166-1175), the American Academy of Neurology's scientific journal, verified that Provigil does not create dependency or lingering withdrawal symptoms. Previous treatments for both narcolepsy and MSassociated fatigue usually involved the use of amphetamines and amphetamine-like stimulant drugs, which can cause high blood pressure, altered heart rhythms, liver toxicity, and anxiety, and could lead to drug dependency and serious withdrawal symptoms when discontinued.

Provigil was approved by the FDA in late 1998, and its off-label use to treat MS fatigue was first reported in January 2000. It is generally well tolerated and has a low incidence of side effects, which might include nervousness, nausea, dry mouth, headache, and diarrhea.

Dr. Glovinsky advises persons with MS to "make every decision in conjunction with one's doctor." Before beginning Provigil treatment, patients should talk with their health care providers about any other drugs they are taking, even over-the-counter, "because the potential for interaction is there." Provigil may reduce the effectiveness of some contraceptive drugs, and women who are attempting to prevent pregnancy might ask their health care providers to change the dose of their birth control pills or recommend another method of contraception.

"This drug can make a huge difference in quality of life," Dr. Glovinsky concluded. "It is a choice that definitely should be considered."

Advisory Board note: While the preliminary report from the company is certainly encouraging, we await more definitive presentation of the results at a scientific meeting or publication in a peer-reviewed journal. It is likely that a larger study will be needed to confirm the positive results.

Vicki Hinson-Smith is a writer and editor who lives and works in Massachusetts and New York, where she specializes in biomedical communications. She has MS.