title: Emerging pharmacotherapies for alcohol dependence: a systematic review focusing on reduction in consumption.
abstract: BACKGROUND
  European Medicines Agency guidelines recognize two different treatment goals for alcohol dependence: abstinence and reduction in alcohol consumption. All currently approved agents are indicated for abstinence. This systematic review aimed to identify drugs in development for alcohol dependence treatment and to establish, based upon trial design, if any are seeking market authorization for reduction in consumption.
  
  
  METHODS
  We searched PubMed and Embase (December 2001-November 2011) to identify agents in development for alcohol dependence treatment. Additional studies were identified by searching ClinicalTrials.gov and the R&D Insight and Clinical Trials Insight databases. Studies in which the primary focus was treatment of comorbidity, or n≤20, were excluded. Studies were then classified as 'abstinence' if they: described a detoxification/alcohol withdrawal period; enrolled patients who had undergone detoxification previously; or presented relapse/abstinence rates as the primary outcome. Studies in patients actively drinking at baseline were classified as 'reduction in consumption'.
  
  
  RESULTS
  Of 602 abstracts identified, 45 full-text articles were eligible. Five monotherapies were in development for alcohol dependence treatment: topiramate, fluvoxamine, aripiprazole, flupenthixol and nalmefene. Nalmefene was the only agent whose sponsor was clearly seeking definitive approval for reduction in consumption. Development status was unclear for topiramate, fluvoxamine, aripiprazole and flupenthixol. Fifteen agents were examined in published exploratory investigator-initiated trials; the majority focused on abstinence. Ongoing (unpublished) trials tended to focus on reduction in consumption.
  
  
  CONCLUSIONS
  While published studies generally focused on abstinence, ongoing trials focused on reduction in consumption, suggesting a change in emphasis in the approach to treating alcohol dependence.
authors.affiliation: Hôpital Paul Brousse, INSERM 669, Université Paris-Sud, Villejuif, France. Electronic address: henri-jean.aubin@pbr.aphp.fr.
authors.forename: Henri-Jean
authors.initials: HJ
authors.lastname: Aubin
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Daeppen
mesh_terms: D064829:Alcohol Abstinence; D000427:Alcohol Deterrents / Q000627:therapeutic use*; D000428:Alcohol Drinking / Q000188:drug therapy*; D000437:Alcoholism / Q000188:drug therapy*; D000068180:Aripiprazole; D005475:Flupenthixol / Q000627:therapeutic use; D016666:Fluvoxamine / Q000627:therapeutic use; D005632:Fructose / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D009271:Naltrexone / Q000031:analogs & derivatives / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use; D011619:Psychotropic Drugs / Q000627:therapeutic use; D015363:Quinolones / Q000627:therapeutic use; D000077236:Topiramate
chemical_list: D000427:Alcohol Deterrents; D010879:Piperazines; D011619:Psychotropic Drugs; D015363:Quinolones; D000077236:Topiramate; D005632:Fructose; D009271:Naltrexone; D000068180:Aripiprazole; D005475:Flupenthixol; D016666:Fluvoxamine; C038981:nalmefene
keywords: Abstinence; Alcohol dependence; Burden; Reduction in consumption; Systematic review; Treatment