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

Abstract

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.

Acute Encephalopathies and Psychiatry

“…Deaths from benzodiazepine withdrawal occur. Thus, seizure precautions and prompt replacement of the sedative medication is emergently required at dosages that stop seizures and suppress hyperadrenergic withdrawal signs 10 .…”

“…High doses of benzodiazepines are required to treat withdrawal tremors, seizures, hallucinations, delusions, autonomic hyperactivity, and delirium 36 . Deaths are reported 10 . Diagnosis is difficult since GHB is non-detectable by routine drug screening and even with special urine testing it is usually no longer detected 12 hours after ingestion 10 .…”

“…Deaths are reported 10 . Diagnosis is difficult since GHB is non-detectable by routine drug screening and even with special urine testing it is usually no longer detected 12 hours after ingestion 10 .…”

Reconsidering GHB: orphan drug or new model antidepressant?

“…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).…”

The impact of gamma hydroxybutyrate (GHB) legal restrictions on patterns of use: Results from an International Survey

“…(Dyer et al, 2001;Gonzalez and Nutt, 2005;McDaniel and Miotto, 2001;Tarabar and Nelson, 2004) Superimposed on the original GHB-related syndromes, abuse of a number of GHB congeners taken as alternatives to the original compound has been linked to additional adverse events attributable to variations in dosing, metabolism, and other toxicokinetic and toxicodynamic parameters. (Palmer, 2004;Wojtowicz et al, 2008;Wood et al, 2008;Zvosec et al, 2001) In response to the growing GHB abuse and its attendant health hazards, the U.S. Controlled Substances Act was amended in 2000 to list GHB as an illicit Schedule I substance, although this regulatory restriction was complicated by the 2002 U.S. Food and Drug Administration (FDA) approval of a prescription formulation of GHB (Xyrem ® ) for the treatment of cataplexy.…”