Narcolepsy Treatment & Management

Updated: May 04, 2023
  • Author: Sagarika Nallu, MD; Chief Editor: Selim R Benbadis, MD  more...
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Approach Considerations

Treatment of narcolepsy has both nonpharmacologic and pharmacologic components. Sleep hygiene is important. Most patients improve if they maintain a regular sleep schedule, usually 7.5–8 hours of sleep per night. Scheduled naps during the day also may help. [5]

Pharmacologic treatment of narcolepsy involves the use of central nervous system (CNS) stimulants such as methylphenidate, modafinil, dextroamphetamine sulfate, methamphetamine, and amphetamine, or solriamfetol, a dopamine/norepinephrine reuptake inhibitor. These medications help reduce daytime sleepiness, improving the symptom in 65–85% of patients. In patients for whom stimulant treatment is problematic, subjective benefit from treatment with codeine has been reported. [6]


Nonpharmacologic Measures

In addition to a regular sleep schedule (usually 7.5–8 hours of sleep per night) and, in some cases, scheduled naps during the day, the following nonpharmacologic measures are also important:

  • Providing emotional support and career or vocational counseling to patients and parents

  • Assisting with documentation for special academic needs, insurance, disability forms, and attaining a driver’s license

  • Questioning patients about high-risk behaviors such as alcohol and drug use, which may exacerbate symptoms

  • Inquiring about depression, family conflict, and other psychosocial problems

Children should be encouraged to participate in after-school activities and sports. A well-designed exercise program can be beneficial and stimulating. School personnel should have the narcoleptic children refrain from activities if they appear drowsy. Avoidance of foods high in refined sugars may improve daytime sleepiness.


Pharmacologic Treatment


Methylphenidate is the stimulant most frequently used for treatment of narcolepsy. It improves sleep tendency in a dose-related fashion. Undesirable side effects include headache, irritability, nervousness, and gastrointestinal complaints. Nocturnal sleep may be impaired, with a resulting decrease in total sleep time.

Modafinil and armodafinil 

Modafinil is a novel wake-promoting agent. [52] The mechanism of action is not understood, but it does not appear to involve altering levels of dopamine or norepinephrine. Unlike traditional medications, modafinil does not appear to affect total sleep time or suppress rapid eye movement (REM) sleep; the most common adverse effect is headache. [53] Its safety in children has not been established.

In a meta-analysis of 9 randomized controlled trials including 1054 patients, modafinil was shown to provide significant benefit to narcoleptic patients with respect to eliminating excessive daytime sleepiness (EDS) and decreasing sleep attacks, naps, and the duration and periods of somnolence each day, in comparison with placebo. [54] Whereas modafinil improved the quality of life in narcoleptic patients as compared with placebo, it did not diminish the number of attacks of cataplexy.

Armodafinil [55] is an enantiomer of modafinil that has fewer side effects. It is indicated for the treatment of EDS associated with narcolepsy. The most common adverse effects are headache, nausea, dizziness, and difficulty sleeping. Its safety has not been established in children younger than 17 years. 


Solriamfetol, a dopamine/norepinephrine reuptake inhibitor (DNRI), was approved in 2019 for EDS in adults with narcolepsy. Approval was based on a phase 3 trial where 239 patients with narcolepsy were randomized to receive solriamfetol 75 mg, 150 mg, or 300 mg (two times the maximum recommended daily dose), or placebo once daily. Compared to the placebo group, patients randomized to 150 mg showed statistically significant improvements on the maintenance of wakefulness test (MWT) and on the Epworth sleepiness scale (ESS) at week 12. These effects were apparent at week 1 and consistent with the results at week 12. At week 12, a higher percentage of patients treated with solriamfetol 150 mg (78.2%) reported patient global impression of change (PGIc) scale improvement relative to placebo (39.7%; p < 0.0001). [56]  

Sodium oxybate

Sodium oxybate [57, 58] is the only treatment for cataplexy that has been approved by the US Food and Drug Administration (FDA). It is also used to treat EDS. Sodium oxybate is a CNS depressant and should not be used with alcohol or other CNS depressants. The original product (Xyrem) approved in 2002 required twice nightly dosing. A new once nightly formulation (Lumryz) was approved in 2023. 

In a double-blind, placebo-controlled randomized study, the use of sodium oxybate (6 mg or 9 mg per night) was shown to reduce nocturnal sleep disruption in narcoleptic patients. [59] After 8 weeks of treatment, patients exhibited increases in the duration of stage 3 sleep. Changes in sleep were measured by means of nocturnal polysomnography (PSG). The benefits of sodium oxybate included improvements in total sleep time, decreased stage 1 sleep, and diminished wakening after sleep onset. [59]

The FDA approved a low-sodium alternative to sodium oxybate, Xywav (calcium/magnesium/potassium/sodium oxybates) for sudden muscle weakness or excessive daytime sleepiness (EDS) in narcolepsy patients aged 7 years and older. Both drugs contain the active ingredient oxybate, but Xywav has 92% less sodium compared to Xyrem.

Approval was based on a global phase 3 trial in which adults and pediatric patients (n=201) treated with Xywav demonstrated safety and statistically significant differences (P < .0001) in the weekly number of cataplexy attacks and Epworth Sleepiness Scale scores compared with placebo. [60]  


In August 2019, the FDA approved pitolisant. It is a nonscheduled, first-in-class histamine3 (H3) receptor antagonist/inverse agonist indicated for excessive daytime sleepiness in adults with narcolepsy. The efficacy of pitolisant was evaluated in 2 multicenter, randomized, double-blind, placebo-controlled studies in patients (n=261) with narcolepsy with or without cataplexy. In both studies, pitolisant demonstrated a statistically significant improvement in the Epworth Sleepiness Scale (EDS) score. [7, 8]  

Other treatments

Amphetamines are commonly used as an off-label treatment for narcolepsy. There is a clinical consensus that tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) potently reduce cataplexy; however, one meta-analysis found no good-quality evidence that antidepressants are effective for narcolepsy or improve quality of life and found scarce evidence of efficacy for cataplexy. [61]

Research into future treatments is focusing on preventing the loss of hypocretin (orexin)-producing neurons by targeting the proposed autoimmune-driven mechanism of narcolepsy. Trials of intravenous (IV) immunoglobulin (IVIG) are in their infancy. Future research may also investigate the restoration of hypocretin signaling with agonists or gene therapy.

Treatment in pediatric patients

For children younger than 7 years who have narcolepsy, pemoline was previously considered the initial drug of choice. However, the FDA concluded that the overall risk of liver toxicity from pemoline outweighed the benefits, and the drug was removed from the US market in 2005.

Currently, no FDA-approved pharmacotherapy is available for children with narcolepsy. However, the medications used to treat narcolepsy in adults have been used off-label in the pediatric population with positive results. In particular, methylphenidate and modafinil have proved effective for patients 6–15 years old. [62]


Diet and Activity

Patients with narcolepsy should avoid heavy meals and alcohol. Activity recommendations include the following:

  • Patients should take scheduled short naps

  • Patients should participate in an exercise program

  • Patients should avoid driving, operating heavy machinery, or other potentially hazardous activity when sleepy

  • Patients with narcolepsy with cataplexy should wear a life preserver when engaged in water activities, should never perform water activities solo, and should educate the rest of their party about cataplectic attacks


Long-Term Monitoring

Children with narcolepsy should be monitored by both the primary pediatrician and the pediatric neurologist. Regular follow-up is necessary for monitoring drug effectiveness, response to treatment, and potential side effects; it should be done at least annually and, if the patient is on a stimulant, preferably every 6 months. A sleep medicine specialist, if available, also should see the patient regularly. Patients should contact narcolepsy support groups.