Narcolepsy is not rare, but it is an underrecognized and underdiagnosed condition. According to current estimates, the disorder affects about one in every 2,000 Americans-a total of more than 135,000 individuals. After obstructive sleep apnea and restless legs syndrome,* narcolepsy is the third most frequently diagnosed primary sleep disorder found in patients seeking treatment at sleep clinics. But the exact prevalence rate remains uncertain, and the disorder may affect a larger segment of the population than currently estimated.

Narcolepsy appears throughout the world in every racial and ethnic group, affecting males and females equally. But prevalence rates vary among populations. Compared to the U.S. population, for example, the prevalence rate is substantially lower in Israel (about one per 500,000) and considerably higher in Japan (about one per 600).

Most cases of narcolepsy are sporadic-that is, the disorder occurs independently in individuals without strong evidence of being inherited. But familial clusters are known to occur. Up to 10 percent of patients diagnosed with narcolepsy with cataplexy report having a close relative with the same symptoms. Genetic factors alone are not sufficient to cause narcolepsy. Other factors-such as infection, immune-system dysfunction, trauma, hormonal changes, stress-may also be present before the disease develops. Thus, while close relatives of people with narcolepsy have a statistically higher risk of developing the disorder than do members of the general population, that risk remains low in comparison to diseases that are purely genetic in origin.

* Obstructive sleep apnea is a temporary cessation of breathing that occurs repeatedly during sleep and is caused by a narrowing of the airway. Restless legs syndrome is a neurological disorder characterized by unpleasant sensations-burning, creeping, tugging-in the legs and an uncontrollable urge to move when at rest

Narcolepsy is not definitively diagnosed in most patients until 10 to 15 years after the first symptoms appear. This unusually long lag-time is due to several factors, including the disorder's subtle onset and the variability of symptoms. As important, however, is the fact that the public is largely unfamiliar with the disorder, as are many health professionals. When symptoms initially develop, people often do not recognize that they are experiencing the onset of a distinct neurological disorder and thus fail to seek medical treatment.

A clinical examination and exhaustive medical history are essential for diagnosis and treatment. However, none of the major symptoms is exclusive to narcolepsy. EDS-the most common of all narcoleptic symptoms-can result from a wide range of medical conditions, including other sleep disorders such as sleep apnea, various viral or bacterial infections, mood disorders such as depression, and painful chronic illnesses such as congestive heart failure and rheumatoid arthritis that disrupt normal sleep patterns. Various medications can also lead to EDS, as can consumption of caffeine, alcohol, and nicotine. Finally, sleep deprivation has become one of the most common causes of EDS among Americans.

This lack of specificity greatly increases the difficulty of arriving at an accurate diagnosis based on a consideration of symptoms alone. Thus, a battery of specialized tests, which can be performed in a sleep disorders clinic, is usually required before a diagnosis can be established.

Two tests in particular are considered essential in confirming a diagnosis of narcolepsy: the polysomnogram (PSG) and the multiple sleep latency test (MSLT). The PSG is an overnight test that takes continuous multiple measurements while a patient is asleep to document abnormalities in the sleep cycle. It records heart and respiratory rates, electrical activity in the brain through electroencephalography (EEG), and nerve activity in muscles through electromyography (EMG). A PSG can help reveal whether REM sleep occurs at abnormal times in the sleep cycle and can eliminate the possibility that an individual's symptoms result from another condition.

The MSLT is performed during the day to measure a person's tendency to fall asleep and to determine whether isolated elements of REM sleep intrude at inappropriate times during the waking hours. As part of the test, an individual is asked to take four or five short naps usually scheduled 2 hours apart over the course of a day. As the name suggests, the sleep latency test measures the amount of time it takes for a person to fall asleep. Because sleep latency periods are normally 10 minutes or longer, a latency period of 5 minutes or less is considered suggestive of narcolepsy. The MSLT also measures heart and respiratory rates, records nerve activity in muscles, and pinpoints the occurrence of abnormally timed REM episodes through EEG recordings. If a person enters REM sleep either at the beginning or within a few minutes of sleep onset during at least two of the scheduled naps, this is also considered a positive indication of narcolepsy.

Narcolepsy cannot yet be cured. But EDS and cataplexy, the most disabling symptoms of the disorder, can be controlled in most patients with drug treatment. Often the treatment regimen is modified as symptoms change.

For decades, doctors have used central nervous system stimulants-amphetamines such as methylphenidate, dextroamphetamine, methamphetamine, and pemoline-to alleviate EDS and reduce the incidence of sleep attacks. For most patients these medications are generally quite effective at reducing daytime drowsiness and improving levels of alertness. However, they are associated with a wide array of undesirable side effects so their use must be carefully monitored. Common side effects include irritability and nervousness, shakiness, disturbances in heart rhythm, stomach upset, nighttime sleep disruption, and anorexia. Patients may also develop tolerance with long-term use, leading to the need for increased dosages to maintain effectiveness. In addition, doctors should be careful when prescribing these drugs and patients should be careful using them because the potential for abuse is high with any amphetamine.

In 1999, the FDA approved a new non-amphetamine wake-promoting drug called modafinil for the treatment of EDS. In clinical trials, modafinil proved to be effective in alleviating EDS while producing fewer, less serious side effects that do ampehtmines. Headache is the most commonly reported adverse effect. Long-term use of modafinil does not appear to lead to tolerance.

Two classes of antidepressant drugs have proved effective in controlling cataplexy in many patients: tricyclics (including imipramine, desipramine, clomipramine, and protriptyline) and selective serotonin reuptake inhibitors (including fluoxetine and sertraline). In general, antidepressants produce fewer adverse effects than do amphetamines. But troublesome side effects still occur in some patients, including impotence, high blood pressure, and heart rhythm irregularities.

On July 17, 2002, the FDA approved Xyrem (sodium oxybate or gamma hydroxybutyrate, also known as GHB) for treating people with narcolepsy who experience episodes of cataplexy.  Due to safety concerns associated with the use of this drug, the distribution of Xyrem is tightly restricted.