Emerging drugs for narcolepsy.

Narcolepsy is characterised by excessive daytime sleepiness, usually associated with cataplexy, hypnagogic hallucinations, sleep paralysis and fragmented nocturnal sleep. Although uncommon, it results in significant disability. Most cases occur sporadically, but genetic factors probably form a susceptibility background on which unknown environmental triggers act. The hypocretin system is strongly implicated in the development of narcolepsy. Cerebrospinal fluid levels of hypocretin-1 are significantly reduced in narcoleptic subjects with cataplexy. Despite the advances in our understanding of narcolepsy, current therapy is primarily symptomatic. Stimulants (standard and novel) combat excessive daytime sleepiness. Antidepressants (tricyclics, dual-action or selective serotonin re-uptake inhibitors) and sodium oxybate are anticataplexy agents. Hypnagogic hallucinations and sleep paralysis respond to antidepressants. Sodium oxybate consolidates sleep. Novel and experimental treatments include histamine antagonists, hypocretin agonists, slow-wave sleep enhancers, intravenous gamma-globulin, tramadol and corticosteroids.