Generalized Anxiety Disorder
Conditions
Keywords
Generalized Anxiety Disorder, Cognitive Behavioral Therapy, Psychotherapy plus medication, Combined treatment
Brief summary
The purpose of this study is to conduct a preliminary evaluation of the efficacy of combined medication and psychotherapy for generalized anxiety disorder (GAD). The general goals of the current study are to conduct a late stage treatment development study. The goal of this stage of research is to provide a preliminary answer to the question and to gather data to estimate intervention parameters (e.g., effect size, attrition rates, response rates) that would assist in planning further research.
Detailed description
The specific aims of this study are to collect preliminary data relevant to the following hypotheses: 1. Primary Hypothesis: Acute phase improvement for combined cognitive behavioral therapy (CBT) plus medication will be superior to medication alone. 2. Secondary Hypotheses: Combined CBT plus medication will be superior to medication alone on a number of secondary outcome measures, including the core feature of GAD (worry), depressive symptoms, functional impairment, and quality of life. 3. Additional Exploratory Aim: We will explore the comparative relapse rates for the combined CBT plus medication treatment and the medication alone treatment condition at 6-month follow-up.
Interventions
BEHAVIORALCognitive Behavioral Therapy
This cognitive behavioral therapy for GAD has a cognitive restructuring component and an applied relaxation component. Patients will be educated about the nature of anxiety and be trained in the recognition and monitoring of situational, physiological, cognitive, and behavioral cues associated with anxious responding. They will be guided through copings skill rehearsals in addition to imaginal and in vivo exposure to anxiety cues. This cognitive behavioral treatment will consist of 1 to 1.5 hour sessions of psychotherapy, which will be held once weekly over a period of 12 weeks.
DRUGVenlafaxine XR
Venlafaxine XR, 75-225 mg/d, oral administration. 14 days at 75 mg/d, 150 mg/d for the remaining 6 months, 225 mg/3 for patients unimproved at week 6, tapered at 75 mg/week (this intervention is provided by protocol 709012).
Sponsors
National Institute of Mental Health (NIMH)
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* GAD diagnosis by structured interview * Hamilton Anxiety Scale score of 18 or less * Clinical Global Impressions Scale score of at least 4 * Hamilton Depression Scale score of 18 or less * Hamilton Depression Scale suicide item score less than 2 * Use of an effective form of contraception throughout the s
Exclusion criteria
* Hypersensitivity to venlafaxine XR * History of seizures * Episode of major depressive disorder in the previous 6 months * History of any psychotic illness, bipolar disorder, or dementia * Substance abuse and dependence during the past 6 months * Other anxiety disorders with the exception of social phobia as long as GAD is primary * Regular use of anxiolytics or antidepressants within 7 days of study onset * Use of fluoxetine or monoamine oxidase inhibitors within 28 days of study onset (low dose usage of benzodiazepines will not prevent participation) * Use of other psychotic medication besides benzodiazepines
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Anxiety Rating Scale (HAM-A) | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 | The HAM-A was used to measure the severity of anxiety symptoms. The scale consists of 14 items; each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \<17 indicates mild severity, 18-24 mild to moderate and 25-30 moderate to severe anxiety. This measure was conducted by research psychiatrists trained and highly experienced in the use of these scales. The evaluators were blind to group assignment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospital Anxiety Depression Scale (HAD)-Depression Score | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 | The HAD was used to assess patients' report of anxiety and depressive symptoms. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. A higher score indicates greater depression. |
| Hamilton Rating Scale for Depression (HAM-D)-17-item Score | Data collected as part of protocol 709012 at baseline, week 12, and week 24 | The 17-item version of the HAM-D was used to assess severity of depressive symptoms. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2.The total score is the sum of the 17 items, with a range from 0 to 50. A higher scores indicates greater depression. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. The evaluators were blind to group assignment. |
| Clinical Global Impression (CGI)-Severity Score | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 | The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale (1=normal; 7 = extremely ill) that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. Evaluators were blind to group assignment. |
| Clinical Global Impression (CGI)-Improvement Score | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 | The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale (1= very much improved; 7 = very much worse) that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. Evaluators were blind to group assignment. |
| Quality of Life Subscale of the General Health Questionnaire (GHQ) | Data collected as part of protocol 709012 at baseline, week 12, and week 24 | The General Health Questionnaire (GHQ) is a psychometric screening tool to identify common psychiatric conditions. Patients completed the 12 quality of life questions (each on a 0 to 3 scale) on this questionnaire. Scores on the 12 items were added up to create summary score (range = 0 to 36). Higher scores indicate worse health. |
| Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 | The HAD was used to assess patients' report of anxiety and depressive symptoms. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. A higher score indicates greater anxiety. |
| Physical Component Score of the 12-Item Short Form Survey (SF-12) | Data collected as part of protocol 709012 at baseline, week 12, and week 24 | The Short Form (12) Health Survey is a 12-item, patient-reported survey of patient health. Physical and Mental Health Component Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. |
| Mental Component Score of the 12-item Short Form Survey (SF-12) | Data collected as part of protocol 709012 at baseline, week 12, and week 24 | The Short Form (12) Health Survey is a 12-item, patient-reported survey of patient health. Physical and Mental Health Component Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. |
| Clinical Response Rate | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 | Clinical response on the HAM-A was defined as a 50% or greater reduction from baseline to last value with the 24-week open label medication phase. |
| 50 Percent or Greater Reduction in PSWQ Score | Data collected as part of protocol 709012 at baseline, week 12, and week 24 | Clinically significant change was defined on the PSWQ as an estimated (based on linear mixed effects model) endpoint score of less than 50.9. This score was calculated using the PSWQ normative data provided by Gillis, Haaga, and Ford (1995) and the baseline PSWQ mean and standard deviation (SD) from the current sample. The PSWQ mean and SD from the normative and current GAD samples were entered into the Jacobson et al. (1984) formula c for clinically significant change. This method provides a cutoff indicating whether or not the level of functioning by a patient is statistically more likely to be in the functional rather than the dysfunctional population. |
| Penn State Worry Questionnaire (PSWQ) | Data collected as part of protocol 709012 at baseline, week 12, and week 24 | The Penn State Worry Questionaire is a 16-item inventory that aims to measure the trait of worry, using Likert rating from 1 (not at all typical of me) to 5 (very typical of me). A total score is calculated (range = 16 to 80), with higher scores indicating greater worry. |
Countries
United States
Participant flow
Recruitment details
Three hundred thirty four patients enrolled in the first phase (6-month open-label) of a parent medication trial for GAD (NCT00183274) were recruited and seen in one of four primary care practices or a psychopharmacology clinic in a university setting from 2005 to 2009. The current study was conducted from October, 2006 to March, 2008.
Pre-assignment details
Of 334 patients who consented to the parent trial, 66 did not receive study drug (64 withdrew consent and 2 were protocol violators), leaving 268 who received at least one dose of open-label venlafaxine XR. For this study, 77 patients were randomly assigned to be offered CBT and 40 patients to not be offered CBT.
Participants by arm
| Arm | Count |
|---|---|
| Combined Treatment Patients received Venlafaxine XR (75-225 mg/d) plus 12 weeks of CBT (one 1 to 1.5 hour session per week) for GAD over a period of 6 months. | 26 |
| Medication Alone Patients received Venlafaxine XR (75-225 mg/d) alone as treatment for GAD over a period of 6 months. | 35 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Did not receive treatment | 3 | 5 |
| Overall Study | Lack of Efficacy | 2 | 1 |
| Overall Study | Lost to Follow-up | 2 | 5 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Combined Treatment | Medication Alone | Total |
|---|---|---|---|
| Age, Continuous | 47.5 years STANDARD_DEVIATION 16 | 46.6 years STANDARD_DEVIATION 19.8 | 47.0 years STANDARD_DEVIATION 18.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 35 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Gender Female | 17 Participants | 18 Participants | 35 Participants |
| Gender Male | 9 Participants | 17 Participants | 26 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 10 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 25 Participants | 42 Participants |
| Region of Enrollment United States | 26 participants | 35 participants | 61 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 26 | 27 / 35 |
| serious Total, serious adverse events | 4 / 26 | 4 / 35 |
Outcome results
Primary
Hamilton Anxiety Rating Scale (HAM-A)
The HAM-A was used to measure the severity of anxiety symptoms. The scale consists of 14 items; each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \<17 indicates mild severity, 18-24 mild to moderate and 25-30 moderate to severe anxiety. This measure was conducted by research psychiatrists trained and highly experienced in the use of these scales. The evaluators were blind to group assignment.
Time frame: Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24
Population: Number analyzed at various time points differ due to patient dropout.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Treatment | Hamilton Anxiety Rating Scale (HAM-A) | Week 2 | 20.9 units on a scale | Standard Deviation 5 |
| Combined Treatment | Hamilton Anxiety Rating Scale (HAM-A) | Week 12 | 10.8 units on a scale | Standard Deviation 7.2 |
| Combined Treatment | Hamilton Anxiety Rating Scale (HAM-A) | Week 6 | 13.5 units on a scale | Standard Deviation 6.5 |
| Combined Treatment | Hamilton Anxiety Rating Scale (HAM-A) | Week 16 | 8.1 units on a scale | Standard Deviation 6.9 |
| Combined Treatment | Hamilton Anxiety Rating Scale (HAM-A) | Week 4 | 17.3 units on a scale | Standard Deviation 5.6 |
| Combined Treatment | Hamilton Anxiety Rating Scale (HAM-A) | Week 20 | 6.2 units on a scale | Standard Deviation 5.5 |
| Combined Treatment | Hamilton Anxiety Rating Scale (HAM-A) | Week 8 | 12.7 units on a scale | Standard Deviation 7.5 |
| Combined Treatment | Hamilton Anxiety Rating Scale (HAM-A) | Week 24 | 6.5 units on a scale | Standard Deviation 5.4 |
| Combined Treatment | Hamilton Anxiety Rating Scale (HAM-A) | Baseline | 25.9 units on a scale | Standard Deviation 2.6 |
| Medication Alone | Hamilton Anxiety Rating Scale (HAM-A) | Week 24 | 3.4 units on a scale | Standard Deviation 1.9 |
| Medication Alone | Hamilton Anxiety Rating Scale (HAM-A) | Baseline | 23.8 units on a scale | Standard Deviation 2.7 |
| Medication Alone | Hamilton Anxiety Rating Scale (HAM-A) | Week 2 | 19.4 units on a scale | Standard Deviation 5.1 |
| Medication Alone | Hamilton Anxiety Rating Scale (HAM-A) | Week 4 | 14.7 units on a scale | Standard Deviation 5.6 |
| Medication Alone | Hamilton Anxiety Rating Scale (HAM-A) | Week 6 | 10.9 units on a scale | Standard Deviation 5.5 |
| Medication Alone | Hamilton Anxiety Rating Scale (HAM-A) | Week 8 | 7.8 units on a scale | Standard Deviation 6 |
| Medication Alone | Hamilton Anxiety Rating Scale (HAM-A) | Week 12 | 5.9 units on a scale | Standard Deviation 4.3 |
| Medication Alone | Hamilton Anxiety Rating Scale (HAM-A) | Week 16 | 4.3 units on a scale | Standard Deviation 3.1 |
| Medication Alone | Hamilton Anxiety Rating Scale (HAM-A) | Week 20 | 4.3 units on a scale | Standard Deviation 3.2 |
Comparison: Mixed model analysis (differential slopes over time) comparing the 26 patients who received combined treatment with at least one CBT session to the 35 patients randomized to venlafaxine XR alone (and received at least one dose) on HAM-A total scores. Only available scores were used (no imputation for missing data). Because the HAM-A demonstrated a relatively rapid improvement early in treatment and then a leveling off, a shifted log-transformation of time of assessment was implemented.p-value: 0.17Mixed Models Analysis
Secondary
50 Percent or Greater Reduction in PSWQ Score
Clinically significant change was defined on the PSWQ as an estimated (based on linear mixed effects model) endpoint score of less than 50.9. This score was calculated using the PSWQ normative data provided by Gillis, Haaga, and Ford (1995) and the baseline PSWQ mean and standard deviation (SD) from the current sample. The PSWQ mean and SD from the normative and current GAD samples were entered into the Jacobson et al. (1984) formula c for clinically significant change. This method provides a cutoff indicating whether or not the level of functioning by a patient is statistically more likely to be in the functional rather than the dysfunctional population.
Time frame: Data collected as part of protocol 709012 at baseline, week 12, and week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined Treatment | 50 Percent or Greater Reduction in PSWQ Score | 19 Participants |
| Medication Alone | 50 Percent or Greater Reduction in PSWQ Score | 28 Participants |
p-value: 0.52Chi-squared
Secondary
Clinical Global Impression (CGI)-Improvement Score
The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale (1= very much improved; 7 = very much worse) that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. Evaluators were blind to group assignment.
Time frame: Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24
Population: Number analyzed at different time points varies due to patient dropout.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Treatment | Clinical Global Impression (CGI)-Improvement Score | Week 12 | 1.9 units on a scale | Standard Deviation 1 |
| Combined Treatment | Clinical Global Impression (CGI)-Improvement Score | Week 8 | 2.3 units on a scale | Standard Deviation 1.2 |
| Combined Treatment | Clinical Global Impression (CGI)-Improvement Score | Week 4 | 2.7 units on a scale | Standard Deviation 0.9 |
| Combined Treatment | Clinical Global Impression (CGI)-Improvement Score | Week 16 | 1.6 units on a scale | Standard Deviation 0.8 |
| Combined Treatment | Clinical Global Impression (CGI)-Improvement Score | Week 2 | 3.3 units on a scale | Standard Deviation 0.7 |
| Combined Treatment | Clinical Global Impression (CGI)-Improvement Score | Week 20 | 1.4 units on a scale | Standard Deviation 0.7 |
| Combined Treatment | Clinical Global Impression (CGI)-Improvement Score | Week 6 | 2.4 units on a scale | Standard Deviation 0.9 |
| Combined Treatment | Clinical Global Impression (CGI)-Improvement Score | Week 24 | 1.4 units on a scale | Standard Deviation 0.6 |
| Combined Treatment | Clinical Global Impression (CGI)-Improvement Score | Baseline | 2.6 units on a scale | Standard Deviation 1.9 |
| Medication Alone | Clinical Global Impression (CGI)-Improvement Score | Week 24 | 1.1 units on a scale | Standard Deviation 0.3 |
| Medication Alone | Clinical Global Impression (CGI)-Improvement Score | Baseline | 3.1 units on a scale | Standard Deviation 1.7 |
| Medication Alone | Clinical Global Impression (CGI)-Improvement Score | Week 8 | 1.5 units on a scale | Standard Deviation 0.8 |
| Medication Alone | Clinical Global Impression (CGI)-Improvement Score | Week 2 | 3.2 units on a scale | Standard Deviation 1 |
| Medication Alone | Clinical Global Impression (CGI)-Improvement Score | Week 4 | 2.4 units on a scale | Standard Deviation 0.8 |
| Medication Alone | Clinical Global Impression (CGI)-Improvement Score | Week 6 | 2.0 units on a scale | Standard Deviation 0.8 |
| Medication Alone | Clinical Global Impression (CGI)-Improvement Score | Week 12 | 1.4 units on a scale | Standard Deviation 0.6 |
| Medication Alone | Clinical Global Impression (CGI)-Improvement Score | Week 16 | 1.2 units on a scale | Standard Deviation 0.4 |
| Medication Alone | Clinical Global Impression (CGI)-Improvement Score | Week 20 | 1.2 units on a scale | Standard Deviation 0.4 |
Comparison: Analyses were conducted using mixed effects models that tested for differential slopes over time between the CBT plus venlafaxine XR and venlafaxine XR alone groups using only available scores (no imputation for missing data).p-value: 0.95Mixed Models Analysis
Secondary
Clinical Global Impression (CGI)-Severity Score
The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale (1=normal; 7 = extremely ill) that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. Evaluators were blind to group assignment.
Time frame: Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24
Population: Number analyzed at each time point differs due to patient dropout.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Treatment | Clinical Global Impression (CGI)-Severity Score | Week 2 | 4.1 units on a scale | Standard Deviation 0.6 |
| Combined Treatment | Clinical Global Impression (CGI)-Severity Score | Week 12 | 2.4 units on a scale | Standard Deviation 1.1 |
| Combined Treatment | Clinical Global Impression (CGI)-Severity Score | Baseline | 4.7 units on a scale | Standard Deviation 0.6 |
| Combined Treatment | Clinical Global Impression (CGI)-Severity Score | Week 16 | 2.1 units on a scale | Standard Deviation 1.1 |
| Combined Treatment | Clinical Global Impression (CGI)-Severity Score | Week 6 | 3.0 units on a scale | Standard Deviation 1 |
| Combined Treatment | Clinical Global Impression (CGI)-Severity Score | Week 20 | 1.7 units on a scale | Standard Deviation 0.9 |
| Combined Treatment | Clinical Global Impression (CGI)-Severity Score | Week 4 | 3.6 units on a scale | Standard Deviation 0.8 |
| Combined Treatment | Clinical Global Impression (CGI)-Severity Score | Week 24 | 1.8 units on a scale | Standard Deviation 1.1 |
| Combined Treatment | Clinical Global Impression (CGI)-Severity Score | Week 8 | 2.9 units on a scale | Standard Deviation 1.3 |
| Medication Alone | Clinical Global Impression (CGI)-Severity Score | Week 24 | 1.2 units on a scale | Standard Deviation 0.4 |
| Medication Alone | Clinical Global Impression (CGI)-Severity Score | Week 2 | 3.9 units on a scale | Standard Deviation 0.7 |
| Medication Alone | Clinical Global Impression (CGI)-Severity Score | Week 4 | 3.2 units on a scale | Standard Deviation 1 |
| Medication Alone | Clinical Global Impression (CGI)-Severity Score | Week 6 | 2.6 units on a scale | Standard Deviation 1 |
| Medication Alone | Clinical Global Impression (CGI)-Severity Score | Week 8 | 1.9 units on a scale | Standard Deviation 1 |
| Medication Alone | Clinical Global Impression (CGI)-Severity Score | Week 12 | 1.6 units on a scale | Standard Deviation 0.7 |
| Medication Alone | Clinical Global Impression (CGI)-Severity Score | Week 16 | 1.4 units on a scale | Standard Deviation 0.6 |
| Medication Alone | Clinical Global Impression (CGI)-Severity Score | Week 20 | 1.4 units on a scale | Standard Deviation 0.6 |
| Medication Alone | Clinical Global Impression (CGI)-Severity Score | Baseline | 4.7 units on a scale | Standard Deviation 0.5 |
Comparison: Analyses were conducted using mixed effects models that tested for differential slopes over time between the CBT plus venlafaxine XR and venlafaxine XR alone groups using only available scores (no imputation for missing data).p-value: 0.06ANCOVA
Secondary
Clinical Response Rate
Clinical response on the HAM-A was defined as a 50% or greater reduction from baseline to last value with the 24-week open label medication phase.
Time frame: Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined Treatment | Clinical Response Rate | 17 Participants |
| Medication Alone | Clinical Response Rate | 25 Participants |
p-value: 0.63Chi-squared
Secondary
Hamilton Rating Scale for Depression (HAM-D)-17-item Score
The 17-item version of the HAM-D was used to assess severity of depressive symptoms. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2.The total score is the sum of the 17 items, with a range from 0 to 50. A higher scores indicates greater depression. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. The evaluators were blind to group assignment.
Time frame: Data collected as part of protocol 709012 at baseline, week 12, and week 24
Population: Numbers analyzed at various time points differ due to patient dropout.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Treatment | Hamilton Rating Scale for Depression (HAM-D)-17-item Score | Week 12 | 7.0 units on a scale | Standard Deviation 3.4 |
| Combined Treatment | Hamilton Rating Scale for Depression (HAM-D)-17-item Score | Baseline | 13.1 units on a scale | Standard Deviation 2.2 |
| Combined Treatment | Hamilton Rating Scale for Depression (HAM-D)-17-item Score | Week 24 | 5.1 units on a scale | Standard Deviation 4 |
| Medication Alone | Hamilton Rating Scale for Depression (HAM-D)-17-item Score | Baseline | 12.3 units on a scale | Standard Deviation 2.8 |
| Medication Alone | Hamilton Rating Scale for Depression (HAM-D)-17-item Score | Week 12 | 3.9 units on a scale | Standard Deviation 2.6 |
| Medication Alone | Hamilton Rating Scale for Depression (HAM-D)-17-item Score | Week 24 | 3.0 units on a scale | Standard Deviation 1.7 |
Comparison: Data collected at week 24 were analyzed using analysis of covariance (ANCOVA) with the baseline score as the covariate.p-value: 0.051ANCOVA
Secondary
Hospital Anxiety Depression Scale (HAD)-Anxiety Score
The HAD was used to assess patients' report of anxiety and depressive symptoms. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. A higher score indicates greater anxiety.
Time frame: Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24
Population: Numbers analyzed at various time points differ due to patient dropout.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Treatment | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Week 2 | 11.7 units on a scale | Standard Deviation 4.8 |
| Combined Treatment | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Week 12 | 6.9 units on a scale | Standard Deviation 4.3 |
| Combined Treatment | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Week 6 | 9.2 units on a scale | Standard Deviation 4.7 |
| Combined Treatment | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Week 16 | 6.9 units on a scale | Standard Deviation 5.2 |
| Combined Treatment | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Week 4 | 10.9 units on a scale | Standard Deviation 4.5 |
| Combined Treatment | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Week 20 | 6.2 units on a scale | Standard Deviation 4.6 |
| Combined Treatment | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Week 8 | 9.0 units on a scale | Standard Deviation 4.7 |
| Combined Treatment | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Week 24 | 6.2 units on a scale | Standard Deviation 3.3 |
| Combined Treatment | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Baseline | 13.6 units on a scale | Standard Deviation 3.4 |
| Medication Alone | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Week 24 | 4.7 units on a scale | Standard Deviation 4.5 |
| Medication Alone | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Baseline | 13.0 units on a scale | Standard Deviation 4.2 |
| Medication Alone | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Week 2 | 10.9 units on a scale | Standard Deviation 5.1 |
| Medication Alone | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Week 4 | 8.3 units on a scale | Standard Deviation 5 |
| Medication Alone | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Week 6 | 7.1 units on a scale | Standard Deviation 4.6 |
| Medication Alone | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Week 8 | 5.7 units on a scale | Standard Deviation 4.1 |
| Medication Alone | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Week 12 | 4.1 units on a scale | Standard Deviation 3.4 |
| Medication Alone | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Week 16 | 4.6 units on a scale | Standard Deviation 3.4 |
| Medication Alone | Hospital Anxiety Depression Scale (HAD)-Anxiety Score | Week 20 | 4.9 units on a scale | Standard Deviation 3.6 |
Comparison: Analyses were conducted using mixed effects models that tested for differential slopes over time between the CBT plus venlafaxine XR and venlafaxine XR alone groups using only available scores (no imputation for missing data).p-value: 0.54Mixed Models Analysis
Secondary
Hospital Anxiety Depression Scale (HAD)-Depression Score
The HAD was used to assess patients' report of anxiety and depressive symptoms. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. A higher score indicates greater depression.
Time frame: Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24
Population: Numbers analyzed at various time points differ due to patient dropout.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Treatment | Hospital Anxiety Depression Scale (HAD)-Depression Score | Week 12 | 5.5 units on a scale | Standard Deviation 4.6 |
| Combined Treatment | Hospital Anxiety Depression Scale (HAD)-Depression Score | Week 6 | 6.3 units on a scale | Standard Deviation 5 |
| Combined Treatment | Hospital Anxiety Depression Scale (HAD)-Depression Score | Week 2 | 8.5 units on a scale | Standard Deviation 5.1 |
| Combined Treatment | Hospital Anxiety Depression Scale (HAD)-Depression Score | Week 16 | 5.6 units on a scale | Standard Deviation 4.9 |
| Combined Treatment | Hospital Anxiety Depression Scale (HAD)-Depression Score | Baseline | 9.8 units on a scale | Standard Deviation 5.7 |
| Combined Treatment | Hospital Anxiety Depression Scale (HAD)-Depression Score | Week 20 | 4.3 units on a scale | Standard Deviation 4.3 |
| Combined Treatment | Hospital Anxiety Depression Scale (HAD)-Depression Score | Week 4 | 7.9 units on a scale | Standard Deviation 5.1 |
| Combined Treatment | Hospital Anxiety Depression Scale (HAD)-Depression Score | Week 24 | 4.7 units on a scale | Standard Deviation 3.9 |
| Combined Treatment | Hospital Anxiety Depression Scale (HAD)-Depression Score | Week 8 | 7.0 units on a scale | Standard Deviation 5.3 |
| Medication Alone | Hospital Anxiety Depression Scale (HAD)-Depression Score | Week 24 | 2.9 units on a scale | Standard Deviation 3.1 |
| Medication Alone | Hospital Anxiety Depression Scale (HAD)-Depression Score | Week 8 | 3.4 units on a scale | Standard Deviation 3.3 |
| Medication Alone | Hospital Anxiety Depression Scale (HAD)-Depression Score | Week 12 | 2.9 units on a scale | Standard Deviation 2.7 |
| Medication Alone | Hospital Anxiety Depression Scale (HAD)-Depression Score | Baseline | 7.3 units on a scale | Standard Deviation 3.4 |
| Medication Alone | Hospital Anxiety Depression Scale (HAD)-Depression Score | Week 2 | 6.8 units on a scale | Standard Deviation 3.9 |
| Medication Alone | Hospital Anxiety Depression Scale (HAD)-Depression Score | Week 4 | 5.3 units on a scale | Standard Deviation 3.8 |
| Medication Alone | Hospital Anxiety Depression Scale (HAD)-Depression Score | Week 6 | 4.5 units on a scale | Standard Deviation 3.3 |
| Medication Alone | Hospital Anxiety Depression Scale (HAD)-Depression Score | Week 16 | 2.0 units on a scale | Standard Deviation 2.3 |
| Medication Alone | Hospital Anxiety Depression Scale (HAD)-Depression Score | Week 20 | 2.1 units on a scale | Standard Deviation 2.3 |
Comparison: Analyses were conducted using mixed effects models that tested for differential slopes over time between the CBT plus venlafaxine XR and venlafaxine XR alone groups using only available scores (no imputation for missing data).p-value: 0.86Mixed Models Analysis
Secondary
Mental Component Score of the 12-item Short Form Survey (SF-12)
The Short Form (12) Health Survey is a 12-item, patient-reported survey of patient health. Physical and Mental Health Component Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Time frame: Data collected as part of protocol 709012 at baseline, week 12, and week 24
Population: Number analyzed at different time points varies due to patient dropout.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Treatment | Mental Component Score of the 12-item Short Form Survey (SF-12) | Baseline | 28.5 units on a scale | Standard Deviation 9.8 |
| Combined Treatment | Mental Component Score of the 12-item Short Form Survey (SF-12) | Week 12 | 46.2 units on a scale | Standard Deviation 12.6 |
| Combined Treatment | Mental Component Score of the 12-item Short Form Survey (SF-12) | Week 24 | 45.5 units on a scale | Standard Deviation 12.7 |
| Medication Alone | Mental Component Score of the 12-item Short Form Survey (SF-12) | Baseline | 31.4 units on a scale | Standard Deviation 10.9 |
| Medication Alone | Mental Component Score of the 12-item Short Form Survey (SF-12) | Week 12 | 48.3 units on a scale | Standard Deviation 9.5 |
| Medication Alone | Mental Component Score of the 12-item Short Form Survey (SF-12) | Week 24 | 49.8 units on a scale | Standard Deviation 10.4 |
Comparison: Data collected at week 24 were analyzed with ANCOVA including baseline data as covariate.p-value: 0.07ANCOVA
Secondary
Penn State Worry Questionnaire (PSWQ)
The Penn State Worry Questionaire is a 16-item inventory that aims to measure the trait of worry, using Likert rating from 1 (not at all typical of me) to 5 (very typical of me). A total score is calculated (range = 16 to 80), with higher scores indicating greater worry.
Time frame: Data collected as part of protocol 709012 at baseline, week 12, and week 24
Population: Number analyzed at different time points varies due to patient dropout.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Treatment | Penn State Worry Questionnaire (PSWQ) | Baseline | 61.8 units on a scale | Standard Deviation 9.5 |
| Combined Treatment | Penn State Worry Questionnaire (PSWQ) | Week 12 | 48.6 units on a scale | Standard Deviation 11.8 |
| Combined Treatment | Penn State Worry Questionnaire (PSWQ) | Week 24 | 46.4 units on a scale | Standard Deviation 11.1 |
| Medication Alone | Penn State Worry Questionnaire (PSWQ) | Baseline | 57.9 units on a scale | Standard Deviation 12.7 |
| Medication Alone | Penn State Worry Questionnaire (PSWQ) | Week 12 | 42.3 units on a scale | Standard Deviation 13 |
| Medication Alone | Penn State Worry Questionnaire (PSWQ) | Week 24 | 45.1 units on a scale | Standard Deviation 14 |
Comparison: Data collected at week 24 were analyzed using ANCOVA with the baseline score as the covariate.p-value: 0.53ANCOVA
Secondary
Physical Component Score of the 12-Item Short Form Survey (SF-12)
The Short Form (12) Health Survey is a 12-item, patient-reported survey of patient health. Physical and Mental Health Component Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Time frame: Data collected as part of protocol 709012 at baseline, week 12, and week 24
Population: Number analyzed at different time points varies due to patient dropout.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Treatment | Physical Component Score of the 12-Item Short Form Survey (SF-12) | Week 24 | 45.5 units on a scale | Standard Deviation 12.7 |
| Combined Treatment | Physical Component Score of the 12-Item Short Form Survey (SF-12) | Baseline | 46.1 units on a scale | Standard Deviation 13.6 |
| Combined Treatment | Physical Component Score of the 12-Item Short Form Survey (SF-12) | Week 12 | 46.2 units on a scale | Standard Deviation 12.5 |
| Medication Alone | Physical Component Score of the 12-Item Short Form Survey (SF-12) | Week 24 | 49.7 units on a scale | Standard Deviation 7 |
| Medication Alone | Physical Component Score of the 12-Item Short Form Survey (SF-12) | Baseline | 52.7 units on a scale | Standard Deviation 10.7 |
| Medication Alone | Physical Component Score of the 12-Item Short Form Survey (SF-12) | Week 12 | 51.9 units on a scale | Standard Deviation 6.9 |
Comparison: Data collected at week 24 were analyzed with ANCOVA with baseline data as covariate.p-value: 0.23ANCOVA
Secondary
Quality of Life Subscale of the General Health Questionnaire (GHQ)
The General Health Questionnaire (GHQ) is a psychometric screening tool to identify common psychiatric conditions. Patients completed the 12 quality of life questions (each on a 0 to 3 scale) on this questionnaire. Scores on the 12 items were added up to create summary score (range = 0 to 36). Higher scores indicate worse health.
Time frame: Data collected as part of protocol 709012 at baseline, week 12, and week 24
Population: Number analyzed at different time points varies due to patient dropout.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Treatment | Quality of Life Subscale of the General Health Questionnaire (GHQ) | Week 12 | 24.8 units on a scale | Standard Deviation 7.3 |
| Combined Treatment | Quality of Life Subscale of the General Health Questionnaire (GHQ) | Baseline | 34.5 units on a scale | Standard Deviation 7 |
| Combined Treatment | Quality of Life Subscale of the General Health Questionnaire (GHQ) | Week 24 | 23.8 units on a scale | Standard Deviation 6.6 |
| Medication Alone | Quality of Life Subscale of the General Health Questionnaire (GHQ) | Baseline | 32.2 units on a scale | Standard Deviation 6.4 |
| Medication Alone | Quality of Life Subscale of the General Health Questionnaire (GHQ) | Week 12 | 20.4 units on a scale | Standard Deviation 5.2 |
| Medication Alone | Quality of Life Subscale of the General Health Questionnaire (GHQ) | Week 24 | 22.9 units on a scale | Standard Deviation 5.6 |
Comparison: Data collected at week 24 were analyzed using ANCOVA with the baseline score as the covariate.p-value: 0.17ANCOVA