Cataplexy is defined as episodes of sudden loss of voluntary muscle tone triggered by emotions generally lasting <2 minutes.
Cataplexy is most commonly associated with and considered pathognomonic for
narcolepsy, a
sleep disorder affecting ~0.05% of the general population. Knowledge of the pathophysiology of
cataplexy has advanced through study of canine, murine, and human models. It is now generally considered that loss of signaling by hypothalamic
hypocretin/
orexin-producing neurons plays a key role in the development of
cataplexy. Although the cause of
hypocretin/
orexin neuron loss in
narcolepsy with
cataplexy is unknown, an autoimmune etiology is widely hypothesized. Despite these advances, a literature review shows that treatment of
cataplexy remains limited. Multiple classes of
antidepressants have been commonly used off-label for
cataplexy in
narcolepsy and are suggested for this use in expert consensus guidelines based on traditional practice, case reports, and small trials. However, systematic research evidence supporting
antidepressants for
cataplexy is lacking. The single
pharmacotherapy indicated for
cataplexy and the guideline-recommended first-line treatment in Europe and the US is
sodium oxybate, the
sodium salt of
gamma-hydroxybutyrate. Clinical trial evidence of its efficacy and safety in
cataplexy is robust, and it is hypothesized that its
therapeutic effects may occur through
gamma-aminobutyric acid receptor type B-mediated effects at noradrenergic, dopaminergic, and thalamocortical neurons. Additional possible mechanisms for
cataplexy therapy suggested by preliminary research include antagonism of the
histamine H3
autoreceptor with
pitolisant and
intravenous immunoglobulin therapy for amelioration of the presumed autoimmune-mediated
hypocretin/
orexin cell loss. Further research and development of therapeutic approaches to
cataplexy are needed.