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CompletedNCT00452543Updated Jul 9, 2012Results posted

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

A Phase 4 interventional study of acamprosate and escitalopram in Major Depressive Disorder, Alcohol Abuse and Alcohol Dependence, sponsored by Massachusetts General Hospital. Completed at 1 site in United States. Open to participants aged 18 Years to 64 Years. Per ClinicalTrials.gov, last updated 2012-07-09.

Sponsored by Massachusetts General Hospital · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
23
Allocation
Randomized
Ages
18 Years to 64 Years
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Major Depressive Disorder
  • Alcohol Abuse
  • Alcohol Dependence

Keywords

  • Major depressive disorder
  • Alcoholism
  • Alcohol abuse
  • Alcohol dependence
03

In context

Alcoholism

1,606 studies on the registry are indexed under Alcoholism; 329 are open to participants now.

This study's enrollment of 23 is below the median of 87 across 1,371 interventional studies indexed under Alcoholism.

Browse Alcoholism studies →

Lead sponsor

Massachusetts General Hospital is the lead sponsor of 2,536 studies on the registry; 446 are open to participants now.

Of its 214 completed or terminated interventional studies of FDA-regulated products, 161 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 64 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
23 participants (actual)

Study arms

  • Experimental
    Escitalopram plus acamprosate

    Drug: acamprosate · Drug: escitalopram · Behavioral: Medical management

  • Placebo comparator
    Escitalopram plus placebo

    Drug: escitalopram · Behavioral: Medical management · Drug: Placebo

Interventions

  • Drugacamprosate

    Acamprosate 333mg, 2 capsules by mouth (i.e., PO), three times per day (i.e., TID), for 12 weeks.

    Also known as: Campral

  • Drugescitalopram

    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.

    Also known as: Lexapro

  • BehavioralMedical management

    Based on the COMBINE study. 1 hour of medical management / behavioral intervention at every study visit (7 times over 12 weeks).

    Also known as: Campral and Lexapro

  • DrugPlacebo

    Placebo, 2 capsules PO TID, for 12 weeks

    Also known as: Campral and Lexapro

06

What researchers measure

Primary outcomes

  1. Change in Mean Score on the Hamilton Rating Scale for Depression -- 17 Items (HAM-D-17)

    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.

    Time frame: From baseline visit to Week 12 (or early discontinuation visit)

  2. Total Drinking Days on the Alcohol Timeline Followback (TLFB)

    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.

    Time frame: From Baseline visit to Week 12 (or early discontinuation visit)

  3. Total Drinks Consumed Per Week on the TLFB

    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.

    Time frame: From Baseline visit to Week 12 (or early discontinuation visit)

  4. Total Drinks Consumed Per Drinking Day on the TLFB

    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.

    Time frame: From Baseline visit to Week 12 (or early discontinuation visit)

07

Results

Posted Jul 9, 2012

Participant flow

Participant flow — Overall Study
MilestoneEscitalopram Plus AcamprosateEscitalopram Plus Placebo
Started1211
Completed75
Not completed56

Outcome measures

PrimaryChange in Mean Score on the Hamilton Rating Scale for Depression -- 17 Items (HAM-D-17)

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.

Time frame:
From baseline visit to Week 12 (or early discontinuation visit)
Reported as:
Mean · Scores on a scale
Change in Mean Score on the Hamilton Rating Scale for Depression -- 17 Items (HAM-D-17)
Scores on a scaleEscitalopram Plus AcamprosateEscitalopram Plus Placebo
Change in Mean Score on the Hamilton Rating Scale for Depression -- 17 Items (HAM-D-17)-5.6 ± 8.5-7.8 ± 9.9
PrimaryTotal Drinking Days on the Alcohol Timeline Followback (TLFB)

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.

Time frame:
From Baseline visit to Week 12 (or early discontinuation visit)
Reported as:
Mean · Drinking days
Total Drinking Days on the Alcohol Timeline Followback (TLFB)
Drinking daysEscitalopram Plus AcamprosateEscitalopram Plus Placebo
Total Drinking Days on the Alcohol Timeline Followback (TLFB)61 ± 5361 ± 86
Statistical analysis
  • Escitalopram Plus Acamprosate vs Escitalopram Plus Placebo · Wilcoxon (Mann-Whitney) · p = <0.05 (Threshold for significance was set a priori at p\<0.05.)
PrimaryTotal Drinks Consumed Per Week on the TLFB

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.

Time frame:
From Baseline visit to Week 12 (or early discontinuation visit)
Reported as:
Mean · Drinks consumed per week
Total Drinks Consumed Per Week on the TLFB
Drinks consumed per weekEscitalopram Plus AcamprosateEscitalopram Plus Placebo
Total Drinks Consumed Per Week on the TLFB15 ± 1315 ± 21
Statistical analysis
  • Escitalopram Plus Acamprosate vs Escitalopram Plus Placebo · Wilcoxon (Mann-Whitney) · p = <0.05 (This p \<0.05 was set a priori.)
PrimaryTotal Drinks Consumed Per Drinking Day on the TLFB

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.

Time frame:
From Baseline visit to Week 12 (or early discontinuation visit)
Reported as:
Mean · Drinks consumed per drinking day
Total Drinks Consumed Per Drinking Day on the TLFB
Drinks consumed per drinking dayEscitalopram Plus AcamprosateEscitalopram Plus Placebo
Total Drinks Consumed Per Drinking Day on the TLFB4 ± 24 ± 4
Statistical analysis
  • Escitalopram Plus Acamprosate vs Escitalopram Plus Placebo · Wilcoxon (Mann-Whitney) · p = <0.05 (This p\<0.05 was set a priori.)

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Escitalopram Plus Acamprosate—2/12 (16.7%)8/12 (66.7%)
Escitalopram Plus Placebo—0/11 (0%)5/11 (45.5%)
Most frequent serious events
Most frequent serious events
EventEscitalopram Plus AcamprosateEscitalopram Plus Placebo
Hospitalization for alcohol intoxicationPsychiatric disorders1/120/11
Blockage in the coronary arteryCardiac disorders1/120/11
Most frequent other events
Showing 10 of 17
Most frequent other events
EventEscitalopram Plus AcamprosateEscitalopram Plus Placebo
DiarrheaGastrointestinal disorders4/120/11
InsomniaGeneral disorders1/122/11
HeadacheGeneral disorders1/122/11
NauseaGastrointestinal disorders2/121/11
GI upsetGastrointestinal disorders1/121/11
Urinary retentionRenal and urinary disorders0/121/11
Jaw tighteningGeneral disorders0/121/11
Dry lipsGeneral disorders0/121/11
Increased sweatingGeneral disorders0/121/11
AnxietyPsychiatric disorders0/121/11

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Escitalopram Plus AcamprosateEscitalopram Plus PlaceboTotal
<=18 years000
Between 18 and 65 years121123
>=65 years000
Age Continuous
Age Continuous(years)Escitalopram Plus AcamprosateEscitalopram Plus PlaceboTotal
Mean49 ± 1343 ± 1447 ± 12
Sex: Female, Male
Sex: Female, Male(Participants)Escitalopram Plus AcamprosateEscitalopram Plus PlaceboTotal
Female4610
Male8513
Region of Enrollment
Region of Enrollment(participants)Escitalopram Plus AcamprosateEscitalopram Plus PlaceboTotal
United States121123
08

Study locations

1 site
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
09

References and documents

Publications

  • Witte J, Bentley K, Evins AE, Clain AJ, Baer L, Pedrelli P, Fava M, Mischoulon D. A randomized, controlled, pilot study of acamprosate added to escitalopram in adults with major depressive disorder and alcohol use disorder. J Clin Psychopharmacol. 2012 Dec;32(6):787-96. doi: 10.1097/JCP.0b013e3182726764. PubMed 23131884 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 9, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00452543
Lead sponsor
Massachusetts General Hospital
Collaborators
National Alliance for Research on Schizophrenia and Depression
Responsible party
Janet Melissa Witte (Dr., Massachusetts General Hospital) — Principal investigator
First posted
Mar 27, 2007
Start date
Mar 2007
Primary completion
May 2010
Completion
May 2010
Results posted
Jul 9, 2012
Last update
Jul 9, 2012

Study contacts

Janet M Witte, MD
principal investigator · Massachusetts General Hospital
Nicholas Bolo, PhD
principal investigator · Mclean Hospital

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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