Narcolepsy and effectiveness of gamma-hydroxybutyrate (GHB): A systematic review and meta-analysis of randomized controlled trials

Boscolo‐Berto, Rafael; Viel, Guido; Montagnese, Sara; Raduazzo, Daniella I.; Ferrara, Santo Davide; Dauvilliers, Yves

doi:10.1016/j.smrv.2011.09.001

Cited by 112 publications

(60 citation statements)

References 29 publications

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“…The evidence of efficiency of sodium oxybate is well documented in the treatment of cataplexy [Boscolo-Berto et al 2011]. Antidepressants are also used for the treatment of cataplexy despite poor evidence of their effect and safety.…”

Section: Narcolepsymentioning

confidence: 99%

Diagnosis and management of central hypersomnias

Šonka

Susta

2012

Ther Adv Neurol Disord

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Central hypersomnias are diseases manifested in excessive daytime sleepiness (EDS) not caused by disturbed nocturnal sleep or misaligned circadian rhythms. Central hypersomnias includes narcolepsy with and without cataplexy, recurrent hypersomnia, idiopathic hypersomnia, with and without long sleep time, behaviorally induced insufficient sleep syndrome, hypersomnia and narcolepsy due to medical conditions, and finally hypersomnia induced by substance intake. The Epworth Sleepiness Scale is a subjective tool mostly used for EDS assessment, while the Multiple Sleep Latency Test serves as an objective diagnostic method for narcolepsy and idiopathic hypersomnias. As for symptomatic therapy of EDS, the central nervous system stimulants modafinil and methylphenidate seem to work well in most cases and in narcolepsy and Parkinson's disease; sodium oxybate also has notable therapeutic value.

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Section: Narcolepsymentioning

confidence: 99%

Diagnosis and management of central hypersomnias

Šonka

Susta

2012

Ther Adv Neurol Disord

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“…GHB was developed in the 1960s as an anaesthetic agent [2], but its use in anaesthesia remained limited due to inadequate analgesia, the emergence of delirium and its proconvulsive effect [3]. As a therapeutic drug (Xyrem®; sodium oxybate), GHB is currently used worldwide in the treatment of narcolepsy with attacks of cataplexy [4]. It is also approved in Austria and Italy to treat alcohol dependence and withdrawal (Alcover®) [5], and it is used off-label for opiate withdrawal.…”

Section: Introductionmentioning

confidence: 99%

The Neurobiological Mechanisms of Gamma-Hydroxybutyrate Dependence and Withdrawal and Their Clinical Relevance: A Review

Kamal

Noorden²,

Franzek³

et al. 2016

Neuropsychobiology

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Objective: γ-Hydroxybutyrate (GHB) has gained popularity as a drug of abuse. In the Netherlands the number of patients in treatment for GHB dependence has increased sharply. Clinical presentation of GHB withdrawal can be life threatening. We aim, through this overview, to explore the neurobiological pathways causing GHB dependency and withdrawal, and their implications for treatment choices. Methods: In this work we review the literature discussing the findings from animal models to clinical studies focused on the neurobiological pathways of endogenous but mainly exogenous GHB. Results: Chronic abuse of GHB exerts multifarious neurotransmitter and neuromodulator effects on γ-aminobutyric acid (GABA), glutamate, dopamine, serotonin, norepinephrine and cholinergic systems. Moreover, important effects on neurosteroidogenesis and oxytocin release are wielded. GHB acts mainly via a bidirectional effect on GABA_B receptors (GABA_BR; subunits GABA_B1 and GABA_B2), depending on the subunit of the GIRK (G-protein-dependent ion inwardly rectifying potassium) channel involved, and an indirect effect of the cortical and limbic inputs outside the nucleus accumbens. GHB also activates a specific GHB receptor and β₁-subunits of α₄-GABA_AR. Reversing this complex interaction of neurobiological mechanisms by the abrupt cessation of GHB use results in a withdrawal syndrome with a diversity of symptoms of different intensity, depending on the pattern of GHB abuse. Conclusion: The GHB withdrawal symptoms cannot be related to a single mechanism or neurological pathway, which implies that different medication combinations are needed for treatment. A single drug class, such as benzodiazepines, gabapentin or antipsychotics, is unlikely to be sufficient to avoid life-threatening complications. Detoxification by means of titration and tapering of pharmaceutical GHB can be considered as a promising treatment that could make polypharmacy redundant.

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“…SO is approved in a variety of European and American countries as an intravenous anaesthetic [7,8] and as a liquid oral medication for patients with narcolepsycataplexy [9][10][11] or alcohol dependence [12,13].…”

Section: Introductionmentioning

confidence: 99%

“…GHB has a high affinity for GHB receptors which do not recognize GABA. GHB also has an indirect effect on dopaminergic, serotonergic, glutamatergic and opioidergic neural pathways [5,6].SO is approved in a variety of European and American countries as an intravenous anaesthetic [7,8] and as a liquid oral medication for patients with narcolepsycataplexy [9][10][11] or alcohol dependence [12,13].It has been well-demonstrated in animal and human studies that SO reduces alcohol consumption and suppresses alcohol withdrawal syndrome [13,14]. The pharmacological effects of SO present several similarities with those of alcohol [15][16][17].…”

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confidence: 99%

Pharmacodynamic interactions of a solid formulation of sodium oxybate and ethanol in healthy volunteers

Pross¹,

Patat²,

Vivet

et al. 2015

Brit J Clinical Pharma

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AIMThe pharmacologic effects of sodium oxybate (SO) have a number of similarities with those of alcohol. This study evaluated the pharmacodynamic interaction of SMO.IR (a solid immediate release formulation of SO) and alcohol (0.7 (males) or 0.57 (females) g kg -1 alcohol using 40% vodka). METHODSIn a randomized, double-blind, double-dummy, crossover trial, 24 healthy volunteers received randomly a) 2.25 g SMO.IR and placebo alcohol preparation, b) 2.25 g f SMO.IR and alcohol, c) 2.25 g SMO.IR matching placebo and alcohol and d) 2.25 g of SMO.IR matching placebo and placebo alcohol preparation. Objective and subjective cognitive parameters, adverse events and vital signs were assessed before, 15 and 165 min after treatment administration. RESULTSAlcohol produced the expected cognitive impairment and the expected subjective sedation rapidly after intake (from 15 min). The objective effects of SMO.IR were much less pronounced than those of alcohol. The reverse was observed for subjective complaints, which were related to lesser stimulation and greater sedation. Nevertheless, 165 min after administration this sedation feeling was less with SMO.IR than with alcohol. There was a significant interaction between SMO.IR and alcohol at 15 min (i.e. increase in alertness and stimulation and decrease in sedation). In addition, an isolated mild decrease in digit vigilance accuracy occurred at 165 min post-dose after the combination. The co-administration of SMO.IR and alcohol was safe and well-tolerated. CONCLUSIONSMO.IR and alcohol have distinct adverse effect profiles. The objective effects of SMO.IR are much less marked than those of alcohol. No deleterious interaction was observed. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Sodium oxybate (SO) has been approved for the treatment of alcohol dependence in Europe. Post-market surveillance has found no significant safety issues in alcohol relapsing patients taking SO, even though SO and alcohol share several pharmacological targets and effects.• Illicit SO (also called 'street GHB' or 'liquid ecstasy') can lead to abuse, misuse, addiction, criminal use and/or overdosing, and may have long term neurotoxic effects.• SMO.IR, a solid immediate-release formulation of sodium oxybate, is being developed to reduce the risk of criminal or accidental misuse of the drug and to obtain worldwide approval for the treatment of alcohol dependence. WHAT THIS STUDY ADDS• SMO.IR and alcohol have distinct adverse effect profiles. The objective sedative effects of SMO.IR are much less marked than those of alcohol and no interaction was observed.• The dose of SMO.IR used in this study (2.25 g) is in the upper range of the therapeutic interval for alcohol dependence and is 30%-80% higher than commonly prescribed doses.• The low level of interaction between alcohol and SMO.IR may account for the good safety profile of the drug even in the context of alcohol relapses. IntroductionSodium oxybate (SO) is the name of the sodium salt of gamma-hydroxybutyric acid when used as a therapeutic agent. Gamm...

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Narcolepsy and effectiveness of gamma-hydroxybutyrate (GHB): A systematic review and meta-analysis of randomized controlled trials

Cited by 112 publications

References 29 publications

Diagnosis and management of central hypersomnias

Diagnosis and management of central hypersomnias

The Neurobiological Mechanisms of Gamma-Hydroxybutyrate Dependence and Withdrawal and Their Clinical Relevance: A Review

Pharmacodynamic interactions of a solid formulation of sodium oxybate and ethanol in healthy volunteers

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