title: A human laboratory study of the effects of quetiapine on subjective intoxication and alcohol craving.
abstract: BACKGROUND
  The available treatments for alcoholism are only modestly effective, and patients vary widely in their treatment response. Quetiapine, an atypical antipsychotic medication with antagonist activity at D1 and D2, 5-HT(1A) and 5-HT(2A), H(1), and α1 and α2 receptors was shown to promote abstinence, reduce drinking days, and reduce heavy drinking days in a 12-week double-blind placebo-controlled trial.
  
  
  OBJECTIVE
  Although quetiapine represents one of the promising pharmacotherapies for the treatment of alcoholism, its mechanisms of action are poorly understood. The objective of this study is to elucidate the biobehavioral mechanisms of action of quetiapine for alcoholism, by examining its effects on subjective intoxication and craving.
  
  
  METHODS
  A total of 20 non-treatment-seeking alcohol-dependent individuals were randomized to one of the following conditions in a double-blind, placebo-controlled design: (1) quetiapine (400 mg/day); or (2) matched placebo. Participants were on the target medication dose (or matched placebo) for 4 weeks during which they completed weekly assessments of drinking, sleep, mood, and anxiety. Participants completed two counterbalanced intravenous placebo-alcohol administration sessions as well as cue-reactivity assessments.
  
  
  RESULTS
  Analyses revealed a significant effect of quetiapine in reducing craving during the alcohol administration, the alcohol cue-exposure, and the weekly reports of alcohol craving. Quetiapine was also found to reduce subjective intoxication and alcohol-induced sedation during the alcohol administration paradigm.
  
  
  CONCLUSIONS
  This study contributes critical new information about mechanisms of response to quetiapine for alcoholism, which, in turn, can inform larger-scale studies and ultimately, clinical practice.
authors.affiliation: Department of Psychology, University of California Los Angeles, 1285 Franz Hall, Box 951563, Los Angeles, CA 90095-1563, USA. lararay@psych.ucla.edu
authors.forename: Lara A
authors.initials: LA
authors.lastname: Ray
authors.forename: Pauline F
authors.initials: PF
authors.lastname: Chin
authors.forename: Andia
authors.initials: A
authors.lastname: Heydari
authors.forename: Karen
authors.initials: K
authors.lastname: Miotto
mesh_terms: D000328:Adult; D000368:Aged; D000435:Alcoholic Intoxication / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D000437:Alcoholism / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003463:Cues; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D000069348:Quetiapine Fumarate; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000517:prevention & control* / Q000523:psychology; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D000431:Ethanol