Rationale for combining acamprosate and naltrexone for treating alcohol dependence.

Department of Neuropharmacology, The Scripps Research Institute, 10550 North Torrey Pines Road, TPC5, La Jolla, California 92037, USA.
Journal of studies on alcohol. Supplement 08/2005;
Source: PubMed

ABSTRACT This article provides an evidence-based review of acamprosate and naltrexone, used alone and in combination. Both medications are gaining increasing availability worldwide by prescription for the treatment of alcohol dependence. There is scientific and clinical interest in examining these drugs in combination, given their high tolerability, moderate effect sizes, different pharmacological profiles and potentially different effects on drinking outcomes.
This article includes a review of the key similarities and differences between acamprosate and naltrexone in the treatment of alcohol dependence; the published double-blind, placebo-controlled trials of acamprosate and naltrexone across a uniform range of outcome criteria to elucidate the differences and similarities in the behavioral effects of these drugs; the two published pharmacokinetic and pharmacodynamic drug interaction studies of acamprosate and naltrexone; and the single-site clinical trial of acamprosate and naltrexone used alone and in combination relative to placebo.
Pharmacokinetic and pharmacodynamic studies report an increase in acamprosate plasma levels with no clinically significant elevation in adverse events when the two drugs are used in combination. Data from dose-response studies for acamprosate alone suggest that the augmentation of acamprosate plasma levels by co-administration of naltrexone may have clinical benefits.
These factors support investigating the efficacy and safety of combining acamprosate and naltrexone for the treatment of alcohol dependence in a large-scale multisite trial, with evaluation of potential predictors of response to each drug alone and in combination relative to placebo.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Managing the treatment of alcohol dependence is challenging due to the chronic, relapsing nature of the disease and the need for education about available pharmacotherapies. An increased understanding of the neurochemistry underlying alcohol dependence and improved clinical trial methodology has led to the development and use of medications in conjunction with psycho-social therapy for this disorder. Psychosocial interventions have been widely used as a method to support abstinence and reduce drinking behaviors; however, psychosocial support without phar-macological treatment has had limited success, with nearly half the patients relapsing within the first year. Currently, 3 US Food and Drug Administration – approved drugs are available for the treatment of alcohol dependence—disulfiram, naltrexone (oral and injectable), and acamprosate. Each drug is effective in reducing drinking via different biological mechanisms. Acamprosate and naltrexone demonstrate promise in the successful management of chronic alcohol use. Meta-analyses of clinical trials show that acamprosate may be best for achieving outcomes such as maintaining complete abstinence, whereas oral naltrexone is best for decreasing the number of heavy drinking days. A long-acting injectable form of naltrexone demonstrated a reduced event rate of heavy drinking, consistent with oral naltrexone data. Although inconsistent in clinical efficacy outcomes, selective serotonin reuptake inhibitors may be beneficial in certain subsets of alcoholics. Other drugs currently being investigated for the treatment of alcohol dependence are serotonin type 3 antagonists, anticonvulsants, and atypical antipsychotics. A lcohol dependence is a chronic disorder that is vastly undertreated and underrecognized. Only 8% of the roughly 8 million people with alcohol dependence are treated within a specialty setting, and of these individuals, less than 10% receive pharmacotherapy. 1 Current treatment strategies include psychosocial therapies and pharmacotherapies; how-ever, psychosocial treatments alone have had limited success in achieving prolonged abstinence; 40% to 70% of alcohol-dependent patients receiving psychosocial therapy alone resume drinking within 1 year after treatment. 2 Therefore, there is a need for improved treatment outcomes that cannot be achieved by psychosocial support alone. 3 A better under-standing of the basic neurobiological and psychosocial components of alcohol dependence has led treatment research-ers to test various strategies in combining both psychosocial and pharmacological treatments. Research in the treatment of systemic and mood disorders has shown that psychosocial treatments affect some components of the disorder, 4 whereas pharmacotherapy affects other aspects. 5 For example, cognitive behavioral therapy is a psychosocial approach designed to improve patients' cognitive and behavioral skills for changing drinking behavior. 4 In contrast, pharmacotherapies use a mechanistic approach and target regulation of specific neuro-transmitters involved in alcohol dependence. 6 Pharmacological treatments may improve drinking behavior by enhancing abstinence and preventing relapse as well as reducing the amount of alcohol that people drink when they do relapse. Several studies have demonstrated the favorable influence of integrating psychotherapy with phar-macological agents for the treatment of patients with alcohol abuse or dependence. 7,8 By using step-by-step psychosocial treatment procedures that incorporate patient feedback, emotional support, and medication monitoring in addition to brief intervention and motivational enhancement into pharma-cotherapy, medication compliance can be improved. Medica-tion noncompliance is typically associated with negative treatment outcomes. Well-integrated psychosocial treatments that enhance medication compliance and treatment retention will increase the effectiveness of pharmacotherapies. 3,9 The 3 currently US FDA-approved medications for relapse prevention in alcohol dependence are disulfiram, naltrexone (oral and injectable forms), and acamprosate. This paper will review the clinical experiences of the current medications, including how these medications should be used in alcoholism treatment, discuss more recent trends in combination therapies, and briefly describe some new promising experimental pharmacological therapies used for the treatment of alcohol dependence.
    Journal of Clinical Psychopharmacology 01/2006; 26:20-29. DOI:10.1097/ · 3.76 Impact Factor
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alcoholic hepatitis (AH) is an acute hepatic inflammation associated with significant morbidity and mortality. Current evidence suggests that the pathogenesis is the end result of the complex interplay between ethanol metabolism, inflammation and innate immunity. Several clinical scoring systems have been derived to predict the clinical outcomes of patients with AH; such as Child-Turcotte-Pugh score, the Maddrey discriminant function, the Lille Model, the model for end stage liver disease scores, and the Glasgow alcoholic hepatitis score. At present, Corticosteroids or pentoxifylline are the current pharmacologic treatment options; though the outcomes from the therapies are poor. Liver transplantation as the treatment of alcoholic hepatitis remains controversial, and in an era of organ shortage current guidelines do not recommend transplantation as the treatment option. Because of the limitations in the therapeutic options, it is no doubt that there is a critical need for the newer and more effective pharmacological agents to treat AH.
    World Journal of Gastroenterology 05/2014; 20(20):6279-6286. DOI:10.3748/wjg.v20.i20.6279 · 2.43 Impact Factor