A practical guide to the therapy of narcolepsy and hypersomnia syndromes.

Stanford Center for Sleep Sciences and Medicine, Stanford University Medical School, Palo Alto, CA, 94304, USA, .
Journal of the American Society for Experimental NeuroTherapeutics (Impact Factor: 3.88). 10/2012; 9(4):739-52. DOI: 10.1007/s13311-012-0150-9
Source: PubMed

ABSTRACT Narcolepsy and other syndromes associated with excessive daytime sleepiness can be challenging to treat. New classifications now distinguish narcolepsy/hypocretin deficiency (also called type 1 narcolepsy), a lifelong disorder with well-established diagnostic procedures and etiology, from other syndromes with hypersomnolence of unknown causes. Klein-Levin Syndrome, a periodic hypersomnia associated with cognitive and behavioral abnormalities, is also considered a separate entity with separate therapeutic protocols. Non hypocretin-related hypersomnia syndromes are diagnoses of exclusion. These diagnoses are only made after eliminating sleep deprivation, sleep apnea, disturbed nocturnal sleep, and psychiatric comorbidities as the primary cause of daytime sleepiness. The treatment of narcolepsy/hypocretin deficiency is well-codified, and involves pharmacotherapies using sodium oxybate, stimulants, and/or antidepressants, plus behavioral modifications. These therapies are almost always needed, and the risk-to-benefit ratio is clear, notably in children. Detailed knowledge of the pharmacological profile of each compound is needed to optimize use. Treatment for other syndromes with hypersomnolence is more challenging and less codified. Preferably, therapy should be conservative (such as modafinil, atomoxetine, behavioral modifications), but it may have to be more aggressive (high-dose stimulants, sodium oxybate, etc.) on a case-by-case, empirical trial basis. As cause and evolution are unknown in these conditions, it is important to challenge diagnosis and therapy over time, keeping in mind the possibility of tolerance and the development of stimulant addiction. Kleine-Levin Syndrome is usually best left untreated, although lithium can be considered in severe cases with frequent episodes. Guidelines are provided based on the literature and personal experience of the author.

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    ABSTRACT: Despite published treatment recommendations and the availability of approved and off-label pharmacologic therapies for narcolepsy, clinical management of this incurable, chronic neurologic disorder remains challenging. While treatment is generally symptomatically driven, decisions regarding which drug(s) to use need to take into account a variety of factors that may affect adherence, efficacy, and tolerability. Type 1 narcolepsy (predominantly excessive daytime sleepiness with cataplexy) or type 2 narcolepsy (excessive daytime sleepiness without cataplexy) may drive treatment decisions, with consideration given either to a single drug that targets multiple symptoms or multiple drugs that each treat a specific symptom. Other drug-related characteristics that affect drug choice are dosing regimens, tolerability, and potential drug-drug interactions. Additionally, the patient should be an active participant in treatment decisions, and the main symptomatic complaints, treatment goals, psychosocial setting, and use of lifestyle substances (i.e., alcohol, nicotine, caffeine, cannabis) need to be discussed with respect to treatment decisions. Although there is a lack of narcolepsy-specific instruments for monitoring therapeutic effects, clinically relevant subjective and objective measures of daytime sleepiness (e.g., Epworth Sleepiness Scale, Maintenance of Wakefulness Test) can be used to provide guidance on whether treatment goals are being met. These considerations are discussed with the objective of providing clinically relevant recommendations for making treatment decisions that can enhance effective management of patients with narcolepsy.
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    ABSTRACT: Narcolepsy is a neurological disorder frequently occurring from childhood and persisting through adolescence and adulthood. Individuals suffering from narcolepsy exhibit excessive daytime somnolence, sleep attacks, cataplexy, dysomnia, metabolic perturbations including weight gain, and problems in social interaction and academic performance. The prevalence of narcolepsy in childhood is not known but can be estimated from adult studies to be greater than 20-60 per 100,000 in Western countries. The 2009 (A) H1N1 vaccination campaign led to an increase of narcoleptic cases both in children and in adults, supporting the autoimmune hypothesis of the disease. This article focuses on the epidemiology, etiology, and particularities of treatment in pediatric narcolepsy and details the effects of the drugs used to treat this condition, including recent trends in the field. Future therapeutic directions are also discussed. At present, medications used to treat children or adolescents have shown efficacy mostly based on clinical experience, given the lack of level 1 evidence-based studies in the pediatric population. Therefore, most compounds used in adult narcolepsy to target clinical symptoms such as wake-promoting or anticataplectic agents are prescribed off-label in pediatric patients. Published research shows the benefit of drug therapy for narcoleptic children, but these must be dispensed with caution in the absence of well conducted clinical trials.
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