Acamprosate in Alcoholics With Comorbid Anxiety or Depression

The Use of Acamprosate in Individuals With Alcohol Dependence and Comorbid Anxiety or Depression

STUDY OBJECTIVES:

The primary objective of this study is to compare the safety and efficacy of acamprosate versus placebo in the treatment of alcohol dependence in adults with co-occurring mood or anxiety disorders (specifically, depression (MDE), generalized anxiety disorder (GAD) or social anxiety disorder). Secondary objectives are to evaluate the effect of acamprosate treatment on mood and anxiety disorders.

STUDY DESIGN:

This is a randomized, double-blind, placebo-controlled trial evaluating acamprosate in the treatment of alcohol dependence in adult outpatients with concurrent mood and/or anxiety disorders. The active study phase will be 12 weeks in duration. There will be a two-week screening period, followed by 12 weeks of study medication and a follow-up assessment at 14 weeks from randomization.

STUDY POPULATION:

A total of 90 (30 per site) men and women aged 18-60 years who have a current diagnosis of alcohol dependence as well as a current DSM-IV diagnosis of either MDE, GAD and/or social anxiety will be recruited to participate in this study. Only those individuals whose psychiatric disorders are stable will be randomized to acamprosate or placebo. Three sites will participate in this trial.

TREATMENTS:

Eligible participants will be randomly assigned to receive either acamprosate or matching placebo for 12 weeks.

EFFICACY ASSESSEMENTS:

The primary efficacy outcome measure will be cumulative days abstinent as measured by self-report.

Study Overview

• Status: Completed
• Conditions: Alcohol Dependence; Generalized Anxiety Disorder; Major Depression; Social Anxiety Disorder
• Intervention / Treatment: Drug: Acamprosate

Detailed Description

Participants who meet all inclusion criteria and none of the exclusion criteria will be randomized to receive either acamprosate or placebo in a 1:1 ratio. Participants will be instructed to take (2) 333 mg tablets three times a day. Participants will be seen weekly for 12 weeks an again 14 weeks from randomization. At each weekly visit, participants will be asked about substance use and possible adverse events. They will also have their vital signs and weight measured at each visit. Psychiatric assessments, including the MADRS,HAM-A, Liebowitz Social Anxiety Scale, and Hospital Anxiety and Depression Scale will be performed at weeks 2, 4, 8, and 12. Alcohol craving will be assessed using the Obsessive Compulsive Drinking Scale at baseline and monthly. A urine drug screen will also be performed monthly. A clinical global impressions scale will be completed for both psychiatric and alcohol abuse symptoms at every visit. A breath alcohol test will be performed at every visit, and a urine drug screen will be performed at baseline and monthly during the trial.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • McLean Hospital
  • New York
    • New York, New York, United States, 10025
      • Columbia University College of Physicians & Surgeons
  • South Carolina
    • Pickens, South Carolina, United States, 29671
      • Behavioral Health Services of Pickens County

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adults ages 18-60
2. Meet DSM-IV criteria for current (past 90 days) alcohol dependence
3. Must identify alcohol as the primary substance of abuse
4. Meet DSM-IV criteria for a current major depressive episode, GAD and/or social anxiety disorder
5. Have a stable psychiatric condition, as evidenced by a baseline CGI change score of 4 or below between the time of initial screening and the baseline visit, and if receiving psychotropic medication, must have a stable dose of medication for at least one month prior to baseline.
6. Must have a negative urine drug screen at the baseline visit; UDS may be repeated no more that twice to obtain an negative UDS
7. May be receiving medication treatment for anxiety/mood disorder as long as the dosage has been stable for 4 weeks prior to randomization.
8. May be engaged in psychosocial treatment for alcohol dependence or for mood/anxiety disorders.
9. Must abstain from alcohol for at least 3 consecutive days but no more than 21 days prior to medication initiation
10. Subjects must be able to adequately provide informed consent and function at an intellectual level sufficient to allow the accurate completion of all assessment instruments
11. Subjects must consent to random assignment, be willing to commit to medication treatment and follow-up assessments
12. CIWA-Ar scale is 8 or less at the baseline visit

Exclusion Criteria:

1. Individuals with a primary psychotic disorder or bipolar disorder
2. Individuals who meet DSM-IV criteria for current (past 90 days) dependence on substances other than alcohol, caffeine or nicotine
3. Individuals with an uncontrolled neurologic condition that could confound the results of the study
4. Individuals with an uncontrolled medical condition that may adversely affect the conduct of this trial or jeopardize the subject's safety
5. Regular use of benzodiazepines for the treatment of psychiatric symptoms (as defined as more than 12 times in the month prior to the screening visit)
6. Individuals receiving pharmacotherapy (e.g. disulfiram or naltrexone) for prevention of alcohol relapse
7. Women of childbearing potential who are lactating or refuse to use adequate forms of birth control
8. Current suicidal or homicidal risk

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Acamprosate tablets	Drug: Acamprosate; 2 333mg tablets three times daily
Placebo Comparator: 2; Matching placebo tablets	Drug: Acamprosate; 2 333mg tablets three times daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Days Drinking	Drinking was assessed using the timeline followback (TLFB), which is a calendar-based instrument used to assess drinking and other substance use on a daily basis.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery-Asberg Depression Rating Scale (MADRS)	This 10-item rating scale is commonly used in the European pharmacotherapy trials, and it may have benefit in assessing substance abusers, because it focuses on cognitive symptoms of depression instead of the physical symptoms, which could be due to substance use and withdrawal (Yonkers and Samson, 2000). Total scores are used; Scale range is 0-60, with higher scores reflecting more severe symptoms.	12 weeks
Liebowitz Social Anxiety Scale	The LSAS is a 24-item semi-structured clinician-administered instrument that assesses social anxiety through the evaluation of fear and avoidance of different social and performance situations. There are two subscales (avoidance and fear), with scores ranging from 0-72; Total score for instrument ranges from 0-144. This study only reports on total score. Higher scores reflect greater anxiety symptoms.	12 weeks
Hospital Anxiety and Depression Scale	This is a 14-item self report assessment that contains two subscales (depression and anxiety) with each subscale ranging from 0-21; the total score ranges from 0-42. We report total scores. Higher scores represent worse symptoms.	12 weeks

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: Columbia University; Mclean Hospital
• Investigators: Principal Investigator: Susan C Sonne, PharmD, BCPP, Medical University of South Carolina; Principal Investigator: Jennifer S Potter, PhD, McLean Hospital; Principal Investigator: Richard Rosenthal, MD, Columbia University College of Physicians & Surgeons

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: May 25, 2006
• First Submitted That Met QC Criteria: May 25, 2006
• First Posted (Estimate): May 26, 2006

Study Record Updates

• Last Update Posted (Estimate): April 13, 2015
• Last Update Submitted That Met QC Criteria: April 10, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Anxiety; Alcoholism; Mood; Acamprosate
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Alcohol-Related Disorders; Substance-Related Disorders; Mood Disorders; Phobic Disorders; Alcoholism; Depression; Depressive Disorder; Disease; Anxiety Disorders; Phobia, Social; Alcohol Deterrents; Acamprosate
• Other Study ID Numbers: CMP-MD-04