The Nightly Use of Sodium Oxybate Is Associated with a Reduction in Nocturnal Sleep Disruption: A Double-Blind, Placebo-Controlled Study in Patients with Narcolepsy

Black, Jed; Pardi, Daniel; Hornfeldt, Carl S.; Inhaber, Neil

doi:10.5664/jcsm.27994

Cited by 72 publications

(29 citation statements)

References 8 publications

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“…It has been shown in many double-blind, randomized studies to effectively reduce stage 1 sleep, decrease wake-after-sleep onset, decrease number of awakenings, and increase slow-wave sleep. 15 The exact mechanism of GHB is unknown, but it is known to act on the GABA-B receptor as well as its own specific GHB receptor. The effects of GHB are thought to be mediated not through its effects on GABA-B however, as a study comparing baclofen, a well-known GABA-B agonist, and GHB to treat excessive daytime sleepiness and cataplexy showed that only GHB had an effect on cataplexy and daytime sleepiness.…”

Section: Pathophysiology and Mechanisms Of Medicationsmentioning

confidence: 99%

Mechanism of action of narcolepsy medications

Gowda

Lundt²

2014

CNS Spectr.

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The medications used to treat narcolepsy are targeted toward alleviating symptoms such as excessive sleepiness and cataplexy. The cause of this neurological sleep disorder is still not completely clear, though a destruction of hypocretin/orexin neurons has been implicated. The destruction of these neurons is linked to inactivity of neurotransmitters including histamine, norepinephrine, acetylcholine, and serotonin, causing a disturbance in the sleep/wake cycles of narcoleptic patients. Stimulants and MAOIs have traditionally been used to counteract excessive daytime sleepiness and sleep attacks by inhibiting the breakdown of catecholamines. Newer drugs, called wake-promoting agents, have recently become first-line agents due to their better side-effect profile, efficacy, and lesser potential for abuse. These agents similarly inhibit reuptake of dopamine, but have a novel mechanism of action, as they have been found to increase neuronal activity in the tuberomamillary nucleus and in orexin neurons. Sodium oxybate, a sodium salt of gamma-hydroxybutyrate (GHB), is another class that is used to treat many symptoms of narcolepsy, and is the only U.S. Food and Drug Administration (FDA)-approved medication for cataplexy. It has a different mechanism of action than either stimulants or wake-promoting agents, as it binds to its own unique receptor. Antidepressants, like selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), have also been used, as similar to stimulants, they inhibit reuptake of specific catecholamines. In this article, we seek to review the mechanisms behind these classes of drugs in relation to the proposed pathophysiology of narcolepsy. Appropriate clinical strategies will be discussed, including specific combinations of medications that have been shown to be effective.

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Section: Pathophysiology and Mechanisms Of Medicationsmentioning

confidence: 99%

Mechanism of action of narcolepsy medications

Gowda

Lundt²

2014

CNS Spectr.

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“…However, GHB became obsolete as an anesthetic due to undesirable side effects such as vomiting and severe cramps and its narrow dose-response margin [2]. In 2005, GHB was approved by the FDA (United States Food and Drug Administration) for the treatment of narcolepsy and in some countries it is also used in the treatment of withdrawal symptoms in alcoholics [3][4][5][6]. Since the 1990s, GHB has been increasingly recognized as a substance of abuse in recreational settings, due to its euphoric and sexually stimulating effects [2,7].…”

Section: Introductionmentioning

confidence: 99%

GHB, GBL and 1,4-BD Addiction

Brunt¹,

Amsterdam²,

Brink

2014

CPD

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A growing body of evidence shows that gamma-hydroxybutyric acid (GHB) is an addictive substance. Its precursors gammabutyrolactone (GBL) and 1,4-butanediol (1,4-BD) show the same properties and may pose even more risks due to different pharmacokinetics. There are indications that problematic GHB use is increasing in the European Union. This review investigates the existing literature on the neurochemistry of GHB and its precursors, their acute toxicity, addiction potential and withdrawal, the proposed molecular mechanism underlying addiction and the treatment of withdrawal and addiction. Current evidence shows that GHB and its precursors are highly addictive, both in humans and animals, probably through a GABAB receptor related mechanism. Severity of withdrawal symptoms can be considered as a medical emergency. Recent studies suggest that benzodiazepines are not very effective, showing a high treatment resistance, whereas detoxification with pharmaceutical GHB proved to be successful. However, relapse in GHB use is frequent and more research is warranted on relapse prevention. This might aid medical practitioners in the field and improve general understanding of the severity of addiction to GHB, GBL and 1,4-BD.

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“…It is hypothesized that the therapeutic effects of sodium oxybate are mediated through GABA(B) actions at noradrenergic and dopaminergic neurons, as well as at thalamocortical neurons, though there may also be some modulation of GABA(A) receptors. Effects on sleep architecture include overall reduction in nocturnal sleep disruption, increase in duration and intensity of slow wave sleep, decrease in light sleep, decrease in nocturnal awakenings, and decrease in total REM sleep [ 7 ]. Clinical effects include decreased daytime sleepiness, as well as resolution of cataplexy, sleep paralysis, and sleep-onset hallucinations [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Resolution of Sleepwalking Behavior after Initiation of Sodium Oxybate in a Patient with Narcolepsy Type 2

Hesselbacher

Sharafkhaneh

2018

Cureus

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A 44-year-old male veteran with long-standing excessive daytime sleepiness was diagnosed with Narcolepsy Type 2. The patient was unable to tolerate effective doses of methylphenidate, due to mood disturbances, or modafinil, due to adverse gastrointestinal effects. Although the patient also reported an ongoing history of sleepwalking with potentially injurious behaviors, a cautious trial of sodium oxybate was initiated. The combination of sodium oxybate and low dose methylphenidate resulted in significant improvement in patient-reported subjective daytime sleepiness. Additionally, self-report of the sleepwalking behaviors markedly improved. This case shows that patients with narcolepsy and sleepwalking may still safely benefit from a cautious trial of sodium oxybate.

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The Nightly Use of Sodium Oxybate Is Associated with a Reduction in Nocturnal Sleep Disruption: A Double-Blind, Placebo-Controlled Study in Patients with Narcolepsy

Cited by 72 publications

References 8 publications

Mechanism of action of narcolepsy medications

Mechanism of action of narcolepsy medications

GHB, GBL and 1,4-BD Addiction

Resolution of Sleepwalking Behavior after Initiation of Sodium Oxybate in a Patient with Narcolepsy Type 2

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