Combination Therapy for the Treatment of Bipolar Disorders

October 3, 2016 updated by: Keming Gao, University Hospitals Cleveland Medical Center

Combination Therapy in Bipolar Rapid Cycling

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Exclusion Criteria:

  • History of intolerability of lithium, divalproex, or lamotrigine

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Lithium + divalproex + lamotrigine
Drug: Lithium
Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 milliequivalent /L (mEq/L).
Other Names:
  • Lithium Carbonate
Drug: Lamotrigine
Patients were assigned in a one to one ratio to adjunctive lamotrigine versus placebo after stratification for illness type (bipolar I versus bipolar II), historical response to lithium (response versus non-response), and length of current exposure to combination treatment with lithium and divalproex (< 2 months versus ≥ 2 months). During Phase 2, patients were continued on the same doses of lithium and divalproex as during the open-label treatment phase and equal capsules of double-blind lamotrigine or matching placebo were gradually added per a structured dosing schedule up to a minimum dose of 150 mg and a maximum dose of 200 mg per day.
Other Names:
  • Lamictal
Drug: Divalproex
Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL.
Other Names:
  • Depakote
  • Valproic Acid
PLACEBO_COMPARATOR: Lithium + divalproex + placebo
Drug: Lithium
Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 milliequivalent /L (mEq/L).
Other Names:
  • Lithium Carbonate
Drug: Divalproex
Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL.
Other Names:
  • Depakote
  • Valproic Acid
Drug: Placebo
Patients were assigned in a one to one ratio to adjunctive lamotrigine versus placebo after stratification for illness type (bipolar I versus bipolar II), historical response to lithium (response versus non-response), and length of current exposure to combination treatment with lithium and divalproex (< 2 months versus ≥ 2 months). During Phase 2, patients were continued on the same doses of lithium and divalproex as during the open-label treatment phase and equal capsules of double-blind lamotrigine or matching placebo were gradually added per a structured dosing schedule up to a minimum dose of 150 mg and a maximum dose of 200 mg per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Proportion of Patients Who Experience a Marked and Persistent Bimodal Response
Time Frame: 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.
Baseline and Week 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospitals Cleveland Medical Center

Collaborators

National Institute of Mental Health (NIMH)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2002

Primary Completion (ACTUAL)

July 1, 2007

Study Completion (ACTUAL)

July 1, 2007

Study Registration Dates

First Submitted

June 25, 2003

First Submitted That Met QC Criteria

June 26, 2003

First Posted (ESTIMATE)

June 27, 2003

Study Record Updates

Last Update Posted (ESTIMATE)

November 6, 2016

Last Update Submitted That Met QC Criteria

October 3, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R21MH062650 (NIH)
  • DSIR AT-SO (NorthShore LIJ Health System)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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