Naltrexone & SSRI in Alcoholics With Depression/PTSD

• ClinicalTrials.gov Identifier: NCT00338962
• Recruitment Status: Completed
• First Posted: June 20, 2006
• Results First Posted: February 5, 2016
• Last Update Posted: February 5, 2016
• Sponsor: Yale University
• Information provided by (Responsible Party): Yale University

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Alcoholism; Depression; PTSD	Drug: paroxetine; Drug: desipramine; Drug: Naltrexone; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 88 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Naltrexone & SSRI in Alcoholics With Depression/PTSD
• Study Start Date: October 2001
• Actual Primary Completion Date: July 2015
• Actual Study Completion Date: July 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Paroxetine and naltrexone; 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.	Drug: paroxetine; paroxetine (40mg/day); Other Name: paxil; Drug: Naltrexone; 50 mg per day; Other Name: Vivitrol
Active Comparator: paroxetine and placebo; Paroxetine was started at 10 mg per day and the dose was gradually increased over 2 weeks to 40 mg per day.	Drug: paroxetine; paroxetine (40mg/day); Other Name: paxil; Drug: Placebo; placebo
Active Comparator: Desipramine and naltrexone; 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.	Drug: desipramine; 200 mg per day; Other Name: Norpramin; Drug: Naltrexone; 50 mg per day; Other Name: Vivitrol
Active Comparator: Desipramine and placebo; Desipramine was started at a dose of 25 mg per day. The dose was gradually increased over 2 weeks to 200 mg per day.	Drug: desipramine; 200 mg per day; Other Name: Norpramin; Drug: Placebo; placebo

Outcome Measures

Primary Outcome Measures :

1. Mean Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS) [ Time Frame: beginning of treatment (week 1), and end of treatment (13 weeks) ]
   The OCDS is a 14-item (rated 0-4), self-administered questionnaire for characterizing and quantifying the obsessive and compulsive cognitive aspects of craving and heavy (alcoholic) drinking, such as drinking-related thought, urges to drink, and the ability to resist those thoughts and urges. A higher total score indicates higher craving and ranges from 0-48.
2. Clinician-Administered PTSD Scale (CAPS) [ Time Frame: beginning of treatment (week 1), and end of treatment (13 weeks) ]

   The CAPS is the gold standard in PTSD assessment. The CAPS-5 is a 30-item structured interview that can be used to:

   Make current (past month) diagnosis of PTSD Make lifetime diagnosis of PTSD Assess PTSD symptoms over the past week Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). A higher score is associated with higher severity of PTSD. The score is interpreted as follows: 0-19=Asymptomatic/few symptoms 20-39=Sub-threshold/mild PTSD 40-59=Threshold PTSD/moderate 60-79=Severe PTSD >80=Extreme PTSD

3. Hamilton Depression Rating Scale (HAM-D) [ Time Frame: beginning of treatment (week 1), and end of treatment (13 weeks) ]
   The HAM-D ranges from 0 (Normal) to >23 (Very Severe Depression)
4. Mean Number of Side Effects [ Time Frame: 12 weeks ]
   Differences in mean number of side effects reported for each group. Side effects and common adverse symptoms were evaluated by the research staff weekly, using a modified version of the ystematic Assessment for Treatment Emergent Events. The symptoms that are known to be associated with treatment with desipramine, paroxetine, and naltrexone were specifically screened or on a weekly basis. The symptoms were then clustered into the following categories: gastrointestinal, emotional, cold and flu symptoms, skin, sexual, neurological, and cardiac.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Connecticut

VA Connecticut Healthcare Systems

West Haven, Connecticut, United States, 06516

Sponsors and Collaborators

Yale University

Investigators

• Principal Investigator: Ismene Petrakis, M.D.; Yale University

More Information

Additional Information:

Published paper 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Petrakis IL, Ralevski E, Desai N, Trevisan L, Gueorguieva R, Rounsaville B, Krystal JH. Noradrenergic vs serotonergic antidepressant with or without naltrexone for veterans with PTSD and comorbid alcohol dependence. Neuropsychopharmacology. 2012 Mar;37(4):996-1004. doi: 10.1038/npp.2011.283. Epub 2011 Nov 16.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT00338962
• Other Study ID Numbers: HIC # 11637
• First Posted: June 20, 2006
• Results First Posted: February 5, 2016
• Last Update Posted: February 5, 2016
• Last Verified: January 2016

Keywords provided by Yale University:

SSRI; treatment; naltrexone; alcohol dependence; Desipramine; depression; PTSD

Additional relevant MeSH terms:

Alcoholism; Depression; Depressive Disorder; Behavioral Symptoms; Mood Disorders; Mental Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Naltrexone; Paroxetine; Desipramine; Alcohol Deterrents; Narcotic Antagonists; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Antidepressive Agents, Tricyclic