Acamprosate Added to Escitalopram and Behavioral Treatment for Comorbid Depression and Alcoholism

This study has been completed.
Sponsor:
Collaborator:
National Alliance for Research on Schizophrenia and Depression
Information provided by (Responsible Party):
Janet Melissa Witte, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00452543
First received: March 26, 2007
Last updated: June 4, 2012
Last verified: June 2012
  Purpose

This is a study about treatment for people who suffer from both major depression and alcohol abuse or dependence. The study will examine whether the addition of acamprosate to escitalopram and behavioral interventions will improve outcomes for this population.


Condition Intervention Phase
Major Depressive Disorder
Alcohol Abuse
Alcohol Dependence
Drug: acamprosate
Drug: escitalopram
Behavioral: Medical management
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo-Controlled Study of Acamprosate Added to Escitalopram and Behavioral Treatment in Major Depressive Disorder (MDD) With Comorbid Alcohol Abuse/Dependence

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Change in Mean Score on the Hamilton Rating Scale for Depression -- 17 Items (HAM-D-17) [ Time Frame: From baseline visit to Week 12 (or early discontinuation visit) ] [ Designated as safety issue: No ]
    Scores on the HAM-D-17 typically fall into the following ranges: a) Not depressed: 0-7; b) Mildly depressed: 7-15; c) Moderately depressed: 15-25; d) Severely depressed: over 25. A decrease of 50% or more in the Hamilton-D score is considered to be a positive response to treatment, while a score of 7 or less is considered typical of remission. We measure the change in total score from Baseline to Week 12 or week of early termination visit.

  • Total Drinking Days on the Alcohol Timeline Followback (TLFB) [ Time Frame: From Baseline visit to Week 12 (or early discontinuation visit) ] [ Designated as safety issue: No ]
    The TLFB assesses recent drinking behavior. On the TLFB, clients retrospectively estimate their daily alcohol consumption in standard drinks over a time period ranging from 7 days to 24 months prior to the interview, and thus the measure provides quantitative estimates of alcohol use. One standard drink on the TLFB was defined as: 12 oz beer (5% alcohol by volume), 5 oz of wine (10-12% abv), 3 oz of fortified wine (16-18% abv), or 1-1.2 oz of hard liquor (86-100 proof; 43-50% abv). We measure the change from Baseline to Week 12 or week of early termination visit.

  • Total Drinks Consumed Per Week on the TLFB [ Time Frame: From Baseline visit to Week 12 (or early discontinuation visit) ] [ Designated as safety issue: No ]
    Total Drinks Consumed per Week on the Time Line Follow Back. We measure the change from Baseline to Week 12 or week of early termination visit.

  • Total Drinks Consumed Per Drinking Day on the TLFB [ Time Frame: From Baseline visit to Week 12 (or early discontinuation visit) ] [ Designated as safety issue: No ]
    Total Drinks Consumed per Drinking Day on the Time Line Follow Back. We measure the change from Baseline to Week 12 or week of early termination visit.


Enrollment: 23
Study Start Date: March 2007
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Escitalopram plus acamprosate Drug: acamprosate
Acamprosate 333mg, 2 capsules by mouth (i.e., PO), three times per day (i.e., TID), for 12 weeks.
Other Name: Campral
Drug: escitalopram
Escitalopram is given for 12 weeks. Dosing is flexible, starting at 10mg PO once per day (i.e., QD) with the possibility of increasing to 30mg PO QD.
Other Name: Lexapro
Behavioral: Medical management
Based on the COMBINE study. 1 hour of medical management / behavioral intervention at every study visit (7 times over 12 weeks).
Other Name: Campral and Lexapro
Placebo Comparator: Escitalopram plus placebo Drug: escitalopram
Escitalopram is given for 12 weeks. Dosing is flexible, starting at 10mg PO once per day (i.e., QD) with the possibility of increasing to 30mg PO QD.
Other Name: Lexapro
Behavioral: Medical management
Based on the COMBINE study. 1 hour of medical management / behavioral intervention at every study visit (7 times over 12 weeks).
Other Name: Campral and Lexapro
Drug: Placebo
Placebo, 2 capsules PO TID, for 12 weeks
Other Name: Campral and Lexapro

Detailed Description:

Depression and alcohol use disorders contribute to a significant proportion of the burden of disease, in the United States and abroad. Patients who suffer from co-morbid depression and alcohol abuse/dependence have illnesses that are more severe, persistent and costly than people with either depression or an alcohol use disorder alone. The treatment of these patients remains controversial. Several studies have demonstrated that antidepressants can be safe and efficacious in the treatment of depression in people who continue to drink, and it is now considered the standard of care to provide such treatment. Other studies have shown that pharmacotherapy with naltrexone or acamprosate can help reduce drinking in alcoholics without co-morbid depression. A logical extension of these findings would be to study the treatment of depressed alcoholics with dual pharmacotherapy, combining an anti-depressant with a medication aimed at treating the alcohol use disorder. We will conduct a randomized, double-blind, placebo controlled trial of escitalopram plus acamprosate and behavioral treatment vs. escitalopram plus placebo and behavioral treatment in 20 depressed alcoholics. Outcome measures will include depression, alcohol use and global functioning.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. DSM-IV diagnostic criteria for MDD (diagnosis based on Structured Clinical Interview for DSM-IV, Patient Edition; SCID I/P)
  2. Written informed consent
  3. Men and women aged 18-64 years
  4. Current diagnosis of alcohol abuse/dependence as per SCID I/P

Exclusion Criteria:

  1. Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician. These patients will be immediately referred to appropriate clinical treatment.
  2. Pregnant women or women of childbearing potential who are not using a medically accepted means of contraception (defined as oral contraceptive pill or implant, condom, diaphragm, spermicide, IUD, s/p tubal ligation, partner with vasectomy).
  3. Known history of serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease.
  4. History of seizure disorder, brain injury, any history of known neurological disease (multiple sclerosis, degenerative disease such as ALS, Parkinson disease and any movement disorders, etc.).
  5. Clinical or lab evidence of untreated hypothyroidism.
  6. History or current diagnosis of the following DSM-IV psychiatric illness: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, patients with mood congruent or mood incongruent psychotic features, patients with substance use disorders (excluding alcohol and nicotine) active within the last 12 months.
  7. Current use of other psychotropic drugs, including current use of benzodiazepines, hypnotics, anticonvulsants. Concomitant use of antihistamine drugs will be allowed. Patients will need to be off all antidepressants for at least two weeks by the time of the baseline visit, and four weeks for fluoxetine, and off benzodiazepines and other psychotropics for at least one week. The decision about whether to taper existing medications should be made by the individual and their primary treater based on clinical care and will not be made for purposes of study enrollment. allowed.
  8. Patients who have failed to respond during the course of their current major depressive episode to at least two adequate antidepressant trials. An adequate antidepressant trial is defined as six weeks or more of treatment with escitalopram > 20mg/day or its antidepressant equivalent: (fluoxetine 40mg/day, sertraline > 100 mg/day, paroxetine > 40 mg/day, fluvoxamine > 100 mg/day, citalopram > 40 mg/day, escitalopram > 20 mg/day, venlafaxine > 150 mg/day, and duloxetine > 60 mg/day).
  9. Any depression-focused or substance-abuse focused psychotherapy (family or marital counseling would be allowed).
  10. Patients who have taken an investigational psychotropic drug within the past year.
  11. Need for medical or inpatient detoxification from alcohol. This determination will be made by the screening clinician, based on clinical judgement as in the multicenter STAR*D study (PHRC #2000-P-001955 in accordance with methods used in the multi-center STAR-D study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00452543

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
National Alliance for Research on Schizophrenia and Depression
Investigators
Principal Investigator: Janet M Witte, MD Massachusetts General Hospital
Principal Investigator: Nicholas Bolo, PhD Mclean Hospital
  More Information

No publications provided by Massachusetts General Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Janet Melissa Witte, Dr., Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00452543     History of Changes
Other Study ID Numbers: 2006-P-001592/1
Study First Received: March 26, 2007
Results First Received: May 24, 2011
Last Updated: June 4, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Major depressive disorder
Alcoholism
Alcohol abuse
Alcohol dependence

Additional relevant MeSH terms:
Alcoholism
Depressive Disorder
Depression
Depressive Disorder, Major
Alcohol-Related Disorders
Substance-Related Disorders
Mental Disorders
Mood Disorders
Behavioral Symptoms
Dexetimide
Citalopram
Acamprosate
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors

ClinicalTrials.gov processed this record on April 22, 2014