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Treatment paradigms for cataplexy in narcolepsy: past, present, and future

Authors Swick TJ, Elliott L

Received 10 July 2015

Accepted for publication 19 October 2015

Published 11 December 2015 Volume 2015:7 Pages 159—169


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Steven A Shea

Todd J Swick1–4

1Department of Neurology, University of Texas School of Medicine-Houston, Houston; 2The Sleep Center at North Cypress Medical Center, Cypress; 3Apnix Sleep Diagnostics, Houston; 4Neurology and Sleep Medicine Consultants, Houston, TX, USA

Abstract: 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.

Keywords: cataplexy, narcolepsy, treatment, sodium oxybate, antidepressants, emerging therapies

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