• Treatment

    Lifestyle treatment of narcolepsy includes taking three or more scheduled sleep-times/naps throughout the day. Patients should also avoid heavy meals and alcohol, which can interfere with sleep.

    People with mild narcolepsy symptoms who do not need medication may be able to maintain alertness with sleep scheduling. The role of scheduled naps for patients who are responding to medications for narcolepsy remains unclear.

    Medications for narcolepsy target the major symptoms of sleepiness and cataplexy. Stimulant drugs are used to manage excessive daytime sleepiness while antidepressants and other compounds address cataplectic symptoms. The FDA has approved three drugs specifically for the treatment of narcolepsy. They are now the first-line treatments:

    • Modafinil (Provigil): For excessive, uncontrollable, daytime sleepiness
    • Armodafinil (Nuvigil)
    • Sodium oxybate (Xyrem): For cataplexy and excessive daytime sleepiness

    Drug Treatments for Sleepiness

    Modafinil. Modafinil (Provigil) is a drug used to treat the excessive sleepiness associated with narcolepsy and other sleep disorders. It has largely replaced methylphenidate (Ritalin) and other stimulants for treatment of narcolepsy sleepiness. Patients who switch to modafinil from stimulants such as methylphenidate have few problems if they gradually taper off the stimulant dose.

    Modafinil helps patients with narcolepsy stay awake during the day. While only some experience normal wake times, patients taking modafinil often have up to a 50% improvement in the ability to stay awake, as well as a 25% reduction in the number of involuntary sleep episodes. It has not been proven to be safe in pregnant women. Pregnant women or those wishing to get pregnant should discuss the risks and benefits of this medication with their doctors.

    Some of modafinil's 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 suggest 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.
    • It does not cause a rebound effect as stimulants do. In other words, people who take modafinil do not usually "crash" when the drug wears off.
    • It has less potential for abuse than stimulant drugs. However, modafinil can still be habit-forming. Patients may need to gradually lower the dose before stopping treatment.

    Side effects of modafinil may include:

    • Headache (the most commonly reported side effect)
    • Nausea
    • Diarrhea
    • Dry mouth
    • Nasal and throat congestion
    • Nervousness and anxiety
    • Dizziness
    • Back pain
    • Difficulty sleeping
    • Decreases in the effects of hormonal methods of birth control, including the pill. (Women of childbearing age who take modafinil should switch to another form of birth control.)
    • Modafinil is approved only for adults and should not be given to children.

    Armodafinil (Nuvigil) is a newer drug, which is nearly identical to modafinil. In clinical trials comparing it with placebo, armodafinil improved wakefulness, memory, attention, and fatigue in patients with narcolepsy.

    Drug Warning

    In October 2007, the FDA added new safety information to the prescribing label of modafinil (Provigil) and armodafinil (Nuvigil). The new information warns that:

    • Rare but serious skin reactions, such as Stevens-Johnson Syndrome, have been reported with modafinil and armodafinil use. Patients should stop taking modafinil at the first signs of any rash, and immediately contact their doctors.
    • Psychiatric side effects, such as anxiety, mania, hallucinations, and suicidal thinking, have been reported. Doctors should be cautious about prescribing modafinil and armodafinil to patients with a history of psychosis, depression, or mania.

    Stimulants. Medications that act as stimulants are standard treatments for narcolepsy. They include:

    • Methylphenidate (Ritalin)
    • Dextroamphetamine (Dexedrine)
    • Methamphetamine (Desoxyn)

    Methylphenidate and dextroamphetamine last for 2 - 5 hours and used to be the standard drugs for excessive daytime sleepiness. These drugs 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. However, the evidence to support their benefit for patients with narcolepsy is not a strong as with modafinil.

    Stimulants can have unpleasant side effects, including:

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

    People with heart disease, hyperthyroidism, glaucoma, anxiety disorder, and high blood pressure should avoid stimulants, or take them only with a doctor's supervision.

    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.

    Drug Treatments for Cataplexy

    Sodium oxybate (Xyrem). Sodium oxybate (Xyrem), also referred to as gamma hydroxybutyrate (GHB), helps reduce the frequency of cataplexy attacks and improve daytime sleepiness. Patients need to take GHB for about 4 weeks before they notice significant benefits. It may take an additional 4 weeks for the drug to reach maximum effect. Food intake can affect the actions of GHB, so patients are advised to take it at a regular time after the evening meal.

    The FDA has placed tight restrictions on the use of this drug. Although the drug appears to be effective and safe when used for narcolepsy, it has a history of illegal and "date-rape" use, with street names such as "Grievous Bodily Harm" or "Liquid Ecstasy." (The last term is not the same as "Ecstasy," another street drug with different effects.) In high doses, it can cause dependence over time. Education through the Xyrem Success Program may be valuable to patients and physicians.

    Very serious side effects -- including seizures, coma, respiratory arrest, and death -- have been reported in people who abused GHB. Trials of Xyrem, however, have not reported these effects with the doses used in treatment for cataplexy.

    Antidepressants. Antidepressant drugs are not approved for treatment of cataplexy, but they are commonly used to manage this condition. Unfortunately, there have been few studies conducted on antidepressant treatment of cataplexy, and there are little data on which type of antidepressant work bests. A 2008 review of antidepressants for narcolepsy noted the lack of good quality evidence to support their use and urged for more clinical trials.

    Antidepressants used for cataplexy, hallucinations, sleep paralysis, and management of REM symptoms include:

    • Tricyclic antidepressants: Protriptyline (Vivactil), clomipramine (Anafranil), imipramine (Janimine, Tofranil), and desipramine (Norpramin, Pertofrane)
    • Selective serotonin reuptake inhibitors (SSRIs): Fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft)
    • Newer antidepressants: Venlafaxine (Effexor)

    Tricyclics were the first antidepressants used for cataplexy; they were also one of the first treatments for cataplexy. They can be helpful for some patients but have many unpleasant side effects, including dry mouth, constipation, and weight gain. Tricyclics can also lower blood pressure and cause disturbances in heart rhythm.

    SSRIs have fewer side effects than tricyclics but may not work as well for cataplexy control. The most common side effects include nausea, drowsiness or insomnia, headache, weight gain, and sexual dysfunction.

    Venlafaxine (Effexor) is a selective serotonin and norepinephrine reuptake inhibitor (SSNRI) that has shown promising results for treatment of cataplexy. Some patients with narcolepsy, and their doctors, report that venlafaxine seems to work best of all the antidepressants.

    Monoamine Oxidase Inhibitors (MAOIs). Selegiline (Eldepryl, Movergan), also known as deprenyl, is an MAOI that blocks monoamine oxidase B, an enzyme that degrades dopamine. MAOIs may play a role in narcolepsy, but how much benefit this group of drugs provides is not well proven.

    Selegiline has significant side effects:

    • It interacts with nearly every antidepressant. Patients suffering from depression should discuss all treatment options with their doctor.
    • 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.

    [For more information, see In-Depth Reports #8: Depression and #51: Parkinson's disease for more complete discussion of MAOIs.]