Acamprosate for treatment of alcohol dependence: mechanisms, efficacy, and clinical utility

Acamprosate, or N-acetyl homotaurine, is an N-methyl-D-aspartate receptor modulator approved by the Food and Drug Administration (FDA) as a pharmacological treatment for alcohol dependence. The exact mechanism of action of acamprosate is still under investigation, but the drug appears to work by promoting a balance between the excitatory and inhibitory neurotransmitters, glutamate and gamma-aminobutyric acid, respectively, and it may help individuals with alcohol dependence by reducing withdrawal-associated distress. Acamprosate has low bioavailability, but also has an excellent tolerability and safety profile. In comparison with naltrexone and disulfiram, which are the other FDA-approved treatments for alcohol dependence, acamprosate is unique in that it is not metabolized by the liver and is also not impacted by alcohol use, so can be administered to patients with hepatitis or liver disease (a common comorbid condition among individuals with alcohol dependence) and to patients who continue drinking alcohol. Acamprosate has demonstrated its efficacy in more than 25 placebo-controlled, double-blind trials for individuals with alcohol dependence, and has generally been found to be more efficacious than placebo in significantly reducing the risk of returning to any drinking and increasing the cumulative duration of abstinence. However, acamprosate appears to be no more efficacious than placebo in reducing heavy drinking days. Numerous trials have found that acamprosate is not significantly more efficacious than naltrexone or disulfiram, and the efficacy of acamprosate does not appear to be improved by combining acamprosate with other active medications (eg, naltrexone) or with psychosocial treatment (eg, cognitive-behavioral therapy). In this review, we present the data on acamprosate, including its pharmacology, efficacy, safety, and tolerability in the treatment of alcohol dependence

Mindfulness-based relapse prevention for substance craving.

Craving, defined as the subjective experience of an urge or desire to use substances, has been identified in clinical, laboratory, and preclinical studies as a significant predictor of substance use, substance use disorder, and relapse following treatment for a substance use disorder. Various models of craving have been proposed from biological, cognitive, and/or affective perspectives, and, collectively, these models of craving have informed the research and treatment of addictive behaviors. In this article we discuss craving from a mindfulness perspective, and specifically how mindfulness-based relapse prevention (MBRP) may be effective in reducing substance craving. We present secondary analyses of data from a randomized controlled trial that examined MBRP as an aftercare treatment for substance use disorders. In the primary analyses of the data from this trial, Bowen and colleagues (2009) found that individuals who received MBRP reported significantly lower levels of craving following treatment, in comparison to a treatment-as-usual control group, which mediated subsequent substance use outcomes. In the current study, we extend these findings to examine potential mechanisms by which MBRP might be associated with lower levels of craving. Results indicated that a latent factor representing scores on measures of acceptance, awareness, and nonjudgment significantly mediated the relation between receiving MBRP and self-reported levels of craving immediately following treatment. The mediation findings are consistent with the goals of MBRP and highlight the importance of interventions that increase acceptance and awareness, and help clients foster a nonjudgmental attitude toward their experience. Attending to these processes may target both the experience of and response to craving

Finding Success in Failure: Using Latent Profile Analysis to Examine Heterogeneity in Psychosocial Functioning Among Heavy Drinkers Following Treatment

Aims- To estimate differences in post-treatment psychosocial functioning among treatment failures\u27 (i.e. heavy drinkers, defined as 4+/5+ drinks for women/men) from two large multi-site clinical trials and to compare these levels of functioning to those of the purported treatment successes\u27 (i.e. non-heavy drinkers). Design- Separate latent profile analyses of data from two of the largest alcohol clinical trials conducted in the United States, COMBINE (Combined Pharmacotherapies and Behavioral Interventions) and Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity), comparing psychosocial outcomes across derived classes of heterogeneous treatment responders. Setting- Eleven US academic sites in COMBINE, 27US treatment sites local to nine research sites in Project MATCH. ParticipantsA total of 962 individuals in COMBINE (69% male, 77% white, mean age: 44years) treated January 2001 to January 2004 and 1528 individuals in Project MATCH (75% male, 80% white, mean age: 40years) treated April 1991 to September 1994. MeasurementsIn COMBINE, we analyzed health, quality of life, mental health symptoms and alcohol consequences 12 months post-baseline. In Project MATCH, we examined social functioning, mental health symptoms and alcohol consequences 15 months post-baseline. Findings- Latent profile analysis of measures of functioning in both samples supported a three-profile solution for the group of treatment failures\u27, characterized by high-, average- and low-functioning individuals. The high-functioning treatment failures\u27 generally performed better across measures of psychosocial functioning at follow-up than participants designated treatment successes\u27 by virtue of being abstainers or light drinkers. Conclusions- Current United States Food and Drug Administration guidance to use heavy drinking as indicative of treatment failure\u27 fails to take into account substantial psychosocial improvements made by individuals who continue occasionally to drink heavily post-treatment

Alcohol use disorder relapse factors:an exploratory investigation of craving, alcohol dependence severity, and meaning in life

For decades predictors of alcohol use disorder (AUD) relapse have been studied, and around 40 different clinical and demographic relapse determinants have been identified. This paper aims to investigate the relationship of two of these AUD relapse factors, namely craving and meaning in life (MiL). We hypothesized that greater meaning in life would be associated with lower cravings and lower relapse rates. An AUD subsample of 81 patients within a clinical population that participated in ongoing exploratory research on religious/spiritual factors related to substance use disorders was followed up to 1 year. Craving (as measured with the Penn Alcohol Craving Scale) and meaning in life (as measured with the Meaning in Life Questionnaire- presence subscale) measures were assessed at baseline and relapse was assessed at 6- and 12-month follow up. Main effects and the interaction between craving and meaning in life in predicting alcohol relapse (with relapse defined as ‘any alcohol use’ and ≥ 3 consecutive days of drinking) were calculated/subject of analyses. We also investigated the relationship between relapse and alcohol dependence severity as measured with the Leeds Dependence Questionnaire. Baseline craving and dependence severity were related to relapse, but there were no associations between meaning in life and levels of craving or alcohol relapse. Our findings suggest a need for additional research on characterizing the Meaning in Life concept

Applying methods for personalized medicine to the treatment of alcohol use disorder

Objective: Numerous behavioral treatments for alcohol use disorder (AUD) are effective, but there are substantial individual differences in treatment response. This study examines the potential use of new methods for personalized medicine to test for individual differences in the effects of cognitive behavioral therapy (CBT) versus motivational enhancement therapy (MET) and to provide predictions of which will work best for individuals with AUD. We highlight both the potential contribution and the limitations of these methods. Method: We performed secondary analyses of abstinence among 1,144 participants with AUD participating in either outpatient or aftercare treatment who were randomized to receive either CBT or MET in Project MATCH. We first obtained predicted individual treatment effects (PITEs), as a function of 19 baseline client characteristics identified a priori by MATCH investigators. Then, we tested for the significance of individual differences and examined the predicted individual differences in abstinence 1 year following treatment. Predictive intervals were estimated for each individual to determine if they were 80% more likely to achieve abstinence in one treatment versus the other. Results: Results indicated that individual differences in the likelihood of abstinence at 1 year following treatment were significant for those in the outpatient sample, but not for those in the aftercare sample. Individual predictive intervals showed that 37% had a better chance of abstinence with CBT than MET, and 16% had a better chance of abstinence with MET. Obtaining predictions for a new individual is demonstrated. Conclusions: Personalized medicine methods, and PITE in particular, have the potential to identify individuals most likely to benefit from one versus another intervention. New personalized medicine methods play an important role in putting together differential effects due to previously identified variables into one prediction designed to be useful to clinicians and clients choosing between treatment options

Relapse prevention for addictive behaviors

The Relapse Prevention (RP) model has been a mainstay of addictions theory and treatment since its introduction three decades ago. This paper provides an overview and update of RP for addictive behaviors with a focus on developments over the last decade (2000-2010). Major treatment outcome studies and meta-analyses are summarized, as are selected empirical findings relevant to the tenets of the RP model. Notable advances in RP in the last decade include the introduction of a reformulated cognitive-behavioral model of relapse, the application of advanced statistical methods to model relapse in large randomized trials, and the development of mindfulness-based relapse prevention. We also review the emergent literature on genetic correlates of relapse following pharmacological and behavioral treatments. The continued influence of RP is evidenced by its integration in most cognitive-behavioral substance use interventions. However, the tendency to subsume RP within other treatment modalities has posed a barrier to systematic evaluation of the RP model. Overall, RP remains an influential cognitive-behavioral framework that can inform both theoretical and clinical approaches to understanding and facilitating behavior change