Questions and Answers: What is modafinil?

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Questions and Answers: What is modafinil?

Questions & Answers

Q. What is modafinil?

A. Modafinil (Provigil) is a unique stimulant that promotes wakefulness. Compared with other stimulants, it has a low potential for abuse, addiction, and physical dependence. It also has few serious side effects — little more than occasional headache, nausea, or nervousness.

Modafinil was first approved by the FDA in 1998 as a treatment for narcolepsy, a rare disorder that causes sudden attacks of daytime sleepiness. It has also been approved for the treatment of sleepiness resulting from night work and shifting sleep schedules or from sleep apnea, a common disorder of nighttime breathing. Doctors are also looking into possible uses of the drug for many other purposes. These include attention deficit disorder, chronic fatigue syndrome, jet lag, and the fatigue caused by chronic illnesses like multiple sclerosis, Parkinson’s disease, and myasthenia gravis. Modafinil is also sometimes added to antidepressants in the treatment of depression and used to counteract the drowsiness caused by some psychiatric drugs.

When modafinil is used for narcolepsy and sleep apnea, the patient takes a single 200-mg dose in the morning. For treatment of attention deficit disorder, the dose is 100 to 300 mg per day. Older people and those with liver conditions usually need lower doses. Modafinil may lower blood levels of oral contraceptives, and it could be risky for anyone with a history of heart disease or psychosis. Pregnant women should avoid modafinil, because we don’t know enough about its effects on the fetus.

Drowsiness is a common problem, and many of us would like something other than coffee to keep us alert. So modafinil, not surprisingly, has become a highly popular drug. It’s expensive — about $5 for a typical dose (not much more than a latte and fewer calories). Nevertheless, prescription sales have reached more than $200 million annually, and an estimated 90% of the drug is being used for purposes that are not FDA-approved. Some worry about the so-called Viagra effect, fearing that modafinil will become a lifestyle drug for people who want a performance edge or more waking hours to work or play. Banned by the United States Olympic Committee, modafinil featured in the 2004 downfall of Kelli White, a champion sprinter.

Neuroscientists don’t know how modafinil works, but they do know that it doesn’t act like other stimulants such as methylphenidate (Ritalin) and amphetamines. Those older and better known medications work through the brain’s reward pathways, releasing the neurotransmitters dopamine and norepinephrine. These drugs can cause euphoria and addiction—though usually not at therapeutic doses. Modafinil may work in some of the same pathways, but either its effect is weaker or its action is more specific, affecting circuits for wakefulness but not those that promote addiction. Some believe that modafinil prevents sleep by acting in the hypothalamus, a structure deep in the brain that monitors body temperature, hunger, thirst, and other physical functions.

Although modafinil may not be more dangerous or addictive than coffee, some researchers question whether it is any better at promoting wakefulness. In one study conducted at the Walter Reed Army Institute of Research — the military is interested in substances that enhance alertness — modafinil and caffeine were found to be equally effective. However, some patients report that modafinil works very well and without caffeine’s uncomfortable stimulating effects.

Should people without an illness that causes fatigue or sleep problems be using modafinil? It may be justified, for example, when they need to be alert the day after a sleepless night flight and a time zone change. But sleep is restorative. It seems to be important for learning and memory, and skimping on it could raise the risk of illness and shorten life. It is probably not a good idea for a healthy person to use modafinil all the time just to reduce the need for sleep.

No doubt, questions will continue to swirl around this promising drug while experts work out guidelines for its use.

— Michael Craig Miller, M.D. Editor in Chief

Last updated:	August 21, 2006