Gamma-hydroxybutyrate Withdrawal Research Articles

Severity and outcomes of admissions for gamma hydroxy-butyrate disorders before and after COVID-19 pandemic restrictions in South Western Sydney

ABSTRACT Background Dependence on gamma-hydroxybutyrate (GHB) is an emerging substance use disorder which can be life-threatening in overdose and withdrawal. The aim of this study was to describe rising GHB-related hospitalizations amidst the ongoing COVID-19 pandemic. Methods A retrospective consecutive case series of adults admitted to hospitals in South Western Sydney Local Health District was identified with clinical coding of GHB-related disorder between March 20 2019 and March 20 2021. Morbidity outcomes and multivariable Kaplan–Meier survival analysis on length of hospital stay were described. Results Sixty-nine of 84 included admissions, (82%) occurred in the 12 months following COVID-19 related border closure. Of 47 admissions for withdrawal, fifteen of 47 (32%) required intensive care, 6 (13%) intubation, 4 (9%) one-to-one ward observation, and 8 (17%) emergency calls for agitated delirium, fall, or seizure. Five cofactors were associated with longer hospital stay in the multivariable analysis: age 30 or older (p < .05), 6 months of regular GHB use (p < .01), and elective admission (p < .05), and diagnosis of psychosis rather than withdrawal (p < .05) or overdose (p < .001). Conclusions Development of a validated GHB withdrawal severity scale based on these risk factors could help identify patients requiring close monitoring for complicated withdrawal and escalation of care.

Inpatient GHB withdrawal management in an inner-city hospital in Sydney, Australia: a retrospective medical record review

RationaleRegular consumption of gamma-hydroxybutyrate (GHB) may result in a dependence syndrome that can lead to withdrawal symptoms. There are limited data on medications to manage GHB withdrawal.ObjectivesTo examine characteristics associated with delirium and discharge against medical advice (DAMA), in the context of implementing a GHB withdrawal management protocol at an inner-city hospital in 2020.MethodsWe retrospectively reviewed records (01 January 2017–31 March 2021), and included admissions that were ≥ 18 years of age, admitted for GHB withdrawal, and with documented recent GHB use. Admissions were assessed for demographics, medications administered, features of delirium, ICU admission, and DAMA. Exploratory analyses were conducted to examine factors associated (p < 0.2) with features of delirium and DAMA.ResultsWe identified 135 admissions amongst 91 patients. Medications administered included diazepam (133 admissions, 98.5%), antipsychotics (olanzapine [70 admissions, 51.9%]), baclofen (114 admissions, 84%), and phenobarbital (8 admissions, 5.9%). Features of delirium were diagnosed in 21 (16%) admissions. Delirium was associated with higher daily GHB consumption prior to admission, while duration of GHB use, time from presentation to first dose of diazepam, and concomitant methamphetamine use were inversely associated with delirium. DAMA occurred amongst 41 (30%) admissions, and was associated with a longer time from presentation to first dose of baclofen, while being female and receiving a loading dose of diazepam were inversely associated.ConclusionsThis study adds to the literature in support of the safety and feasibility of diazepam and baclofen for the management of GHB withdrawal. Prospective, randomised trials are required.

Current Insights on the Impact of Gamma-Hydroxybutyrate (GHB) Abuse.

Recreational gamma-hydroxybutyrate (GHB) use, although less common than other substance use, is increasingly recognised and is over-represented in emergency toxicology presentations. This narrative review summarizes GHB pharmacology, current patterns of use, potential harms and management of GHB toxicity and withdrawal. There is a complex interplay between GHB and GABA as GHB is both a prodrug and metabolite of GABA and GHB activates both GHB and GABA receptors. GHB is rapidly absorbed, with effects seen within minutes of ingestion. Metabolism is non-linear at higher doses. While GHB is listed as a controlled substance, its precursor’s gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are easily available as both have industrial applications. National surveys indicate low rates of GHB use, with identification of high-risk populations in men who have sex with men and polysubstance users. GHB is one of the three drugs most commonly used in chemsex. GHB is often co-ingested with other interacting psychoactive substances. Acute toxicity is dose-dependent, and management is supportive care. Withdrawal management is generally with benzodiazepines with addition of baclofen for more severe withdrawal. Barbiturates may have a role. Titration and tapering of pharmaceutical GHB is commonly used in the Netherlands. Complicated withdrawal with delirium may require intensive care and treatment with intravenous sedation. There are high rates of relapse after withdrawal and medications for longer-term management are currently being investigated. Chronic use is associated with poorer mental, physical and sexual health, social dysfunction and poor work performance. Laboratory detection is complicated as GHB is an endogenous substance with a short half-life, and therefore not often routinely assayed in the clinical setting. Future research should focus on improving GHB detection and management of GHB withdrawal and dependence. Interventions specific for high-risk groups should be developed and assessed.

Inpatient management of gamma-hydroxybutyrate withdrawal.

To describe the baseline characteristics, treatment and retention in patients electively admitted for gamma-hydroxybutyrate (GHB) withdrawal management. All patients admitted between July 2010 to June 2016 who used GHB two or more times per week with a minimum duration of 3 months were identified and data extracted by file review. Twelve cases satisfied the inclusion criteria, of whom 50% were female; 75% were using GHB daily, with an average daily amount of 16 ml. Average duration of use was 60 months. All subjects were using amphetamine type stimulants and nicotine. Psychiatric comorbidity and unintentional overdose were common; 50% completed treatment. Medications used included diazepam and neuroleptic. Two patients completed withdrawal with no medications. No subject using greater than 90 ml GHB in the preceding week completed treatment. Pattern of GHB use did not predict medication requirements during withdrawal management. There were low numbers attending for elective treatment for GHB use. Heavier GHB use predicted poor treatment retention. Polysubstance use and psychiatric co-morbidities need consideration in treatment planning.

Course and complications of GHB detoxification treatment: a1-year case series

Gamma-hydroxybutyrate (GHB) and its precursors have gained popularity over the last decade as adrug in the party and club scene; however, the clinical knowledge of these substances is low. In the literature there have been case reports of severe dependence and withdrawal but there is a lack of systematic knowledge about the clinical course and complications of detoxification treatment. The aim of this article is to evaluate the prevalence, treatment course, complications and compliance of GHB patients seeking inpatient qualified detoxification treatment (QDT). Aretrospective evaluation of the hospital charts of all patients admitted to this clinic in 2017 for QDT of GHB. The Jewish Hospital in Berlin (Jüdisches Krankenhaus Berlin) provides specialized inpatient units for addictive diseases and ageneral intensive care unit. The control population came from a prospective study of all patients with addictive diseases who were treated in the same hospital in 2012. In 2017 atotal of 18patients with GHB addiction were treated in this hospital. This corresponds to a 1‑year prevalence of 2.28% of all addictive diseases in this year. During detoxification treatment 52% of the GHB patients had to be temporarily transferred to the intensive care unit, 5% had to be temporarily mechanically ventilated and 26% suffered from withdrawal delirium. Of the patients 42% terminated treatment prematurely against medical advice. Withdrawal treatment from GHB is asevere and potentially dangerous condition, the prevalence of complications was higher than for most other drugs and the rate of intensive care and withdrawal delirium was very high. Further studies are urgently needed with the aim of reducing the complication rates of GHB withdrawal and enhancing therapy adherence.

Baclofen in gamma-hydroxybutyrate withdrawal: patterns of use and online availability

PurposeGamma-hydroxybutyrate (GHB) withdrawal is a life-threatening condition that does not always respond to standard treatment with benzodiazepines. Baclofen has potential utility as a pharmacological adjunct and anecdotal reports suggest that it is being used by drug users to self-manage GHB withdrawal symptoms. Here, we investigate current patterns of use and the online availably of baclofen.MethodsData triangulation techniques were applied to published scientific literature and publicly accessible Internet resources (grey literature) to assess the use of baclofen in GHB withdrawal. An Internet snapshot survey was performed to identify the availability of baclofen for online purchase and the compliance of retailers with the UK regulations. Data were collected according to pre-defined criteria.ResultsA total of 37 cases of baclofen use in GHB withdrawal were identified in the scientific literature, as well as 51 relevant discussion threads across eight Internet forums in the grey literature. Baclofen was available to purchase from 38 online pharmacies, of which only one conformed to the UK regulations.ConclusionsThere is limited published evidence on the use of baclofen in GHB withdrawal, but both scientific and grey literature suggests clinical utility. Online pharmacies are readily offering prescription-only-medication without prescription and due to inadequate regulation, pose a danger to the public.

Incidence of Gamma-Hydroxybutyrate (GHB) abuse and dependence in a rural crisis resolution team in the Netherlands

IntroductionGHB abuse and dependence are common in the Western region of Northern Brabant, a rural region in the south of the Netherlands.AimThe main goal is to look at the incidence and management of GHB abuse and dependence seen by the CRT in a rural area.MethodThis is a retrospective data analysis based on patient files of all assessments of the Western Northern Brabant crisis resolution team (CRT) from 2013 till 2015. Inclusion criterion was current or recent (&lt;24 hours) use of GHB with or without alcohol and other drugs. Several parameters were studied: frequency, duration and dose of GHB use, reason for referral and treatment/policy, which is used (admission, prescribed medication).ResultsOn a total of 4093 cases 50 persons were included. It shows that the percentage over the years has remained about the same (resp. 1.13%, 1.54% and 1.02%). Of all cases 41.5% used GHB only, 39.6% also used other drugs, and 9.4% GHB with alcohol and other drugs. During the assessment in the emergency department 37.7% was treated with a benzodiazepine, while 43.4% received no psychotropic medication.ConclusionGHB abuse and dependence are not commonly seen in the CRT, but the withdrawal symptoms can be challenging and GHB withdrawal is often accompanied by aggressive outbursts. Therefore, it is very important to make a decision whether outpatient or inpatient treatment is necessary and if psychotropic medication is needed.

Improving GHB withdrawal with baclofen: study protocol for a feasibility study for a randomised controlled trial.

BackgroundGHB (gamma-hydroxybutyrate) and its pro-drugs GBL (gamma-butyrolactone) and 1,4-butanediol (1,4-BD) are central nervous system depressants whose street names include ‘G’ and ‘liquid ecstasy’. They are used recreationally predominately for their stimulant and pro-sexual effects or for sedation to help with sleep and/or to ‘come down’ after using stimulant recreational drugs. Although overall population prevalence is low (0.1 %), in some groups such as men who have sex with men, GHB/GBL use may reach 20 %. GHB/GBL dependence may be associated with severe withdrawal with individuals presenting either acutely to emergency departments or to addiction services for support. Benzodiazepines are currently prescribed for GHB/GBL detoxification but do not prevent all complications, such as behavioural disinhibition, that may require hospitalisation or admission to a high dependency/intensive care unit. The GABAB receptor mediates most effects of GHB/GBL and the GABAB agonist, baclofen, has shown promise as an adjunct to benzodiazepines in reducing withdrawal severity when prescribed both during withdrawal and as a 2-day ‘preload’ prior to detoxification. The key aim of this feasibility study is provide information about recruitment and characteristics of the proposed outcome measure (symptom severity, complications including delirium and treatment escalation) to inform an application for a definitive randomised placebo controlled trial to determine the role of baclofen in the management of GHB/GBL withdrawal and whether starting baclofen 2 days earlier improves outcomes further.Methods/designThis is a prospective, randomised, double-blind, placebo-controlled feasibility study that will recruit participants (aged over 18 years) who are GHB/GBL-dependent and wish to undergo planned GHB/GBL detoxification or are at risk of acute withdrawal and are inpatients requiring unplanned withdrawal. We aim to recruit 88 participants: 28 unplanned inpatients and 60 planned outpatients.During detoxification we will compare baclofen 10 mg three times a day with placebo as an adjunct to the usual benzodiazepine regimen. In the planned outpatient arm, we will also compare a 2-day preload of baclofen 10 mg three times a day with placebo. Ratings of GHB/GBL withdrawal, sleep, depression, anxiety as well as GHB/GBL use will be collected. The main data analyses will be descriptive about recruitment and characterising the impact of adding baclofen to the usual benzodiazepine regimen on measures and outcomes of GHB/GBL withdrawal to provide estimates of variability and effect size. A qualitative approach will evaluate research participant and clinician acceptability and data collected to inform cost-effectiveness.DiscussionThis feasibility study will inform a randomised controlled trial to establish whether adding baclofen to a benzodiazepine regimen reduces the severity and complications of GHB/GBL withdrawal.Trial registrationISRCTN59911189. Registered 14 October 2015. Protocol: v3.1, 1 February 2016

Gamma-hydroxybutyrate (GHB) withdrawal syndrome: First case report in Lithuania (Kaunas addiction treatment center)

Gamma-hydroxybutyrate (GHB) is a γ-aminobutyric acid (GABA) precursor and metabolite that naturally occurs in the human body. Initially, GHB was used as an anaesthetic agent but was later also found to have anabolic, hypnotic, antidepressant, anxiolytic as well as cholesterol lowering effects. Recently though, research into GHB has been carried out primarily in assessing its effectiveness in treating alcohol and opioid withdrawal syndrome. There are no epidemiological data about GHB consumption in Lithuania, however during last decade there were observed many fatal cases of GHB users due to GHB intoxication or withdrawal abroad. In this article we will present the clinical case and problems which face the patient of 2-year daily GHB consumption. There were observed mild to moderate abstinence state presented with its clinical course and peculiarities. Whereas using GHB is becoming more popular in Lithuania, it is very important to pay attention to this substance and problems related to its usage.Disclosure of interestThe authors have not supplied their declaration of competing interest.

A Case Series of Pharmaceutical Gamma-Hydroxybutyrate in 3 Patients With Severe Benzodiazepine-Resistant Gamma-Hydroxybutyrate Withdrawal in the Hospital

Received January 23, 2014; revised March 7, 2014; accepted March 7, 2014. From Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands (M.S.vN); Novadic-Kentron Addiction Care Network, Vught, Nijmegen, The Netherlands (R.M.K., B.A.G.D.); Nijmegen Institute for Scientist-Practitioners in Addiction (NISPA), Nijmegen, The Netherlands (R.M.K., C.A.J.); Department of Intensive Care Medicine, Leiden University Medical Center, Leiden, The Netherlands (R.M.). Send correspondence and reprint requests to Martijn S. van Noorden,MD, PhD,Department of Psychiatry, LeidenUniversityMedical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands; e-mail: m.s. van_noorden@lumc.nl & 2015 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved. 1 Both authors contributed equally. Introduction

Gamma-hydroxybutyrate withdrawal syndrome: a case report

IntroductionTo raise awareness among health care workers of the risk of withdrawal symptoms after longstanding and intense abuse of gamma-hydroxybutyric acid.Case presentationA 23 year old Caucasian woman presented with gamma-hydroxybutyric addiction and withdrawal syndrome. The symptoms of gamma-hydroxybutyric withdrawal in this patient initially went unrecognized, upon which her situation deteriorated in such a way that she needed to be admitted to the Intensive Care Unit for airway protection and mechanical ventilation. Treatment with high doses of benzodiazepines led to liberation of the ventilator and further recovery.ConclusionWithdrawal symptoms of gamma-hydroxybutyric addiction are often not well recognized and the responsible physicians at Emergency Department, Intensive Care Unit and the Psychiatry ward need better understanding of diagnose and treatment. Gamma-hydroxybutyric acid withdrawal is potentially life threatening and its management may require a multidisciplinary approach. Early recognition of gamma-hydroxybutyric acid withdrawal may lead to better management of these patients.

Gamma-hydroxybutyrate withdrawal syndrome: a case report

Gamma-hydroxybutyrate withdrawal syndrome: a case report

Gamma-hydroxybutyrate withdrawal syndrome: a case report

Gamma-hydroxybutyrate withdrawal syndrome: a case report

Gamma-hydroxybutyrate withdrawal syndrome: dangerous but not well-known

Gamma-hydroxybutyrate (GHB) is an endogenous inhibitory neurotransmitter and anesthetic agent that is being abused as a ‘club drug.’ Withdrawal symptoms after cessation of GHB use are common and depend on the intensity of use. However, GHB withdrawal syndrome and delirium are unfamiliar to most psychiatrists, probably due to the fact that neither textbooks nor guidelines cover the subject. The GHB withdrawal syndrome may have a fulminant course that progresses to delirium. In those severe cases, admission to a general hospital and involvement of a psychiatrist become necessary. We present two cases of severe GHB withdrawal delirium, provide an overview of the literature and conclude with treatment recommendations.

Baclofen and Gamma-Hydroxybutyrate Withdrawal

Benzodiazepine treatment of life-threatening gamma-hydroxybutyrate (GHB) withdrawal is frequently unsatisfactory. Animal studies suggest strongly that treatment with GABA(B) agonists, such as baclofen, will be a more effective strategy. A case report from the medical intensive care unit (ICU) of the university tertiary care hospital. A 61-year-old woman was admitted to the medical ICU for severe withdrawal symptoms from chronic GHB use. This manifested as delirium, tremor, and seizures despite only small decreases in GHB dose and treatment with benzodiazepines. The addition of baclofen allowed the rapid sequential decreases in the GHB dose without seizure or delirium and resulted in long-term improvement of her tremor. Baclofen, a GABA(B) agonist, may be a useful agent in the treatment of severe GHB withdrawal.

335: Gamma Hydroxybutyrate Withdrawal Syndrome in the Emergency Department: Clinical Course and Autonomic Instability

Gamma hydroxybutyrate (GHB) and its analogs are drugs of abuse that were also sold as “supplements.” GHB withdrawal may be lethal; the literature to date has focused on severe cases. We investigated Emergency department (ED) presentations of GHB withdrawal to characterize signs and symptoms, autonomic instability, and clinical course.

Epileptic Seizure in GHB Withdrawal

DEAR SIR,We wish to describe the first documented case of gamma hydroxybutyrate (GHB)-related withdrawal seizures.A 24-year-old Caucasian man presented to the emergency department with paranola and...

The gamma-hydroxybutyrate withdrawal syndrome.

gamma-Hydroxybutyrate (GHB) is endogenous inhibitory transmitter that, when administered in pharmacological doses, has sedative-hypnotic properties. It is used in anaesthesia for the treatment of narcolepsy/catalepsy and in alcohol/opioid detoxification treatment regimens. Based on its purported anabolic effects, GHB use became established among bodybuilders. As the euphorigenic effects of GHB became publicised, attendees at dance clubs and rave parties began to use it alone or in combination with other psychoactive drugs. Following the ban of GHB in 1990, several precursor products (e.g. gamma-butyrolactone, butanediol) became widely used as replacement drugs until their ultimate proscription from lawful use in 2000. GHB and its precursors, like most sedative-hypnotic agents, can induce tolerance and produce dependence. Although many GHB users will experience a mild withdrawal syndrome upon drug discontinuation, those with chronic heavy GHB use can experience severe withdrawal. This syndrome clinically resembles the withdrawal syndrome noted from alcohol and other sedative-hypnotic drugs (e.g. benzodiazepines). Distinct clinical features of GHB withdrawal are its relatively mild and brief autonomic instability with prolonged psychotic symptoms. Patients with fulminant GHB withdrawal require aggressive treatment with cross-tolerant sedative hypnotics, such as benzodiazepines.

Gamma‐hydroxybutyric Acid Tolerance and Withdrawal in a Rat Model

Long‐term daily use of gamma‐hydroxybutyrate (GHB) and related compounds has recently been associated with a withdrawal syndrome. To the best of the authors' knowledge, there are currently no animal models of GHB withdrawal. Objectives: The authors studied and described the effect of chronic dosing of GHB (3–6 days) on tolerance and withdrawal in a rat model. Methods: Rats were administered GHB every three hours via intraperitoneal catheter. Groups of rats (2 per group) were dosed with GHB for either 3 (24 doses), 4 (32 doses), 5 (40 doses), or 6 (48 doses) days. The GHB dose was 0.25 g/kg for doses 1–8, 0.75 g/kg for doses 9–12, 1 g/kg for doses 13–16, 1.25 g/kg for doses 17–24, 1.5 g/kg for doses 25–32, 1.75 g/kg for doses 33–40, and 2 g/kg for doses 41–48. Following the last dose of GHB, the rats were scored using a 16‐point ethanol intoxication–withdrawal scale rating spontaneous behaviors, response to handling, grooming, and neurological signs. Lower scores indicate intoxication, while higher scores indicate withdrawal. Scores were recorded at hours 0, 1, 2, 3, 4, 5, 6, 9, 12, and 24. Results:Tolerance: Rats dosed with GHB for more days were less intoxicated one hour after their last GHB dose despite receiving higher doses. Withdrawal: The scores for all rats dosed with GHB increased at hours 4 (p = 0.028), 5 (p = 0.037), 6 (p = 0.007), and 9 (p = 0.024) after the last dose, indicating withdrawal. The scores demonstrated a linear increase dependent upon the number of days of GHB dosing at hours 3 (p &lt; 0.000), 4 (p = 0.004), 5 (p = 0.002), and 12 (p = 0.039) as well as prior to the last dose at hour 0 (p = 0.000). No rats developed seizures. Conclusions: Tolerance and mild withdrawal in rats can be induced by administering intraperitoneal GHB every three hours for 3–6 days. More prolonged dosing and higher doses of GHB may be necessary to induce severe withdrawal.

Two Cases of Severe Gamma-Hydroxybutyrate Withdrawal Delirium on a Psychiatric Unit: Recommendations for Management

Many psychiatric professionals are unfamiliar with gamma-hydroxybutyrate (GHB), an increasingly popular drug of abuse. GHB withdrawal can lead to psychosis and agitation, and patients may present to psychiatric facilities for treatment. Withdrawal may progress to delirium, with the potential for severe or even fatal medical complications. Therefore, it is imperative for psychiatric professionals to understand how to treat these patients. In this article, we describe two cases of severe GHB withdrawal syndrome that were treated in our inpatient psychiatric unit. These are among the most severe cases reported. Pertinent literature is reviewed and suggestions for treatment are discussed.