Naltrexone & SSRI in Alcoholics With Depression/PTSD
Condition: Alcoholism; Depression; PTSD
MeSH terms: Alcoholism; Depression; Depressive Disorder
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to evaluate the efficacy of naltrexone in combination with an
      SSRI to reduce alcohol consumption in alcoholic patients with comorbid PTSD and depression.

      We hypothesize that the combination of naltrexone and SSRI will exhibit a greater decrease in
      alcohol consumption than that seen with treatment with SSRI alone, or with a combination of
      another class of antidepressant and naltrexone. We also hypothesize that SSRI will be
      effective in treating PTSD and depressive symptoms and naltrexone will be well tolerated.
    

Detailed description: 
      OBJECTIVE: Alcoholics with current comorbid mental disorders constitute the majority of
      alcoholics in clinical settings. Although there are two FDA approved medications for the
      treatment of alcoholism (naltrexone and disulfiram), there are no established
      pharmacotherapies for individuals with comorbid alcoholism and psychiatric illnesses. Studies
      suggest that the class of antidepressants known as serotonin selective reuptake inhibitors
      (SSRIs) is effective in reducing alcohol use in depressed individuals. In addition, a small
      open label study has shown that SSRIs have similar effects on individuals with comorbid PTSD
      and alcoholism. Preclinical studies have shown that the combination of a serotonergic agent
      and naltrexone was more effective than either medication alone in suppressing alcohol intake.
      To address this issue, we are conducting a 13 week randomized clinical trial evaluating the
      effects of paroxetine, desipramine and naltrexone in reducing alcohol use in alcohol
      dependent individuals who currently meet DSM-IV diagnosis for Depressive Disorder or PTSD.
      RESEARCH PLAN: One hundred and twenty subjects who are alcohol dependent patients with
      comorbid PTSD or Depressive Disorder will be recruited from the following West Haven VA
      sources: the Substance Abuse Treatment program, the PTSD clinic, the Women's clinic, clinical
      referrals and advertisement. These subjects will be randomized in a double-blind fashion to
      one of four cells. We will compare paroxetine versus desipramine and naltrexone versus
      placebo. The antidepressant will be started at a low dose and titrated upward on a fixed
      schedule. The target dose will be 40mg for paroxetine and 200mg for desipramine. Minimum
      dosage permitted for study retention will be 20mg for paroxetine and 150mg for desipramine.
      Pharmacological treatments will last 13 weeks. Psychosocial treatment will involve medication
      compliance therapy, using the Microelectric Event Monitoring (MEMS) bottle caps. The specific
      aim of the research is to compare the relative effectiveness of paroxetine versus desipramine
      and naltrexone versus placebo in reducing the quantity and frequency of alcohol consumption.
      METHODOLOGY: The primary outcome measures of major interest will include: frequency and
      quantity of alcohol consumption, self-reported craving, self-reported psychiatric and
      emotional distress, diagnostic assessment or psychiatric symptoms and side effects. These
      outcomes will be measured by the following: self-assessments, Timeline Followback, Hamilton
      Depression and anxiety scales, CAPS, ASI, Quality of Life, breathalyzer tests and monthly
      liver function tests.
    

Intervention name(s): paroxetine; desipramine; Naltrexone; Placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): paroxetine (40mg/day); 200 mg per day; 50 mg per day; placebo
Other intervention name(s): paxil; Norpramin; Vivitrol
Intervention MeSH terms: Naltrexone; Paroxetine; Desipramine
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: SSRI; treatment; naltrexone; alcohol dependence; Desipramine; depression; PTSD