Combination Therapy for the Treatment of Bipolar Disorders

This study has been terminated.
(Funding Expiration)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Dr. Keming Gao, University Hospital Case Medical Center
ClinicalTrials.gov Identifier:
NCT00063362
First received: June 25, 2003
Last updated: December 23, 2013
Last verified: December 2013
  Purpose

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


Condition Intervention Phase
Bipolar Disorder
Drug: Lithium
Drug: Lamotrigine
Drug: Divalproex
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Combination Therapy in Bipolar Rapid Cycling

Resource links provided by NLM:


Further study details as provided by University Hospital Case Medical Center:

Primary Outcome Measures:
  • The Proportion of Patients Who Experience a Marked and Persistent Bimodal Response [ Time Frame: Baseline and Week 28 ] [ Designated as safety issue: No ]

    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.



Enrollment: 49
Study Start Date: February 2002
Study Completion Date: July 2007
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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.

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.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00063362

Sponsors and Collaborators
University Hospital Case Medical Center
Investigators
Principal Investigator: Keming Gao, MD, PhD Case Western Reserve University / University Hospitals of Cleveland
  More Information

No publications provided

Responsible Party: Dr. Keming Gao, Director, Mood and Anxiety Clinic, University Hospital Case Medical Center
ClinicalTrials.gov Identifier: NCT00063362     History of Changes
Other Study ID Numbers: R21 MH62650, R21MH062650, DSIR AT-SO
Study First Received: June 25, 2003
Results First Received: November 4, 2013
Last Updated: December 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University Hospital Case Medical Center:
Depression

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Lamotrigine
Valproic Acid
Anticonvulsants
Lithium Carbonate
Lithium
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Antipsychotic Agents
Antidepressive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Cardiovascular Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers

ClinicalTrials.gov processed this record on August 21, 2014