Update on Novel Medications to Treat Narcolepsy
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INSOMNIA AND PSYCHOTHERAPY (H ATTARIAN & M KAY-STACEY, SECTION EDITORS)
Update on Novel Medications to Treat Narcolepsy Bimaje Akpa 1 & Kenneth Lee 2
# Springer Nature Switzerland AG 2020
Abstract Purpose of Review Narcolepsy is a chronic, disabling neurologic disorder characterized by excessive daytime sleepiness (EDS) and in up to 60% of patients, cataplexy. Currently, new treatments with varying mechanisms of action have recently been approved or are in clinical development. This review aims to summarize the progress to date on this information on these agents. Recent Findings Over the last decade, researchers have made great strides in understanding the biology of narcolepsy. The discovery of ORX deficiency in NT1 opened new therapeutic options oriented towards ORX-based therapies, especially nonpeptide ORX receptor agonists that are currently under development. These agents include novel oxybate formulations (once-nightly [FT218]; low sodium [JZP-258]), a selective norepinephrine-reuptake inhibitor (AXS-12), and a product combining modafinil and an astroglial connexin inhibitor (THN102). Summary Novel treatments in narcolepsy may provide further patient-oriented individualized treatment. Further developments could conceivably be used for development of further novel therapeutic options. Keywords Hypocretin, orexin . Narcolepsy . Hypersomnia . Cataplexy . Sodium oxybate
Introduction Narcolepsy is a lifelong and disabling neurological sleep disorder with a prevalence of 0.08% [1] that was first described in the nineteenth century by the French physician Jean-BaptisteEdouard [2]. Onset of symptoms is usually within the first two decades of life, typically between the ages of 10 to 20 [3]. The prevalence is equal among genders [4] and there are no differences in the rates of narcolepsy across countries, although some epidemiologic data suggests that the prevalence may be higher in Japan [4]. Symptoms include excessive daytime sleepiness (EDS), cataplexy, fragmented sleep, hypnopompic and hypnagogic hallucinations, and sleep paralysis. EDS is the cardinal symptom of narcolepsy and is often the presenting symptom [5•]. Cataplexy as defined by the National Institute This article is part of the Topical Collection on Insomnia and Psychotherapy * Kenneth Lee [email protected] 1
Department of Pulmonary and Critical Care, University of Chicago, 5841 S. Maryland Avenue, SC2030, Rm S-205, Chicago, IL 60637, USA
2
Department of Neurology, University of Chicago, 5841 S. Maryland Avenue, SC2030, Rm S-205, Chicago, IL 60637, USA
of Neurological Disorders and Stroke is abrupt loss of muscular tone during wakefulness that leads to loss of muscular control [6]. The American Academy of Sleep Medicine (AASM) and The International Classification of Sleep Disorders (ICSD-3) classify narcolepsy into two main categories—narcolepsy type 1 (Na-1) and narcolepsy type 2 (Na-2) [7, 8]. Diagnostic criteria is variable (Table 1) though EDS is universal in both Na-1 and Na-2. However, Na-1 is defined by the presence of ca
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