Trial Outcomes & Findings for Pilot Study of Cognitive Behavioral Therapy for Anxiety and Bipolar I Disorder (NCT NCT01892306)

Last Updated: 2017-05-12

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

34 participants

Primary outcome timeframe

Six months

Results posted on

2017-05-12

Participant Flow

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).

Participants were excluded from the trial before assignment to study arms based on exclusion criteria related to diagnosis and unstable medication regime.

Participant milestones

Participant milestones
Measure	Treatment as Usual Plus UP CBT 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	Treatment as Usual Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Overall Study STARTED	13	16
Overall Study COMPLETED	8	10
Overall Study NOT COMPLETED	5	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment as Usual Plus UP CBT n=13 Participants 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	Treatment as Usual n=16 Participants Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist	Total n=29 Participants Total of all reporting groups
Affective Control Scale (ACS)	4.48 units on a scale STANDARD_DEVIATION 0.70 • n=93 Participants	4.24 units on a scale STANDARD_DEVIATION 0.53 • n=4 Participants	4.36 units on a scale STANDARD_DEVIATION 0.61 • n=27 Participants
Difficulties in Emotion Regulation Scale (DERS)	2.84 units on a scale STANDARD_DEVIATION 0.53 • n=93 Participants	3.00 units on a scale STANDARD_DEVIATION 0.56 • n=4 Participants	2.92 units on a scale STANDARD_DEVIATION 0.54 • n=27 Participants
Age, Continuous	43.08 years STANDARD_DEVIATION 13.84 • n=93 Participants	44.25 years STANDARD_DEVIATION 14.27 • n=4 Participants	43.72 years STANDARD_DEVIATION 13.84 • n=27 Participants
Sex: Female, Male Female	7 Participants n=93 Participants	6 Participants n=4 Participants	13 Participants n=27 Participants
Sex: Female, Male Male	6 Participants n=93 Participants	10 Participants n=4 Participants	16 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) White	11 Participants n=93 Participants	13 Participants n=4 Participants	24 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Anxiety Sensitivity Index (ASI)	33 units on a scale STANDARD_DEVIATION 10.07 • n=93 Participants	26.56 units on a scale STANDARD_DEVIATION 13.47 • n=4 Participants	29.45 units on a scale STANDARD_DEVIATION 12.30 • n=27 Participants
NEO Five Factor Inventory of Personality, Neuroticism Subscale (NEO-FFI-N)	5.69 units on a scale STANDARD_DEVIATION 1.03 • n=93 Participants	5.88 units on a scale STANDARD_DEVIATION 1.54 • n=4 Participants	5.79 units on a scale STANDARD_DEVIATION 1.32 • n=27 Participants

PRIMARY outcome

Timeframe: Six months

Population: 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.

Outcome measures

Outcome measures
Measure	Treatment as Usual Plus UP CBT n=13 Participants 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	Treatment as Usual n=15 Participants Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Reductions Over Time in Anxiety Symptoms as Measured by Hamilton Anxiety Rating Scale Month 2	11.78 Units on scale Standard Deviation 8.99	17.70 Units on scale Standard Deviation 7.62
Reductions Over Time in Anxiety Symptoms as Measured by Hamilton Anxiety Rating Scale Month 3	13.86 Units on scale Standard Deviation 9.30	22.33 Units on scale Standard Deviation 7.68
Reductions Over Time in Anxiety Symptoms as Measured by Hamilton Anxiety Rating Scale Month 4	13.5 Units on scale Standard Deviation 7.03	18 Units on scale Standard Deviation 8.87
Reductions Over Time in Anxiety Symptoms as Measured by Hamilton Anxiety Rating Scale Month 5	10 Units on scale Standard Deviation 5.55	19.1 Units on scale Standard Deviation 8.29
Reductions Over Time in Anxiety Symptoms as Measured by Hamilton Anxiety Rating Scale Month 6	15.71 Units on scale Standard Deviation 10.29	18.89 Units on scale Standard Deviation 10.82
Reductions Over Time in Anxiety Symptoms as Measured by Hamilton Anxiety Rating Scale Baseline	14 Units on scale Standard Deviation 7.8	18.81 Units on scale Standard Deviation 6.10

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment as Usual Plus UP CBT n=13 Participants 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	Treatment as Usual n=15 Participants Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Reductions Over Time in Depression Symptoms as Measured by Hamilton Depression Rating Scale (HAM-D) Baseline	10.54 Units on scale Standard Deviation 6.96	13.63 Units on scale Standard Deviation 4.87
Reductions Over Time in Depression Symptoms as Measured by Hamilton Depression Rating Scale (HAM-D) Month 2	8 Units on scale Standard Deviation 7.94	11.2 Units on scale Standard Deviation 6.60
Reductions Over Time in Depression Symptoms as Measured by Hamilton Depression Rating Scale (HAM-D) Month 3	11.86 Units on scale Standard Deviation 6.12	16.89 Units on scale Standard Deviation 6.13
Reductions Over Time in Depression Symptoms as Measured by Hamilton Depression Rating Scale (HAM-D) Month 4	11.63 Units on scale Standard Deviation 6.63	11.9 Units on scale Standard Deviation 5.13
Reductions Over Time in Depression Symptoms as Measured by Hamilton Depression Rating Scale (HAM-D) Month 5	9 Units on scale Standard Deviation 6.36	16 Units on scale Standard Deviation 5.70
Reductions Over Time in Depression Symptoms as Measured by Hamilton Depression Rating Scale (HAM-D) Month 6	10.14 Units on scale Standard Deviation 7.69	12.89 Units on scale Standard Deviation 7.42

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment as Usual Plus UP CBT n=13 Participants 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	Treatment as Usual n=15 Participants Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Treatment Acceptability as Measured by Client Satisfaction Questionnaire (CSQ) Baseline	28.5 Units on scale Standard Deviation 3.79	27.25 Units on scale Standard Deviation 3.82
Treatment Acceptability as Measured by Client Satisfaction Questionnaire (CSQ) Month 2	29.43 Units on scale Standard Deviation 2.64	26.64 Units on scale Standard Deviation 4.40
Treatment Acceptability as Measured by Client Satisfaction Questionnaire (CSQ) Month 3	29.63 Units on scale Standard Deviation 3.35	26.22 Units on scale Standard Deviation 2.28
Treatment Acceptability as Measured by Client Satisfaction Questionnaire (CSQ) Month 4	28 Units on scale Standard Deviation 4.08	26.9 Units on scale Standard Deviation 4.28
Treatment Acceptability as Measured by Client Satisfaction Questionnaire (CSQ) Month 5	29.43 Units on scale Standard Deviation 3.46	26.6 Units on scale Standard Deviation 4.40
Treatment Acceptability as Measured by Client Satisfaction Questionnaire (CSQ) Month 6	29.75 Units on scale Standard Deviation 3.41	26.88 Units on scale Standard Deviation 4.02

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment as Usual Plus UP CBT n=13 Participants 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	Treatment as Usual n=15 Participants Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Association Between Anxiety Symptom Change (HAM-A) and Difficulties in Emotion Regulation Scale (DERS)	.759 beta coefficients Standard Error .784	.180 beta coefficients Standard Error 1.754

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment as Usual Plus UP CBT n=13 Participants 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	Treatment as Usual n=15 Participants Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Association Between Anxiety Symptom Change (HAM-A) and Reaction to Emotions (Affective Control Scale-ACS)	.766 beta coefficients Standard Error .774	.022 beta coefficients Standard Error 1.782

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment as Usual Plus UP CBT n=13 Participants 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	Treatment as Usual n=15 Participants Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Association Between Anxiety Symptom Change (HAM-A) and Anxiety Sensitivity (Anxiety Sensitivity Index-ASI)	0.371 beta coefficients Standard Error 1.118	0.062 beta coefficients Standard Error 1.779

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment as Usual Plus UP CBT n=13 Participants 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	Treatment as Usual n=15 Participants Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Association Between Anxiety Symptom Change (HAM-A) and Neuroticism (NEO Five-Factor Inventory- NEO-FFI-N)	0.720 beta coefficients Standard Error 0.836	0.471 beta coefficients Standard Error 1.572

OTHER_PRE_SPECIFIED outcome

Timeframe: Six Months

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment as Usual Plus UP CBT n=7 Participants 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	Treatment as Usual n=8 Participants Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Association Between Change on Depression (HAM-D) and Baseline Resting State Functional Connectivity of Anterior Insula and Ventrolateral Prefrontal Cortex	-.89 beta coefficient Standard Error .257	.57 beta coefficient Standard Error .841

Adverse Events

Treatment as Usual Plus UP CBT

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Treatment as Usual

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment as Usual Plus UP CBT n=13 participants at risk 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	Treatment as Usual n=16 participants at risk Existing psychiatrist-administered psychopharmacotherapy Treatment as usual: Existing optimized pharmacotherapy as delivered by treating psychiatrist
Psychiatric disorders Hospitalization	7.7% 1/13 • Number of events 1	0.00% 0/16

Other adverse events

Adverse event data not reported

Additional Information

Kristen Ellard, PhD

Massachusetts General Hospital

Phone: 617-726-6422

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place