Psychosocial and Medication Treatment for Anxiety in Alcoholism

CBT And Venlafaxine Treatments For Anxiety In Alcoholism

The proposed project is written as a "typical clinical practice" test and is a fully-controlled trial of a combined anxiety-focused CBT and pharmacotherapy (venlafaxine; CBT-VEN) delivered for patients with comorbid alcohol-use and anxiety disorders. The CBT and pharmacotherapy will be contrasted with relaxation training and placebo medication. One hundred and eighty participants will be recruited and, subsequent to a platform of outpatient treatment for alcoholism, will be randomly assigned to a 12-week treatment condition. All treatment conditions will begin with a 1-week placebo run-in, after which participants will begin a trial of venlafaxine or placebo. The treatments will conclude with a 2-week medication/placebo taper. Follow-up assessments will be conducted at post-treatment and at 3, 6, 9, and 12-months. The long-term objectives of this research are to develop a real-world combination of psychosocial and pharmacological treatments for patients with comorbid alcohol-use and anxiety disorders that compromise prognosis, and to evaluate the effectiveness of combined psychosocial and pharmacological treatments that target anxiety among patients with this comorbidity.

Study Overview

• Status: Completed
• Conditions: Alcohol-Related Disorders; Anxiety Disorders
• Intervention / Treatment: Drug: Venlafaxine; Behavioral: CBT; Other: Placebo medication; Other: Progressive muscle relaxation therapy (PMR)

Detailed Description

Difficulties in anxiety management are frequent causes of relapse to alcohol use. Empirical data support the role of anxiety in alcohol relapse, and both psychosocial and pharmacological treatments for alcohol problems increasingly address the role of negative affect in alcohol-use disorders. Due to the lack of large, well-controlled treatment outcome trials, the optimal treatment (or combination of treatments) remains unknown. Real world practice in the treatment of alcohol-use disorders frequently begins with brief detoxification and stabilization, and is often followed by some combination of CBT and pharmacotherapy for patients complaining of mood difficulties while attempting early abstinence from alcohol.

The purpose of the present study is to evaluate the relative benefits of psychosocial and psychopharmacological therapy for the treatment of co-morbid anxiety and alcohol dependence among patients attempting early abstinence from alcohol. We will address the following four questions:

1. During the course of intervention, is treatment of anxiety disorders with combined treatments of established utility (among non-alcohol-use-disordered patients) superior in managing both return to drinking and anxiety symptoms than either monotherapy, or a fully inactive control treatment?
2. During the follow-up period, will patients who received the combined active treatments fare better in maintaining abstinence relative to the single active treatments, and those in the control condition?
3. What psychosocial variables (such as increases or lapses to elevated anxiety) mediate return to pre-treatment levels of alcohol use?
4. Will baseline indices of alcohol dependence and anxiety disorder severity moderate the relationship between treatment and outcome during both the acute and follow-up phases of the study?

• Study Type: Interventional
• Enrollment (Actual): 162
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Boston, Massachusetts, United States, 02215
      • Center for Anxiety and Related Disorders

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants must be English-speaking males or females
• Participants must be between 18 and 65 years old
• Meet criteria for DSM-IV diagnosis of alcohol abuse or dependence
• Meet criteria for Panic disorder, Social Phobia or Generalized Anxiety Disorder
• Physically able to attend sessions at the Counseling Center
• Able to read and write
• Able to complete the structured interview and self-report assessment packet
• Able to attend all treatment sessions and follow-up assessments
• Able to sign a witnessed informed consent form
• Participants express a desire to completely stop drinking alcohol or reduce alcohol consumption with the possible long-term goal of abstinence

Exclusion Criteria:

• Meet DSM-IV diagnostic criteria for bipolar disorder, schizophrenia, bulimia/anorexia, or dementia
• Currently taking anti-craving agents (e.g. Naltrexone, methadone)
• Currently taking medication that has clinically significant interactions with venlafaxine
• Previous use of venlafaxine
• Currently taking other antidepressant medications
• Currently taking medication known to decrease anxiety or alcohol consumption (e.g. antabuse)
• Currently prescribed medications with known abuse potential (e.g., subjects on opioid agonist therapy)
• Currently prescribed medications as a sleep aid (e.g. Ambien)
• Currently taking herbal supplements that have been shown to interact with venlafaxine or affect anxiety symptoms
• Currently pregnant, breastfeeding, plans of becoming pregnant during the course of the study, or not using medically acceptable form of birth control (oral contraceptives, barrier [diaphragm or condom] with spermicide, intrauterine progesterone contraceptive system, levonorgestrel implant, medroxyprogesterone acetate contraceptive injection).
• Planning to relocate out-of-state within four months of protocol initiation
• History of psychotic symptoms within the past 30 days
• Experiencing severe symptoms of depression or have engaged in suicidal behaviors within the past 30 days
• Medical contraindications to the use of venlafaxine [severe renal disease, cirrhosis, uncontrolled blood pressure, recent cardiovascular problems (e.g., heart attack), and seizure disorders; currently taking a monoamine oxidase inhibitor, MAOI]
• Self-reported anxiety less than 15 on the Hamilton Rating Scale for Anxiety
• Participant is a member of the same household of another subject already participating in the study
• Participant is legally mandated (e.g., to avoid incarceration, monetary or other penalties, etc.) to participate in an alcohol treatment program
• Participant has a current or recent (past 30 days) DSM-IV diagnosis of other substance abuse or dependence, with the exception of nicotine, marijuana, and caffeine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Venlafaxine & CBT; CBT is Cognitive Behavioral Treatment which will be tailored to participants. Participants will be assigned to a 12-week treatment condition; all treatment conditions will begin with a 1-week placebo run-in, after which participants will begin a trial of venlafaxine. The treatments will conclude with a 2-week medication taper.	Drug: Venlafaxine; Participants will be assigned to a 12-week treatment condition; all treatment conditions will begin with a 1-week placebo run-in, after which participants will begin a trial of venlafaxine. The treatments will conclude with a 2-week medication taper.; Other Names: Effexor XR; Behavioral: CBT; CBT is Cognitive Behavioral Therapy. Participants will be assigned to a 12-week treatment condition; all treatment conditions will begin with a 1-week placebo run-in, after which participants will begin a trial. The treatments will conclude with a 2-week medication/placebo taper.
Active Comparator: Placebo & CBT; CBT is Cognitive Behavioral Treatment which will be tailored to participants.For patients with comorbid alcohol-use and anxiety disorders, CBT and pharmacotherapy will be contrasted with relaxation training and placebo medication; all treatment conditions will begin with a 1-week placebo run-in, after which participants will begin a trial of venlafaxine or placebo.	Behavioral: CBT; CBT is Cognitive Behavioral Therapy. Participants will be assigned to a 12-week treatment condition; all treatment conditions will begin with a 1-week placebo run-in, after which participants will begin a trial. The treatments will conclude with a 2-week medication/placebo taper.; Other: Placebo medication; For patients with comorbid alcohol-use and anxiety disorders, CBT and pharmacotherapy will be contrasted with relaxation training and placebo medication; all treatment conditions will begin with a 1-week placebo run-in, after which participants will begin a trial of venlafaxine or placebo.
Active Comparator: Venlafaxine & PMR; Progressive Muscle Relaxation Therapy (PMR) is a technique of alternately tensing and relaxing muscles groups in sequence throughout the body. . Participants will be assigned to a 12-week treatment condition; all treatment conditions will begin with a 1-week placebo run-in, after which participants will begin a trial. The treatments will conclude with a 2-week medication/placebo taper.	Drug: Venlafaxine; Participants will be assigned to a 12-week treatment condition; all treatment conditions will begin with a 1-week placebo run-in, after which participants will begin a trial of venlafaxine. The treatments will conclude with a 2-week medication taper.; Other Names: Effexor XR; Other: Progressive muscle relaxation therapy (PMR); For patients with comorbid alcohol-use and anxiety disorders, CBT and pharmacotherapy will be contrasted with relaxation training and placebo medication; all treatment conditions will begin with a 1-week placebo run-in, after which participants will begin a trial of venlafaxine or placebo.
Placebo Comparator: Placebo & PMR; Progressive Muscle Relaxation Therapy (PMR) is a technique of alternately tensing and relaxing muscles groups in sequence throughout the body. . For patients with co-morbid alcohol-use and anxiety disorders, CBT and pharmacotherapy will be contrasted with relaxation training and placebo medication; all treatment conditions will begin with a 1-week placebo run-in, after which participants will begin a trial of venlafaxine or placebo.	Other: Placebo medication; For patients with comorbid alcohol-use and anxiety disorders, CBT and pharmacotherapy will be contrasted with relaxation training and placebo medication; all treatment conditions will begin with a 1-week placebo run-in, after which participants will begin a trial of venlafaxine or placebo.; Other: Progressive muscle relaxation therapy (PMR); For patients with comorbid alcohol-use and anxiety disorders, CBT and pharmacotherapy will be contrasted with relaxation training and placebo medication; all treatment conditions will begin with a 1-week placebo run-in, after which participants will begin a trial of venlafaxine or placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression Scale-I (CGI-I)	Global improvement of alcohol dependence: Rate the total improvement in the participant's alcohol dependence symptoms whether or not, in your judgment, it is due entirely to treatment. Compared to his/her admission to the project, how much has s/he changed? (1-Not assessed, first rating, 2-Very much improved, 3-Much improved, 4-Minimally improved, 5-Unchanged, 6-Minimally worse, 7-Much worse, 8-Very much worse)	Session 1 (Baseline) , Session 8 (8 weeks of treatment), Session 11 (11 weeks of treatment)
Clinical Global Impression Scale-S (CGI-S)	Global severity of alcohol dependence: Considering your total clinical experience with the alcohol dependent population how severe are his/her alcohol dependence symptoms at this time? (1-Normal, no symptoms, 2-Borderline symptoms, 3-Mild symptoms, 4-Moderate symptoms, 5-Marked symptoms, 6-Severe symptoms, 7-Among the most extreme symptoms)	1 (Baseline) , Session 8 (8 weeks of treatment), Session 11 (11 weeks of treatment)
Craving Desire Scale (CDS)	The Craving Desire Scale (CDS) is a 3-item scale ("1. I do want to drink now", "2. I crave a drink right now", 3. "I have a desire for a drink right now") used to identify the degree of current alcohol craving, with responses provided on a Likert scale of 1-7: with 1 meaning strongly disagree, and 7 meaning strongly agree to each of the 3 items. Total scores can range from 3 to 21 with higher scores indicating greater craving for alcohol.	1 (Baseline) , Session 8 (8 weeks of treatment), Session 11 (11 weeks of treatment)
Number of Participants Abstinent	Abstaining from the consumption of intoxicating beverages.	Session 8 (8 weeks of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Completion	The number and percent of participants that completed the treatment in each arm of the study.	12 months
Medication Compliance Rates	The medication compliance rate is the percentage of participants in each study arm who took their medication based on pill counts.	12 months
DASS Stress Subscale Score	DASS (Depression Anxiety Stress Scales) assesses depression, anxiety and stress responses. Each of the three DASS scales contains 14 items, divided into subscales of 2-5 items with similar content. The stress subscale was used which assesses difficulty relaxing, nervous arousal, and being easily upset/agitated, irritable/over-reactive and impatient. Subjects are asked to use 4-point severity/frequency scales to rate the extent to which they have experienced each state over the past week. Stress scores can range form 0-56 with 0-14=normal, 15-18=mild, 19-25=moderate, 26-33=severe. and 34+=extremely severe stress.	Session 1 (baseline), Session 11 (11 weeks of treatment)
HAM-A Scale	The Hamilton Anxiety Rating Scale (HAM-A) is a psychological questionnaire used by clinicians to rate the severity of a patient's anxiety. The HAM-A probes 14 parameters each item is scored on a 5-point scale, ranging from 0=not present to 4=severe. total scores can range from 0 to 56.where <17 indicates mild anxiety, 18-24 moderate anxiety and 25-30 severe anxiety. Higher scores reflect more anxiety.	Session 1 (baseline), Session 8 (8 weeks of treatment)
HAM-D Scale	HAM-D (Hamilton Rating Scale for Depression) is a multiple item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. The scoring is based on 17 items. Eight of the items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine items are scored on a 3 point scale from 0-2 where 0=none or absent and 2= severe. The total scores for the HAM-D can range from 0 to 50. The total scores are interpreted as: 0-7=normal, 8-13=mild, 14-18= moderate, 19-22= severe, and 23+=very severe depression. The higher the score the more severe the participant's depression.	Session 1 (baseline), Session 8 (8 weeks of treatment)

Collaborators and Investigators

• Sponsor: Boston Medical Center
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Domenic Ciraulo, MD, Boston Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2003
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: November 2, 2005
• First Submitted That Met QC Criteria: November 2, 2005
• First Posted (Estimate): November 4, 2005

Study Record Updates

• Last Update Posted (Actual): January 24, 2018
• Last Update Submitted That Met QC Criteria: January 21, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Alcohol Dependence; Alcoholism; Venlafaxine; Alcohol Abuse; Anxiety Disorders; Alcohol-Use Disorders; Cognitive Behavioral Treatment
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Substance-Related Disorders; Alcoholism; Disease; Anxiety Disorders; Alcohol-Related Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride
• Other Study ID Numbers: H-22529; R01AA013727-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes