Severe gamma-hydroxybutyrate withdrawal: a case report and literature review

Craig, Kathryn; Gomez, Hernan F.; McManus, John; Bania, Theodore C.

doi:10.1016/s0736-4679(99)00163-8

Cited by 124 publications

(90 citation statements)

References 23 publications

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“…[25][26][27] In cases where the same patient presented with multiple episodes of withdrawal, each episode was considered separately. Twenty-seven articles, all case series or case reports, fulfilled study eligibility criteria, [5][6][7][8][9][10][11][12][13][14][15][16][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] describing 57 patients with withdrawal: GHB in 36 cases, 1,4-BD in 3 cases and GBL in 18 cases. Mean age was 31 years (range 18-57 yr) and 65% (37/57) were male.…”

Section: Resultsmentioning

confidence: 99%

“…2 Furthermore, GHB and its analogues are not detected on standard drug screens, increasing their attractiveness as drugs of abuse. 2,6 GHB is rapidly cleared from the urine, making detection difficult. One study found that GHB doses of 75-100 mg/kg would be undetectable in the urine by 12 hours after administration.…”

Section: Discussionmentioning

confidence: 99%

“…13,46 Benzodiazepines are therefore useful agents for treatment of these patients, although high doses may be required. 6,29 In cases where benzodiazepines are ineffective in controlling symptoms, treatment with pentobarbital may be appropriate. Sivilotti and colleagues 15 identified 4 patients withdrawing from GBL who had an inadequate response to benzodiazepines but experienced rapid symptom control following pentobarbital administration.…”

Section: Treatmentmentioning

confidence: 99%

“…4 GBL and 1,4-BD are present in some health food products and industrial solvents, making them relatively accessible to people who seek to use them as recreational drugs. 5 Withdrawal symptoms of GHB, 1,4-BD and GBL are related to central nervous system (CNS) and autonomic dysregulation, 2,[5][6][7][8][9][10][11][12][13][14][15][16] and are similar to withdrawal from other sedative-hypnotic drugs such as ethanol and benzodiazepines. 17 While the prevalence of seizures and death during withdrawal from ethanol and benzodiazepines are known, the frequency of these complications during withdrawal from GHB analogues is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Withdrawal from gamma-hydroxybutyrate, 1,4-butanediol and gamma-butyrolactone: a case report and systematic review

Wojtowicz

Yarema

Wax

2008

CJEM

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1,4-Butanediol (1,4-BD) is an industrial solvent that is metabolized to gamma-hydroxybutyrate (GHB), a gamma-aminobutyric acid agonist and central nervous system depressant. GHB and its analogues are popular drugs of abuse. Withdrawal from these agents is characterized by autonomic instability and altered mental status. We report a case of withdrawal from 1,4-BD lasting 6 days and complicated by new onset of seizures and rhabdomyolysis. In addition, we conducted a systematic review of the English literature pertaining to withdrawal from GHB, 1,4-BD and gamma-butyrolactone (GBL). Data collected from source articles included last use prior to symptom onset, clinical features on presentation, duration of symptoms and outcome. Twenty-seven studies with 57 episodes of withdrawal were included. Thirty-six cases (63%) involved GHB, 3 cases (5%) involved 1,4-BD and 18 (32%) involved GBL. The most common patient symptoms were tremor (67%), hallucinations (63%), tachycardia (63%) and insomnia (58%). Seizures and rhabdomyolysis each occurred in 7% of cases, but only 1 death occurred. Emergency physicians must consider withdrawal from these agents when patients present with clinical features suggestive of a sedative-hypnotic withdrawal syndrome. RÉSUMÉLe butane-1,4-diol (BD-1,4) est un solvant industriel qui se métabolise en 4-hydroxybutanoate (GHB), un agoniste de l'acide 4-aminobutanoïque et un dépresseur du système nerveux central. Le GHB et ses analogues sont des drogues populaires faisant l'objet d'abus. Le sevrage de ces agents se manifeste par une instabilité autonome et un état mental altéré. Nous présentons un cas de sevrage de BD-1,4 ayant duré 6 jours et ayant été compliqué par une nouvelle apparition de convulsions et de rhabdomyolyse. Nous avons en outre réalisé une revue systématique de la littéra-ture anglaise portant sur le sevrage du GHB, du BD-1,4 et du gamma-butyrolactone (GBL). Les données recueillies des articles sources incluaient des renseignements sur la dernière utilisation avant la survenue de symptômes, les manifestations cliniques à l'arrivée des patients à l'urgence, la durée des symptômes et les résultats. La revue portait sur 27 études décrivant 57 épisodes de sevrage. Trente-six cas (63 %) étaient liés au GHB, 3 cas (5 %) au BD-1,4 et 18 (32 %) au GBL. Les tremblements (67 %), les hallucinations (63 %), la tachycardie (63 %) et l'insomnie (58 %) étaient les symptômes les plus courants observés chez les patients. Les convulsions et la rhabdomyolyse se sont manifestées respectivement dans 7 % des cas, mais seulement 1 décès a eu lieu. Lorsqu'un patient présente des manifestations cliniques évoquant le syndrome de sevrage de sédatifs hypnotiques, les médecins d'urgence devraient considérer la possibilité de sevrage de ces agents.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Withdrawal from gamma-hydroxybutyrate, 1,4-butanediol and gamma-butyrolactone: a case report and systematic review

Wojtowicz

Yarema

Wax

2008

CJEM

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“…While GHB is given in doses of 4.5 to 9 g in two doses at night in a medical context, illicit use occurs with frequent dosing of 5 to 30 g GHB throughout day and night (Barker et al, 2007;Craig et al, 2000;Degenhardt et al, 2003;Miotto et al, 2001;Sumnall et al, 2008;Wojtowicz et al, 2008).…”

Section: Subjective Effects Medical Use and Abusementioning

confidence: 99%

Reconsidering GHB: orphan drug or new model antidepressant?

et al. 2011

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For six decades, the principal mode of action of antidepressant drugs is the inhibition of monoamine re-uptake from the synaptic cleft. Tricyclic antidepressants, selective serotonin re-uptake inhibitors (SSRIs) and the new generation of dual antidepressants all exert their antidepressant effects by this mechanism. In the early days of the monoaminergic era, other efforts have been made to ameliorate the symptoms of depression by pharmacological means. The gamma-aminobutyric acid (GABA) system was and possibly still is one of the main alternative drug targets. Gammahydroxybutyrate (GHB) was developed as an orally active GABA analogue. It was tested in animal models of depression and human studies. The effects on sleep, agitation, anhedonia and depression were promising. However, the rise of benzodiazepines and tricyclic antidepressants brought GHB out of the scope of possible treatment alternatives. GHB is a GABA(B) and GHB receptor agonist with a unique spectrum of behavioural, neuroendocrine and sleep effects, and improves daytime sleepiness in various disorders such as narcolepsy, Parkinson's disease and fibromyalgia. Although it was banned from the US market at the end of the 1990s because of its abuse and overdose potential, it later was approved for the treatment of narcolepsy. New research methods and an extended view on other neurotransmitter systems as possible treatment targets of antidepressant treatment brought GHB back to the scene. This article discusses the unique neurobiological effects of GHB, its misuse potential and possible role as a model substance for the development of novel pharmacological treatment strategies in depressive disorders. AbstractFor six decades, the principal mode of action of antidepressant drugs is the inhibition of monoamine re-uptake from the synaptic cleft. Tricyclic antidepressants, selective serotonin re-uptake inhibitors (SSRIs) and the new generation of dual antidepressants all exert their antidepressant effects by this mechanism. In the early days of the monoaminergic era, other intents have been made to ameliorate symptoms of depression by pharmacological means.The gamma-aminobutyric acid (GABA) system was and possibly still is one of the main alternative drug targets. Gammahydroxybutyrate (GHB) was developed as an orally activeGABA analogue. It was tested in animal models of depression and human studies. The effects on sleep, agitation, anhedonia and depression were promising. But the rise of benzodiazepines and tricyclic antidepressants brought GHB out of scope of possible treatment alternatives. GHB is a GABA B and GHB receptor agonist with a unique spectrum of behavioral, neuroendocrine and sleep effects, and improves daytime sleepiness in various disorders such as narcolepsy, Parkinson's disease and fibromyalgia. Although it was banned from the US-market end of the 1990-ies because of its abuse and overdose potential, it later was approved for the treatment of narcolepsy. New research methods and an extended view on other neurotransmitter systems a...

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