An evaluation of sodium oxybate as a treatment option for narcolepsy

ABSTRACT

Introduction: Narcolepsy is a lifelong central nervous system (CNS) disorder characterized by excessive daytime sleepiness, cataplexy, disturbed nocturnal sleep, hypnagogic hallucinations, and sleep paralysis. Treatment is symptomatic and challenging. Current therapies with wake promoting agents, stimulants, and antidepressants improve symptoms but residual sleepiness or cataplexy may persist. Drug tolerance may develop. Adverse drug effects limit therapy. In the United States, sodium oxybate has been approved to treat daytime sleepiness and cataplexy in adults with narcolepsy since 2002. In 2018, it was approved for children ages 7–17 years with cataplexy with narcolepsy.

Areas covered: This drug review includes an overview of narcolepsy, current pharmacotherapy, drug chemistry, pharmacodynamics, pharmacokinetics, and metabolism of sodium oxybate. Published results from 11 randomized control trials are reviewed. Databases searched included PubMed, Google Scholar, Lexi-Comp, Scopus, Science, and Ovid.

Expert opinion: Sodium oxybate is an effective therapy for excessive daytime sleepiness and cataplexy in adults and children ages 7–17 years. It is also an effective therapy for disrupted nocturnal sleep. Sodium oxybate improves narcolepsy symptoms and enhances quality of life in narcolepsy patients.

KEYWORDS:

• Cataplexy
• daytime sleepiness
• drug evaluation
• narcolepsy
• nocturnal sleep disruption
• review
• sodium oxybate
• sodium 4-hydroxybutyrate

Article Highlights

• Narcolepsy is a lifelong CNS disorder that is associated with significant impairment of quality of life.

• There is currently no cure for narcolepsy. Available treatments address symptoms.

• SXB is the only medication approved by the US Food and Drug Administration to treat narcolepsy with cataplexy in adults and children 7-17 years of age and is currently the only medication that addresses all symptoms of narcolepsy.

• Improvements in daytime sleepiness and cataplexy are dose-dependent. Improvement in cataplexy may start ~ 4 weeks after treatment onset, while peak effect may take at least 3 months.

• SXB improves sleep continuity and increases slow wave sleep duration and delta power.

• Analysis of postmarketing data and clinical experience indicated a very low risk of abuse/misuse of SXB.

• Treatment emergence adverse events (TEAEs) were reported by ~67% of patients. The most common side effects were headache, nasopharyngitis, dizziness, decreased weight, and nausea. Uncommon side effects included somnambulism and urinary incontinence. Serious adverse events, reported in ~6% of patients, included depression, angina, inguinal hernia, and suicide attempt.

This box summarizes key points contained in the article.

Box 1. Drug Summary Box

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Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One referee is a consultant for Jazz Pharmaceuticals. They are also a member of Flamel Ireland and a member of the 2002 Multicentric Study group on sodium oxybate. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was not funded.