Bipolar Disorder, Depression
Conditions
Keywords
Bipolar II Disorder, Bipolar II Depression, Psychotherapy, IPSRT, Seroquel, Quetiapine, Placebo, Sugar Pill
Brief summary
This proposed study is designed to compare the efficacy of interpersonal and social rhythm therapy (IPSRT) alone to IPSRT plus medication as an acute treatment for bipolar II depression. The investigators propose to conduct a randomized, controlled, trial comparing the effects of IPSRT plus pill placebo to IPSRT plus quetiapine on depressive symptoms in individuals suffering from Bipolar II depression. The investigators will also examine the impact of treatment on psychosocial function.
Detailed description
Specifically, we will enroll 160 individuals meeting DSM-IV criteria for BP II disorder, currently depressed, and randomly assign them to 20 weeks of treatment with IPSRT plus placebo (IPSRT-PLA) (N=80) or IPSRT plus quetiapine (IPSRT-QUE) (N=80). We will evaluate potential moderators of response to treatment including circadian phase preference, intercurrent hypomanic symptoms during the index depressive episode, clinical and demographic factors (i.e, number of previous episodes, family history of mood disorders), and prior treatment response to antidepressant medications.
Interventions
DRUGIPSRT plus quetiapine
Subjects will be seen approximately weekly/biweekly during the 20 week acute phase. All subjects will return at weeks 36 and 52 for follow-up assessments to evaluate the enduring effects of treatment. The therapist will administer IPSRT and the psychiatrist will administer medication management procedures (quetiapine or placebo). Medication Dosing The research pharmacy will dispense medication in the following unit-dose packs: Dose A (50 mg of QUE or PLA) Dose B (100 mg of QUE or PLA) Dose C (separate packs of 50 mg and 100 mg QUE capsules or PLA) Dose D (200 mg of QUE or PLA) Dose E (separate packs of 50 mg and 200 mg QUE capsules or PLA) Dose F (separate packs of 100mg and 200mg QUE capsules or PLA)
DRUGIPSRT plus placebo (IPSRT-PLA)
Subjects will be seen approximately weekly/biweekly during the 20 week acute phase. All subjects will return at weeks 36 and 52 for follow-up assessments to evaluate the enduring effects of treatment. The therapist will administer IPSRT and the psychiatrist will administer medication management procedures (quetiapine or placebo). Medication Dosing The research pharmacy will dispense medication in the following unit-dose packs: Dose A (50 mg of QUE or PLA) Dose B (100 mg of QUE or PLA) Dose C (separate packs of 50 mg and 100 mg QUE capsules or PLA) Dose D (200 mg of QUE or PLA) Dose E (separate packs of 50 mg and 200 mg QUE capsules or PLA) Dose F (separate packs of 100mg and 200mg QUE capsules or PLA)
Sponsors
National Institute of Mental Health (NIMH)
Holly Swartz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adults age 18 - 65 * Meets criteria for bipolar II disorder, currently in an episode of major depression, as defined by the DSM-IV (American Psychiatric Association, 1994) and documented by the use of the Structured Clinical Interview for Axis I DSM-IV Disorders (SCID-I), and by a rating of \>15 on the 17-item Hamilton Rating Scale for Depression (HRSD-17) * Ability and willingness to give informed, written consent. * Subjects may participate in this study if they are currently taking psychotropic medications at time of informed consent. They will remain in the study (and be randomized) if they still meet eligibility criteria after a one week wash-out period.
Exclusion criteria
* Severe or poorly controlled concurrent medical disorders that may cause confounding depressive symptoms (i.e., untreated hypothyroidism or lupus) or require medication(s) that could cause depressive symptoms (i.e., high doses of beta blockers or alpha interferon) * Meets criteria for one of the following concurrent DSM-IV psychiatric disorders: any psychotic or organic mental disorder, bipolar I disorder, current alcohol or drug dependence, primary obsessive compulsive disorder or primary eating disorders. (primary refers to the diagnosis associated with the most functional impairment); borderline personality disorder; antisocial personality disorder * Acute suicidal or homicidal ideation or requiring psychiatric hospitalization. Subjects who require inpatient treatment will be excluded (or discontinued) from the study and referred to one of WPIC's inpatient mood disorder units, or, if preferred, to an inpatient facility nearer to the patient's home * Severe cognitive deficits that would preclude treatment with psychotherapy and/or prevent completion of study questionnaires * Non-fluent in English. Subjects must be able to speak and understand English because one of the study interventions, IPSRT, is an experimental talk-therapy. This therapy cannot practically be translated. * Current participation in another form of individual psychotherapy. Concurrent participation in couples therapy, peer support groups (such as Alcoholics Anonymous), or family therapy will be permitted * Prior lack of response to a trial of at least 12 weeks of IPSRT conducted by a certified therapist * Prior lack of response to at least 6 weeks of 300 mg of quetiapine * Currently pregnant or planning to become pregnant during the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Remission | 20 weeks | Number of Remitted Participants (defined as 3 consecutive weeks with HRSD-17≤8 and YMRS≤8) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ)-Short Form | 20 weeks | Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ-SF; Total Scores) describes difference in Quality of Life Scores from Baseline to Week 20; The QLESQ-SF is a self-report measure of life satisfaction, with 16 items rated from 1 (very poor) to 5 (very good) to produce a score from 0 to 80 with higher scores indicating better quality of life. In this report, we record change in scores from baseline to follow up |
Countries
United States
Participant flow
Recruitment details
adult outpatients with BD II depression recruited from provider referrals, advertisements, and research registries from 2010-1015
Pre-assignment details
Participants who met eligibility criteria but were on psychotropic medications at time of informed consent were gradually tapered off medications and re-evaluated to ensure that they still met eligibility criteria following one week off of all medications prior to randomization
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects will receive 20 weeks of an experimental psychotherapy called interpersonal and social rhythm therapy (IPSRT) plus placebo (sugar pill). This condition will be called IPSRT-PLA.
IPSRT plus placebo (IPSRT-PLA): Subjects will be seen approximately weekly/biweekly during the 20 week acute phase. All subjects will return at weeks 36 and 52 for follow-up assessments to evaluate the enduring effects of treatment.
The therapist will administer IPSRT and the psychiatrist will administer medication management procedures (quetiapine or placebo).
Medication Dosing
The research pharmacy will dispense medication in the following unit-dose packs:
Dose A (50 mg of QUE or PLA) Dose B (100 mg of QUE or PLA) Dose C (separate packs of 50 mg and 100 mg QUE capsules or PLA) Dose D (200 mg of QUE or PLA) Dose E (separate packs of 50 mg and 200 mg QUE capsules or PLA) Dose F (separate packs of 100mg and 200mg QUE capsules or PLA) | 45 |
| IPSRT Plus Quetiapine Subjects will receive 20 weeks of an experimental psychotherapy called interpersonal and social rhythm therapy (IPSRT) plus the FDA approved medication quetiapine (Seroquel). This condition will be called IPSRT-QUE.
IPSRT plus quetiapine: Subjects will be seen approximately weekly/biweekly during the 20 week acute phase. All subjects will return at weeks 36 and 52 for follow-up assessments to evaluate the enduring effects of treatment.
The therapist will administer IPSRT and the psychiatrist will administer medication management procedures (quetiapine or placebo).
Medication Dosing
The research pharmacy will dispense medication in the following unit-dose packs:
Dose A (50 mg of QUE or PLA) Dose B (100 mg of QUE or PLA) Dose C (separate packs of 50 mg and 100 mg QUE capsules or PLA) Dose D (200 mg of QUE or PLA) Dose E (separate packs of 50 mg and 200 mg QUE capsules or PLA) Dose F (separate packs of 100mg and 200mg QUE capsules or PLA) | 47 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 8 | 11 |
| Overall Study | preferred other treatment | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Refused participation | 1 | 3 |
| Overall Study | Withdrawal by Subject | 8 | 3 |
Baseline characteristics
| Characteristic | Placebo | IPSRT Plus Quetiapine | Total |
|---|---|---|---|
| Age, Continuous | 33.9 years STANDARD_DEVIATION 11.2 | 30.9 years STANDARD_DEVIATION 10.3 | 32.4 years STANDARD_DEVIATION 10.8 |
| Race/Ethnicity, Customized Race African American | 6 Participants | 10 Participants | 16 Participants |
| Race/Ethnicity, Customized Race Caucasian | 35 Participants | 31 Participants | 66 Participants |
| Race/Ethnicity, Customized Race Other | 4 Participants | 6 Participants | 10 Participants |
| Region of Enrollment United States | 45 Participants | 47 Participants | 92 Participants |
| Sex: Female, Male Female | 26 Participants | 32 Participants | 58 Participants |
| Sex: Female, Male Male | 19 Participants | 15 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 47 |
| other Total, other adverse events | 35 / 44 | 44 / 44 |
| serious Total, serious adverse events | 0 / 45 | 0 / 47 |
Outcome results
Primary
Remission
Number of Remitted Participants (defined as 3 consecutive weeks with HRSD-17≤8 and YMRS≤8)
Time frame: 20 weeks
Population: Intent to treat; patients were assessed weekly
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IPSRT Plus Quetiapine | Remission | 16 Participants |
| Placebo | Remission | 13 Participants |
Comparison: time effect for HRSD-17p-value: <0.0001Mixed Models Analysis
Secondary
Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ)-Short Form
Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ-SF; Total Scores) describes difference in Quality of Life Scores from Baseline to Week 20; The QLESQ-SF is a self-report measure of life satisfaction, with 16 items rated from 1 (very poor) to 5 (very good) to produce a score from 0 to 80 with higher scores indicating better quality of life. In this report, we record change in scores from baseline to follow up
Time frame: 20 weeks
Population: Analyzed data from participants for whom values were available both at baseline and at twenty weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IPSRT Plus Quetiapine | Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ)-Short Form | 10.6 units on a scale | Standard Deviation 10.9 |
| Placebo | Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ)-Short Form | 4.7 units on a scale | Standard Deviation 11.4 |
p-value: >0.05Regression, Linear