Pharmacological Treatment Of Alcohol Dependence Research Articles

Pharmacological treatments for alcohol dependence: Evidence on uptake, inequalities and comparative effectiveness from a UK population-based cohort.

We assessed the prevalence of prescribing of certain medications for alcohol dependence and the extent of any inequalities in receiving prescriptions for individuals with such a diagnosis. Further, we compared the effectiveness of two of the most prescribed medications (acamprosate and disulfiram) for alcohol dependence and assessed whether there is inequality in prescribing either of them. We used a nationwide dataset on prescriptions and hospitalisations in Scotland, UK (N = 19,748). We calculated the percentage of patients receiving alcohol dependence prescriptions after discharge, both overall and by socio-economic groups. Binary logistic regressions were used to assess the odds of receiving any alcohol-dependence prescription and the comparative odds of receiving acamprosate or disulfiram. Comparative effectiveness in avoiding future alcohol-related hospitalisations (N = 11,239) was assessed using Cox modelling with statistical adjustment for potential confounding. Upto 7% of hospitalised individuals for alcohol use disorder received prescriptions for alcohol dependence after being discharged. Least deprived socio-economic groups had relatively more individuals receiving prescriptions. Inequalities in prescribing for alcohol dependence existed, especially across sex and comorbidities: males had 12% (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.81-0.96) and those with a history of mental health hospitalisations had 10% (OR 0.90, 95% CI 0.82-0.98) lower odds of receiving prescriptions after an alcohol-related hospitalisation. Prescribing disulfiram was superior to prescribing acamprosate in preventing alcohol-related hospitalisations (hazard ratio ranged between 0.60 and 0.81 across analyses). Disulfiram was relatively less likely prescribed to those from more deprived areas. Inequalities in prescribing for alcohol dependence exists in Scotland with lower prescribing to men and disulfiram prescribed more to those from least deprived areas.

OMEGA-3 Interventions in Alcohol Dependence and Related Outcomes: A Systematic Review and Propositions.

Background Pharmacological treatment for alcohol dependence has only three approved drugs: disulfiram, naltrexone and acamprosate. The effects of these drugs are, however, limited, presenting several side effects and a modestly higher efficacy compared to placebo. The administration of omega-3 might bring new perspectives to relapse prevention.Methods This systematic review aimed to analyze the available literature, compiling the studies that used omega-3 to prevent relapse in alcohol dependents.Results The databases used were PubMed and Web of Science. We identified 2,231 studies and only five articles addressed the administration of omega-3 and alcoholism. Preclinical studies evaluating the effects of PUFAs related to chronic alcohol administration showed improvements in behavioral, cellular and molecular levels. The clinical trial yielded inconclusive results.Conclusion Despite the reduced number of studies, omega-3 interventions seem to be promising for controlling issues related to alcohol dependence.

A proof-of-concept investigation into ketamine as a pharmacological treatment for alcohol dependence: study protocol for a randomised controlled trial

BackgroundWorldwide, alcohol abuse is a burgeoning problem. Abstinence is key to allow recovery of physical and mental health as well as quality of life, but treatment for alcohol dependence is associated with high relapse rates. Preliminary data have suggested that a combined repeated ketamine and psychological therapy programme may be effective in reducing relapse in severe alcohol use disorder. This non-commercial proof-of-concept trial is aimed at making a preliminary assessment of the effectiveness of this combined treatment in this patient group.Methods/designThis is a phase II, randomised, double-blind, placebo-controlled, parallel-group clinical trial taking place in two sites in the UK: the South West of England and London. Ninety-six recently detoxified alcoholics, with comorbid depressive symptoms, will be randomised to one of four treatment arms. Patients will receive either three sessions of ketamine (0.8 mg/kg administered intravenously (IV) over 40 minutes) or placebo (50 ml saline 0.9% IV over 40 minutes) plus either seven sessions of manualised psychological therapy or an alcohol education control. Patients will be assessed at 3 and 6 months on a range of psychological and biological variables. The primary endpoints are (1) relapse rates at 6 months and (2) percentage days abstinent at 6 months. Secondary endpoints include 3 and 6 month percentage days abstinence, tolerability (indicated by dropout), adverse events, depressive symptoms, craving and quality of life.DiscussionThis study will provide important information on a new combined psychological and pharmacological intervention aimed at reducing relapse rates in alcoholics. The findings would have broad application given the worldwide prevalence of alcoholism and its associated medical, psychological and social problems.Trial registrationClinicalTrials.gov, NCT02649231. Registered on 5 January 2016.

Bayesian mixed treatment comparisons meta-analysis for correlated outcomes subject to reporting bias.

Many randomized controlled trials (RCTs) report more than one primary outcome. As a result, multivariate meta-analytic methods for the assimilation of treatment effects in systematic reviews of RCTs have received increasing attention in the literature. These methods show promise with respect to bias reduction and efficiency gain compared to univariate meta-analysis. However, most methods for multivariate meta-analysis have focused on pairwise treatment comparisons (i.e., when the number of treatments is two). Current methods for mixed treatment comparisons (MTC) meta-analysis (i.e., when the number of treatments is more than two) have focused on univariate or very recently, bivariate outcomes. To broaden their application, we propose a framework for MTC meta-analysis of multivariate (≥ 2) outcomes where the correlations among multivariate outcomes within- and between-studies are accounted for through copulas, and the joint modeling of multivariate random effects, respectively. We consider a Bayesian hierarchical model using Markov Chain Monte Carlo methods for estimation. An important feature of the proposed framework is that it allows for borrowing of information across correlated outcomes. We show via simulation that our approach reduces the impact of outcome reporting bias (ORB) in a variety of missing outcome scenarios. We apply the method to a systematic review of RCTs of pharmacological treatments for alcohol dependence, which tends to report multiple outcomes potentially subject to ORB.

Serotonin's Complex Role in Alcoholism: Implications for Treatment and Future Research.

Current pharmacological treatments for alcohol dependence have focused on reducing alcohol consumption, but to date there are few treatments that also address the negative affective symptoms during acute and protracted alcohol withdrawal which are often exacerbated in people with comorbid anxiety and depression. Selective serotonin reuptake inhibitors (SSRIs) are sometimes prescribed to ameliorate these symptoms but can exacerbate anxiety and cravings in a select group of patients. In this critical review, we discuss recent literature describing an association between alcohol dependence, the SERT linked polymorphic region (5-HTTLPR), and pharmacological response to SSRIs. Given the heterogeneity in responsiveness to serotonergic drugs across the spectrum of alcoholic subtypes, we assess the contribution of specific 5-HT circuits to discrete endophenotypes of alcohol dependence. 5-HT circuits play a distinctive role in reward, stress, and executive function which may account for the variation in response to serotonergic drugs. New optogenetic and chemogenetic methods for dissecting 5-HT circuits in alcohol dependence may provide clues leading to more effective pharmacotherapies. Although our current understanding of the role of 5-HT systems in alcohol dependence is incomplete, there is some evidence to suggest that 5-HT3 receptor antagonists are effective in people with the L/L genotype of the 5-HTTLPR polymorphism while SSRIs may be more beneficial to people with the S/L or S/S genotype. Studies that assess the impact of serotonin transporter polymorphisms on 5-HT circuit function and the subsequent development of alcohol use disorders will be an important step forward in treating alcohol dependence.

Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence.

Alcohol use disorders (AUD) cause significant morbidity and mortality worldwide, but pharmacological treatments for them are underused, despite evidence of efficacy. Acamprosate, naltrexone, nalmefene and disulfiram are all approved in one or more region for the treatment of AUD. Baclofen currently has a temporary indication in France. Safety considerations for using psychopharmacological treatments in this patient group include the impact of concurrent alcohol consumption at high levels; multiple physical comorbidities that may interfere with pharmacological effects, distribution and metabolism; and concomitant medication for the treatment of comorbid physical and psychiatric conditions. The five drugs, including an extended-release injectable suspension of naltrexone, have different safety profiles that need to be balanced with the treatment objective (initiation or continuation of abstinence, or reduction of drinking), individual patient preferences and comorbid conditions. Appropriate treatment will be based on the unique risk-benefit profile in each case.

Glutamatergic plasticity and alcohol dependence-induced alterations in reward, affect and cognition

IntroductionAlcohol dependence is characterized by a reduction in reward threshold, development of a negative affective state, and significant cognitive impairments. Dependence-induced glutamatergic neuroadaptations in the neurocircuitry mediating reward, affect and cognitive function are thought to underlie the neural mechanism for these alterations. These changes serve to promote increased craving for alcohol and facilitate the development of maladaptive behaviors that promote relapse to alcohol drinking during periods of abstinence. ObjectiveTo review the extant literature on the effects of chronic alcohol exposure on glutamatergic neurotransmission and its impact on reward, affect and cognition. ResultsEvidence from a diverse set of studies demonstrates significant enhancement of glutamatergic activity following chronic alcohol exposure. In particular, up-regulation of GluN2B-containing NMDA receptor expression and function is a commonly observed phenomenon that likely reflects activity-dependent adaptive homeostatic plasticity. However, this observation as well as other glutamatergic neuroadaptations are often circuit and cell-type specific. DiscussionDependence-induced alterations in glutamate signaling contribute to many of the symptoms experienced in addicted individuals and can persist well into abstinence. This suggests that they play an important role in the development of behaviors that increase the probability for relapse. As our understanding of the complexity of the neurocircuitry involved in the addictive process has advanced, it has become increasingly clear that investigations of cell-type and circuit-specific effects are required to gain a more comprehensive understanding of the glutamatergic adaptations and their functional consequences in alcohol addiction. ConclusionWhile pharmacological treatments for alcohol dependence and relapse targeting the glutamatergic system have shown great promise in preclinical models, more research is needed to uncover novel, possibly circuit-specific, therapeutic targets that exhibit improved efficacy and reduced side effects.

Pharmacotherapy for alcohol dependence: A stratified approach

Alcohol dependence is a common disorder in many societies worldwide, and remains difficult to identify and treat. It is also a risk factor for many secondary non-communicable diseases. Pharmacotherapy is one available treatment option, but appears to be underutilised in practice. Major barriers to use of medications in this area include lack of clinical guidance and questionable efficacy. However, for each medication there appears to be a subpopulation that responds positively, and understanding the moderating factors to treatment efficacy is an important research goal. Thus, this review provides a narrative regarding potential stratification techniques in pharmacological treatment of alcohol dependence, with a specific focus on typologies and pharmacogenetics. In addition, we discuss the basic background of stratified medicine and recent studies on genetic predisposition to alcohol dependence. A growing repository of data exists for both approved and non-approved pharmacotherapies, but failure to replicate findings, inadequate sample sizes, and insufficient funding has resulted in a translational gap. Implementing evidence-based stratified/personalised therapy and identifying new therapeutic agents may lead to improved clinical outcomes and reduced financial burden. Despite some promising findings to date, much work is still required.

Transcranial Magnetic Stimulation and Deep Brain Stimulation in the treatment of alcohol dependence.

Alcohol dependence is a major social, economic, and public health problem. Alcoholism can lead to damage of the gastrointestinal, nervous, cardiovascular, and respiratory systems and it can be lethal, costing hundreds of billions to the health care system. Despite the existence of cognitive-behavioral therapy, psychosocial interventions, and spiritually integrated treatment to treat it, alcohol dependence has a high relapse rate and poor prognosis, albeit with high interindividual variability. In this review, we discuss the use of two neuromodulation techniques, namely repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation (DBS), and their advantages and disadvantages compared to first-line pharmacological treatment for alcohol dependence. We also discuss rTMS and DBS targets for alcohol dependence treatment, considering experimental animal and human evidence, with careful consideration of methodological issues preventing the identification of feasible targets for neuromodulation treatments, as well as inter-individual variability factors influencing alcoholism prognosis. Lastly, we anticipate future research aiming to tailor the treatment to each individual patient by combining neurofunctional, neuroanatomical and neurodisruptive techniques optimizing the outcome.

Peripherally Circulating Ghrelin Does Not Mediate Alcohol‐Induced Reward and Alcohol Intake in Rodents

Development of alcohol dependence, a chronic and relapsing disease, largely depends on the effects of alcohol on the brain reward systems. By elucidating the mechanisms involved in alcohol use disorder, novel treatment strategies may be developed. Ghrelin, the endogenous ligand for the growth hormone secretagogue receptor 1A, acts as an important regulator of energy balance. Recently ghrelin and its receptor were shown to mediate alcohol reward and to control alcohol consumption in rodents. However, the role of central versus peripheral ghrelin for alcohol reward needs to be elucidated. Given that ghrelin mainly is produced by peripheral organs, the present study was designed to investigate the role of circulating endogenous ghelin for alcohol reward and for alcohol intake in rodents. We showed that the Spiegelmer NOX-B11-2, which binds and neutralizes acylated ghrelin in the periphery with high affinity and thus prevents its brain access, does not attenuate the alcohol-induced locomotor activity, accumbal dopamine release and expression of conditioned place preference in mice. Moreover, NOX-B11-2 does not affect alcohol intake using the intermittent access 20% alcohol 2-bottle-choice drinking paradigm in rats, suggesting that circulating ghrelin does not regulate alcohol intake or the rewarding properties of alcohol. In the present study, we showed however, that NOX-B11-2 reduced food intake in rats supporting a role for circulating ghrelin as physiological regulators of food intake. Moreover, NOX-B11-2 did not affect the blood alcohol concentration in mice. Collectively, the past and present studies suggest that central, rather than peripheral, ghrelin signaling may be a potential target for pharmacological treatment of alcohol dependence.

Gabapentin Treatment for Alcohol Dependence

Approved medications for alcohol dependence are prescribed for less than 9% of US alcoholics. To determine if gabapentin, a widely prescribed generic calcium channel/γ-aminobutyric acid-modulating medication, increases rates of sustained abstinence and no heavy drinking and decreases alcohol-related insomnia, dysphoria, and craving, in a dose-dependent manner. A 12-week, double-blind, placebo-controlled, randomized dose-ranging trial of 150 men and women older than 18 years with current alcohol dependence, conducted from 2004 through 2010 at a single-site, outpatient clinical research facility adjoining a general medical hospital. Oral gabapentin (dosages of 0 [placebo], 900 mg, or 1800 mg/d) and concomitant manual-guided counseling. Rates of complete abstinence and no heavy drinking (coprimary) and changes in mood, sleep, and craving (secondary) over the 12-week study. RESULTS Gabapentin significantly improved the rates of abstinence and no heavy drinking. The abstinence rate was 4.1% (95% CI, 1.1%-13.7%) in the placebo group, 11.1% (95% CI, 5.2%-22.2%) in the 900-mg group, and 17.0% (95% CI, 8.9%-30.1%) in the 1800-mg group (P = .04 for linear dose effect; number needed to treat [NNT] = 8 for 1800 mg). The no heavy drinking rate was 22.5% (95% CI, 13.6%-37.2%) in the placebo group, 29.6% (95% CI, 19.1%-42.8%) in the 900-mg group, and 44.7% (95% CI, 31.4%-58.8%) in the 1800-mg group (P = .02 for linear dose effect; NNT = 5 for 1800 mg). Similar linear dose effects were obtained with measures of mood (F2 = 7.37; P = .001), sleep (F2 = 136; P < .001), and craving (F2 = 3.56; P = .03). There were no serious drug-related adverse events, and terminations owing to adverse events (9 of 150 participants), time in the study (mean [SD], 9.1 [3.8] weeks), and rate of study completion (85 of 150 participants) did not differ among groups. Gabapentin (particularly the 1800-mg dosage) was effective in treating alcohol dependence and relapse-related symptoms of insomnia, dysphoria, and craving, with a favorable safety profile. Increased implementation of pharmacological treatment of alcohol dependence in primary care may be a major benefit of gabapentin as a treatment option for alcohol dependence. clinicaltrials.gov Identifier: NCT00391716.

New and Old Drugs to Treat Alcohol Use Disorders

Around 2 billion people consume alcoholic beverages worldwide, and almost 10% of the world’s population is affected by AlcoholUse Disorders (AUDs) [1]. Alcohol consumption is responsible for approximately 3.8% of all deaths [2] and accounts for 5.5% of the global burden of disease [3]. So far, only three drugs [Naltrexone (NTX), Acamprosate (ACM), and Disulfiram (DF)] have been approved by the Food and Drug Administration for the treatment of alcohol dependence [4]; however, emerging data from clinical trials suggest that these medications are relatively ineffective in maintaining the abstinence from alcohol. The predict study conducted in Germany by Mann et al. [5] clearly documented that neither ACM nor NTX are more efficient than placebo in reducing the number of relapses throughout the complete treatment period and the subsequent 18 months of follow-up. The results of the predict study have been compared with those of the COMBINE trial performed in the United States (US) [6]. The main outcome of the predict study was the time elapsed before the first episode of heavy drinking, and, contrary to the positive NTX effect reported by the combine study, neither ACM nor NTX provided an additional benefit compared with placebo. It is worth noting that patients drank a significantly greater amount of alcohol before enrolment and more often fulfilled DSM-IV criteria for alcohol dependence in the predict than in the combine study, suggesting that the patient populations included in these trials were substantially different. A similar lack of efficacy also emerged from a previous European trial where NTX plus ACM were more effective than placebo and ACM alone in reducing episodes of heavy drinking, but not NTX alone [7]. A meta-analysis published a few years ago [8] stated that neither NTX nor ACM were able to maintain complete abstinence from alcohol; rather, these agents are effective in reducing relapses and the number of drinks per drinking days, and, consequently, the organ damage caused by alcohol consumption. The main aim in treating alcohol dependence is complete abstinence. In the light of the results of the studies reported above, ACM and NTX should be rationally indicated only when this purpose cannot be achieved, with the aim of reducing alcohol intake and, therefore, achieve a “harm reduction”. Indeed, total abstinence was obtained in an equivalent proportion of patients both in predict and combine studies, i.e. 39.3% and 38.9% respectively. Nevertheless, NTX and ACM remain the first line of pharmacological treatment for alcohol dependence. Are there any other pharmacological possibilities? An interesting position was expressed by Jonathan Chick and David Nutt in their “perspective” paper which appeared in 2011: “For a condition where existing therapies are only effective in a proportion of patients, and which has high morbidity and mortality, the time now seems right for reappraising the use of substitute prescribing for alcohol dependence” [9].

Pharmacotherapy for alcohol dependence: Perceived treatment barriers and action strategies among Veterans Health Administration service providers.

Although access to and consideration of pharmacological treatments for alcohol dependence are consensus standards of care, receipt of these medications by patients is generally rare and highly variable across treatment settings. The goal of the present project was to survey and interview the clinicians, managers, and pharmacists affiliated with addiction treatment programs within Veterans Health Administration (VHA) facilities to learn about their perceptions of barriers and facilitators regarding greater and more reliable consideration of pharmacological treatments for alcohol dependence. Fifty-nine participants from 19 high-adopting and 11 low-adopting facilities completed the survey (facility-level response rate = 50%) and 23 participated in a structured interview. The top 4 barriers to increased consideration and use of pharmacotherapy for alcohol dependence were consistent across high- and low-adopting facilities and included perceived low patient demand, pharmacy procedures or formulary restrictions, lack of provider skills or knowledge regarding pharmacotherapy for alcohol dependence, and lack of confidence in treatment effectiveness. Low patient demand was rated as the most important barrier for oral naltrexone and disulfiram, whereas pharmacy or formulary restrictions were rated as the most important barrier for acamprosate and extended-release naltrexone. The 4 strategies rated across low- and high-adopting facilities as most likely to facilitate consideration and use of pharmacotherapy for alcohol dependence were more education to patients about existing medications, more education to health care providers about medications, increased involvement of physicians in treatment for alcohol dependence, and more compelling research on existing medications. This knowledge provides a foundation for designing, deploying, and evaluating targeted implementation efforts.

Efficacy of Disulfiram for the Treatment of Alcohol Dependence Assessed with a Multicenter Randomized Controlled Trial

The efficacy of disulfiram in preventing an alcoholic relapse has been controversial. The aim of our study was to assess the efficacy of supervised disulfiram for the treatment of alcohol dependence with a multi-institutional study in Japan. In a single-blinded, randomized placebo-controlled study, we recruited 109 patients diagnosed with alcohol dependence under ICD-10 criteria. The patients were randomly allocated to 4 treatment groups, depending on whether they took disulfiram (200mg daily) or a placebo or whether they received adjunctive therapy consisting of mailed letters which delineated and emphasized the harmful effect of alcohol and the management of alcohol craving. The proportion of abstinence among the 4 groups at 26weeks after discharge was the primary outcome measure. The proportion of abstinence was compared with the severity of alcohol dependence and craving. Furthermore, we examined the proportion of abstinence in patients with inactive aldehyde dehydrogenase-2 (ALDH2). There were no significant differences among the 4 groups in terms of abstinent patients or study dropouts. The ratio of abstinence was not related to the severity of alcohol dependence or the degree of alcohol craving. Patients with inactive ALDH2 significantly sustained abstinence with the use of disulfiram (p=0.044). Supervised oral disulfiram use followed by intervention via letters seems to be ineffective for increasing abstinence. Further studies are necessary to prove the efficacy of disulfiram for the pharmacological treatment of alcohol dependence. We indicated the effectiveness of disulfiram for the maintenance of abstinence in patients with inactive ALDH2.

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.

The Effect of Naltrexone on Alcohol’s Stimulant Properties and Self‐Administration Behavior in Social Drinkers: Influence of Gender and Genotype

Few pharmacological treatments for alcohol dependence are available. Moreover, the best supported treatment, naltrexone hydrochloride, appears to work for only some. To investigate potential predictors of these differential responses, 40 social drinkers (20 women) were administered 6 days of treatment with naltrexone vs. placebo in a double-blind, counterbalanced, crossover design. At the end of each treatment period, participants received a single dose of their preferred alcoholic beverage followed by the opportunity to work for additional alcohol units using a progressive ratio (PR) breakpoint paradigm. All subjects but one were genotyped for the A118G polymorphism of the mu opioid receptor gene (OPRM1). Naltrexone decreased the ethanol-induced 'euphoria' to a priming dose of alcohol in two subgroups: (i) in women, and (ii) in subjects with the A118G polymorphism of the mu opioid receptor gene (OPRM1). Naltrexone did not decrease motivation to work for additional alcoholic beverages on the PR task regardless of gender or genotype. The results add to the evidence that naltrexone decreases positive subjective effects of alcohol, with preferential effects in distinct subgroups. Similar effects in heavier drinkers might decrease alcohol use.

Opioid Antagonists for Pharmacological Treatment of Alcohol Dependence – A Critical Review

Alcohol dependence is a widespread psychiatric disorder. While relapse prevention therapy in alcoholism was exclusively dominated by social and psychological treatments for many years, in the last decades the benefits of pharmacological agents for the rehabilitation treatment in alcoholism have become increasingly evident. Naltrexone, an opiate receptor antagonist, blocks the pleasant and reinforcing effects of alcohol by preventing the stimulation of opioid receptors and the reduction of dopamine release in the ventral tegmental area (VTA). Clinical evidence about the effectiveness of the substance is not always consistent, but meta-analyses confirm naltrexone's effect on the risk of heavy drinking. Evidence about the abstinence-maintaining effects of the substance comes from a relatively small database and needs further investigation. The evaluation of differential effects of naltrexone depending on biological or psychological profiles, which could further enhance the effectiveness of treatments for alcohol dependence, remains a challenge. Nalmefene, another opioid antagonist, as well as naltrexone depot, a sustained release formulation of naltrexone, are further promising strategies for the treatment of alcohol dependence. The review at hand gives on overview of the current evidence on opioid antagonists for the treatment of alcohol dependence regarding the possible mechanism of action, the substances' safety profiles and their effectiveness. The corresponding evidence is critically reviewed taking into consideration the influence of the study design on the magnitude and consistency of effect sizes as well the impact of patient characteristics on the response to the treatment with opioid antagonists. Future studies on the role of different subtypes of alcoholics according to their genetic or psychological profile to explain or even predict the effects of opioid antagonists in the treatment of alcohol dependence are needed.

Advances in Pharmacological Treatment of Alcohol Dependence

Advances in Pharmacological Treatment of Alcohol Dependence

Treatment of alcohol abuse: an evidence-based review.

This article represents the proceedings of a symposium at the 2002 annual meeting of the Research Society on Alcoholism in San Francisco, CA, organized and cochaired by Mats Berglund and Sten Thelander. The presentations were (1) Preventive interventions against hazardous consumption of alcohol, by Mikko Salaspuro; (2) Treatment of alcohol withdrawal, by Johan Franck; (3) Psychosocial treatment for alcohol problems, by Sven Andréasson and Agneta Ojehagen; and (4) Pharmacological treatment of alcohol dependence, by Mats Berglund.

Tratamiento farmacológico de la dependencia alcohólica

ObjectiveNeurobiological advances on alcohol dependence make feasible using further drugs in the treatment of alcoholism. Material and methodsThe farmacological treatment of alcoholism it is reviewed. ResultsAnticraving agents are the first choice in the pharmacological treatment of alcohol dependence. ConclusionesNearly all studies have shown that acamprasate and naltrexone are more efficacy than placebo. Also, when acamprosate and naltrexone have been compared, naltrexone was more efficacy than acamprosate in several outcome variables. Antidepressants are useful agents for patientswith alcohol dependence and depressive disorders. Recently the use of anticonvulsivants in the treatment of alcohol dependence is being proposed.