March 13, 2000 (New York) -- A new drug, modafinil, helps people who suffer from narcolepsy feel less sleepy and stay awake longer. The drug appears to avoid some of the pitfalls associated with the use of stimulants, like amphetamines, which are the traditional medications used to treat the condition, according to a report in the March issue of the journal Neurology.
"Narcolepsy is an important condition that affects one in 2,000 people," study co-author Paul T. Gross, MD, tells WebMD. "It's an underdiagnosed condition because the main symptom is sleepiness and everybody gets sleepy at times. But there are people who have significant pathological sleepiness that is over and above what the average person would expect, and it interferes with their daily lives."
In addition to abnormal sleepiness, narcolepsy is characterized by sudden attacks in which people are unable to move their bodies and therefore fall down, attacks of paralysis while they are trying to sleep, and hallucinations.
The study was conducted at 21 centers across the U.S. Patients had been previously diagnosed with narcolepsy and most were considered moderately to severely ill by their physicians. Participants were randomly assigned to receive modafinil 200 mg per day, modafinil 400 mg per day, or a placebo (sugar pill) for nine weeks. Neither the investigators nor the patients knew which medication the patient was taking.
During treatment with modafinil, patients tended to be more able to stay awake and less likely to fall asleep than with placebo. Patients also said they felt significantly less sleepy after nine weeks of modafinil treatment.
About 60% of the patients were rated on one test by their doctors as significantly improved with modafinil at both the 200 mg dose and the 400 mg dose compared with those who received a placebo. Nearly 40% of the patients in the placebo group were rated as significantly improved. Modafinil also appeared to be well tolerated and safe.
Laboratory measurements indicated that modafinil did not disturb nighttime sleep. Most side effects were mild to moderate in severity, and the most frequent side effects were headache and nausea. However, modafinil may enhance the metabolism of oral contraceptives if taken at the same time. This might require an increase in the dosage of the oral contraceptive for it to remain effective.
"We now have an effective medication [for narcolepsy] with few side effects that's easy to prescribe and that's easy for the patients because they don't have to keep getting new prescriptions often," Gross says. Patients taking stimulants, such as amphetamines, to treat narcolepsy have to get new prescriptions filled frequently because this class of drugs is more tightly controlled by law and physicians can only prescribe a limited amount at a time.
After nine weeks of treatment, the drug was stopped for 80% of the patients to see how stopping the medication would affect them -- if it would affect them.
During the two weeks following drug discontinuation, patients complained of feeling more sleepy, but no signs of amphetamine withdrawal syndrome -- such as sadness, fatigue, vivid unpleasant dreams, sleep changes, and increased appetite -- were apparent. This suggests that the treated patients had not become dependent on the drug.
"This is a very important addition to our [arsenal] for narcolepsy," says Gross, who is director of the sleep disorders center at the Lahey Clinic in Burlington, Mass., and was the lead investigator of the U.S. Modafinil in Narcolepsy Multicenter Group.
"This study demonstrates that modafinil is very efficient for most patients with narcolepsy without any noticeable side effects," says Seiji Nishino, MD, PhD, who reviewed the study for WebMD. "Because it's easy to use, we should see good compliance, especially because it produces few side effects. I think it will make a big difference [in the treatment of people with narcolepsy]." Nishino is associate director of the Center for Narcolepsy at Stanford University.
Gross says it is important to realize that although modafinil improved alertness in a profoundly sleepy population, it did not completely resolve all symptoms of excessive daytime sedation. He also warns that improvements in sleepiness may not occur until about three hours after taking the medication.
Nishino is quick to point out that traditional treatments may still be useful for narcolepsy, "[So] if modafinil doesn't work, we can still use the classical stimulants."
This study was funded by a grant from Cephalon Inc., the manufacturer of modafinil.
- Narcolepsy is an underdiagnosed condition that affects one out of 2,000 people and is characterized by excessive daytime sleepiness, sudden attacks in which sufferers are unable to move their bodies and therefore fall down, attacks of paralysis while trying to sleep, and hallucinations.
- Researchers have found that the drug modafinil can help narcolepsy patients be less sleepy and stay awake longer with fewer negative side effects.
- Currently, stimulants such as amphetamines are used to treat narcolepsy, but these are difficult to prescribe because of legal restrictions on the drugs.