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Naltrexone & SSRI in Alcoholics With Depression/PTSD

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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:
Information provided by (Responsible Party):
Yale University

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.

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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


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




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.



Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00338962


Locations
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United States, Connecticut
VA Connecticut Healthcare Systems
West Haven, Connecticut, United States, 06516
Sponsors and Collaborators
Yale University
Investigators
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Principal Investigator: Ismene Petrakis, M.D. Yale University

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT00338962     History of Changes
Other Study ID Numbers: HIC # 11637
First Posted: June 20, 2006    Key Record Dates
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:
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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