Official Title: “Acute Antidepressant Therapy in Bipolar II Major Depression”

This study examines the relative safety and benefit of antidepressant therapy (versus recommended mood stabilizer therapy)of bipolar type II major depressive episode. We hypothesize that antidepressant therapy will be superior to mood stabilizer therapy with little or no difference in treatment emergent manic symptoms.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: October 2006

Bipolar type II (BP II) major depressive episode (MDE), affects 2.5% of the US adult population and results in an estimated healthcare cost of $40 billion annually. BP II disorder is a distinct clinical entity that differs from BP I disorder, and is characterized by a preponderance of MDEs that result in particularly high morbidity and mortality rates.

The treatment of BP II MDE remains a challenge for clinicians. Concerns over antidepressant drug (AD) induced manic switch episodes have led current practice guidelines to recommend treating BP II MDE with mood stabilizer (MS) monotherapy and to avoid AD monotherapy. To date, there are no controlled clinical trials to test the validity of these empirical guidelines. Results from our preliminary BP II MDE studies have shown that fluoxetine monotherapy may be safe and effective initial treatment of BP II MDE with a low manic switch rate. Based upon these observations, we now ask (Specific aim #1): "What is the relative safety and efficacy of initial AD monotherapy vs. MS monotherapy of BP II MDE?" and "What is the relative manic switch rate of initial AD vs. MS monotherapy of BP II MDE?" To answer these questions, patients with BP II MDE will be treated in a 12-week, randomized, parallel group comparison of venlafaxine monotherapy vs. lithium monotherapy. We hypothesize that AD monotherapy will have superior efficacy vs. MS monotherapy, and that there will be a similar manic switch rate among both treatment conditions. If our hypotheses are correct, we believe that these results may have an important public health impact on the current practice guidelines for treating BP II MDE.

Intervention(s) in this Clinical Trial

• Drug: Venlafaxine
  • 37.5 mg - 375 mg daily, 12 Weeks
• Drug: Lithium Carbonate
  • 300 mg - 2100 mg daily, 12 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Antidepressant
• Active Comparator: 2
  • Drug

Primary Measures

• Reduction in Hamilton Depression Rating Scale score.
  • Time Frame: 12 Weeks
    Safety Issue?: No

Secondary Measures

• Change in Young Mania Rating Scale score.
  • Time Frame: 12 Weeks
    Safety Issue?: Yes

Inclusion Criteria:

• men and women (all races and ethnicity) greater than or equal to18 years of age,
• DSM IV diagnosis of BP II disorder,
• Current DSM IV MDE,
• HAM-D17 score greater than or equal to 16,
• Drug free from prior psychotropic medication greater than or equal to 7 days (2 weeks for MAOIs)

Exclusion Criteria:

• History of mania,
• Other primary DSM IV Axis I diagnosis,
• Alcohol or drug dependence within 3 months,
• History of nonresponse to Effexor-XR or lithium in the present MDE,
• History of allergic reaction to Effexor-XR or lithium,
• Medical contraindications to treatment with Effexor-XR or lithium,
• Unstable medical condition,
• Pregnant or breast-feeding women,
• Women of child-bearing potential not using a medically approved form of contraception,
• Actively suicidal or requiring hospitalization,
• Requiring concurrent antidepressant, neuroleptic or mood stabilizer therapy,
• Prior investigational study within 4 weeks of starting active therapy.

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 Sponsor: Stanley Medical Research Institute

Overall Clinical Trial Officials and Contacts

Jay D Amsterdam, MD Principal Investigator Depression Research Unit, School of Psychiatry, University of Pennsylvania  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00641927

Study ID Number: 01-005

ClinicalTrials.gov Identifier: NCT00641927

Health Authority: United States: Food and Drug Administration