B.A.G. Dijkstra

Gamma-hydroxybutyrate detoxification by titration and tapering

Objective: To determine the effectiveness and safety of a new detoxification procedure in γ-hydroxybutyrate (GHB)-dependent patients. GHB is an endogenous inhibitory neurotransmitter and anesthetic agent that is being abused as a club drug. In many GHB-dependent patients a severe withdrawal syndrome develops that does not respond to treatment with high dosages of benzodiazepines and often requires an admission to an intensive care unit. Methods: Based on the knowledge of detoxification procedures in opioid and benzodiazepine dependence, we developed a titration and tapering procedure. A consecutive series of 23 GHB-dependent inpatients were transferred from illegal GHB (mostly self-produced) in various concentrations to pharmaceutical GHB. They were given initial doses that resulted in a balance between sedation and withdrawal symptoms. After this titration period, patients were placed on a 1-week taper. Results: We have found that after titration the patients experienced a low level of withdrawal symptoms. During tapering these symptoms decreased significantly and no patient developed a delirium or a psychosis. None of the patients had to be transferred to a medium or intensive care unit. Conclusions: This detoxification procedure proved to be safe and convenient in patients with moderate to severe GHB dependence.

Does naltrexone affect craving in abstinent opioid-dependent patients?

Naltrexone blocks the opioid receptors that modulate the release of dopamine in the brain reward system and therefore blocks the rewarding effects of heroin and alcohol. It is generally assumed that naltrexone leads to reduction of craving, but few studies have been performed to prove this. The purpose of the present study was to examine the effect of the administration of naltrexone on craving level after rapid opioid detoxification induced by naltrexone. A naturalistic study was carried out in which patients were followed during 10 months after rapid detoxification. Data about abstinence, relapse, and naltrexone use were collected by means of urine specimens. Craving was measured by the visual analogue scale craving, the Obsessive Compulsive Drug Use Scale, and the Desires for Drug Questionnaire. Results showed that patients who relapsed in opioid use experienced obviously more craving than abstinent people. Patients who took naltrexone did not experience significant less craving than those who did not. These results suggest that the use of opioids is associated with increased craving and that abstinence for opioids is associated with less craving, independent of the use of naltrexone. This is in contrast to the general opinion. Because of the naturalistic design of the study, no firm conclusions can be drawn, but the results grounded the needs of an experimental study.

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

Psychometric evaluation of the Dutch version of the Subjective Opiate Withdrawal Scale (SOWS)

Aim: To evaluate the psychometric properties of the Dutch version of the 16-item Subjective Opiate Withdrawal Scale (SOWS). The SOWS measures withdrawal symptoms at the time of assessment. Methods: The Dutch SOWS was repeatedly administered to a sample of 272 opioid-dependent inpatients of four addiction treatment centers during rapid detoxification with or without general anesthesia. Examination of the psychometric properties of the SOWS included exploratory factor analysis, internal consistency, test-retest reliability, and criterion validity. Results: Exploratory factor analysis of the SOWS revealed a general pattern of four factors with three items not always clustered in the same factors at different points of measurement. After excluding these items from factor analysis four factors were identified during detoxification (‘temperature dysregulation’, ‘tractus locomotorius’, ‘tractus gastro-intestinalis’ and ‘facial disinhibition’). The 13-item SOWS shows high internal consistency and test-retest reliability and good validity at different stages of withdrawal. Conclusion: The 13-item SOWS is a reliable and valid instrument to assess opioid withdrawal during rapid detoxification. Three items were deleted because their content does not correspond directly with opioid withdrawal symptoms.

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

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 GABAB receptors (GABABR; subunits GABAB1 and GABAB2), 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-GABAAR. 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.

Decision rules for GHB (gamma-hydroxybutyric acid) detoxification: A vignette study

BACKGROUND GHB dependent patients can suffer from a severe and sometimes life-threatening withdrawal syndrome. Therefore, most of the patients are treated within inpatient settings. However, some prefers an outpatient approach to treatment. The aim of this study was to develop decision rules for addiction physicians to determine whether an outpatient or inpatient setting should be chosen for a safe GHB detoxification. METHODS A prospective vignette study was performed. Forty addiction medicine specialists from various treatment settings and residents of the Addiction Medicine postgraduate Master training were asked to contribute vignettes of GHB dependent patients. A focus group of 15 psychiatrists and addiction medicine specialists was asked to recommend an outpatient or inpatient setting for GHB detoxification treatment per vignette. Finally, five addiction medicine specialists, experts in GHB dependence treatment in the Netherlands, assessed the bio-psychosocial reasons for the choices of the focus group and formulated the recommended criteria. RESULTS Based on the bio-psychosocial state of twenty vignette patients, addiction physicians and psychiatrists established the criteria and conditions recommended for the indication of an outpatient GHB detoxification. Intensity of addiction (GHB dose ≤32 g/d and frequency of abuse ≤2 h) was stated as the primary criterion in determining the setting as well as the complexity of the psychiatric comorbid disorders. The importance of a stable support system was emphasised. CONCLUSION The vignette study resulted in a set of criteria with which addiction medicine specialists can make a weighted decision as to an outpatient or inpatient setting for GHB detoxification.

Pharmacological Treatment in γ-Hydroxybutyrate (GHB) and γ-Butyrolactone (GBL) Dependence: Detoxification and Relapse Prevention

The misuse of γ-hydroxybutyrate (GHB) for recreational purposes has resulted in an increase in GHB-related problems such as intoxications, dependence and withdrawal in several countries in Europe, Australia and the US over the last decade. However, prevalence rates of misuse of GHB and its precursor, γ-butyrolactone (GBL), are still relatively low. In this qualitative review paper, after a short introduction on the pharmacology of GHB/GBL, followed by a summary of the epidemiology of GHB abuse, an overview of GHB dependence syndrome and GHB/GBL withdrawal syndrome is provided. Finally, the existing literature on management of GHB detoxification, both planned and unplanned, as well as the available management of GHB withdrawal syndrome, is summarized. Although no systematic studies on detoxification and management of withdrawal have been performed to date, general recommendations are given on pharmacological treatment and preferred treatment setting.

Baclofen as relapse prevention in the treatment of gamma-hydroxybutyrate dependence: a case series

Abstract In the last decade, gamma-hydroxybutyrate (GHB) abuse and dependence have increased. It has been reported that GHB dependence has a high rate of relapse, serious complications of intoxication, and a potentially life-threatening withdrawal syndrome. Nevertheless, in clinical practice, there is no known medical treatment to support GHB relapse prevention. We describe a case series of patients who were supported through an off-label treatment with baclofen to avoid a relapse into GHB abuse, for a period of 12 weeks. Nine of 11 patients did not relapse while taking a dose ranging from 30 to 60 mg per day, one patient relapsed after 5 weeks, and one stopped after 7 weeks. Baclofen was well tolerated; patients reported mild side effects such as fatigue, nausea, dry mouth, excessive sweating, and depressive feelings. Although systematic evidence is still lacking, our practice-based experience suggests that treatment with baclofen to assist abstinence might be effective in patients with GHB dependence. Further systematic controlled studies are necessary to establish the exact efficacy and safety of baclofen as relapse prevention for GHB-dependent patients.

Prediction of abstinence in opioid-dependent patients.

Objectives:Opioid detoxification with subsequent naltrexone is found to be an effective method as the first step in an abstinence-oriented approach. The aim of this study is to investigate the predictive value of variables for abstinence in opioid-dependent patients. Methods:Opioid-dependent patients were followed up to 1 month after detoxification. Predictor variables were assessed at baseline, during detoxification, and at discharge. Primary outcome was abstinence assessed by analyzing urine samples and self-reports. Logistic regression was used to identify predictors of abstinence. Results:Of 272 participants, 211 could be rated as abstinent (59.2%) or nonabstinent (40.8%) at 1 month follow-up. Significant baseline predictors were severity score of justice/police (ASI) and physical quality of life (SF-36); discharge predictors were general quality of health (SF-36) and sleeping problems (SCL-90); change in sleeping problems (SCL-90) during detoxification was also a predictor. The explained variance of these predictors was very low and clinical significance was limited. Conclusions:Considering the results it seems not possible to predict who will be abstinent or not 1 month after detoxification. Because rapid detoxification is found to be an effective detoxification method in selected patients, it seems warranted to recommend that patients with similar characteristics (ie, patients motivated for an abstinence-based treatment and low non–drug-related severity scores on the ASI) should be regarded as eligible for rapid detoxification.

Opioid detoxification: from controlled clinical trial to clinical practice.

Controlled clinical trials have high internal validity but suffer from difficulties in external validity. This study evaluates the generalizability of the results of a controlled clinical trial on rapid detoxification in the everyday clinical practice of two addiction treatment centers. The results show that rapid detoxification in everyday practice differs with regard to patient characteristics, enrolment, and completion rates (86.8% vs. 100%). However, abstinence rates after rapid detoxification in the controlled clinical trial (61.8%) were generalizable to everyday clinical practice (59.0%). Implementation factors that may have influenced the results, such as referral problems and treatment delivery, are discussed.