Psychotherapy for Bipolar II Depression, Pilot Study, Phase II

Study Overview
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Brief Summary
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Purpose of this study is to examine the effectiveness of an experimental psychotherapy (talk therapy) for the treatment of bipolar II depression. The name of this psychotherapy is Interpersonal and Social Rhythm Therapy for Bipolar II Depression (IPSRT-BPII). Subjects will be randomly assigned to receive either IPSRT-BPII or the medication Seroquel (quetiapine) to manage their symptoms of bipolar II depression. Subjects will receive the assigned therapy for up to 20 weeks.

Detailed Description
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The proposed pilot study is an experimental design intended to investigate the preliminary efficacy of Interpersonal Social Rhythm Therapy for Bipolar II Depression (IPSRT-BPII). A total of 56 eligible subjects with a diagnosis of bipolar II disorder will be randomly assigned to one of two treatment groups : Seroquel (n=28) or IPSRT-BPII (n=28). Following baseline assessment, all participants will undergo up to 20 weeks of their assigned treatment. Patients assigned to IPSRT-BPII who fail to respond (at least 50% reduction in HRSD-25 scores and YMRS ≤ 10) by week 12 will have Seroquel added to IPSRT-BPII. Subjects who achieve remission (defined as 3 consecutive weeks where both HRSD-25 and YMRS scores average ≤ 7) and have participated in the trial for a minimum of 12 weeks will be moved into a continuation phase where they will receive maintenance treatment (bi-monthly therapy sessions and/or pharmacotherapy) until week 20. Patients who do not achieve remission by Week 20 will be discontinued from treatment and referred for follow-up care. All subjects (remitters and non-remitters) will be assessed at 20 weeks.

Official Title
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Psychotherapy for Bipolar II Depression, Pilot Study, Phase II

Conditions
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Bipolar II Disorder

Intervention / Treatment
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* Behavioral: Interpersonal and Social Rhythm Therapy (IPSRT-BPII)
* Drug: Seroquel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets DSM-IV Criteria for Bipolar Disorder, Type II, currently depressed; HRSD-25 ≥15 Age 18-65 years; Able to give informed consent; Women of child bearing potential will be included if they agree to use adequate contraception for the duration of the study. Exclusion Criteria: Not competent to give informed consent in the opinion of the investigator (e.g., psychotic at time of evaluation); Unwilling or unable to comply with study requirements; Meets DSM-IV criteria for borderline personality disorder or antisocial personality disorder; Active substance abuse within the past 6 months(episodic abuse related to mood episodes will not exclude a subject); Currently a high suicide risk, as assessed by an active plan and intent to behave in a way that risks ending ones life; Non-English speaking; Significant, unstable, medical illness that might confound symptom scores or preclude treatment with pharmacotherapy Currently applying for disability because of psychiatric illness (we have found that these individuals have a vested interested in appearing to remain ill which potentially confounds outcome scores). Women who are pregnant, lactating or plan to become pregnant during their study participation.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Psychotherapy<br>Subjects randomized to the Psychotherapy arm will receive Interpersonal and Social Rhythm Therapy (IPSRT-BPII) | Behavioral: Interpersonal and Social Rhythm Therapy (IPSRT-BPII)<br>* IPSRT is comprised of three components: psychoeducation, social rhythm therapy, and standard IPT as developed for unipolar depression. Psychoeducation focuses on a) the illness and its consequences, b) treatment options and associated side effects, and c) prodromal symptoms/detection of early warning symptoms.<br>* Other names: IPSRT;|
| Experimental: Medication<br>Subjects randomized to the medication arm will receive the FDA approved medication Seroquel (quetiapine) | Drug: Seroquel<br>* Subjects will be started at 100 mg/day titrated to a maximum of 800 mg /day Day 1-BID doses totaling 100 mg/day, increased to 400 mg/day on Day 4 in increments of up to 100 mg/day in BID divided doses, by Day 6 begin titration up to a maximum dose of 800 mg/day in increments no greater than 200 mg/day. This titration schedule may be adjusted based on the subject's response and ability to tolerate Seroquel. Subjects who are unable to tolerate the study medications, or for whom the study medications are an inappropriate clinical choice, will be treated openly by a clinic physician according to the standard of care guidelines designated by the American Psychiatric Association (2002) for the treatment of bipolar disorder.<br>* Other names: Quetiapine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Greater Than or Equal to 50% Reduction in Depression Scores, With a Mania Score Less Than or Equal to 10 | Overall response rates (defined as greater than or equal to 50% reduction in depression scores without an increase in mania scores) were 29% (n=4) in the IPSRT group and 27% (n=3) in the quetiapine group. HRSD-25 scores are based on first 17 responses. Eight items are scored on a 5-pt scale, from 0 (not present) to 4 (severe.) Other nine items on the assessment are scored from 0-2. The higher the score on the HRSD-25, the worse the outcome is considered to be. A score of 0-7 is considered to be normal; 8-13 indicates mild depression, 14-18 indicates moderate depression, 19-22 indicates severe depression, and any score greater than or equal to 23 indicates very severe depression. The YMRS is an 11 point assessment. There are 4 items assessed on a scale ranging from 0 to 8 and the other 7 items are graded on a 0 to 4 scale. As with the HRSD, the higher the score on the YMRS indicates the presence of more or more severe manic symptoms and is associated with a worse outcome. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life (QOL) Collected Using the Q-LES-Q (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form) | The total score is derived by summing item scores 1 to 14. Higher scores are indicative of greater enjoyment or satisfaction in each domain. The Q-LES-Q-SF % maximum total score is calculated as 100% × (Q-LES-Q-SF total score - 14) / 56, and can range from 0% to 100%. | Baseline and Week 12 | 
| Descriptive Measures of the Feasibility of IPSRT-BPII | Feasibility was assessed by ability to enroll, randomize, and retain participants in this trial. Completion of the study was used as evidence of feasibility. | Week 12 | 
| Number of Participants With a Response | Number of participants with response defined as an average of 50% (or greater) reduction in the subject's baseline HRSD-25 score over three consecutive weeks and a current YMRS score ≤ 10 | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Interpersonal Therapy, Social Rhythm Therapy, Bipolar Disorder, Depression, Seroquel