Prehabilitation in alcohol dependence as a treatment model for sustainable outcomes. A narrative review of literature on the risks associated with detoxification, from animal models to human translational research

In this review paper we discuss how the overarching concept of pre-habilitation is applicable to alcohol dependence. Central to pre-habilitation are the concepts of expected harm, risks and proactive planning to eliminate the harm or cope with the risks. We review the evidence from animal models, psychological experimental studies, as well as pharmacological studies, on the potential risks and harms associated with medically assisted alcohol detoxification and the current treatment paradigm for alcohol dependence. Animal models provide an approximation mostly of the physical aspect of alcohol withdrawal and detoxification process and make predictions about the development of the phenomena in humans. Despite their limitations, these models provide good evidence that withdrawal from chronic ethanol use induces cognitive impairment, which is worsened by repeated bouts of withdrawal and that these impairments are dependent on the duration of alcohol withdrawal. Initial clinical observations with alcohol dependent patients confirmed increased incidence of seizures. In recent years, accumulating evidence suggest that patients who have had repeated episodes of withdrawal also show changes in their affect, increased craving as well as significant deterioration of cognitive abilities, when compared to patients with fewer withdrawals. Alcohol dependence is associated with tolerance and withdrawal, with neuroadaptations in GABA-A and glutamatergic N-methyl-D-aspartate (NMDA) receptors playing key roles. It is suggested that dysregulation of the NMDA receptor system underpins alcohol related memory impairments. Finally we discuss the Structured Preparation for Alcohol Detoxification (SPADe) as an example of how pre-habilitation has been applied in clinical practice. We discuss the importance of partial control over drinking as an interim step towards abstinence and early introduction of lifestyle changes for both the patient and the immediate environment prior detoxification and while the patient is still drinking

A dose-finding design for dual-agent trials with patient-specific doses for one agent with application to an opiate detoxification trial.

There is a growing interest in early phase dose-finding clinical trials studying combinations of several treatments. While the majority of dose finding designs for such setting were proposed for oncology trials, the corresponding designs are also essential in other therapeutic areas. Furthermore, there is increased recognition of recommending the patient-specific doses/combinations, rather than a single target one that would be recommended to all patients in later phases regardless of their characteristics. In this paper, we propose a dose-finding design for a dual-agent combination trial motivated by an opiate detoxification trial. The distinguishing feature of the trial is that the (continuous) dose of one compound is defined externally by the clinicians and is individual for every patient. The objective of the trial is to define the dosing function that for each patient would recommend the optimal dosage of the second compound. Via a simulation study, we have found that the proposed design results in high accuracy of individual dose recommendation and is robust to the model misspecification and assumptions on the distribution of externally defined doses

A Feasibility Study of an Intervention for Structured Preparation before Detoxification in Alcohol Dependence: the SPADe trial protocol

Background: Alcohol-related harm is currently estimated to cost the National Health Service (NHS) in England £3.5bn a year. Of the estimated 1.6 million people with some degree of alcohol dependence, some 600,000 are believed to be moderately or severely dependent and may benefit from intensive treatment. Outcomes from medically assisted withdrawal, also referred to as detoxification, are often poor, with poor engagement in relapse prevention interventions and subsequent high relapse rates. Detoxification is costly both financially and to the individual. It has been found that people who experience multiple detoxifications show more emotional and cognitive impairments. These changes may confer upon them the inability to resolve conflict and increased sensitivity to stress thus contributing to increased vulnerability risk of relapse. The study aims to test the feasibility of using a group intervention aiming to prepare participants for long term abstinence before, rather than after, they have medically assisted detoxification. The current study will establish key parameters that influence trial design such as recruitment, compliance with the intervention, retention, and sensitivity of alternative outcome measures, in preparation for a future Randomised Controlled Trial (RCT). This paper presents the protocol of the feasibility study. Methods: The study corresponds to Phase 2 of the Medical Research Council (MRC) complex interventions guidelines which cover the development and feasibility testing of an intervention. The work is in three stages. The development, adaptation, and implementation of the Structured Preparation before Alcohol Detoxification (SPADe) intervention (stage 1), a randomised feasibility study with economic evaluation (stage 2) and a qualitative study (stage 3). Fifty participants will be recruited from two community alcohol treatment services in England. Participants will be randomised in two arms: the treatment as usual arm (TAU), which includes planned medically assisted detoxification and aftercare and the intervention arm in which participants will receive structured group preparation before detoxification in addition to TAU. The main outcomes are duration of continuous abstinence with no incidents of lapse or relapse, percentage of days abstinent and time to relapse. Discussion: The socioeconomic harms associated with alcohol have been well documented yet existing treatment options have not been able to reduce high relapse rates. This study will build on existing naturalistic studies underpinned by psychological interventions offered early and before detoxification from alcohol, which aim to reverse automatised habitual behaviours and thus may help us to understand how better to support people to remain abstinent and improve post detoxification outcomes. Trial registration: Name of registry: ISRCTN; Trial Registration Number: 14621127; Date of Registration: 22/02/2017; URL of trial registry record: http://www.isrctn.com/ISRCTN1462112

Significant reductions in human visual gamma frequency by the GABA reuptake inhibitor tiagabine revealed by robust peak frequency estimation

The frequency of visual gamma oscillations is determined by both the neuronal excitation–inhibition balance and the time constants of GABAergic processes. The gamma peak frequency has been linked to sensory processing, cognitive function, cortical structure, and may have a genetic contribution. To disentangle the intricate relationship among these factors, accurate and reliable estimates of peak frequency are required. Here, a bootstrapping approach that provides estimates of peak frequency reliability, thereby increasing the robustness of the inferences made on this parameter was developed. The method using both simulated data and real data from two previous pharmacological MEG studies of visual gamma with alcohol and tiagabine was validated. In particular, the study by Muthukumaraswamy et al. [2013a] (Neuropsychopharmacology 38(6):1105–1112), in which GABAergic enhancement by tiagabine had previously demonstrated a null effect on visual gamma oscillations, contrasting with strong evidence from both animal models and very recent human studies was re-evaluated. After improved peak frequency estimation and additional exclusion of unreliably measured data, it was found that the GABA reuptake inhibitor tiagabine did produce, as predicted, a marked decrease in visual gamma oscillation frequency. This result demonstrates the potential impact of objective approaches to data quality control, and provides additional translational evidence for the mechanisms of GABAergic transmission generating gamma oscillations in humans

An exploration of identity change in post-detoxification alcohol dependent individuals

Purpose: Dependent alcohol use is a severe addictive disorder with significant enduring consequences for health and social functioning. We aimed to inductively explore the process of identity change for alcohol dependent people progressing through a ‘pre-habilitation’ intervention, alcohol detoxification and post-detoxification recovery support. Design: Qualitative study as a part of a process evaluation situated within a UK feasibility trial of a group-based intervention in preparation for structured alcohol detoxification. Semi-structured qualitative interviews (face-to-face or telephone) collected self-reported data on experiences of treatment provision as part of the feasibility trial. Thematic analysis of transcripts and iterative categorisation of identity related themes and concepts was conducted with verification of analysis undertaken by a second coder. Findings: Identity change was revealed in participant narratives around the meta themes of external (social-identity) and internal (self-identity) concepts. External influences impacting social identity were key, having influenced initiation into alcohol use, influencing acceptance of the stigmatised ‘alcoholic’ label, and then being central to the treatment journey. Internal influences on self-identity also impacted on the process of identity change. In recovery, there was hope in discovering a new ‘normal’ identity or rediscovering normality. Originality: Analysis demonstrates that moving from regular alcohol use to problematic use is a journey of identity change that is influenced at the macro (cultural), meso (group) and micro (relational) social levels. Throughout the treatment journey, social influences in gaining a new non-drinker identity are key. Findings suggest a need for long term support through treatment and community-based groups specifically to foster positive identity change that may not have been addressed previously

Service Users’ Views and Experiences of Alcohol Relapse Prevention Treatment and Adherence: New Role for Pharmacists?

Aims: To understand service users’ views and experiences of alcohol relapse prevention medication, views of a telephone behaviouralmodification intervention delivered by pharmacists and the use of Contingency Management (CM) to support acamprosate adherence following assisted alcohol withdrawal.Methods: Four focus groups were conducted within four alcohol treatment and recovery groups across England (UK), with service users with lived experience of alcohol dependence (26 participants). Semi-structured topic guide was used to explore participants’ views and experiences of alcohol relapse prevention medication, a telephone behavioural modification medication intervention delivered by pharmacists, and the use of CM to support acamprosate adherence. These were audio-recorded, transcribed verbatim and thematically analysed inductively and deductively.Results: Four themes were identified: concerns about support and availability of alcohol relapse prevention medication; lack of knowledge and understanding about acamprosate treatment; positive perceptions of acamprosate adherence telephone support from pharmacists; and negative perceptions of CM to support acamprosate adherence. There were misunderstandings about acamprosate’s mode of action and strong negative beliefs about CM. However, most were positive about pharmacists’ new role to support acamprosate adherence.Conclusion: This study highlighted challenges service users face to commence alcohol relapse prevention medication. It appears service users could benefit from a pharmacist-led telephone intervention to improve understanding about acamprosate medication, particularly, if delivered in an engaging and motivating way

Service Users’ Views and Experiences of Alcohol Relapse Prevention Treatment and Adherence: New Role for Pharmacists?

Aims: To understand service users' views and experiences of alcohol relapse prevention medication, views of a telephone behavioural modification intervention delivered by pharmacists and the use of Contingency Management (CM) to support acamprosate adherence following assisted alcohol withdrawal. // Methods: Four focus groups were conducted within four alcohol treatment and recovery groups across England (UK), with service users with lived experience of alcohol dependence (26 participants). Semi-structured topic guide was used to explore participants' views and experiences of alcohol relapse prevention medication, a telephone behavioural modification medication intervention delivered by pharmacists, and the use of CM to support acamprosate adherence. These were audio-recorded, transcribed verbatim and thematically analysed inductively and deductively. // Results: Four themes were identified: concerns about support and availability of alcohol relapse prevention medication; lack of knowledge and understanding about acamprosate treatment; positive perceptions of acamprosate adherence telephone support from pharmacists; and negative perceptions of CM to support acamprosate adherence. There were misunderstandings about acamprosate's mode of action and strong negative beliefs about CM. However, most were positive about pharmacists' new role to support acamprosate adherence. // Conclusion: This study highlighted challenges service users face to commence alcohol relapse prevention medication. It appears service users could benefit from a pharmacist-led telephone intervention to improve understanding about acamprosate medication, particularly, if delivered in an engaging and motivating way

Striatal dopamine D2/D3 receptor binding in pathological gambling is correlated with mood-related impulsivity

AbstractPathological gambling (PG) is a behavioural addiction associated with elevated impulsivity and suspected dopamine dysregulation. Reduced striatal dopamine D2/D3 receptor availability has been reported in drug addiction, and may constitute a premorbid vulnerability marker for addictive disorders. The aim of the present study was to assess striatal dopamine D2/D3 receptor availability in PG, and its association with trait impulsivity. Males with PG (n=9) and male healthy controls (n=9) underwent [11C]-raclopride positron emission tomography imaging and completed the UPPS-P impulsivity scale. There was no significant difference between groups in striatal dopamine D2/D3 receptor availability, in contrast to previous reports in drug addiction. However, mood-related impulsivity (‘Urgency’) was negatively correlated with [11C]-raclopride binding potentials in the PG group. The absence of a group difference in striatal dopamine binding implies a distinction between behavioural addictions and drug addictions. Nevertheless, our data indicate heterogeneity in dopamine receptor availability in disordered gambling, such that individuals with high mood-related impulsivity may show differential benefits from dopamine-based medications

Brief intervention for alcohol misuse in people attending sexual health clinics: study protocol for a randomized controlled trial.

BACKGROUND: Over the last 30  years the number of people who drink alcohol at harmful levels has increased in many countries. There have also been large increases in rates of sexually transmitted infections. Available evidence suggests that excessive alcohol consumption and poor sexual health may be linked. The prevalence of harmful alcohol use is higher among people attending sexual health clinics than in the general population, and a third of those attending clinics state that alcohol use affects whether they have unprotected sex. Previous research has demonstrated that brief intervention for alcohol misuse in other medical settings can lead to behavioral change, but the clinical- and cost-effectiveness of this intervention on sexual behavior have not been examined. METHODS: We will conduct a two parallel-arm, randomized trial. A consecutive sample of people attending three sexual health clinics in London and willing to participate in the study will be screened for excessive alcohol consumption. Participants identified as drinking excessively will then be allocated to either active treatment (Brief Advice and referral for Brief Intervention) or control treatment (a leaflet on healthy living). Randomization will be via an independent and remote telephone randomization service and will be stratified by study clinic. Brief Advice will comprise feedback on the possible health consequences of excessive alcohol consumption, written information about alcohol and the offer of an appointment for further assessment and Brief Intervention. Follow-up data on alcohol use, sexual behavior, health related quality of life and service use will be collected by a researcher masked to allocation status six months later. The primary outcome for the study is mean weekly alcohol consumption during the previous three months, and the main secondary outcome is the proportion of participants who report unprotected sex during this period. DISCUSSION: Opportunistic intervention for excessive alcohol use has been shown to be effective in a range of medical settings. The SHEAR study will examine whether delivering such interventions in sexual health clinics results in reductions in alcohol consumption and will explore whether this is associated with changes in sexual behavior.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are