Bipolar II Depression: Lithium, SSRI, or the Combination

NCT ID: NCT00276965

Last Updated: 2013-05-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 139 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2012-07-31

Brief Summary

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

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.

Conditions

Bipolar Disorder; Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

A

Participants will take lithium only.

Group Type: EXPERIMENTAL

Lithium carbonate

Intervention Type: DRUG

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).

B

Participants will take lithium and sertraline.

Group Type: EXPERIMENTAL

Sertraline

Intervention Type: DRUG

Sertraline or placebo for sertraline starting at 25 mg per day, up to maximum of 200 mg per day

Lithium carbonate

Intervention Type: DRUG

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).

C

Participants will take sertraline only.

Group Type: EXPERIMENTAL

Sertraline

Intervention Type: DRUG

Sertraline or placebo for sertraline starting at 25 mg per day, up to maximum of 200 mg per day

Interventions

Sertraline

Sertraline or placebo for sertraline starting at 25 mg per day, up to maximum of 200 mg per day

Intervention Type: DRUG

Lithium carbonate

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).

Intervention Type: DRUG

Other Intervention Names

Zoloft; Eskalith, Lithobid

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: collaborator

Lindner Center of HOPE

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lori Altshuler, MD

Role: PRINCIPAL_INVESTIGATOR

UCLA Mood Disorders Research Program

Locations

UCLA

Los Angeles, California, United States

Stanford University - Bipolar Research Program

Palo Alto, California, United States

Lindner Center of HOPE, affliated with University of Cincinnati Medical Center

Mason, Ohio, United States

Countries

United States

Other Identifiers

R01MH074707

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DATR A5-ETMA

Identifier Type: -

Identifier Source: secondary_id

R01MH074707

Identifier Type: NIH

Identifier Source: org_study_id

View Link