The effect of zimelidine, a serotonin-reuptake blocker, on cataplexy and daytime sleepiness of narcoleptic patients.

Narcolepsy is a neurological syndrome characterized by two major symptoms: excessive daytime sleepiness and cataplexy. Pharmacological and biochemical evidence support the hypothesis that dopaminergic mechanisms are involved in excessive daytime sleepiness. The pathophysiology of cataplexy and the action mechanisms of anticataplectic agents remain controversial issues. Cataplexy is usually controlled by tricyclic antidepressants, but these drugs interact with several central monoamine systems and also exert an anticholinergic effect. In the present study, zimelidine, a selective serotonin reuptake inhibitor without anticholinergic activity, was administered to 11 narcoleptic patients for 1-16 months. Cataplexy improved markedly in all patients, while no changes could be documented on excessive daytime sleepiness, either by self-report or polysomnographic nap recording. These results confirm the hypothesis that hypersomnolence and cataplexy are subject to different control mechanisms; support a serotoninergic, but not a cholinergic, theory of cataplexy; and suggest that selective serotonin reuptake inhibitors may be the treatment of choice for cataplexy.