Safety and Effectiveness of Antidepressant Therapy in Treating Bipolar Type II Major Depression

Official Title: “Treatment of Bipolar Type II Major Depression”

This study will compare the safety and effectiveness of antidepressant therapy versus mood stabilizing therapy in treating people with bipolar type II major depression.

Bipolar type II (BP II) depression affects 2.5% of the U.S. adult population. People with BP II disorder do not experience the manic episodes that are characteristic of BP I disorder, but rather they experience more modest mood swings with a greater number of major depressive episodes (MDEs). These MDEs are associated with high rates of disease and death. The treatment of BP II depression remains a challenge for clinicians. Mood stabilizer (MS) monotherapy is the current recommended treatment for BD II MDE, but there is reason to believe that antidepressant drug (AD) monotherapy could also be an effective treatment.

However, concerns over AD-induced manic switch episodes have limited the use of this treatment option. Preliminary studies using the ADs fluoxetine or venlafaxine have shown success in treating and lowering the manic switch rate of those with BP II MDE. This study will compare the safety and effectiveness of AD monotherapy versus MS monotherapy in treating people with BP II major depression.

Participation in this double-blind study will last up to 9 months. After screening, which includes a medical and psychiatric history review, a physical exam, an electrocardiogram (EKG) test, clinical laboratory tests, a urine-based drug test, and a pregnancy test if applicable, participants will be randomly placed into one of two treatment groups.

Participants in the AD monotherapy group will be treated with venlafaxine, and participants in the MS monotherapy group will be treated with lithium. During the first 12 weeks, there will be a total of nine study visits lasting between 45 and 60 minutes. In these visits, participants will receive their study drug and will undergo various assessments, including a review of medication history and side effects, vital sign measurements, and questionnaires about depression and daily functioning. Blood samples will be taken at most visits.

Participants who respond well during the initial 12 weeks of therapy with either drug will have the option to continue treatment for 6 additional months. During this time, participants will continue their assigned treatment and will attend five monthly study visits that will repeat previous assessments and procedures.

For information on a related study, please follow this link:

http://clinicaltrials.gov/show/NCT00044616

Intervention(s) in this Clinical Trial

• Drug: Venlafaxine
  • 75 to 375 mg
• Drug: Lithium Carbonate
  • 300 to 2400 mg

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: I
  • Antidepressant therapy
• Active Comparator: II
  • Mood stabilizer therapy

Primary Measures

• Reduction in Hamilton Depression rating score
  • Time Frame: Measured at Weeks 12 and 36
    Safety Issue?: No

Secondary Measures

• Increase in Young Mania rating scale score
  • Time Frame: Measured at Weeks 12 and 36
    Safety Issue?: No

Inclusion Criteria:

• Meets DSM-IV criteria for Axis I bipolar II disorder
• Meets DSM-IV criteria for Axis I major depressive episode
• Score of 16 on 17-item HAM-D rating scale
• Not taking monoamine oxidase inhibitors (MAOI) for more than 2 weeks prior to study entry
• Willing to use an effective form of birth control throughout the study

Exclusion Criteria:

• History of mania
• Current primary Axis I diagnosis other than bipolar II disorder
• Alcohol or drug dependence within 3 months prior to study entry
• Contraindication to treatment with venlafaxine or lithium
• Unstable medical condition (e.g., thyroid disease, hypertension, or angina pectoris)
• Pregnant or breastfeeding
• Experiencing suicidal thoughts
• Requires hospitalization
• Requires concurrent neuroleptic or MS therapy
• Requires concurrent AD therapy
• Current psychotic features
• Inadequate trial of therapy at the time of initial screening visit
• History of intolerance to either venlafaxine or lithium
• Unlikely to participate in a 36-week trial
• Presence of apparent secondary gain

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: National Institute of Mental Health (NIMH) NIH

Overall Clinical Trial Officials and Contacts

Jay D. Amsterdam, MD Principal Investigator University of Pennsylvania  

Overall Contact: Jay D. Amsterdam, MD 215-662-3462 jamsterd@mail.med.upenn.edu

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00602537

Study ID Number: R01 MH060353-02

ClinicalTrials.gov Identifier: NCT00602537

Health Authority: United States: Federal Government