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Abad VC, Guilleminault C. New developments in the management of narcolepsy. Nat Sci Sleep. 2017;9:39-57doi: 10.2147/NSS.S103467.
Abad, V. C., & Guilleminault, C. (2017). New developments in the management of narcolepsy. Nature and science of sleep, 939-57. https://doi.org/10.2147/NSS.S103467
Abad, Vivien C, and Guilleminault, Christian. "New developments in the management of narcolepsy." Nature and science of sleep vol. 9 (2017): 39-57. doi: https://doi.org/10.2147/NSS.S103467
Abad VC, Guilleminault C. New developments in the management of narcolepsy. Nat Sci Sleep. 2017 Mar 03;9:39-57. doi: 10.2147/NSS.S103467. eCollection 2017. PMID: 28424564; PMCID: PMC5344488.
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Nat Sci Sleep. 2017 Mar 03;9:39-57. doi: 10.2147/NSS.S103467. eCollection 2017.

New developments in the management of narcolepsy.

Nature and science of sleep

Vivien C Abad, Christian Guilleminault

Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Division of Sleep Medicine, Stanford University Outpatient Center, Redwood City, CA, USA.

PMID: 28424564 PMCID: PMC5344488 DOI: 10.2147/NSS.S103467

Abstract

Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%-0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy's strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an autoimmune etiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss. Current treatment modalities alleviate the main symptoms of excessive daytime somnolence (EDS) and cataplexy and, to a lesser extent, reduce nocturnal sleep disruption, hypnagogic hallucinations, and sleep paralysis. Sodium oxybate (SXB), a sodium salt of γ hydroxybutyric acid, is a first-line agent for cataplexy and EDS and may help sleep disruption, hypnagogic hallucinations, and sleep paralysis. Various antidepressant medications including norepinephrine serotonin reuptake inhibitors, selective serotonin reuptake inhibitors, and tricyclic antidepressants are second-line agents for treating cataplexy. In addition to SXB, modafinil and armodafinil are first-line agents to treat EDS. Second-line agents for EDS are stimulants such as methylphenidate and extended-release amphetamines. Emerging therapies include non-hypocretin-based therapy, hypocretin-based treatments, and immunotherapy to prevent hypocretin neuronal death. Non-hypocretin-based novel treatments for narcolepsy include pitolisant (BF2.649, tiprolisant); JZP-110 (ADX-N05) for EDS in adults; JZP 13-005 for children; JZP-386, a deuterated sodium oxybate oral suspension; FT 218 an extended-release formulation of SXB; and JNJ-17216498, a new formulation of modafinil. Clinical trials are investigating efficacy and safety of SXB, modafinil, and armodafinil in children. γ-amino butyric acid (GABA) modulation with GABA

Keywords: JZP-110; cataplexy; emerging treatment; hypocretin peptide; immunotherapy; narcolepsy; pitolisant; sodium oxybate

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

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