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.


CONCLUSIONS
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.
Wise
Merrill S
MS
Methodist Healthcare Sleep Disorders Center Memphis, Tennessee, USA.
Arand
Donna L
DL
Auger
R Robert
RR
Brooks
Stephen N
SN
Watson
Nathaniel F
NF
D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000627:therapeutic use*; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use; D002385:Cataplexy / Q000188:drug therapy* / Q000209:etiology; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D006970:Disorders of Excessive Somnolence / Q000188:drug therapy* / Q000209:etiology; D019317:Evidence-Based Medicine; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000077408:Modafinil; D009290:Narcolepsy / Q000188:drug therapy* / Q000209:etiology; D016032:Randomized Controlled Trials as Topic; D012978:Sodium Oxybate / Q000009:adverse effects / Q000627:therapeutic use
D000929:Antidepressive Agents, Tricyclic; D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D005473:Fluoxetine; D012978:Sodium Oxybate; D000077408:Modafinil