Combination Therapy for the Treatment of Bipolar Disorders

Bipolar Disorder Clinical Trial

Official title:

Combination Therapy in Bipolar Rapid Cycling

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00063362
• Other study ID #: R21MH062650
• Secondary ID: R21MH062650DSIR
• Status: Terminated
• Phase: Phase 3
• First received: June 25, 2003
• Last updated: December 23, 2013
• Start date: February 2002
• Est. completion date: July 2007

Study information

• Verified date: December 2013
• Source: University Hospital Case Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 49
• Est. completion date: July 2007
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

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).
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Case Medical Center	National Institute of Mental Health (NIMH)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Proportion of Patients Who Experience a Marked and Persistent Bimodal Response	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: Montgomery Asberg Depression Rating Scale (MADRS) total score of <= 19; Young Mania Rating Scale (YMRS) total score of <= 12.5; 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	No