Narcolepsy

Description

Treatment

Nonmedical treatment of narcolepsy includes taking three or more scheduled sleep-times throughout the day. One study suggested that the optimal sleep pattern is a combination of scheduled nighttime sleep (e.g., from 11:00 to 7:30) and two 15-minute naps (for example one before lunch and another before dinner). Patients should also avoid heavy meals and alcohol, which can interfere with sleep.

People with mild narcolepsy symptoms that do not require medication may be able to maintain alertness with sleep scheduling. In one 2001 study, scheduled sleep periods were also helpful for patients who were extremely sleepy in spite of medications. The benefits of scheduled naps, however, are not clear for patients whose condition responds to medication. In the same study, patients who took stimulants and were able to maintain alertness or were only moderately sleepy derived no additional benefit from the naps.

Stimulants

Brands. Medications that act as stimulants are standard treatments for narcolepsy. The include the following:

• Methylphenidate (Ritalin).
• Dextroamphetamine (Dexedrine).
• Pemoline (Cylert).

Methylphenidate and dextroamphetamine last for two to five hours and are the standard agents for excessive daytime sleepiness. Pemoline is effective for eight to 10 hours. These agents are useful for people who can manage wakefulness with a night's sleep and scheduled naps. They can improve mood, mental acuity, and other aspects of mental functioning.

Side Effects. Stimulants can have significant side effects, including the following:

• Weight loss.
• Dizziness.
• Nausea.
• Changes in blood pressure and rapid heartbeat.
• Headache.

There are some differences between these agents:

• Methylphenidate, which is the standard agent for treating attention deficit hyperactivity disorder, is safer than dextroamphetamine. Small studies suggest that high doses may help avert catalepsy, although more research is needed to confirm this effect. Psychosis from overdose is very rare. Psychologic dependence can occur, but abuse has not been reported in children who have taken it for years.
• Dextroamphetamine has more severe effects than methylphenidate, which can include mood changes and jerky muscle movements. Prolonged use may cause serious depression. Overdose, which can occur at doses of only 100 to 500 mg, can cause psychosis and even death. This drug should not be used during pregnancy. There is also a risk for addiction and abuse.

Stimulants should be avoided or taken only under a physician's guidance in people with heart disease, hyperthyroidism, glaucoma, anxiety disorder, and high blood pressure.

Drug Holidays. These drugs become ineffective if used continuously, and patients are advised to take a drug holiday one day a week or to withdraw gradually and resume treatment at a lower dose. Patients should not engage in activities that require being awake, such as driving, during withdrawal.

Modafinil

Modafinil (Provigil, Alertec) is a novel drug that promotes long-lasting wakefulness. It is now approved for narcolepsy. Before treatment, patients in one study were able to stay awake only an average of six minutes out of twenty. After taking the medication, awake time increased to 12 to 14 minutes and some patients had normal wake times. In another study, modafinil increased the ability to stay awake by 50% and reduced the number of involuntary sleep episodes by about 25%.

Some of its additional benefits include what it does not do:

• Modafinil does not appear to affect natural hormones important in sleep, including cortisol (the major stress hormone), melatonin, and growth hormone. Therefore, studies are reporting that it does not interfere with voluntary naps during the day or with the quantity or quality of nighttime sleep.
• It does not cause anxiety to the degree that the standard stimulants do.
• Patients do not appear to have a rebound effect as stimulants do. In other words, people who take do not usually "crash" when the drug wears off.
• It has less potential for abuse than the stimulants. In one trial, no one developed dependence on the drug after up to nine weeks of daily use.

Modafinil does not appear to reduce cataplexy. Some evidence suggests that taking it along with Ritalin may help prevent cataplexy attacks and does not appear to have any harmful interactions. It should be noted, however, that long-term safety and effectiveness of modafinil is not yet known. In one study, modafinil appeared safe for at least 16 weeks of use, but longer studies are needed. Although most current research suggests that modafinil poses less of a risk for abuse than many of the stimulants used for narcolepsy, some evidence suggests that it might have stimulant properties that could lead to abuse.

Side Effects. Side effects include the following:

• Headache (the most commonly reported side effect).
• Nausea.
• Diarrhea.
• Dry mouth.
• Nasal and throat congestion.
• Nervousness.
• Dizziness.
• Possible interference with hormonal methods of birth control, including the Pill. (Women of childbearing age who take modafinil should switch to another form of birth control.)

Patients who switch to modafinil from stimulants, such as methylphenidate (Ritalin), experience few problems if they taper the stimulant dose gradually.

Gamma-Hydroxybutyrate (GHB)

Gamma hydroxybutyrate (Xyrem), also referred to as sodium oxybate or GHB, is proving to reduce the frequency of cataplexy attacks and to improve daytime sleepiness. It takes about four weeks for significant benefits, which reach their peak at about eight weeks. Food intake can affect its activity, so patients are advised to take it at a regular time after the evening meal. Xyrem has been approved by the FDA for narcolepsy, but with tight restrictions on its use. Although the drug appears to be effective and safe when used for narcolepsy, it has a history of illegal use, with street names such as "Grievous Bodily Harm" or "Liquid Ecstasy." (The last term is not to be confused with "Ecstasy," another street drug with different effects.) In high doses, it can cause dependence in over time. In addition very serious side effects, including seizures, coma, respiratory arrest, and death have been reported in people who abused it. Trials of Xyrem, however, have not reported these effects with the doses used in treatment for cataplexy. Patients still report side effects, although they tend to be mild. They include nausea, headache, dizziness, urine leakage, and sleepwalking.

Monoamine Oxidase Inhibitors (Selegiline)

Selegiline (Eldepryl, Movergan), also known as deprenyl, is an antioxidant drug that blocks monoamine oxidase B, an enzyme that degrades dopamine and may play a role in narcolepsy.

Adverse Effects. Selegiline has side effects that are important:

• It has adverse interactions with nearly every antidepressant, some very serious. Patients suffering from depression should discuss all treatment options with their physician.
• People taking any monoamine oxidase inhibitor are at risk for high blood pressure if they consume tyramine-containing foods or beverages, including aged cheeses, most red wines, vermouth, dried meats and fish, canned figs, fava beans, and concentrated yeast products.

Antidepressants

Antidepressants have been very useful in controlling symptoms of narcolepsy, particularly cataplexy.

Tricyclic Antidepressants. The tricyclic antidepressants protriptyline (Vivactil), clomipramine (Anafranil), imipramine (Janimine, Tofranil), and viloxazine appear to suppress REM sleep and may be added to the stimulant regimen in severe cases. These antidepressants do not cause sedation and are useful in managing cataplexy, sleep paralysis, and hypnagogic hallucinations (the hallucinations that occur between sleep and wakefulness). Side effects are fairly common with these medications and many people cannot tolerate them. The most often reported include the following:

• Dry mouth.
• Constipation.
• Blurred vision.
• Sexual dysfunction.
• Weight gain.
• Difficulty in urinating.
• Drowsiness.
• Dizziness. Blood pressure may drop suddenly when sitting up or standing.

Tricyclics can have serious, although rare, side effects.

• They tend to cause disturbances in heart rhythm, which can pose a danger for some patients with certain heart diseases. One study comparing nortriptyline with paroxetine, an SSRI, reported nine times more adverse cardiac events with the use of the tricyclic than with the SSRI.
• Also of concern is a study reporting that tricyclics, particularly imipramine, may be responsible for 10% of cases of a lung disease called idiopathic pulmonary fibrosis (IPF), which can cause lung inflammation and scarring. Initial symptoms are breathlessness and dry cough. The two newer tricyclics, mianserin and dothiepin, also increased the risk.
• They can cause fatal overdose.
• Abrupt withdrawal, notably from clomipramine, has caused severe and prolonged cataplexy in some cases.

Selective Serotonin Reuptake Inhibitors (SSRI). Selective serotonin reuptake inhibitors (SSRIs) may also be helpful in combination with stimulants. For example, fluoxetine (Prozac), the standard SSRI, and citalopram (Celexa), another SSRI, have been reported to be effective in treating cataplexy that does not respond to standard treatments. Side effects include the following:

• Nausea and gastrointestinal problems. These effects usually wear off over time.
• Agitation, insomnia, mild tremor, and impulsivity occur in 10% and 20% of people who take SSRIs, these symptoms may be particularly problematic in patients who also suffer from anxiety, sleeplessness, or both. Such side effects may persist. On the other hand, about 20% of SSRI-treated patients experience drowsiness, which may be counteracted by taking the medication at bedtime.
• Dry mouth is common and can increase the risk for cavities and mouth sores.
• Headache.
• Some weight loss during the first few weeks of treatment may occur, but over time patients on maintenance treatment typically return to their pretreatment weight.
• Sexual dysfunction, including delayed or loss of orgasm and low sexual drive, occurs in 30% to 40% of patients on SSRIs and accounts for a substantial amount of noncompliance. (Citalopram may pose a lower risk for this side effect than other SSRIs.)

Designer Antidepressants. Reboxetine (Edronax) is a unique antidepressant, known as a selective noradrenaline reuptake inhibitor. A 2001 study reported that it reduced sleepiness and increased the time it took to fall asleep by about 50%.