title: Prazosin effects on stress- and cue-induced craving and stress response in alcohol-dependent individuals: preliminary findings.
abstract: BACKGROUND
  Stress, alcohol cues, and dysregulated stress responses increase alcohol craving and relapse susceptibility, but few pharmacologic agents are known to decrease stress- and cue-induced alcohol craving and associated stress dysregulation in humans. Here we report findings from a preliminary efficacy study of the alpha-1 receptor antagonist, prazosin, in modulating these relapse-relevant factors in alcohol-dependent individuals.
  
  
  METHODS
  Seventeen early abstinent, treatment-seeking alcohol-dependent individuals (12 men and 5 women) were randomly assigned to receive either placebo or 16 mg daily prazosin in a double-blind, placebo-controlled manner over 4 weeks. During week 4, all patients participated in a 3-day laboratory experiment involving 5-minute guided imagery exposure to stress, alcohol cue, and neutral-relaxing/control conditions, 1 exposure per day, on consecutive days in a random, counterbalanced order. Alcohol craving, anxiety, negative emotion, cardiovascular measures, and plasma hypothalamic-pituitary-adrenal (HPA; cortisol, adenocorticotropic hormone) were assessed repeatedly in each session.
  
  
  RESULTS
  The prazosin group (n = 9) versus the placebo group (n = 8) showed significantly lower alcohol craving, anxiety, and negative emotion following stress exposure. The placebo group also showed significantly increased stress- and cue-induced alcohol craving, anxiety, negative emotion, and blood pressure (BP), as well as a blunted HPA response relative to the neutral condition, while the prazosin group showed no such increases in craving, anxiety, negative emotion, and BP, and no blunted HPA response to stress and alcohol cue exposure.
  
  
  CONCLUSIONS
  Prazosin appears efficacious in decreasing stress- and cue-induced alcohol craving and may normalize the stress dysregulation associated with early recovery from alcoholism. Further research to assess the efficacy of prazosin in reducing alcohol craving and stress-related relapse risk is warranted.
authors.affiliation: The Connecticut Mental Health Center, Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06519, USA. helen.fox@yale.edu
authors.forename: Helen C
authors.initials: HC
authors.lastname: Fox
authors.forename: George M
authors.initials: GM
authors.lastname: Anderson
authors.forename: Keri
authors.initials: K
authors.lastname: Tuit
authors.forename: Julie
authors.initials: J
authors.lastname: Hansen
authors.forename: Anne
authors.initials: A
authors.lastname: Kimmerling
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Siedlarz
authors.forename: Peter T
authors.initials: PT
authors.lastname: Morgan
authors.forename: Rajita
authors.initials: R
authors.lastname: Sinha
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000437:Alcoholism / Q000188:drug therapy* / Q000523:psychology*; D001007:Anxiety / Q000209:etiology / Q000517:prevention & control; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003463:Cues; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D004644:Emotions / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007092:Imagination; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D011224:Prazosin / Q000009:adverse effects / Q000627:therapeutic use*; D055502:Secondary Prevention; D013315:Stress, Psychological / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D011224:Prazosin