Bipolar II Depression: Lithium, SSRI, or the Combination

Study Overview
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Brief Summary
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This study will compare the safety and effectiveness of a mood stabilizing medication, an antidepressant medication, and a combination of both medications to treat symptoms of bipolar type II depression.

Detailed Description
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Bipolar type II depression (BD II) is a less severe type of bipolar disorder. BD II is characterized by one or more depressive episodes and at least one hypomanic episode. During hypomanic episodes, people experience especially energetic or anxious moods, and their thoughts are more sporadic than usual, but they do not experience the severity of mania. Symptoms of BD II are known to impair daily functioning as well as cause distress and even suicide. Antidepressant medication alone is not recommended for people with bipolar disorder because manic symptoms usually worsen. It is unknown whether the same recommendation should apply to people with BD II. Sertraline is a selective serotonin reuptake inhibitor (SSRI) antidepressant that increases levels of serotonin, helping the brain to maintain mental stability. It is often used to treat depression, panic attacks, and other disorders. Lithium is a mood stabilizing medication that decreases abnormal brain activity and is used to treat and prevent recurring episodes of mania in people with bipolar disorders. This study will evaluate the effectiveness of lithium alone, sertraline alone, and lithium with sertraline to treat symptoms of BD II. Participation in this double-blind study will last up to 18 weeks. Participants will be randomly assigned to receive either lithium, sertraline, or lithium and sertraline. Both medications will initially be given at a low dose and then gradually increased over 2 weeks. For the remainder of the study, dosages will be adjusted as necessary. Study visits will occur every week for the first 6 weeks and then every other week for the remaining 10 weeks. During all study visits, participants will complete a psychiatric assessment and questionnaires about their current mood and any treatment side effects. Urine and blood collection may occur at selected times during the study.

Official Title
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Comparing the Safety and Effectiveness of a Mood Stabilizing Medication, an Antidepressant Medication, and a Combination of Both Medications to Treat Symptoms of Bipolar Type II Depression

Conditions
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Bipolar Disorder, Depression

Intervention / Treatment
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* Drug: Sertraline
* Drug: Lithium carbonate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets DSM-IV criteria for bipolar type II disorder by Structured Clinical Interview for DSM-IV (SCID) Meets DSM-IV criteria for current depressive episode Inventory of Depressive Symptomology (IDS-C) score greater than 22 Clinical Global Impression Scale for Bipolar Illness (CGI-BP) depression subscale score greater than 3 (mildly ill or greater) and mania subscale score of 1 (not ill) Young Mania Rating Scale (YMRS) score less than 8 Willing to discontinue antidepressant medication Considered stable and does not require adjustments in treatment for other conditions or illnesses Willing to use an effective form of birth control throughout the study Speaks English Exclusion Criteria: Pregnant or breastfeeding Unsuccessfully treated for more than 6 weeks with sertraline or lithium for depression Suicidal Significant alcohol or substance abuse or dependence within 3 months of study entry Diagnosed with Axis II borderline personality disorder Psychotic Organic mood disorder (e.g., head trauma or cerebrovascular accident preceding mood episode) Active hepatitis, liver failure, or kidney failure Creatinine greater than 1 mg/dL Liver function tests greater than 3 times the upper limit of normal Abnormal thyroid-stimulating hormone Unstable medical condition

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Participants will take lithium only. | Drug: Lithium carbonate<br>* Lithium or placebo for lithium starting at 150 mg per day; target dose of 900mg per day. Maximum dose based on clinical response and serum levels (maximum serum level of 1.2 mEq/L).<br>* Other names: Eskalith, Lithobid;|
| Experimental: B<br>Participants will take lithium and sertraline. | Drug: Sertraline<br>* Sertraline or placebo for sertraline starting at 25 mg per day, up to maximum of 200 mg per day<br>* Other names: Zoloft;Drug: Lithium carbonate<br>* Lithium or placebo for lithium starting at 150 mg per day; target dose of 900mg per day. Maximum dose based on clinical response and serum levels (maximum serum level of 1.2 mEq/L).<br>* Other names: Eskalith, Lithobid;|
| Experimental: C<br>Participants will take sertraline only. | Drug: Sertraline<br>* Sertraline or placebo for sertraline starting at 25 mg per day, up to maximum of 200 mg per day<br>* Other names: Zoloft;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine switch rate to Mania/hypomania |  | Measured at week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Side effects |  | Measured at week 16 | 
| Antidepressant response |  | Measured at week 16 | 
| Mood variability |  | Measured at week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar II Depression