Recent Advances in the Treatment of Narcolepsy

A diagnosis of narcolepsy requires pharmacologic treatment in more than 90% of patients. Wake-promoting compounds are used to treat excessive daytime sleepiness (EDS), and anticataplectics are used for cataplexy. The treatment of EDS includes the use of amphetamine-like CNS stimulants (such as dextroamphetamine and methylphenidate), modafinil, and its R-enantiomer, armodafinil. Because of its high safety and low side-effect profiles, modafinil has become the first-line treatment of choice for EDS associated with narcolepsy. However, wake-promoting compounds do not improve cataplexy and dissociated manifestation of REM sleep, and so antidepressants (monoamine uptake inhibitors) are additionally used for the treatment of cataplexy and REM sleep abnormalities. Tricyclic antidepressants potently reduce REM sleep and thus have been used for the treatment of cataplexy and REM sleep abnormalities, but these have recently been replaced by more selective serotonin and/or noradrenaline uptake inhibitors with better side-effect profiles. As sodium oxybate (the approved formula of gamma-hydroxybutyrate in the United States), given at night, improves both EDS and cataplexy, the number of US patients treated with sodium oxybate is increasing, while much progress has been made in understanding the modes of action of amphetamine-like CNS stimulants.