Prazosin to Reduce Stress-Induced Alcohol/Drug Craving and Relapse
Condition: Alcohol Dependence
MeSH terms: Alcoholism
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      To test the preliminary efficacy of 16.0 mg of Prazosin daily versus placebo in treatment
      seeking alcohol dependent individuals. This proposal is a laboratory and treatment outcome
      study to examine the effects of Prazosin on brief exposure to stress, drug cues and neutral
      situations on alcohol and drug craving, mood and neurobiological reactivity in a sample of
      cocaine and/or alcohol dependent individuals. Prazosin will be beneficial for reduction in
      stress and alcohol cue induced craving and related arousal. In a sample of treatment-seeking
      alcohol dependent men and women, we propose to examine (a) differences in measures of alcohol
      craving, emotion state, hypothalamic-pituitary-adrenal (HPA) activation, physiological
      arousal and plasma catecholamine response to stress imagery and to alcohol cue imagery as
      compared to neutral imagery; (b) reduction in alcohol abstinence symptoms; and (c)
      improvement in alcohol treatment outcomes as measured by reductions in heavy drinking days,
      any drinking days, secondarily on drinks/day, anxiety, mood and sleep.
    

Detailed description: 
      This is a proof-of-concept (POC) experimental therapeutics study with 2 arms. The first is a
      double-blind placebo controlled laboratory study with 40 individuals meeting current alcohol
      dependence criteria (DSM-IVTR) who are admitted to the Clinical Neuroscience Research Unit
      and initiated on Prazosin vs Placebo (16mg/day) after admission and initial detoxification
      (if required). Experimental laboratory sessions are conducted after subjects achieved full
      dose after the 2-week titration, in week 3-4 of inpatient stay. The laboratory outcomes
      included alcohol craving, anxiety, negative affect and neuroendocrine and sympathetic arousal
      measures. Individuals who wished to remain on study medication for the outpatient (Arm 2)
      were maintained on study medication throughout the outpatient phase for a total period of 12
      weeks.

      Arm 2 of the POC study is a 12-week randomized clinical trial (RCT) of Prazosin (16mg/day)
      versus Placebo in 100 treatment seeking alcohol dependent individuals, to assess whether high
      anxiety and distress, including alcohol craving, manifest as increased alcohol withdrawal
      symptoms at treatment entry moderates Prazosin effects on alcohol use outcomes. Primary
      alcohol use outcomes include heavy drinking days, any drinking days and secondarily
      drinks/day. Additional secondary outcomes include alcohol craving, anxiety and mood symptoms
      and sleep disturbances. Patients from Arm 1 who wished to continue on study medication for
      the outpatient phase were included in Arm 2. Arm 2 patients were initiated on study
      medication upon presenting with a negative breathalyzer without any minimum pre-treatment
      alcohol abstinence period prior to medication initiation.
    

Intervention name(s): Prazosin Tablet; Placebo Tablet
Intervention type(s): Drug; Drug
Intervention description(s): Target medication dosing was three times/day (t.i.d. dosing) with 5 mg in the morning, 5 mg in the afternoon and 6 mg at night reached at the end of the 2-week period, and maintained at this or their highest tolerated dose until week 11, followed by a 5-day taper in week 12, as in previous research.The titration schedule was as follows: 1 mg dose at bedtime for 2 nights, followed by a 1mg dose morning and night (8 AM/8 PM) on day 3, then 2 mg dose t.i.d., on days 4-6, 3 mg dose (2 pills each) morning and afternoon, and 4 mg dose (2 pills) at night for days 7-9, increased to 4 mg dosing t.i.d. on days 10-13, and from day 14 through week 11, 5 mg (1 pill) each in the morning and afternoon, and 6 mg for the night (2 pills) dose. This was followed by a 5-day taper in week 12. Patients were initiated on study medication upon presenting with a negative breathalyzer without any minimum pre-treatment alcohol abstinence period prior to medication initiation.; Placebo tablets identical in appearance and dosing schedule as the active study medication was utilized
Intervention MeSH terms: Prazosin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Interaction effects of Alcohol withdrawal distress with Prazosin versus Placebo effects during the trial.
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment