Combination Therapy for the Treatment of Bipolar Disorders

NCT ID: NCT00063362

Last Updated: 2016-11-07

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

49 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-02-28

Study Completion Date

2007-07-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Bipolar Disorder

Keywords

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Depression

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Lithium + divalproex + lamotrigine

Group Type EXPERIMENTAL

Lithium

Intervention Type DRUG

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).

Lamotrigine

Intervention Type DRUG

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.

Divalproex

Intervention Type DRUG

Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL.

Lithium + divalproex + placebo

Group Type PLACEBO_COMPARATOR

Lithium

Intervention Type DRUG

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).

Divalproex

Intervention Type DRUG

Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL.

Placebo

Intervention Type DRUG

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.

Interventions

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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).

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Lithium Carbonate Lamictal Depakote Valproic Acid

Eligibility Criteria

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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
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

University Hospitals Cleveland Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Keming Gao

Director, Mood and Anxiety Clinic

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Keming Gao, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Case Western Reserve University / University Hospitals of Cleveland

Countries

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United States

Other Identifiers

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R21MH062650

Identifier Type: NIH

Identifier Source: secondary_id

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DSIR AT-SO

Identifier Type: -

Identifier Source: secondary_id

R21MH062650

Identifier Type: NIH

Identifier Source: org_study_id

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