Daytime sleepiness treatment

Treatment of excessive daytime sleepiness in narcolepsy and other sleep disorders may require the use of sustained- and immediate-release stimulants to effectively promote wakefulness throughout the day and at key times that require alertness. 

FIGURE 38-1. Primary assessment and initial treatment for complaint of excessive daytime sleepiness. RLS, restless-legs syndrome NPSG, nocturnal polysomnography OSA, obstructive sleep apnea DA, dopamine agonist MSLT, multiple sleep latency test BZDRA, benzodiazepine receptor agonist SNRI, serotonin and norepinephrine reuptake inhibitor TCA, tricyclic antidepressant CPAP, continuous positive airway pressure. 

Modafinil is considered the standard for treatment of excessive daytime sleepiness. Plasma concentrations peak in 2 to 4 hours, and the half-life is 15 hours. Preliminary evidence suggests no tolerance or withdrawal after abrupt discontinuation and no risk of abuse. 

Other Hypersomnias. Narcolepsy is not the only hypersomnia, but it is by far the most common. Primary hypersomnia shares sleep attacks and excessive daytime sleepiness with narcolepsy but does not feature cataplexy or REM-associated abnormalities. Another rare hypersomnia is Kleine-Levin syndrome (KLS), which most often occurs in teenage boys. KLS consists of intermittent bouts of hypersomnia and bizarre behaviors including compulsive eating and sexual inappropriateness. Distinguishing these hypersomnias from narcolepsy may help clarify the patient s prognosis, but the treatment alternatives are very similar. 

Tranylcypromine, another MAOl, has also been shown to be effective in the treatment of social phobia. Versiani et al. [1988] implemented a 1-year, open trial of tranylcypromine in 32 subjects. Daily doses ranged from 40 to 60 mg. Twenty-nine subjects met criteria for completion of this study. Marked improvement was noted in 62% of patients [18/29], and moderate improvement was shown in 17.2% [5/29]. Six of the 29 subjects were deemed nonresponders [20.6%]. The most commonly cited side effects were orthostatic dizziness [75.5%], insomnia [44.7%], and daytime sleepiness [41.3%]. 

Some stimulants are approved for treatment of narcolepsy. Stimulants mainly improve excessive daytime sleepiness, and the effects may be dose related (Mitler et al. 1990). However, cataplexy usually does not respond to stimulants (Hyman et al. 1995). Stimulants are often administered in divided daily doses, and doses are often titrated weekly on the basis of clinical response. 

Broughton RJ, Fleming JA, George CF, et al Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy. Neurology 49 444-451, 1997... 

Mitler MM, Harsh J, Hirshkowitz M, et al Long-term efficacy and safety of modafinil (Provigil) for the treatment of excessive daytime sleepiness associated with narcolepsy. Sleep Med 1 231-243, 2000... 

Insomnia can have a serious impact on a person s quality of life. Acute insomnia can lead to daytime sleepiness and reduced ability to concentrate, remember things, use logical reasoning, and even impair your ability to drive a car. Chronic insomnia can have major health consequences, such as an increased susceptibility to depression and some forms of heart disease and a reduced ability to fight off colds or infections. There is also a tremendous cost to society caused by insomnia—billions of dollars are spent each year on treatment, healthcare services, and hospital costs. An equal cost can be attributed to lost productivity at work and property and personal damage from accidents caused by sleepy insomniacs. 

With no effective treatment for narcolepsy currently available, the approximately 100,000 to 125,000 people in the United States afflicted with the often debilitating disease are eager for this research to yield a therapeutic drug. Narcolepsy causes excessive daytime sleepiness often accompanied by cataplexy, a sudden... 

Methylphenidate is marketed in the United States under the prescription names Concerta, Metadate, Methylin, and Ritalin (26). It is available in immediate and sustained-release formulations for the treatment of attention deficit/hyperactivity disorder (ADHD) and the symptomatic management of narcolepsy (a disorder characterized by excessive daytime sleepiness). 

Clinically, methylphenidate also is used for the treatment of daytime sleepiness associated with narcolepsy. It is a mainstay treatment for this problem and has a long record of efficacy in alleviating the sleepiness symptoms (31) and maintaining alertness and performance in narcoleptic patients (32,33). 

Pemoline, an oxizolidine compound, acts similarly to methylphenidate—through catecholamine uptake inhibition in the CNS (27) with minimal sympathomimetic effects (57). Although pemoline is not the first-line stimulant for the treatment of ADHD, it has been successfully used for the treatment of this disorder in both children and adults (28,30). Pemoline has also been used for the treatment of daytime sleepiness associated with narcolepsy (31), and although it is somewhat effective for this purpose (33), it is not a first-line choice owing to its potentially lethal liver toxicity. 

The recommended dose of modafinil is 200 mg/day for the treatment of excessive daytime sleepiness associated with narcolepsy however, doses of 400 mg/day are FDA-approved. While there is evidence that the higher dose is well tolerated, it has not been established that it confers additional therapeutic benefit (196). In sleep-deprived subjects, doses of 600 mg/day have been administered, but the preponderance of evidence suggests that 300M00 mg/day is probably sufficient and less likely to produce unwanted side effects. 

Ivanenko A, Tauman R, Gozal D (2003) Modafinil in the treatment of excessive daytime sleepiness in children. Sleep Med 4 579-582... 

Many elderly persons, whether demented or cognitively intact, have medical conditions that disrupt sleep. Untreated insomnia and daytime sleepiness have been associated with nursing home placement and mortality. Medically ill older adults admitted to acute care hospitals are particularly vulnerable to sleep disruptions, which appear to be created as much by the various treatments and procedures, unfamiliar routines, and environmental conditions, as by the pain, anxiety, and discomfort associated with their underlying medical condition. Medical conditions especially likely to disrupt sleep are congestive heart failure, chronic obstructive pulmonary disease, Parkinson s disease, gastroesophageal reflux disease, arthritis, and nocturia. 

A number of poll respondents either sought treatment or self-medicated for their sleep problems. Fifteen percent of the respondents reported using either a prescription sleep medication (8 %) and/or an over-the-counter (OTC) sleep aid (10 %) at least a few nights per month during the past year to help them sleep. Sleep aids were used predominantly by adult females who mentioned having daytime sleepiness. 

Narcolepsy is a rare disease characterized by excessive daytime sleepiness. It has a prevalence of 0.05% in the general population and affects an estimated 140,000 people in the United States. In 2002, the FDA approved sodium oxybate (Xyrem ) for the treatment of cataplexy in patients with narcolepsy. The active ingredient in this drug is gamma hydroxybutyrate, or GHB. The development and marketing of sodium oxybate was permitted after a revision of the Date Rape Prevention Act of 2000 (see Chapter 5) that allowed GHB to be legally administered for medical purposes. 

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