Treatment of narcolepsy and other hypersomnias of central origin.

OBJECTIVE: The purpose of this paper is to summarize current knowledge about treatment of narcolepsy and other hypersomnias of central origin. METHODS: The task force performed a systematic and comprehensive review of the relevant literature and graded the evidence using the Oxford grading system. This paper discusses the strengths and limitations of the available evidence regarding treatment of these conditions, and summarizes key information about safety of these medications. Our findings provide the foundation for development of evidence-based practice parameters on this topic by the Standards of Practice Committee of the American Academy of Sleep Medicine. RESULTS: The majority of recent papers in this field provide information about use of modafinil or sodium oxybate for treatment of sleepiness associated with narcolepsy. Several large randomized, placebo-controlled studies indicate that modafinil and sodium oxybate are effective for treatment of hypersomnia due to narcolepsy. We identified no studies that report direct comparison of these newer medications versus traditional stimulants, or that indicate what proportion of patients treated initially with these medications require transition to traditional stimulants or to combination therapy to achieve adequate alertness. As with the traditional stimulants, modafinil and sodium oxybate provide, at best, only moderate improvement in alertness rather than full restoration of alertness in patients with narcolepsy. Several large randomized placebo-controlled studies demonstrate that sodium oxybate is effective for treatment of cataplexy associated with narcolepsy, and earlier studies provide limited data to support the effectiveness of fluoxetine and tricyclic antidepressants for treatment of cataplexy. Our findings indicate that very few reports provide information regarding treatment of special populations such as children, older adults, and pregnant or breastfeeding women. The available literature provides a modest amount of information about improvement in quality of life in association with treatment, patient preferences among the different medications, or patient compliance. CONCLUSION: Several recent studies provide evidence that modafinil and sodium oxybate are effective for treatment of hypersomnia due to narcolepsy. No studies were identified that report direct comparison of these newer medications with traditional stimulants. Despite significant advances in understanding the pathophysiology of narcolepsy, we do not have an ideal treatment to restore full and sustained alertness. Future investigations should be directed toward development of more effective and better tolerated therapies, and primary prevention.

Excessive daytime sleepiness: considerations for the psychiatrist.

Excessive daytime sleepiness or pathologic sleepiness is a complaint found in patients who experience somnolence at unwanted times and adversely affects their daytime function. Although psychiatric illness, chronic medical illness, or medication side effects may be causes for fatigue, insufficient sleep is the most common cause of excessive daytime sleepiness in the general population. When an individual complains of frank sleepiness, in addition to insufficient sleep, important considerations in these patients are disturbances in the normal homeostatic mechanisms that govern sleep and wakefulness. This article summarizes the clinical presentation, the differential diagnosis, commonly used diagnostic tools, and treatment options for patients complaining of excessive daytime sleepiness.

Conditions of primary excessive daytime sleepiness.

Excessive daytime somnolence is a prevalent problem in medical practice and in society. It exacts a great toll in quality of life, personal and public safety, and productivity. The causes of EDS are myriad, and careful evaluation is needed to determine the cause in each case. Although much progress has been made in discovering the pathophysiology of narcolepsy, much more remains to be understood, and far less is known about other primary conditions of EDS. Several methods have been developed to assess EDS, although each of them has limitations. Treatment is available for the great majority of cases.

Narcolepsy and syndromes of primary excessive daytime somnolence.

Excessive daytime sleepiness (EDS) or somnolence is common in our patients and in society in general. The most common cause of EDS is "voluntary" sleep restriction. Other common causes include sleep-fragmenting disorders such as the obstructive sleep apnea syndrome. Somewhat less familiar to the clinician are EDS conditions arising from central nervous system dysfunction. Of these so-called primary disorders of somnolence, narcolepsy is the most well known and extensively studied, yet often misunderstood and misdiagnosed. Idiopathic hypersomnia, the recurrent hypersomnias, and EDS associated with nervous system disorders also must be well-understood to provide appropriate evaluation and management of the patient with EDS. This review summarizes the distinguishing features of these clinical syndromes of primary EDS. A brief overview of the pharmacological management of primary EDS is included. Finally, in view of the tremendous advances that have occurred in the past few years in our understanding of the pathophysiology of canine and human narcolepsy, we also highlight these discoveries.