Naltrexone & SSRI in Alcoholics With Depression/PTSD

Yale University

Status and phase: Completed; Phase 3

Conditions: Alcoholism; PTSD; Depression

Treatments: Drug: Naltrexone; Drug: paroxetine; Drug: Placebo; Drug: desipramine

Study type: Interventional

Funder types: Other

Identifiers

NCT00338962

HIC # 11637

Details and patient eligibility

About

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.

Full 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.

Enrollment: 88 patients

Sex: All

Ages: 21 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• DSM-IV diagnosis of alcohol dependence and current DSM-IV depressive disorder or PTSD
• a recent episode of heavy drinking
• outpatient, sober from alcohol and other abused substance for at least 2 days before randomization
• stable medication regiment for at least 2 weeks
• women on adequate methods of contraception

Exclusion criteria

• current opioid dependence or abuse
• history (within the last 3 months) of opioid dependence or abuse
• pregnant
• history of psychotic disorders or current treatment with antipsychotic medications
• medication thought to influence drinking including: acamprosate, disulfiram, naltrexone, ondansetron, valproic acid or tegretol
• current (within the lst 6 months) use of MAO inhibitors
• suicidal active ideation or intent
• significant underlying medical condition
• history of cardiac condition abnormalities

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Triple Blind

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88 participants in 4 patient groups

Paroxetine and naltrexone

Active Comparator group

Description:

Paroxetine was started at 10 mg per day and the dose was gradually increased over 2 weeks to 40 mg per day. Naltrexone was started at 25 mg the first day and 50 mg per day for the rest of the treatment.

Treatment:

Drug: paroxetine

Drug: Naltrexone

paroxetine and placebo

Active Comparator group

Description:

Paroxetine was started at 10 mg per day and the dose was gradually increased over 2 weeks to 40 mg per day.

Treatment:

Drug: Placebo

Drug: paroxetine

Desipramine and naltrexone

Active Comparator group

Description:

Desipramine was started at a dose of 25 mg per day. The dose was gradually increased over 2 weeks to 200 mg per day. Naltrexone was started at 25 mg the first day and 50 mg per day for the rest of the treatment.

Treatment:

Drug: desipramine

Drug: Naltrexone

Desipramine and placebo

Active Comparator group

Description:

Desipramine was started at a dose of 25 mg per day. The dose was gradually increased over 2 weeks to 200 mg per day.

Treatment:

Drug: desipramine

Drug: Placebo