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Content Update

September 16, 2019

Newly Approved Medication for Narcolepsy with or without Cataplexy: The U.S. FDA approved a medication with novel mechanism of action for narcolepsy treatment. Pitolisant (Wakix), the first selective histamine 3 (H3) receptor inverse agonist, was approved in 2019 for narcolepsy.

The H3 receptor inverse agonist was approved for treating excessive daytime sleepiness (EDS) in narcolepsy in adults because of its hypothesized role in increasing wake-promoting histamine. While other treatments for EDS are available, this is the first treatment with the mechanism of action involving histamine.


For the chapter in the Wells Handbook, please go to Chapter 70. Sleep-Wake Disorders.



  • image Common causes of insomnia include concomitant psychiatric disorders, significant psychosocial stressors, excessive alcohol use, caffeine intake, and nicotine use.

  • image Good sleep hygiene, including relaxing before bedtime, exercising regularly, establishing a regular bedtime and wake-up time, and discontinuing alcohol, caffeine, and nicotine, alone and in combination with drug therapy, should be part of patient education and treatments for insomnia.

  • image Long-acting benzodiazepines should be avoided in the elderly.

  • image Benzodiazepine-receptor agonist tolerance and dependence are avoided by using low-dose therapy for the shortest possible duration.

  • image Obstructive sleep apnea may be an independent risk factor for the development of hypertension. When hypertension is present, it is often refractory to drug therapy until sleep-disordered breathing is alleviated.

  • image Nasal continuous positive airway pressure (PAP) is the first-line therapy for obstructive sleep apnea, and weight loss should be encouraged in all obese patients.

  • image Pharmacologic management of narcolepsy is focused on two primary areas: treatment of excessive daytime sleepiness and rapid eye movement (REM) sleep abnormalities.

  • image Short-acting benzodiazepine receptor agonists, ramelteon, or melatonin taken at appropriate target bedtimes for east or west travel reduce jet lag and shorten sleep latency.

  • image Dopamine agonists are standard therapy for restless legs syndrome (RLS) but have adverse effects that require careful monitoring by patients and providers.

Approximately 70 million Americans suffer with a sleep-related problem, and as many as 60% of those experience a chronic disorder.1 In a study by the National Institute on Aging, of 9,000 patients aged 65 years and older, more than 80% report a sleep-related disturbance.1


Sleep Cycles

Sleep is divided into two phases: nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. Each night humans typically experience four to six cycles of NREM and REM sleep, with each cycle lasting between 70 and 120 minutes.2 There are four stages of NREM sleep. Healthy sleep will typically progress through the four stages of NREM sleep prior to the first REM period. From wakefulness, sleep typically progresses quickly through stages 1 and 2. Stage 1 of NREM sleep is the stage between wakefulness and sleep, and individuals describe ...

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