The treatment of narcolepsy includes drug and behavioral therapies. Treatment options are individualized depending on the severity of the symptoms, life conditions (for example, type of work or responsibilities) of the patients, and the specific goals (for example, relief of certain symptoms) of therapy. Management of symptoms takes weeks to months to achieve and requires continued communication among the physician, patient, family members, and others. Good treatment management typically produces significant improvement of the symptoms rather than a resolution of all symptoms.
The types, number, and severity of the symptoms determine which drugs are used to treat the narcolepsy.
- Severe daytime sleepiness may require treatment with high doses of stimulant medication, and sometimes a combination of stimulants may be needed.
- Rare or infrequent cataplexy and other associated symptoms may not require any drug treatment, or treatment on an "as needed" regimen may be adequate.
- Insomnia and depression may also require treatment.
- Therapy should be catered to the individual needs of the patient. For example, improved alertness may be critical throughout the day for most students and working adults, but may be critical only at certain times of the day (for example, driving times) for other people.
Alerting medications are used for the treatment of excessive daytime sleepiness.
Amphetamines [for example, dextroamphetamine (Dexedrine), methamphetamine hydrochloride (Desoxyn), dextroamphetamine (Dextrostat), amphetamine and dextroamphetamine (Adderall)] and methylphenidate (Ritalin) are generalized central nervous system stimulants. These medications are used in narcolepsy to decrease sleepiness and improve alertness. However, they can also produce undesirable side effects including elevation of blood pressure, nervousness, irritability, and rarely, paranoid reactions. Alerting medications can also lead to drug dependency due to the feeling of euphoria they can cause. However, drug dependency has rarely been described in individuals with narcolepsy.
Pemoline (Cylert) is used as an alerting medication but it is less effective than traditional stimulants. This drug has the potential risk of toxic side effects on the liver and liver blood tests need to be monitored frequently.
Modafinil (Provigil), approved by the Food and Drug Administration (FDA) in 1999, has alerting effects similar to those of the traditional stimulant. Modafinil is not a general CNS stimulant like amphetamines, but the precise way it works is unknown. This drug has a much lower risk for high blood pressure and mental side effects because it acts in a different way than classic stimulants. It does not have significant effects on the sympathetic nervous system and does not cause mood changes, euphoria, or dependence. Furthermore, modafinil does not become ineffective with prolonged use. Headache and nausea are the most commonly reported side effects, and they are usually mild and temporary. These side effects can be reduced by a slow increase from a low initial dose up to the desired dose. This medication does not affect cataplexy and other REM sleep symptoms.
Modafinil is usually used in a single daily dose. Switching patients from amphetamines to modafinil may cause the reappearance of cataplexy in patients previously well controlled. Increasing the dose or adding an anti-cataplectic medication usually solves this problem.
Armodafinil (Nuvigil): Approved by the FDA in June 2007, is an oral drug used to promote wakefulness. It is similar to modafinil (Provigil).Armodafinil promotes wakefulness by stimulating the brain; however, the exact mechanism of action of armodafinil is unknown. Armodafinil may work by increasing the amount of dopamine (a chemical neurotransmitter that nerves use to communicate with each other) in the brain by reducing the reuptake of dopamine into nerves. The most common side effect of ararmodafinil is headache. Other side effects including anxiety, dizziness, diarrhea, dry mouth, insomnia, nausea, fatigue, and rash may occur.The drug is recommended for single daily dosing, either in the morning, or one hour prior to a work shift.
Monoamine oxidase inhibitors (MAOIs): A class of antidepressants called monoamine oxidase inhibitors (MAOIs) can also be used for treatment of excessive daytime sleepiness. This includes phenelzine (Nardil) and selegiline (Eldepryl).
Anticataplectic medication is the general name for drugs that are used to treat cataplexy. These drugs may also be used for the other REM related symptoms, such as hypnagogic hallucinations and sleep paralysis. Tricyclic antidepressants (TCAs), used in lower than antidepressant doses, are often effective in controlling cataplexy. These medications act on neurotransmitter systems to produce suppression of REM sleep and consequently improve the symptoms of cataplexy.
In some cases, the side effects may limit the use of TCAs, although in most cases the side effects are temporary. The most frequent side effects are called "anticholinergic side effects," including dry mouth, dry eyes, blurred vision, urine retention, constipation, impotence, increased appetite, drowsiness, nervousness, confusion, restlessness, and headache. Some of the TCAs may increase periodic limb movements in sleep, which could further disrupt already disturbed nighttime sleep in narcoleptic patients. If TCAs are abruptly discontinued, a significant worsening of the cataplexy and other REM related symptoms could occur. This "rebound phenomenon" may appear in 72 hours after discontinuation of the medication and peak in approximately 10 days from the withdrawal.
The most frequently used TCAs for the treatment of cataplexy and other REM related symptoms are protriptyline (Vivactil), imipramine (Tofranil), clomipramine (Anafranil), desipramine (Norpramine), and amitriptyline (Elavil). Sedating TCAs such as clomipramine, amitriptyline, and imipramine, are usually prescribed for evening use, whereas the alerting ones (protriptyline and desipramine) are recommended for use during the day.
Selective serotonin reuptake inhibitors (SSRIs) are also useful in treating cataplexy at doses that are comparable to those used to treat depression. The most frequently used SSRIs for treatment of cataplexy and REM related symptoms are fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa), and venlafaxine (Effexor). The SSRIs may not be as effective as the TCAs, but they have fewer side effects. The most frequently reported side effects are dizziness, lightheadedness, nausea, and mild tremor. Rarely, mild constipation or diarrhea may occur. Fluoxetine (Prozac) given late in the day may cause insomnia.
Sodium oxybate (Xyrem), also known as gamma-hydroxybutyrate or GHB, was approved by the FDA in 2002 to treat cataplexy, and in 2005 was also approved to treat excessive daytime sleepiness (EDS). This drug is usually administered in two doses; the first is given at bedtime and the second four hours later. It unifies sleep and improves the disturbed nighttime sleep characteristic of narcolepsy. This nighttime benefit may help decrease daytime drowsiness and cataplexy. Sodium oxybate is unrelated to drugs that are known to be sleep-inducing (hypnotic) and is not used for insomnia. It can cause drowsiness and should only be taken at night.
Non-drug treatments include education of the patient and family members and modification of behavior patterns. Understanding the symptoms of narcolepsy may help relieve some of the frustrations, fears, anger, depression, and resentment of patients and family members. Emotional reactions are responses to both the unusual nature of the symptoms and society's ignorance of this disease. National organizations and local narcolepsy support groups are additional sources of information and assistance. (See "For more information" below.)
Behavioral approaches include establishing a regular, structured sleep-wake schedule. Planned naps of 15 to 30 minutes or longer may be beneficial in reducing daytime sleepiness. Certain dietary restrictions should be observed (for example, avoidance of large meals and alcohol). Regular exercise and exposure to bright light can improve alertness. Occupational, marriage, and family counseling may help improve the patient's quality of life.
Special considerations may be needed for school schedules and working conditions. Occupations that require working in shifts, changing the work schedule, or driving should be avoided. The dangers of driving while sleepy and/or experiencing cataplexy need to be addressed and the patients should be advised to avoid driving with these symptoms. However, many patients with narcolepsy are able to drive for short distances at certain times of the day and after taking their stimulant medications. Reporting requirements to the Department of Motor Vehicles (DMV) differ from state to state. Some states require that individuals who have any lapses of consciousness or sleepiness be reported to the DMV.
What is the outcome (prognosis) for patients with narcolepsy?
Narcolepsy is a life-long disease. The symptoms may vary in severity during the patient's lifespan, but they never disappear completely. Symptoms usually gradually worsen over time, and then tend to become stable. Even then, the excessive daytime sleepiness may become more pronounced and require additional medication. At other times, cataplexy or the other symptoms may decrease or even disappear for a time.
Different factors contribute to changes in a patient's symptoms, including an irregular sleep/wake schedule, the use of substances or drugs that affect the central nervous system, infections of the brain, and the development of additional sleep disorders, such as sleep apnea syndrome (SAS), periodic limb movements in sleep syndrome (PLMS), or others. Regular doctor check-ups and adherence to the drug plan and behavioral treatment may diminish these fluctuations and improve the patient's symptoms and quality of life.
A primary care physician, usually in collaboration with a sleep medicine specialist, can recognize the symptoms of narcolepsy, initiate the proper evaluation, and manage the treatment that is recommended by the specialist.