Pharmacotherapy options for cataplexy

Narcolepsy with cataplexy is a rare disabling sleep disorder characterized by two major symptoms: excessive daytime sleepiness and cataplexy characterized by a sudden bilateral loss of voluntary muscular tone triggered by strong positive emotional factors. Pathophysiological studies have shown that the disease is caused by the early loss of hypothalamic hypocretin neurons.

Following a literature search on PubMed using "narcolepsy," "cataplexy," "treatment," "medication," and "drug" as keywords, we critically analyzed and reviewed current evidence about optimal management of cataplexy in humans. The management of cataplexy has evolved over the past few years with the widespread use of antidepressants, especially those with adrenergic uptake inhibitor properties and gamma-hydroxybutyrate (sodium oxybate).

Based on class 1 evidence studies, first-line pharmacological treatment of cataplexy should be sodium oxybate. Second-line treatment should be antidepressants with norepinephrine/serotonine reuptake inhibitor venlafaxine based on its good benefit-risk ratio; however, this recommendation lacks class 1 evidence and is based on expert opinion only. Given the major developments in understanding the neurobiological basis of cataplexy, future therapeutic targets are clearly oriented toward immune-based therapies at early stages of the disease and hypocretin replacement therapy.