Narcolepsy is characterized by hypersomnia. Some patients respond to treatment with tricyclic antidepressants or MAO inhibitors. Alternatively, CNS stimulants such as amphetamines may be useful. Therapy with amphetamines is complicated by the risk of abuse and the likelihood of the development of tolerance and a variety of behavioral changes (see above). Amphetamines may disturb nocturnal sleep, which increases the difficulty of avoiding daytime attacks of sleep in these patients. Modafinil (provigil), a CNS stimulant, may be beneficial via an unknown mechanism. In the U.S., modafinil is a schedule IV-controlled substance.

Occasionally, narcolepsy results from mutations in orexin neuropeptides (also called hypocre-tins), which are expressed in the lateral hypothalamus, or in their G protein—coupled receptors. Although such mutations are not present in most subjects with narcolepsy, the levels of orexins in the CSF are diminished, suggesting that deficient orexin signaling may play a pathogenic role. The association of these neuropeptides and their cognate GPCRs with narcolepsy provides an attractive target for the development of novel pharmacotherapies for this disorder.

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