Combination Therapy for the Treatment of Bipolar Disorders

Phase 3

Terminated

• Conditions: Bipolar Disorder
• Interventions: Drug: Lithium; Drug: Divalproex; Drug: Lamotrigine; Drug: Placebo

• Registration Number: NCT00063362
• Lead Sponsor: University Hospitals Cleveland Medical Center

Brief Summary

This study will compare triple and double drug regimens in the treatment of patients with depression, hypomania, or mania.

Detailed Description

Early studies have shown lithium to produce a high percentage of satisfactory clinical response in patients with bipolar disorders. These studies, however, do not include lithium-refractory subgroups, such as bipolar II disorder patients. When the wide spectrum of bipolar disorders is considered, the lithium response rate decreases significantly. More broadly effective regimens are needed.

Participants in this study will be randomly assigned to receive either lithium plus divalproex or lithium, divalproex, and lamotrigine for 7 months. Symptoms of depression and mania will be assessed with scales and patient questionnaires.

Study Timeline

• Study Start: 2002-02
• Study First Submitted: 2003-06-25
• Study First Submitted QC: 2003-06-26
• Study First Posted: 2003-06-27
• Primary Completion: 2007-07
• Study Completion: 2007-07
• Results First Submitted: 2013-11-04
• Results First Submitted QC: 2013-12-23
• Results First Posted: 2014-01-30
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-03
• Last Update Posted: 2016-11-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 49

Inclusion Criteria

• Bipolar I or II Disorder
• Meet criteria for rapid cycling, defined as four or more episodes over the past 12 months
• Meet criteria for a major depressive episode

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Exclusion Criteria

• History of intolerability of lithium, divalproex, or lamotrigine

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lithium + divalproex + placebo	Divalproex	-
Lithium + divalproex + lamotrigine	Lithium	-
Lithium + divalproex + lamotrigine	Divalproex	-
Lithium + divalproex + placebo	Placebo	-
Lithium + divalproex + placebo	Lithium	-
Lithium + divalproex + lamotrigine	Lamotrigine	-

Primary Outcome Measures

Name	Time	Method
The Proportion of Patients Who Experience a Marked and Persistent Bimodal Response	Baseline and Week 28	A marked bimodal response is defined by the following three conditions over four consecutive weeks while on triple therapy and after three weeks of ltg: 1. Montgomery Asberg Depression Rating Scale (MADRS) total score of \<= 19; 2. Young Mania Rating Scale (YMRS) total score of \<= 12.5; 3. Global Assessment Scale (GAS) score \>= 51; The MADRS measures the severity of a subject's depression symptoms with a possible total score ranging from 0 - 60, with higher scores indicating more severe depression.; The YMRS measures the severity of a subject's manic symptoms with a possible total score ranging from 0 - 60, with higher scores indicating more severe mania.; The GAS measures a used to rate subjectively the social, occupational, and psychological functioning of a subject and ranges in score from 0-100, with a higher score indicating better social, occupational, and psychological functioning.