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

Study Overview
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Brief Summary
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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.

Official Title
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Transdiagnostic Treatment for Anxiety and Bipolar I Disorder

Conditions
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Bipolar Disorder, Anxiety Disorders

Intervention / Treatment
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* Behavioral: UP CBT
* Drug: Treatment as usual


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reductions Over Time in Anxiety Symptoms as Measured by Hamilton Anxiety Rating Scale | 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. | Six months | 
| Reductions Over Time in Depression Symptoms as Measured by Hamilton Depression Rating Scale (HAM-D) | 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. | Six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Acceptability as Measured by Client Satisfaction Questionnaire (CSQ) | 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. | Six months | 
| Association Between Anxiety Symptom Change (HAM-A) and Difficulties in Emotion Regulation Scale (DERS) | 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. | Six Months | 
| Association Between Anxiety Symptom Change (HAM-A) and Reaction to Emotions (Affective Control Scale-ACS) | 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. | 6 months | 
| Association Between Anxiety Symptom Change (HAM-A) and Anxiety Sensitivity (Anxiety Sensitivity Index-ASI) | 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. | 6 months | 
| Association Between Anxiety Symptom Change (HAM-A) and Neuroticism (NEO Five-Factor Inventory- NEO-FFI-N) | 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. | 6 months |