Psychosocial and Medication Treatment for Anxiety in Alcoholism

• Sponsor: Boston Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00248612
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 162
• Locations: 2
• Arms: 4
• Actual Duration (Months): 66
• Patients Per Site: 81
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Alcohol-Related Disorders; Anxiety Disorders	Drug: Venlafaxine; Behavioral: CBT; Other: Progressive muscle relaxation therapy (PMR); Other: Placebo medication	Phase 2/Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 162 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: CBT And Venlafaxine Treatments For Anxiety In Alcoholism
• Actual Study Start Date: Sep 1, 2003
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

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: 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.; 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.

Outcome Measures

Primary Outcome Measures

1. Clinical Global Impression Scale-I (CGI-I) [Session 1 (Baseline) , Session 8 (8 weeks of treatment), Session 11 (11 weeks of treatment)]

   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)

2. Clinical Global Impression Scale-S (CGI-S) [1 (Baseline) , Session 8 (8 weeks of treatment), Session 11 (11 weeks of treatment)]

   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)

3. Craving Desire Scale (CDS) [1 (Baseline) , Session 8 (8 weeks of treatment), Session 11 (11 weeks of treatment)]

   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.

4. Number of Participants Abstinent [Session 8 (8 weeks of treatment)]

   Abstaining from the consumption of intoxicating beverages.

Secondary Outcome Measures

1. Treatment Completion [12 months]

   The number and percent of participants that completed the treatment in each arm of the study.

2. Medication Compliance Rates [12 months]

   The medication compliance rate is the percentage of participants in each study arm who took their medication based on pill counts.

3. DASS Stress Subscale Score [Session 1 (baseline), Session 11 (11 weeks of treatment)]

   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.

4. HAM-A Scale [Session 1 (baseline), Session 8 (8 weeks of treatment)]

   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.

5. HAM-D Scale [Session 1 (baseline), Session 8 (8 weeks of treatment)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Boston Medical Center	Boston	Massachusetts	United States	02118
2	Center for Anxiety and Related Disorders	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Boston Medical Center
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Domenic Ciraulo, MD, Boston Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Boston Medical Center
• ClinicalTrials.gov Identifier: NCT00248612
• Other Study ID Numbers: H-22529; R01AA013727-01A1
• First Posted: Nov 4, 2005
• Last Update Posted: Jan 24, 2018
• Last Verified: Jan 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by Boston Medical Center: Venlafaxine; Alcoholism; Anxiety Disorders; Alcohol-Use Disorders; Alcohol Abuse; Alcohol Dependence; Cognitive Behavioral Treatment
• Additional relevant MeSH terms: Disease; Alcoholism; Alcohol-Related Disorders; Anxiety Disorders; Venlafaxine Hydrochloride

Study Results

Participant Flow

Recruitment Details	Following telephone screening (n=950), 162 eligible subjects completed an in-clinic baseline assessment #1 to determine eligibility for inclusion in the study.
Pre-assignment Detail	Once subjects achieved the four day period of abstinence they completed a second baseline assessment in which eligibility was re-assessed. 81 Eligible subjects were then randomized into the four study arms.

Arm/Group Title	Venlafaxine & CBT	Placebo & CBT	Venlafaxine & PMR	Placebo & PMR
Arm/Group Description	Venlafaxine (Effexor XR): 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. They will also receive tailored cognitive behavioral training (CBT)	Placebo and CBT (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.	Venlafaxine and PMR (progressive muscle relaxation therapy).	Placebo medication and PMR (progressive muscle relaxation therapy)
Period Title: Overall Study
STARTED	24	21	14	22
COMPLETED	24	21	14	22
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Venlafaxine & CBT	Placebo & CBT	Venlafaxine & PMR	Placebo & PMR	Total
Arm/Group Description	Venlafaxine (Effexor XR) and CBT (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 of venlafaxine. The treatments will conclude with a 2-week medication taper.	Placebo and CBT (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.	Venlafaxine and PMR (progressive muscle relaxation therapy).	Placebo medication and PMR (progressive muscle relaxation therapy)	Total of all reporting groups
Overall Participants	24	21	14	22	81
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	24 100%	21 100%	14 100%	22 100%	81 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	6 25%	4 19%	3 21.4%	5 22.7%	18 22.2%
Male	18 75%	17 81%	11 78.6%	17 77.3%	63 77.8%
Race/Ethnicity, Customized (Count of Participants)
White	21 87.5%	18 85.7%	12 85.7%	19 86.4%	70 86.4%
African American	2 8.3%	1 4.8%	0 0%	2 9.1%	5 6.2%
Other	1 4.2%	2 9.5%	2 14.3%	1 4.5%	6 7.4%
Region of Enrollment (Count of Participants)
United States	24 100%	21 100%	14 100%	22 100%	81 100%
Drinking status (percent of days) [Mean (Standard Deviation) ]
percent days drinking	72.0 (24.5)	76.0 (25.6)	88.0 (12.7)	76.5 (25.8)	77 (23.8)
percent days heavy drinking	63.1 (28.0)	59.1 (33.7)	76.9 (19.1)	67.2 (28.6)	65.6 (28.2)
ADS Scores (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	15.0 (7.6)	15.8 (7.7)	16.6 (6.6)	16.1 (5.9)	15.8 (7.6)
Drinks per day (number of drinks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [number of drinks]	8.4 (6.5)	7.0 (4.6)	9.6 (4.3)	9.7 (7.5)	8.6 (6.1)

Outcome Measures

1. Primary Outcome

Title	Clinical Global Impression Scale-I (CGI-I)
Description	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)
Time Frame	Session 1 (Baseline) , Session 8 (8 weeks of treatment), Session 11 (11 weeks of treatment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Venlafaxine & CBT	Placebo & CBT	Venlafaxine & PMR	Placebo & PMR
Arm/Group Description	Venlafaxine (Effexor XR): 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.	Placebo and CBT (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.	Placebo medication and PMR (progressive muscle relaxation therapy).	Placebo medication and PMR (progressive muscle relaxation therapy)
Measure Participants	24	21	14	22
Session 1 CGI-I	3.65 (1.34)	3.81 (1.21)	3.86 (1.10)	4.05 (0.65)
Session 8 CGI-I	3.61 (1.38)	3.13 (0.89)	3.50 (1.09)	3.53 (1.19)
Session 11 CGI-I	3.13 (1.30)	2.61 (0.78)	3.00 (1.15)	2.92 (0.95)

2. Primary Outcome

Title	Clinical Global Impression Scale-S (CGI-S)
Description	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)
Time Frame	1 (Baseline) , Session 8 (8 weeks of treatment), Session 11 (11 weeks of treatment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Venlafaxine & CBT	Placebo & CBT	Venlafaxine & PMR	Placebo & PMR
Arm/Group Description	Venlafaxine (Effexor XR): 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.	Placebo and CBT (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.	Placebo medication and PMR (progressive muscle relaxation therapy).	Placebo medication and PMR (progressive muscle relaxation therapy)
Measure Participants	24	21	14	22
Session 1 CGI-S	4.00 (1.24)	3.76 (0.89)	3.93 (0.92)	4.18 (1.18)
Session 8 CGI-S	3.28 (1.49)	2.88 (1.26)	3.25 (1.42)	3.40 (1.18)
Session 11 CGI-S	3.00 (1.88)	2.53 (1.18)	2.60 (1.51)	2.85 (1.34)

3. Primary Outcome

Title	Craving Desire Scale (CDS)
Description	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.
Time Frame	1 (Baseline) , Session 8 (8 weeks of treatment), Session 11 (11 weeks of treatment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Venlafaxine & CBT	Placebo & CBT	Venlafaxine & PMR	Placebo & PMR
Arm/Group Description	Venlafaxine (Effexor XR): 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.	Placebo and CBT (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.	Placebo medication and PMR (progressive muscle relaxation therapy).	Placebo medication and PMR (progressive muscle relaxation therapy)
Measure Participants	24	21	14	22
Session 1 CDS	8.63 (6.03)	8.14 (5.02)	8.21 (5.94)	7.55 (5.06)
Session 8 CDS	6.44 (5.28)	7.41 (5.06)	4.45 (1.75)	5.56 (3.41)
Session 11 CDS	4.38 (1.94)	6.11 (4.76)	5.10 (2.08)	4.25 (2.70)

4. Primary Outcome

Title	Number of Participants Abstinent
Description	Abstaining from the consumption of intoxicating beverages.
Time Frame	Session 8 (8 weeks of treatment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Venlafaxine & CBT	Placebo & CBT	Venlafaxine & PMR	Placebo & PMR
Arm/Group Description	Venlafaxine (Effexor XR) and CBT (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 of venlafaxine. The treatments will conclude with a 2-week medication taper.	Placebo and CBT (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.	Venlafaxine and PMR (progressive muscle relaxation therapy).	Placebo medication and PMR (progressive muscle relaxation therapy)
Measure Participants	24	21	14	22
Count of Participants [Participants]	2 8.3%	4 19%	3 21.4%	1 4.5%

5. Secondary Outcome

Title	Treatment Completion
Description	The number and percent of participants that completed the treatment in each arm of the study.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Venlafaxine & CBT	Placebo & CBT	Venlafaxine & PMR	Placebo & PMR
Arm/Group Description	Venlafaxine (Effexor XR) and CBT (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 of venlafaxine. The treatments will conclude with a 2-week medication taper.	Placebo and CBT (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.	Venlafaxine and PMR (progressive muscle relaxation therapy).	Placebo medication and PMR (progressive muscle relaxation therapy)
Measure Participants	24	21	14	22
Count of Participants [Participants]	18 75%	17 81%	11 78.6%	15 68.2%

6. Secondary Outcome

Title	Medication Compliance Rates
Description	The medication compliance rate is the percentage of participants in each study arm who took their medication based on pill counts.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Venlafaxine & CBT	Placebo & CBT	Venlafaxine & PMR	Placebo & PMR
Arm/Group Description	Venlafaxine (Effexor XR): 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.	Placebo and CBT (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.	Venlafaxine and PMR (progressive muscle relaxation therapy).	Placebo medication and PMR (progressive muscle relaxation therapy)
Measure Participants	24	21	14	22
Number [percentage of participants]	96.89 403.7%	97.06 462.2%	88.70 633.6%	95.39 433.6%

7. Secondary Outcome

Title	DASS Stress Subscale Score
Description	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.
Time Frame	Session 1 (baseline), Session 11 (11 weeks of treatment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Venlafaxine & CBT	Placebo & CBT	Venlafaxine & PMR	Placebo & PMR
Arm/Group Description	Venlafaxine (Effexor XR) and CBT (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 of venlafaxine. The treatments will conclude with a 2-week medication taper.	Placebo and CBT (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.	Venlafaxine and PMR (progressive muscle relaxation therapy).	Placebo medication and PMR (progressive muscle relaxation therapy)
Measure Participants	24	21	14	22
Session 1 DASS stress subscale	16.7 (7.6)	19.2 (9.1)	21.5 (11.3)	16.6 (8.2)
Session 11 DASS stress subscale	8.1 (4.6)	9.6 (7.9)	4.1 (7.9)	11.2 (11.1)

8. Secondary Outcome

Title	HAM-A Scale
Description	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.
Time Frame	Session 1 (baseline), Session 8 (8 weeks of treatment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Venlafaxine & CBT	Placebo & CBT	Venlafaxine & PMR	Placebo & PMR
Arm/Group Description	Venlafaxine (Effexor XR) and CBT (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 of venlafaxine. The treatments will conclude with a 2-week medication taper.	Placebo and CBT (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.	Venlafaxine and PMR (progressive muscle relaxation therapy).	Placebo medication and PMR (progressive muscle relaxation therapy)
Measure Participants	24	21	14	22
Session 1 HAM-A	13.5 (5.9)	14.2 (7.3)	16.5 (6.8)	12.9 (4.1)
Session 8 HAM-A	9.8 (6.9)	9.1 (5.5)	7.9 (5.5)	9.1 (4.2)

9. Secondary Outcome

Title	HAM-D Scale
Description	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.
Time Frame	Session 1 (baseline), Session 8 (8 weeks of treatment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Venlafaxine & CBT	Placebo & CBT	Venlafaxine & PMR	Placebo & PMR
Arm/Group Description	Venlafaxine (Effexor XR) and CBT (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 of venlafaxine. The treatments will conclude with a 2-week medication taper.	Placebo and CBT (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.	Venlafaxine and PMR (progressive muscle relaxation therapy).	Placebo medication and PMR (progressive muscle relaxation therapy)
Measure Participants	24	21	14	22
Session 1 HAM-D	12.0 (5.7)	11.7 (6.0)	13.0 (7.2)	13.6 (5.0)
Session 8 HAM-D	8.8 (6.6)	8.5 (4.6)	5.9 (5.6)	10 (6.2)

Adverse Events

Time Frame	12 months
Arm/Group Title	Venlafaxine & CBT		Placebo & CBT		Venlafaxine & PMR		Placebo & PMR
Arm/Group Description	Venlafaxine (Effexor XR): 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.		Placebo and CBT (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.		Venlafaxine medication and PMR (progressive muscle relaxation therapy).		Placebo medication and PMR (progressive muscle relaxation therapy)
All Cause Mortality
	Venlafaxine & CBT		Placebo & CBT		Venlafaxine & PMR		Placebo & PMR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/21 (0%)		0/14 (0%)		0/22 (0%)
Serious Adverse Events
	Venlafaxine & CBT		Placebo & CBT		Venlafaxine & PMR		Placebo & PMR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/24 (12.5%)		1/21 (4.8%)		2/14 (14.3%)		1/22 (4.5%)
Gastrointestinal disorders
nausea	1/24 (4.2%)	1	0/21 (0%)	0	0/14 (0%)	0	0/22 (0%)	0
General disorders
insomnia	0/24 (0%)	0	0/21 (0%)	0	0/14 (0%)	0	0/22 (0%)	0
elevated blood pressure	0/24 (0%)	0	0/21 (0%)	0	0/14 (0%)	0	1/22 (4.5%)	1
profuse sweating	1/24 (4.2%)	1	0/21 (0%)	0	0/14 (0%)	0	0/22 (0%)	0
vertigo	1/24 (4.2%)	1	0/21 (0%)	0	0/14 (0%)	0	0/22 (0%)	0
Psychiatric disorders
suicidal ideation	3/24 (12.5%)	3	0/21 (0%)	0	1/14 (7.1%)	1	0/22 (0%)	0
agitation/restlessness	1/24 (4.2%)	1	0/21 (0%)	0	1/14 (7.1%)	1	0/22 (0%)	0
depression	1/24 (4.2%)	1	1/21 (4.8%)	1	1/14 (7.1%)	1	0/22 (0%)	0
anxiety	1/24 (4.2%)	1	0/21 (0%)	0	1/14 (7.1%)	1	0/22 (0%)	0
Other (Not Including Serious) Adverse Events
	Venlafaxine & CBT		Placebo & CBT		Venlafaxine & PMR		Placebo & PMR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/21 (0%)		0/14 (0%)		0/22 (0%)

Limitations/Caveats

Small size of treatment groups leading to diminished meaningful difference between comparison groups at follow-up; Failure of randomization leading to unequal number of subjects in each treatment group.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.