Pilot Study of Cognitive Behavioral Therapy for Anxiety and Bipolar I Disorder

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01892306
• Collaborator: (none)
• Enrollment: 34
• Location: 1
• Arms: 2
• Duration (Months): 18
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

The specific goal of this research study is to investigate the feasibility, acceptability, and preliminary efficacy of a transdiagnostic, cognitive-behavioral therapy developed specifically to target common core processes across mood and anxiety disorders [Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP)], for the treatment of patients with bipolar I disorder (BD-I) and comorbid anxiety. The study will compare treatment-as-usual with pharmacotherapy (TAU) plus 18 one-hour sessions of treatment with the UP to TAU alone. Patients in both treatment conditions will be followed over a 12-month period and will be assessed monthly to track changes in mood, anxiety and emotion-related symptoms; functional impairment; and relapse rates. Data on the acceptability of the treatment will be gathered concurrently through monthly patient self-reported ratings of treatment satisfaction, and by tracking rates of acceptance for randomization into the study, number of completed sessions, and dropout rates. The study will examine: 1) whether combined cognitive behavioral treatment (UP) for BD-I and comorbid anxiety disorders is an acceptable and feasible approach to treatment; 2) whether treatment with the UP for BD-I and comorbid anxiety disorders as an adjunct to pharmacotherapy treatment-as-usual (TAU) leads to greater symptom reduction and reduced functional impairment than pharmacotherapy alone, 3) whether treatment for BD-I and comorbid anxiety disorders with the UP improves relapse rates over a 6-month follow-up relative to TAU; and 4) whether reduction in symptoms, relapse rates, and functional impairment are mediated by changes in emotion regulation skills. The broader aim of this study is to address the need for improved treatments for bipolar disorder.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder; Anxiety Disorders	Behavioral: UP CBT; Drug: Treatment as usual	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Transdiagnostic Treatment for Anxiety and Bipolar I Disorder
• Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment as usual plus UP CBT Existing psychiatrist-administered psychopharmacotherapy plus weekly transdiagnostic CBT	Behavioral: UP CBT; The UP is an 18-session weekly cognitive behavioral intervention for anxiety and mood disorders; Other Names: Unified Protocol (UP) for transdiagnostic treatment of emotional disorders
Active Comparator: Treatment as usual Existing psychiatrist-administered psychopharmacotherapy	Drug: Treatment as usual; Existing optimized pharmacotherapy as delivered by treating psychiatrist

Outcome Measures

Primary Outcome Measures

1. Reductions Over Time in Anxiety Symptoms as Measured by Hamilton Anxiety Rating Scale [Six months]

   The Hamilton Anxiety Rating Scale (HAM-A) is a well-validated clinician administered rating of anxiety-related symptoms. Ratings are made on a 0 (no symptoms) to 4 (most severe in frequency/duration/interference/distress) for each item (14 items), with a minimum score of 0 and a maximum score of 56 calculated by summing scores of all 14 items. Higher scores indicate greater impairment.

2. Reductions Over Time in Depression Symptoms as Measured by Hamilton Depression Rating Scale (HAM-D) [Six months]

   The Hamilton Depression Rating Scale (HAM-D) is a well-validated clinician administered rating of depression-related symptoms. Scores are calculated by summing scores across all 17-items, with a minimum score of 0 and a maximum score of 54. Higher scores indicate greater impairment.

Secondary Outcome Measures

1. Treatment Acceptability as Measured by Client Satisfaction Questionnaire (CSQ) [Six months]

   The Client Satisfaction Questionnaire (CSQ) is an 8-item scale that assesses perceptions of acceptability and quality of outpatient treatment. Ratings are made on a 1 (poor) to 4 (excellent) scale for each item and then summed for a total score, with a minimum score of 8 and a maximum score of 32. Higher scores indicate greater satisfaction with treatment.

2. Association Between Anxiety Symptom Change (HAM-A) and Difficulties in Emotion Regulation Scale (DERS) [Six Months]

   Emotion regulation skills were assessed using a measure of emotion regulation (Difficulties in Emotion Regulation Scale- DERS), a 36-item Likert-type scale (1-6) calculated by averaging scores across all items. See Baseline Characteristics for baseline DERS score. See Primary Outcome Measure for a description of HAM-A.

3. Association Between Anxiety Symptom Change (HAM-A) and Reaction to Emotions (Affective Control Scale-ACS) [6 months]

   Reactions to emotions, were assessed using the Affective Control Scale, or ACS, a 42-item Likert-type scale (1-7) calculated by averaging scores across all items. See Baseline Characteristics for baseline ACS score. See Primary Outcome Measure for description of HAM-A.

4. Association Between Anxiety Symptom Change (HAM-A) and Anxiety Sensitivity (Anxiety Sensitivity Index-ASI) [6 months]

   Anxiety sensitivity, were assessed using the Anxiety Sensitivity Index, or ASI, a 16-item Likert-type scale (0-4) calculated by summing scores across items. See Baseline Characteristics for baseline ASI scores. See Primary Outcome Measures for a description of HAM-A.

5. Association Between Anxiety Symptom Change (HAM-A) and Neuroticism (NEO Five-Factor Inventory- NEO-FFI-N) [6 months]

   Neuroticism was assessed using the NEO Five Factor Inventory (NEO-FFI-N) which is a subscale of the NEO-FFI, a 60-item Likert-type scale (1-5) calculated by summing scores for each subscale. Only the 15-item Neuroticism subscale is included in this study. See Baseline Characteristics for baseline NEO-FFI-N. See Primary Outcome Measure for description of HAM-A.

Other Outcome Measures

1. Association Between Change on Depression (HAM-D) and Baseline Resting State Functional Connectivity of Anterior Insula and Ventrolateral Prefrontal Cortex [Six Months]

   Resting state functional magnetic resonance imaging (rsfMRI) data (non-task, eyes opened) was acquired to investigate anterior insula and ventrolateral prefrontal cortex functional connectivity as a predictor of change on depression (HAM-D). See primary outcome description of HAM-D.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Men and women age 18-65

• DSM-IV diagnosis of bipolar I disorder and at least one of three additional anxiety disorders:

generalized anxiety disorder, panic disorder, or social phobia.

• HAM-D-17 score <16 (i.e. depressive symptoms)

• YMRS score < 12 (i.e. no or very low manic symptoms)

• Current, stabilized (> 3 months) pharmacotherapy treatment under the care of a psychiatrist consisting of optimized, stable maintenance pharmacotherapy at maximum tolerated dosages according to Texas Implementation of Medication Algorithm.

Exclusion Criteria:

• Active suicidality (HAM-D-17 suicide item #3 score > 3) in the past 2 months. Potential participants scoring 3 or higher on the HAM-D-17 suicide item will be immediately evaluated by the PI and Sponsor and referred to a higher level of care if clinically indicated.

• DSM-IV bipolar I disorder subtype rapid cycling

• DSM-IV manic or mixed episode in the past 2 months

• DSM-IV major depressive episode in the past 2 months

• Psychotropic medication not in accordance with the revised Texas Implementation of Medication Algorithm

• Current Pregnancy

• Medical illness or non-psychiatric medical treatment that would likely interfere with study participation.

• Neurologic disorder, previous ECT, or history of head trauma (i.e. known structural brain lesion)

• Current or past history of selected DSM-IV Axis I disorders other than bipolar disorder including: organic mental disorder, substance abuse within the past 12 months and/or history of substance abuse for > 1 year; current substance dependence (including alcohol), as assessed by the Structured Clinical Interview for DSM-IV-TR, Substance Use Disorders (Section E); schizophrenia, delusional disorder, psychotic disorders not otherwise specified, obsessive compulsive disorder and posttraumatic stress disorder (due to low prevalence of ~6.5% each).

• Concurrent psychotherapy other than cognitive-behavioral therapy as provided in this study (to rule out other uncontrolled effects of concurrent psychotherapies)

• Presence of metallic implants that would interfere with safety during fMRI scanning (i.e. cardiac pacemaker, metal plates, etc.)

• Claustrophobia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital Bipolar Clinic and Research Program	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Andrew A. Nierenberg, MD, Director, Bipolar Clinic and Research Program, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01892306
• Other Study ID Numbers: 1F32MH098490-01
• First Posted: Jul 4, 2013
• Last Update Posted: May 12, 2017
• Last Verified: May 1, 2017

• Additional relevant MeSH terms: Disease; Anxiety Disorders; Bipolar Disorder

Study Results

Participant Flow

Recruitment Details	37 were invited to consent. 34 consented to be screened for inclusion. 5 did not meet study inclusion criteria thus were not randomized (1 not on a stabilized medication; 1 did not meet criteria for anxiety disorder; 2 were currently substance dependent; 1 reported psychosis). 29 were randomized to TAU or TAU plus 18 sessions of CBT (UP+TAU).
Pre-assignment Detail	Participants were excluded from the trial before assignment to study arms based on exclusion criteria related to diagnosis and unstable medication regime.

Arm/Group Title	Treatment as Usual Plus UP CBT	Treatment as Usual
Arm/Group Description	Existing psychiatrist-administered psychopharmacotherapy plus weekly transdiagnostic CBT UP CBT: The UP is an 18-session weekly cognitive behavioral intervention for anxiety and mood disorders	Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Period Title: Overall Study
STARTED	13	16
COMPLETED	8	10
NOT COMPLETED	5	6

Baseline Characteristics

Arm/Group Title	Treatment as Usual Plus UP CBT	Treatment as Usual	Total
Arm/Group Description	Existing psychiatrist-administered psychopharmacotherapy plus weekly transdiagnostic CBT UP CBT: The UP is an 18-session weekly cognitive behavioral intervention for anxiety and mood disorders	Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist	Total of all reporting groups
Overall Participants	13	16	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.08 (13.84)	44.25 (14.27)	43.72 (13.84)
Sex: Female, Male (Count of Participants)
Female	7 53.8%	6 37.5%	13 44.8%
Male	6 46.2%	10 62.5%	16 55.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 7.7%	1 6.3%	2 6.9%
White	11 84.6%	13 81.3%	24 82.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 7.7%	2 12.5%	3 10.3%
Difficulties in Emotion Regulation Scale (DERS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	2.84 (0.53)	3.00 (0.56)	2.92 (0.54)
Affective Control Scale (ACS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.48 (0.70)	4.24 (0.53)	4.36 (0.61)
Anxiety Sensitivity Index (ASI) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	33 (10.07)	26.56 (13.47)	29.45 (12.30)
NEO Five Factor Inventory of Personality, Neuroticism Subscale (NEO-FFI-N) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5.69 (1.03)	5.88 (1.54)	5.79 (1.32)

Outcome Measures

1. Primary Outcome

Title	Reductions Over Time in Anxiety Symptoms as Measured by Hamilton Anxiety Rating Scale
Description	The Hamilton Anxiety Rating Scale (HAM-A) is a well-validated clinician administered rating of anxiety-related symptoms. Ratings are made on a 0 (no symptoms) to 4 (most severe in frequency/duration/interference/distress) for each item (14 items), with a minimum score of 0 and a maximum score of 56 calculated by summing scores of all 14 items. Higher scores indicate greater impairment.
Time Frame	Six months

Outcome Measure Data

Analysis Population Description

ITT analysis, data imputed to account for 30% missing data. A total of 28 people were included in the ITT analysis - one TAU participant initiated CBT through a private practitioner mid-study (an exclusion criteria) and was subsequently excluded from the analysis.

Arm/Group Title	Treatment as Usual Plus UP CBT	Treatment as Usual
Arm/Group Description	Existing psychiatrist-administered psychopharmacotherapy plus weekly transdiagnostic CBT UP CBT: The UP is an 18-session weekly cognitive behavioral intervention for anxiety and mood disorders	Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Measure Participants	13	15
Baseline	14 (7.8)	18.81 (6.10)
Month 2	11.78 (8.99)	17.70 (7.62)
Month 3	13.86 (9.30)	22.33 (7.68)
Month 4	13.5 (7.03)	18 (8.87)
Month 5	10 (5.55)	19.1 (8.29)
Month 6	15.71 (10.29)	18.89 (10.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment as Usual Plus UP CBT
	Comments	Scores on the HAM-A were analyzed using a mixed-effects linear regression analysis over 6 timepoints.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.02
	Comments
	Method	Mixed Models Analysis
	Comments

2. Primary Outcome

Title	Reductions Over Time in Depression Symptoms as Measured by Hamilton Depression Rating Scale (HAM-D)
Description	The Hamilton Depression Rating Scale (HAM-D) is a well-validated clinician administered rating of depression-related symptoms. Scores are calculated by summing scores across all 17-items, with a minimum score of 0 and a maximum score of 54. Higher scores indicate greater impairment.
Time Frame	Six months

Outcome Measure Data

Analysis Population Description

ITT analysis, data imputed to account for 30% missing data. A total of 28 people were included in the ITT analysis - one TAU participant initiated CBT through a private practitioner mid-study (an exclusion criteria) and was subsequently excluded from the analysis.

Arm/Group Title	Treatment as Usual Plus UP CBT	Treatment as Usual
Arm/Group Description	Existing psychiatrist-administered psychopharmacotherapy plus weekly transdiagnostic CBT UP CBT: The UP is an 18-session weekly cognitive behavioral intervention for anxiety and mood disorders	Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Measure Participants	13	15
Baseline	10.54 (6.96)	13.63 (4.87)
Month 2	8 (7.94)	11.2 (6.60)
Month 3	11.86 (6.12)	16.89 (6.13)
Month 4	11.63 (6.63)	11.9 (5.13)
Month 5	9 (6.36)	16 (5.70)
Month 6	10.14 (7.69)	12.89 (7.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment as Usual Plus UP CBT, Treatment as Usual
	Comments	Scores on the HAM-D were analyzed using a mixed-effects linear regression analysis over 6 timepoints.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Mixed Models Analysis
	Comments

3. Secondary Outcome

Title	Treatment Acceptability as Measured by Client Satisfaction Questionnaire (CSQ)
Description	The Client Satisfaction Questionnaire (CSQ) is an 8-item scale that assesses perceptions of acceptability and quality of outpatient treatment. Ratings are made on a 1 (poor) to 4 (excellent) scale for each item and then summed for a total score, with a minimum score of 8 and a maximum score of 32. Higher scores indicate greater satisfaction with treatment.
Time Frame	Six months

Outcome Measure Data

Analysis Population Description

ITT analysis, data imputed to account for 30% missing data. A total of 28 people were included in the ITT analysis - one TAU participant initiated CBT through a private practitioner mid-study (an exclusion criteria) and was subsequently excluded from the analysis.

Arm/Group Title	Treatment as Usual Plus UP CBT	Treatment as Usual
Arm/Group Description	Existing psychiatrist-administered psychopharmacotherapy plus weekly transdiagnostic CBT UP CBT: The UP is an 18-session weekly cognitive behavioral intervention for anxiety and mood disorders	Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Measure Participants	13	15
Baseline	28.5 (3.79)	27.25 (3.82)
Month 2	29.43 (2.64)	26.64 (4.40)
Month 3	29.63 (3.35)	26.22 (2.28)
Month 4	28 (4.08)	26.9 (4.28)
Month 5	29.43 (3.46)	26.6 (4.40)
Month 6	29.75 (3.41)	26.88 (4.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment as Usual Plus UP CBT, Treatment as Usual
	Comments	Scores on the CSQ were analyzed using a mixed-effects linear regression analysis over 6 timepoints.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.24
	Comments
	Method	Mixed Models Analysis
	Comments

4. Secondary Outcome

Title	Association Between Anxiety Symptom Change (HAM-A) and Difficulties in Emotion Regulation Scale (DERS)
Description	Emotion regulation skills were assessed using a measure of emotion regulation (Difficulties in Emotion Regulation Scale- DERS), a 36-item Likert-type scale (1-6) calculated by averaging scores across all items. See Baseline Characteristics for baseline DERS score. See Primary Outcome Measure for a description of HAM-A.
Time Frame	Six Months

Outcome Measure Data

Analysis Population Description

ITT analysis, data imputed to account for 30% missing data. A total of 28 people were included in the ITT analysis - one TAU participant initiated CBT through a private practitioner mid-study (an exclusion criteria) and was subsequently excluded from the analysis.

Arm/Group Title	Treatment as Usual Plus UP CBT	Treatment as Usual
Arm/Group Description	Existing psychiatrist-administered psychopharmacotherapy plus weekly transdiagnostic CBT UP CBT: The UP is an 18-session weekly cognitive behavioral intervention for anxiety and mood disorders	Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Measure Participants	13	15
Mean (Standard Error) [beta coefficients]	.759 (.784)	.180 (1.754)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment as Usual
	Comments	Linear regression - Dependent variable: HAM-A symptom change; Independent variable: Baseline DERS scores.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.62
	Comments
	Method	Regression, Linear
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment as Usual Plus UP CBT
	Comments	Linear Regression - Dependent variable: HAM-A symptom change; Independent variable: Baseline DERS scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.03
	Comments
	Method	Regression, Linear
	Comments

5. Secondary Outcome

Title	Association Between Anxiety Symptom Change (HAM-A) and Reaction to Emotions (Affective Control Scale-ACS)
Description	Reactions to emotions, were assessed using the Affective Control Scale, or ACS, a 42-item Likert-type scale (1-7) calculated by averaging scores across all items. See Baseline Characteristics for baseline ACS score. See Primary Outcome Measure for description of HAM-A.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

ITT analysis, data imputed to account for 30% missing data. A total of 28 people were included in the ITT analysis - one TAU participant initiated CBT through a private practitioner mid-study (an exclusion criteria) and was subsequently excluded from the analysis.

Arm/Group Title	Treatment as Usual Plus UP CBT	Treatment as Usual
Arm/Group Description	Existing psychiatrist-administered psychopharmacotherapy plus weekly transdiagnostic CBT UP CBT: The UP is an 18-session weekly cognitive behavioral intervention for anxiety and mood disorders	Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Measure Participants	13	15
Mean (Standard Error) [beta coefficients]	.766 (.774)	.022 (1.782)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment as Usual
	Comments	Linear regression - Dependent variable: HAM-A symptom change; Independent variable: Baseline ACS scores.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	Regression, Linear
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment as Usual Plus UP CBT
	Comments	Linear Regression - Dependent variable: HAM-A symptom change; Independent variable: Baseline ACS scores.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Regression, Linear
	Comments

6. Secondary Outcome

Title	Association Between Anxiety Symptom Change (HAM-A) and Anxiety Sensitivity (Anxiety Sensitivity Index-ASI)
Description	Anxiety sensitivity, were assessed using the Anxiety Sensitivity Index, or ASI, a 16-item Likert-type scale (0-4) calculated by summing scores across items. See Baseline Characteristics for baseline ASI scores. See Primary Outcome Measures for a description of HAM-A.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

ITT analysis, data imputed to account for 30% missing data. A total of 28 people were included in the ITT analysis - one TAU participant initiated CBT through a private practitioner mid-study (an exclusion criteria) and was subsequently excluded from the analysis.

Arm/Group Title	Treatment as Usual Plus UP CBT	Treatment as Usual
Arm/Group Description	Existing psychiatrist-administered psychopharmacotherapy plus weekly transdiagnostic CBT UP CBT: The UP is an 18-session weekly cognitive behavioral intervention for anxiety and mood disorders	Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Measure Participants	13	15
Mean (Standard Error) [beta coefficients]	0.371 (1.118)	0.062 (1.779)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment as Usual
	Comments	Linear Regression - Dependent variable: HAM-A symptom change; Independent variable: Baseline ASI scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.87
	Comments
	Method	Regression, Linear
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment as Usual Plus UP CBT
	Comments	Linear Regression - Dependent variable: HAM-A symptom change; Independent variable: Baseline ASI scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments
	Method	Regression, Linear
	Comments

7. Secondary Outcome

Title	Association Between Anxiety Symptom Change (HAM-A) and Neuroticism (NEO Five-Factor Inventory- NEO-FFI-N)
Description	Neuroticism was assessed using the NEO Five Factor Inventory (NEO-FFI-N) which is a subscale of the NEO-FFI, a 60-item Likert-type scale (1-5) calculated by summing scores for each subscale. Only the 15-item Neuroticism subscale is included in this study. See Baseline Characteristics for baseline NEO-FFI-N. See Primary Outcome Measure for description of HAM-A.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

ITT analysis, data imputed to account for 30% missing data. A total of 28 people were included in the ITT analysis - one TAU participant initiated CBT through a private practitioner mid-study (an exclusion criteria) and was subsequently excluded from the analysis.

Arm/Group Title	Treatment as Usual Plus UP CBT	Treatment as Usual
Arm/Group Description	Existing psychiatrist-administered psychopharmacotherapy plus weekly transdiagnostic CBT UP CBT: The UP is an 18-session weekly cognitive behavioral intervention for anxiety and mood disorders	Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Measure Participants	13	15
Mean (Standard Error) [beta coefficients]	0.720 (0.836)	0.471 (1.572)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment as Usual
	Comments	Linear Regression - Dependent variable: HAM-A symptom change; Independent variable: Baseline NEO- Neuroticism scores.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	Regression, Linear
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment as Usual Plus UP CBT
	Comments	Linear Regression - Dependent variable: HAM-A symptom change; Independent variable: Baseline NEO-Neuroticism scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.04
	Comments
	Method	Regression, Linear
	Comments

8. Other Pre-specified Outcome

Title	Association Between Change on Depression (HAM-D) and Baseline Resting State Functional Connectivity of Anterior Insula and Ventrolateral Prefrontal Cortex
Description	Resting state functional magnetic resonance imaging (rsfMRI) data (non-task, eyes opened) was acquired to investigate anterior insula and ventrolateral prefrontal cortex functional connectivity as a predictor of change on depression (HAM-D). See primary outcome description of HAM-D.
Time Frame	Six Months

Outcome Measure Data

Analysis Population Description

Participating in the fMRI portion of the study was optional. A total of 15 participants consented to participate in fMRI portion (7 TAU+UP, 8 TAU). Data from all 15 subjects were analyzed.

Arm/Group Title	Treatment as Usual Plus UP CBT	Treatment as Usual
Arm/Group Description	Existing psychiatrist-administered psychopharmacotherapy plus weekly transdiagnostic CBT UP CBT: The UP is an 18-session weekly cognitive behavioral intervention for anxiety and mood disorders	Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Measure Participants	7	8
Mean (Standard Error) [beta coefficient]	-.89 (.257)	.57 (.841)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment as Usual Plus UP CBT
	Comments	Fisher's z-transformed values for functional connectivity between anterior insula and ventrolateral prefrontal cortex were entered in separate treatment group-specific linear regression models as the independent variable with change in primary outcomes (HAM-D) as dependent variable.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Regression, Linear
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment as Usual
	Comments	Fisher's z-transformed values for functional connectivity between anterior insula and ventrolateral prefrontal cortex were entered in separate treatment group-specific linear regression models as the independent variable with change in primary outcomes (HAM-D) as dependent variable.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.14
	Comments
	Method	Regression, Linear
	Comments

Adverse Events

Arm/Group Title	Treatment as Usual Plus UP CBT		Treatment as Usual
Arm/Group Description	Existing psychiatrist-administered psychopharmacotherapy plus weekly transdiagnostic CBT UP CBT: The UP is an 18-session weekly cognitive behavioral intervention for anxiety and mood disorders		Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
All Cause Mortality
	Treatment as Usual Plus UP CBT		Treatment as Usual
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Treatment as Usual Plus UP CBT		Treatment as Usual
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/13 (7.7%)		0/16 (0%)
Psychiatric disorders
Hospitalization	1/13 (7.7%)	1	0/16 (0%)	0
Other (Not Including Serious) Adverse Events
	Treatment as Usual Plus UP CBT		Treatment as Usual
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.