Narcolepsy Treatments and Medications

Shrouded in mystery and misconception, narcolepsy, affects up to 200,000 Americans. Although it is rare, all of us likely have met at least one person with narcolepsy without knowing it. Narcolepsy may seem distant and unimaginable, but it’s an everyday experience for some. The condition presents challenges, some quite significant, but people with narcolepsy learn to live with it.

What is narcolepsy?

Narcolepsy is a chronic, lifelong neurological condition that affects the ability of the brain to maintain continuous wakefulness and sleep. The symptoms of narcolepsy include daytime sleepiness, sudden muscle weakness, temporary paralysis, fragmented sleep, and hallucinations. At its core, narcolepsy brings on rapid eye movement (REM) sleep, or “dreaming,” considerably faster than people without narcolepsy.

Evidence suggests narcolepsy starts as an autoimmune condition, one that is most likely inherited. Some infections (such as the H1N1 flu) may trigger an immune response in children at a young age. For reasons we don’t understand, the immune system overreacts to the infection and attacks neurons in the brain that produce the chemical hypocretin (orexin), which is used throughout the brain to stay awake and alert. As a result, patients with narcolepsy have far less hypocretin in the brain and spinal fluid than other people, leading to the brain’s inability to regulate sleep and wakefulness.

Fortunately, narcolepsy is comparatively rare—fewer than one in two thousand people may have the condition. However, it also is underdiagnosed and often confused with other sleep disorders.

While narcolepsy cannot be cured or reversed, medications and lifestyle changes may relieve symptoms, sometimes dramatically. However, several promising new treatments are on the horizon. For instance, immunosuppressant therapies have shown promise in reversing narcolepsy in its earliest stages. As of today, however, treatment focuses entirely on controlling symptoms.

How is narcolepsy diagnosed?

If your primary care provider suspects you might have narcolepsy or another sleep disorder, he or she will likely refer you to a sleep specialist. A sleep specialist will look for five major symptoms in two distinct categories to arrive at a diagnosis of narcolepsy. The five symptoms include:

• Excessive daytime sleepiness: This classic and required symptom of a narcolepsy diagnosis involves frequent “sleep attacks,” a chronic, sudden, unexpected, and overwhelming need to fall asleep during the day.

• Cataplexy: Unique to narcolepsy is the sudden loss of muscle tone and control when the patient experiences a strong emotion. Cataplexy may be very minor, such as slurred speech, drooping eyelids, or “knee-buckling.” It can also be quite severe—patients can go completely limp and fall to the floor.

• Sleep disruption: REM sleep disturbances often prevent people with narcolepsy from being able to sleep continuously through the night. Going to sleep may be easy, but they may fully awaken after only a few hours of sleep.

• Hypnagogic hallucinations: Sleep hallucinations can occur during hypnagogia, the period between wakefulness and falling asleep. Many people can experience hypnagogic hallucinations occasionally, but patients with narcolepsy experience them more frequently.

• Sleep paralysis: During REM sleep, the body is paralyzed and the muscles lose tone, called REM atonia. In people with narcolepsy, sleep paralysis can happen right as they are falling asleep or waking up.

The physician is looking for all these symptoms and how often they occur. Other causes include bad sleep hygiene or obstructive sleep apnea, so a healthcare provider will follow certain steps to determine a diagnosis:

• The physician will want to know how frequently and for how long sleep attacks have occurred. Patients can help by keeping a daily log of their sleep and sleep attacks.

• The specialist will ask patients to fill out a self-assessment, such as the Epworth Sleepiness Scale or the Swiss Narcolepsy Scale, to get an objective idea of the extent and frequency of the symptoms.

• The doctor or provider will ask specific questions about cataplexy. The patient may not recognize incidents of cataplexy, so the questions could seem random and unrelated.

• Patients are tested for REM sleep disturbances. Patients can expect to spend a night hooked up to a polysomnogram (PSG) undergoing an in-lab sleep study. This device will indicate how long after falling asleep it takes the patient to enter REM sleep. Normally it takes 90 minutes, but patients with narcolepsy usually take less than 15 minutes.

• On the day following the PSG, the patient will spend their waking hours taking a Multiple Sleep Latency Test (MSLT). There are several short scheduled naps, during which the test will measure how quickly the patient falls asleep and how quickly and how often they enter REM sleep during these naps.

• Finally, the physician or healthcare professional may also draw some cerebrospinal fluid to test for low levels of hypocretin, a significant indicator of narcolepsy.

Narcolepsy treatment options

Once narcolepsy is diagnosed, there are several treatment options available. The underlying condition is a neurological disorder that cannot be reversed, but the symptoms can be reduced and managed. This will be accomplished largely through prescription medications that address particular symptoms of the disease.

Behavior changes are a second major component of relieving narcolepsy symptoms. Patients will be taught techniques to maintain good sleep hygiene and monitor their sleep behaviors. Dietary changes will be advised. Cognitive-behavioral therapy may be used to help patients develop successful strategies to manage medications, behaviors, and diet.

Finally, the last pillar of treatment is managing the social and psychological consequences. This may include support groups, advocacy, and school and work accommodations.

Narcolepsy medications

Wakefulness-promoting agents

Wakefulness-promoting agents are the initial drugs clinicians prescribe to relieve excessive daytime sleepiness. Although the exact way in which they work is unknown, they have been shown to work differently than stimulants to improve alertness.

Wakefulness-promoting agents, however, do not help relieve other REM disorders characteristic of narcolepsy, such as cataplexy, hypnagogic hallucinations, the inability to sleep continuously through the night, or sleep paralysis.

Stimulants

Stimulants help reduce daytime sleepiness by increasing the activity of the brain. They alter chemicals throughout the nervous system to increase alertness, attention, and energy. They are, however, subject to abuse and dependence, so physicians prescribe them only when patients do not respond well to wakefulness-promoting agents. Like wakefulness-promoting agents, stimulants do not address the other REM disorders of narcolepsy.

Antidepressants

Antidepressants may help relieve the REM disturbances of narcolepsy (cataplexy, sleep paralysis, and hypnagogic hallucinations) and are often prescribed off-label as a second-line therapy. One of the side effects of antidepressants is the suppression of REM sleep, but this is exactly what is needed to reduce the incidence of REM disorders in people with narcolepsy.

Sodium oxybate and other sedatives

Many of the daytime symptoms of narcolepsy originate from the inability to sleep continuously through the night. Clinicians have addressed this core problem by prescribing depressants (sedatives), such as benzodiazepines, which put people to sleep. However, patients with narcolepsy do not have a problem falling asleep, they have a problem with staying asleep through the night. For this reason, the first drug of choice to treat both daytime sleepiness and cataplexy is sodium oxybate (brand-name Xyrem), a unique depressant that produces continual sleep through the night. By increasing the length and quality of nighttime sleep, sodium oxybate can dramatically reduce daytime sleepiness and cataplexy.

What is the best medication for narcolepsy?

The best medications for narcolepsy are the ones that minimize symptoms and allow the patient to live as normal a life as possible. These will not be the same for everyone. Narcolepsy medications produce different effects—and side effects—in different people.

To relieve excessive daytime sleepiness, doctors will prescribe stimulants or wakefulness-promoting agents. Antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, and selective serotonin and norepinephrine reuptake inhibitors) are very effective at reducing REM disorders like cataplexy, hypnagogic hallucinations, and sleep paralysis.

Daytime sleepiness and cataplexy, however, are in large part due to the inability to sleep continuously through the night. For these problems, clinicians may use central nervous system depressants to help with nighttime sleepiness. The drug of choice is sodium oxybate, but some physicians prescribe benzodiazepines or other sedatives if the patient can’t tolerate sodium oxybate.

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Best medication for narcolepsy