What is the diagnosis and treatment for narcolepsy (hypersomnia disorder)?

From the Guidelines

Narcolepsy treatment should prioritize sodium oxybate for adults, as it has been shown to improve excessive daytime sleepiness, cataplexy, and disease severity, with a strong recommendation from the American Academy of Sleep Medicine 1. The treatment of narcolepsy typically involves a combination of medication and lifestyle modifications.

• First-line medications include stimulants like modafinil (200-400mg daily) or armodafinil (150-250mg daily) to promote wakefulness, with strong recommendations for modafinil 1 and conditional recommendations for armodafinil 1.
• For more severe cases, methylphenidate (10-60mg daily in divided doses) or amphetamine salts (5-60mg daily in divided doses) may be prescribed, with conditional recommendations for methylphenidate 1.
• Sodium oxybate (Xyrem, 4.5-9g at bedtime in two divided doses) can improve nighttime sleep and reduce cataplexy, with a strong recommendation for its use in adults 1 and a conditional recommendation for pediatric patients 1.
• Antidepressants such as venlafaxine (37.5-225mg daily) or fluoxetine (20-60mg daily) may help manage cataplexy symptoms. Lifestyle modifications are equally important:
• maintaining a regular sleep schedule
• taking 15-20 minute scheduled naps during the day
• avoiding alcohol and heavy meals before bedtime
• exercising regularly but not close to bedtime Patients should inform employers or schools about their condition and may require accommodations. Narcolepsy is a lifelong condition, but with proper treatment and management, most people can lead relatively normal lives. The American Academy of Sleep Medicine provides guidelines for the treatment of central disorders of hypersomnolence, including narcolepsy, with recommendations for various medications and lifestyle modifications 1.

From the FDA Drug Label

14 CLINICAL STUDIES 14. 1 Narcolepsy The effectiveness of modafinil tablets in improving wakefulness in adult patients with excessive sleepiness associated with narcolepsy was established in two US 9-week, multi-center, placebo-controlled, parallel-group, double-blind studies of outpatients who met the criteria for narcolepsy

1 INDICATIONS AND USAGE 1.1 Narcolepsy XYWAV is indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy.

Narcolepsy Treatment:

• Modafinil tablets are effective in improving wakefulness in adult patients with excessive sleepiness associated with narcolepsy 2.
• Sodium oxybate (XYWAV) is indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy 3. Key Points:
• Modafinil and sodium oxybate are used to treat narcolepsy symptoms.
• Modafinil is used for excessive daytime sleepiness, while sodium oxybate treats cataplexy and excessive daytime sleepiness.

From the Research

Narcolepsy Treatment Options

• First line treatments for excessive daytime sleepiness (EDS) in narcolepsy patients include modafinil/armodafinil and sodium oxybate 4
• Other options with a stimulant effect, such as methylphenidate and amphetamines, are considered if the former do not control the symptoms 4, 5
• Pitolisant, a histamine 3 (H3)-receptor antagonist/inverse agonist, is approved by the European Medicines Agency (EMA) for the treatment of narcolepsy with or without cataplexy in adults and by the FDA for the treatment of EDS in adults with narcolepsy 4, 5
• Solriamfetol, a dopamine and norepinephrine reuptake inhibitor, was approved by the Food and Drug Administration for the treatment of EDS in adult narcolepsy patients 4, 5

Mechanisms of Action

• Medications approved for the treatment of EDS in narcolepsy mainly act on dopaminergic and noradrenergic pathways 5
• Sodium oxybate is thought to act via GABAB receptors 5
• Pitolisant increases the synthesis and release of histamine in the brain and modulates the release of other neurotransmitters (eg, norepinephrine, dopamine) 5

Treatment Evolution

• Narcolepsy treatment has changed dramatically over the last century, with the early use of caffeine and progression to various stimulants and wake-promoting agents 6
• The development of new medications, such as modafinil, has improved the treatment of excessive sleepiness in narcolepsy patients 7
• Combination treatment with medications that act via different neural pathways is necessary for optimal symptom management in many patients with narcolepsy 5