Not Two Sides of the Same Coin: A Qualitative Comparative Analysis of Post-Treatment Abstinence and Relapse.

Purpose: Substance use disorder (SUD) can be a chronic relapsing condition with poor treatment outcomes. Studies exploring factors associated with abstinence or relapse after treatment are often quantitative in nature, applying linear statistical approaches, while abstinence and relapse result from non-linear, complex, dynamic and synergistic processes. This study aims to explore these underlying dynamics using qualitative comparative analysis (QCA) as a mixed methods approach to further our understanding of factors contributing to post-treatment abstinence and relapse. Patients and Methods: In a prospective study, we gathered both qualitative and quantitative data pertaining to post-treatment substance use and the factors linked to substance use outcomes. These factors encompassed psychiatric comorbidity, intellectual disability, social disintegration, post-treatment support, and engagement in activities among patients who had undergone inpatient treatment for severe SUD (n = 58). QCA, a set-theoretic approach that considers the complex interplay of multiple conditions, was applied to discern which factors were necessary or sufficient for the occurrence of either abstinence or relapse. Results: We found two solutions predicting abstinence, and five for relapse. Post-treatment conditions (support and engagement in activities) were important for retaining abstinence. For relapse, individual baseline characteristics (intellectual disability, social disintegration, psychiatric comorbidity) combined with (post-)treatment factors (post-treatment support, activities) were important. Conclusion: Although abstinence and relapse represent opposing outcomes, they each exhibit distinct dynamics. To gain a comprehensive understanding of these dynamics, it is advisable to examine them as separate outcomes. For clinical practice, it can be worthwhile to recognize that fostering the conditions conducive to abstinence may differ from preventing the factors that trigger relapse.

This study explores why some people who struggle with addiction stay clean after treatment, while others relapse. Previous studies often used traditional statistical methods, with inconclusive results due to their inability to capture the complexity of this process. To address this, we used a different approach called qualitative comparative analysis (QCA). We collected information from 58 individuals who received inpatient treatment for their addiction. We looked at different factors like mental health problems, intellectual disability, the support they got from professionals and their social network, and whether they kept themselves busy with activities. We investigated how these factors are related to staying clean or relapse. With the help of QCA, we analyzed how these factors work together to cause either drug-free living or relapse. We found that staying clean was strongly linked to getting support after treatment and being involved in activities like hobbies or work. On the other hand, relapse was more likely in people with personal problems, like intellectual disabilities and mental health problems, when support and activities were lacking after treatment. In summary, our study indicates that staying clean and relapse are different processes with different factors at play. Helping someone stay clean may therefore require different strategies than preventing relapse. This insight can guide development of more personalized healthcare for individuals dealing with addiction.

Using the Recovery Capital Model to Explore Barriers to and Facilitators of Recovery in Individuals with Substance Use Disorder, Psychiatric Comorbidity and Mild-to-Borderline Intellectual Disability: A Case Series.

Recovery capital (RC) encompasses the wide range of resources individuals can employ to recover from Substance Use Disorder (SUD). It consists of five subdomains: human, social, cultural, financial, and community RC. Negative recovery capital (NRC) represents the obstacles to recovery. Research on (N)RC in complex multimorbid populations is scarce. This study offers an initial exploration of the viability of (N)RC in three individuals with SUD, psychiatric comorbidities, and an intellectual disability (a triple diagnosis) in inpatient addiction treatment. We collected case file data, ranked recovery goals, and conducted follow-up interviews. The data were subjected to template analysis, using (N)RC domains as codes. All domains were prevalent and relevant, showing dynamic and reciprocal effects, influenced by critical life events acting as catalysts. Notably, during treatment, patients prioritized individual skill development despite challenges in other domains. RC emerges as a valuable concept for mapping recovery barriers and facilitators in individuals with a triple diagnosis, serving as an alternative to the medical model and complementing the biopsychosocial model. It provides a systematic framework to assess critical factors for recovery in complex cases and accordingly align interventions. Future studies should explore the intersections of NRC domains and the dynamic nature of (N)RC to enhance the understanding of the challenges faced by individuals with a triple diagnosis.

Regression-Based Normative Data for the Montreal Cognitive Assessment (MoCA) and Its Memory Index Score (MoCA-MIS) for Individuals Aged 18-91.

(1) Background: There is a need for a brief assessment of cognitive function, both in patient care and scientific research, for which the Montreal Cognitive Assessment (MoCA) is a psychometrically reliable and valid tool. However, fine-grained normative data allowing for adjustment for age, education, and/or sex are lacking, especially for its Memory Index Score (MIS). (2) Methods: A total of 820 healthy individuals aged 18-91 (366 men) completed the Dutch MoCA (version 7.1), of whom 182 also completed the cued recall and recognition memory subtests enabling calculation of the MIS. Regression-based normative data were computed for the MoCA Total Score and MIS, following the data-handling procedure of the Advanced Neuropsychological Diagnostics Infrastructure (ANDI). (3) Results: Age, education level, and sex were significant predictors of the MoCA Total Score (Conditional R2 = 0.4, Marginal R2 = 0.12, restricted maximum likelihood (REML) criterion at convergence: 3470.1) and MIS (Marginal R2 = 0.14, REML criterion at convergence: 682.8). Percentile distributions are presented that allow for age, education and sex adjustment for the MoCA Total Score and the MIS. (4) Conclusions: We present normative data covering the full adult life span that can be used for the screening for overall cognitive deficits and memory impairment, not only in older people with or people at risk of neurodegenerative disease, but also in younger individuals with acquired brain injury, neurological disease, or non-neurological medical conditions.

Cognitive Impairments in Patients with GHB Use Disorder Predict Relapse in GHB Use.

BACKGROUND: The recreational use of gamma hydroxybutyrate (GHB) is associated with frequent overdoses, coma and the risk of developing GHB use disorder (GUD). Several studies suggest negative effects of GHB use or related comas on cognition. Since relapse rates are high in GUD and cognitive impairment has been associated with relapse in other substance use disorders, we aimed to (1) investigate the prevalence of cognitive impairment before and after detoxification, (2) analyse the relationship between GHB use, comas, and cognitive impairment, and (3) explore the association between cognitive impairment and relapse after detoxification in GUD patients. METHODS: In these secondary analyses of a prospective cohort study, a consecutive series of patients with GUD (n = 103) admitted for detoxification were recruited at six addiction care facilities in the Netherlands. The Montreal Cognitive Assessment (MoCA) was used to screen for cognitive impairments before and after detoxification. The follow-up duration for the assessment of relapse in GHB use was 3 months. RESULTS: A substantial number of patients with GUD screened positive for cognitive impairment before (56.3%) and after (30.6%) detoxification. Impairment on the MoCA memory domain was most frequent (58.8%). Cognitive impairment was not related to the severity of GUD or number of GHB-induced comas. Logistic regression analysis showed that only the memory score independently predicted relapse. DISCUSSION: Cognitive impairment seems highly prevalent among patients with GUD, possibly related to the risk of relapse. The absence of a relationship between the severity of GUD, level of GHB use, the number of GHB-induced comas, and cognitive impairment suggest that other factors may also contribute to the observed cognitive impairment.

"I Wish I Had Help Earlier. We Could Have Been Happier Sooner." Overcoming the Bystander Effect in the Care for Alcohol-Dependent Parents.

Parental alcohol dependency is associated with risks for the well-being of their children. However, guiding these families to support is often complicated. We interviewed 10 alcohol dependent parents, and held 3 focus group interviews with child welfare social workers, and alcohol and other drug workers. We identified a reluctance to act among professional and non-professional bystanders. Family members, neighbours, teachers, and general practitioners are often aware of parental drinking problems, but are reluctant to discuss them with the parents or to alert services designed to support families. The aim of this paper is to share the experiences of parents and show that parents appreciate interventions if done in a certain manner. Although parents were reluctant to discuss their drinking problem, they considered these problems as symptoms of underlying severe distress. They were highly motivated to get help for these underlying problems and wondered why they were not questioned about their distress by those around them. The silence of others reinforced pre-existing feelings of worthlessness and hopelessness. In this paper we analyse other's hesitation to intervene as a form of the bystander effect, and make suggestions on how this bystander effect can be overcome.

Characterization of the GHB Withdrawal Syndrome.

The gamma-hydroxybutyric acid (GHB) withdrawal syndrome can have a fulminant course, complicated by severe complications such as delirium or seizures. Detoxification by tapering with pharmaceutical GHB is a safe way to manage GHB withdrawal. However, a detailed description of the course of the GHB withdrawal syndrome is currently lacking. This study aimed to (1) describe the course of GHB withdrawal symptoms over time, (2) assess the association between vital signs and withdrawal symptoms, and (3) explore sex differences in GHB withdrawal. In this observational multicenter study, patients with GHB use disorder (n = 285) were tapered off with pharmaceutical GHB. The most reported subjective withdrawal symptoms (SWS) were related to cravings, fatigue, insomnia, sweating and feeling gloomy. The most prevalent objective withdrawal symptoms (OWS) were related to cravings, fatigue, tremors, sweating, and sudden cold/warm feelings. No association between vital signs and SWS/OWS was found. Sex differences were observed in the severity and prevalence of specific withdrawal symptoms. Our results suggest that the GHB withdrawal syndrome under pharmaceutical GHB tapering does not strongly differ from withdrawal syndromes of other sedative drugs. The lack of association between vital signs and other withdrawal symptoms, and the relative stability of vitals over time suggest that vitals are not suitable for withdrawal monitoring. The reported sex differences highlight the importance of a personalized approach in GHB detoxification.

Success Rates of Monitoring for Healthcare Professionals with a Substance Use Disorder: A Meta-Analysis.

In the past decades, monitoring programs have been developed for healthcare professionals with substance use disorders. We aimed to explore estimates of abstinence and work retention rates after participation in such monitoring programs. A literature search was performed using PubMed, Embase, PsycINFO, and CINAHL. Twenty-nine observational studies reporting on success rates (abstinence and work retention) of monitoring for healthcare professionals with a substance use disorder were included in the meta-analysis. Quality-effects models calculated pooled success rates and corresponding 95%-Confidence Intervals (CI), with subgroup analyses on monitoring elements and patient characteristics. Pooled success rates were 72% for abstinence (95%-CI = 63-80%) and 77% for work retention (95%-CI = 61-90%). Heterogeneity across studies was partly explained by the starting moment of monitoring, showing higher abstinence rates for studies that started monitoring after treatment completion (79%; 95%-CI = 72-85%) compared to studies that started monitoring with treatment initiation (61%; 95%-CI = 50-72%). About three-quarters of healthcare professionals with substance use disorders participating in monitoring programs are abstinent during follow-up and working at the end of the follow-up period. Due to selection and publication bias, no firm conclusions can be drawn about the effectiveness of monitoring for healthcare professionals with SUD.

Psychometric properties of the Montreal Cognitive Assessment (MoCA) in healthy participants aged 18-70.

Objectives: The Montreal Cognitive Assessment (MoCA) is a cognitive screen, available in three alternate versions. Aims of the current study were to examine the effects of age, education and intelligence on MoCA performance and to determine the alternate-form equivalence and test-retest reliability of the MoCA, in a group of healthy participants.Method: In 210 participants, two MoCA versions and an estimator for premorbid intelligence were administered at two time points.Results: Age, education and estimated premorbid intelligence correlated significantly with the total score (MoCA-TS) and the Memory Index Score (MoCA-MIS). Systematic differences between MoCA version 7.1 and alternate versions 7.2 and 7.3 were only found for the items animal naming, abstract reasoning and sentence repetition. Test-retest reliability of the MoCA-TS was good between 7.1 and 7.2 (ICC: 0.64) and excellent between 7.1 and 7.3 (ICC: 0.82). For the MoCA-MIS, coefficients were poor (ICC: 0.32) to fair (ICC: 0.48), respectively.Conclusion: Adequate norms are needed that take the effects of age, education and intelligence on MoCA performance into account. All three MoCA versions are largely equivalent based on MoCA-TS and the test-retest reliabilities show that this score is suitable to monitor cognitive change over time. Comparisons of the domain-specific scores should be interpreted with caution.Key pointsThe MoCA total score is a reliable cognitive measure.All three MoCA versions are largely equivalent.Age, education and intelligence are predictors of MoCA performance in healthy participants.Future studies should focus on collecting normative data for age, education and intelligence for use in clinical practice.

A Qualitative Approach in Understanding Illness Perception and Treatment Needs in Patients with Gamma Hydroxybutyrate Use Disorder.

BACKGROUND: The party drug gamma hydroxybutyrate (GHB) is highly addictive. GHB use disorder (GUD) has poor treatment outcome, with relapse rates over 60% within 3 months after detoxification. In order to get a better understanding of the limited treatment success, we explored GUD patients' illness perceptions and treatment needs. METHODS: In a qualitative cross-sectional observational study, using a semi-structured interview based on the works of Kleinmann, illness perceptions were explored among treatment seeking GUD patients (n = 20). The analysis was based on the principles of Grounded Theory by the 2 interviewers and an independent researcher. RESULTS: GUD patients had mainly positive views toward GHB. GHB was perceived as strongly rewarding and perceived as the solution to psychosocial problems, rather than the cause. After repeated readmissions, GUD patients perceived themselves as addicted to GHB and GHB use as more problematic. They reported a need for personalized treatment goals, which were mainly aimed toward dealing with psychiatric symptoms and social reintegration. CONCLUSION: GUD shares many characteristics with other substance use disorders, in line with gradual development from positive reinforcement in early-stage GUD to negative reinforcement in later stages of more compulsive GHB use. Future studies should investigate whether personalization of treatment goals, such as social reintegration, lead to better treatment outcomes.

Prevalence of cognitive impairment in patients with substance use disorder.

INTRODUCTION AND AIMS: Cognitive impairments in substance use disorder predict treatment outcome and are assumed to differ between substances. They often go undetected, thus the current study focuses on the prevalence of and differences in cognitive functioning across substances by means of a cognitive screen at the early stage of addiction treatment. DESIGN AND METHODS: The Montreal Cognitive Assessment was administered to outpatients seeking treatment for substance use disorder. Patient characteristics (age, years of regular use, polysubstance use, severity of dependence/abuse, depression, anxiety and stress) were also taken into account. RESULTS: A total of 656 patients were included (n = 391 used alcohol, n = 123 used cannabis, n = 100 used stimulants and n = 26 used opioids). The prevalence of cognitive impairments was 31%. Patients using alcohol had a lower total- and memory domain score than those using cannabis. Patients using opioids scored lower on visuospatial abilities than those using cannabis or stimulants. Younger patients scored higher than older patients. No effect was found for the other investigated characteristics. DISCUSSION AND CONCLUSIONS: Given the high prevalence of cognitive impairments, standard screening at an early stage of treatment is important to determine the course of treatment and maximise treatment outcome. Caution is needed in interpreting results about opioids due to an underrepresentation of this patient group, and more research is needed on the effect of age on Montreal Cognitive Assessment performance.

Treatment delivery of the community reinforcement approach in outpatient addiction treatment.

OBJECTIVE: Treatment model adherence is an important predictor of treatment outcome. In clinical practice evidence-based treatments are delivered in widely varying degrees. This study examines which Community Reinforcement Approach (CRA) procedures are delivered by addiction care therapists and how this is associated with therapist characteristics. METHOD: The study integrated two observational designs. Firstly, using a prospective design, 24 therapists registered every CRA procedure delivered during every patient contact over a six month period. Secondly, using a cross-sectional design, personal characteristics of 69 therapists were assessed including their self-reported delivery of CRA procedures and their perceptions with regard to the meaningfulness and complexity of these procedures. RESULTS: The number of CRA procedures delivered varied substantially among therapists both at session and patient level. More experienced therapists and those that had received advanced training previously, delivered more CRA procedures. Finally, the delivery of CRA procedures was positively associated with experienced meaningfulness and negatively associated with difficulty. CONCLUSIONS: The results confirm the relation between treatment delivery and experienced meaningfulness and difficulty of CRA procedures and provides support for advanced training to enhance the delivery of a wider range of CRA procedures.

Baclofen to Prevent Relapse in Gamma-Hydroxybutyrate (GHB)-Dependent Patients: A Multicentre, Open-Label, Non-Randomized, Controlled Trial.

BACKGROUND: Gamma-hydroxybutyrate (GHB) dependence is associated with a severe, potentially lethal, withdrawal syndrome and relapse rates as high as 60% within 3 months of detoxification. Baclofen has been shown to decrease self-administration of GHB in mice and reduce relapse in a case series of GHB-dependent patients. Controlled studies on the effectiveness of baclofen to prevent relapse in GHB-dependent patients are lacking. AIM: The aim of this study was to assess effectiveness of baclofen in preventing relapse in GHB-dependent patients. METHODS: This was an out-patient, multicentre, open-label, non-randomized, controlled trial in GHB-dependent patients (n = 107) in the Netherlands. Treatment as usual (TAU, n = 70) was compared with TAU plus baclofen 45-60 mg/day for 3 months (n = 37). Outcome measures were rates of lapse (any use) and relapse (using GHB on average once a week or more), based on self-report. Side effects were monitored with a baclofen side-effects questionnaire. Treatment groups were compared using Chi square analyses, with both per-protocol (PP) and intention-to-treat (ITT) analyses. RESULTS: GHB-dependent patients treated with baclofen after detoxification showed no reduced lapse rates, but reduced relapse and dropout rates, compared with patients receiving TAU only (24 vs 50%). While both ITT and PP analyses revealed similar results, the effectiveness of baclofen prescribed PP was slightly higher than in ITT analysis. Patients reported overall limited side effects, with the most frequently reported being feeling tired (28%), sleepiness (14%) and feeling depressed (14%). No serious adverse events were reported. CONCLUSIONS: This study showed potential effectiveness of baclofen in preventing relapse in patients with GHB dependence after detoxification. Though promising, future studies with longer follow-up and a randomized double-blind design should confirm these findings before recommendations for clinical practice can be made. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register with number NTR4528.

Treatment of substance use disorders: Effects on patients with higher or lower levels of PTSD symptoms.

While guidelines advise integrated treatment of patients with substance use disorder (SUD) and posttraumatic stress disorder (PTSD), recent studies and reviews find no convincing evidence of different outcomes following treatment between non-trauma focused integrated programs and SUD treatment alone. In this study, we analyzed whether SUD patients with higher levels of PTSD symptoms receiving standard, non-integrated SUD treatment (N=145) differed in outcomes compared to patients with lower levels of PTSD symptoms (N=152). Patients with higher levels of PTSD symptoms showed no difference in days of substance use, but significantly more craving and psychiatric symptoms (depression, anxiety and stress) were measured at baseline. After 3 and 6months of SUD treatment, there was no difference between the groups in decreased days of substance use. After 6months of SUD treatment, depression, anxiety and stress were significantly diminished in both groups. However, those with higher levels of PTSD symptoms at the start of the SUD treatment still reported significantly higher scores on depression, anxiety and stress after 6months of SUD treatment. These findings corroborate earlier studies that SUD patients with PTSD symptoms do not necessarily have poorer addiction treatment outcomes. However, as anxiety and PTSD symptoms predict relapse, future research should note the effect of higher symptom levels on long-term SUD treatment results. Additionally, more research is needed to determine which patients need additional treatment in conjunction with or following SUD treatment.

Treatment consumption and treatment re-enrollment in GHB-dependent patients in The Netherlands.

BACKGROUND: The objective of this study was to assess treatment consumption and re-enrollment in treatment in patients with gamma-hydroxybutyrate (GHB)-dependence in Dutch Addiction Treatment Centers (ATCs) in comparison with other addictions. METHODS: A cohort-study using nationwide administrative data from regular Dutch ATCs associated with the Dutch National Alcohol and Drugs Information System (LADIS), covering an estimated 95% of ATCs. We selected in- and out-patients with alcohol, drug and/or behavioral addictions with a first treatment episode in 2008-2011 and consecutive treatments until 2013 (n=71,679). Patients still in treatment at that date (n=3686; 5.1%), forensic patients (n=1949; 2.7%) and deceased patients (n=570; 0.8%) were excluded, leaving 65,474 patients (91.3%). Of those, 596 (0.9%) patients had GHB dependence. We analyzed number of treatment contacts, treatment duration, admissions and admission duration of the first treatment episode, and re-enrollment (defined as having started a second treatment episode in the study period). RESULTS: GHB-dependent patients showed the highest number of treatment contacts, duration of treatment and chance of being admitted. Re-enrollment rates were 2-5 times higher in GHB-dependent patients than other patients with adjusted HR of other addictions ranging from 0.18 (95% confidence interval [CI]: 0.15-0.21) to 0.53 (95% CI: 0.47-0.61). CONCLUSIONS: This study demonstrates high levels of treatment consumption and high rates of treatment re-enrollment in GHB-dependent patients. These findings highlight the urgency of developing effective relapse prevention interventions for GHB-dependent patients.

Psychiatric comorbidity, psychological distress, and quality of life in gamma-hydroxybutyrate-dependent patients.

Understanding the psychiatric state and psychological distress level of patients with gamma-hydroxybutyrate dependence is important to develop effective detoxification and relapse management methods. The aim of the current study was to assess the prevalence among gamma-hydroxybutyrate-dependent individuals of psychiatric comorbidity and psychological distress levels and their association with the individuals' pattern of misuse and quality of life. There were 98 patients tested with the Mini International Neuropsychiatric Interview-plus, the Brief Symptom Inventory, the Depression Anxiety Stress scale, and the EuroQoL-5D as a part of the Dutch gamma-hydroxybutyrate detoxification monitor in 7 addiction treatment centers. Participants were selected from those undergoing inpatient gamma-hydroxybutyrate detoxification treatment between March 2011 and September 2012. Males accounted for 68% of the participants and the average age was 28-years-old. A high rate of psychiatric comorbidity (79%) was detected, including anxiety (current 38%, lifetime 40%), mood (13%, 31%), and psychotic disorders (13%, 21%). The level of psychological distress was significantly higher than the standard outpatient reference group, especially in patients with current psychiatric comorbidity (Brief Symptom Inventory Global Severity Index mean 1.61 versus 1.09, p ≤ 0.01). Increased gamma-hydroxybutyrate misuse (higher dose and shorter interval between doses) was associated with the presence of lifetime psychosis, current mood disorders (rpb = 0.23, p = 0.025), and psychoticism as a symptom of psychological distress. Current anxiety, mood disorders and high psychological stress had a negative effect on participants' quality of life. Gamma-hydroxybutyrate dependence is characterized by serious psychiatric comorbidity and psychological distress, both of which are, in turn, associated with increased gamma-hydroxybutyrate use and a lower quality of life. This needs to be considered during detoxification to avoid complicated withdrawal. Providing treatment for patients' mental health issues is vital for ensuring treatment compliance, avoiding relapse and improving the patients' quality of life.

Detoxification with titration and tapering in gamma-hydroxybutyrate (GHB) dependent patients: The Dutch GHB monitor project.

BACKGROUND AND AIMS: Gamma-hydroxybutyrate (GHB) detoxification procedures have been insufficiently studied for effectiveness and safety. Based on case reports, benzodiazepines are generally regarded as first-choice agents in GHB detoxification. Detoxification by titration and tapering (DeTiTap) with pharmaceutical GHB in an open-label consecutive case series of 23 GHB-dependent patients showed to be feasible, effective and safe. This study further explored the feasibility, effectiveness and safety of this detoxification procedure in a large group of patients. METHOD: A large observational multicenter study was carried out in six addiction treatment centers in the Netherlands. GHB-dependent inpatients (229 unique patients, 274 admissions) were titrated on and tapered off with pharmaceutical GHB. RESULTS: Successful detoxification was achieved in 85% of cases. Detoxification was carried out in 12.5days in most patients. The DeTiTap procedure proved to be feasible and significantly reduced the experienced withdrawal symptoms and craving (p≤0.001). Several symptoms were found to influence the course of subjective withdrawal symptoms. During detoxification, psychological symptoms such as depression, anxiety, and stress decreased (p≤0.05). The main complications were hypertension and anxiety. Six patients were sent to the general hospital for observation, but all six were able to continue detoxification in the addiction treatment centers. Most patients (69%) relapsed within three months after detoxification. CONCLUSIONS: The DeTiTap procedure using pharmaceutical GHB seems a safe alternative to benzodiazepines as a GHB detoxification procedure. However, the high relapse rates warrant further investigation.

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.

The Effect of Co-occurring Substance Use on Gamma-hydroxybutyric Acid Withdrawal Syndrome.

OBJECTIVES: Gamma-hydroxybutyric acid (GHB) withdrawal is a complex syndrome which can be potentially life-threatening. Additionally, GHB-dependent patients frequently report co-occurring substance use of other psychoactive drugs. We assessed the add-on effect of co-use on GHB withdrawal symptoms. METHODS: We conducted an open-label, pretest-posttest design study with 95 patients selected from 229 inpatients admitted for detoxification, who were divided into GHB only (GO, n = 40), GHB plus sedatives (GSE, n = 38), and GHB plus stimulants (GST, n = 17) groups. GHB withdrawal was evaluated by means of the Subjective Withdrawal Scale. Co-use add-on effects on the severity of withdrawal symptoms were evaluated 2.5 hours after the last illicit GHB self-administration (T1) when withdrawal was expected and 2.5 hours later, after administration of a very low dose of pharmaceutical GHB (T2). RESULTS: The GO group reported high scores of psychomotor retardation symptoms at both T1 and T2, and also high cravings, agitation, and restlessness at T1, and anxiety at T2. The GSE group reported the highest score in psycho-autonomic distress symptoms at both T1 and T2, whereas the GST group reported the highest score in psycho-motor stress factor at T2. There was no significant difference in withdrawal intensity in all symptom clusters between T1 and T2 for both GSE and GO groups. However, after 5 hours, the GST group reported significant decreases in intensity for all symptoms except for psycho-motor stress. At T1, GST and GSE groups reported more muscle twitches than the GO group as a significant add-on effect to the GHB withdrawal. At T2, the GST group experienced more agitation (P = 0.009), restlessness (P = 0.001), and rapid pulse (P = 0.034) than the GO group. CONCLUSIONS: Co-use, especially of stimulants, caused an add-on effect on the GHB withdrawal symptoms within the first 5 hours.

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

OBJECTIVE: x03B3;-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 x03B3;-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 ß1-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.