Trial Outcomes & Findings for Combination Therapy for the Treatment of Bipolar Disorders (NCT NCT00063362)

Last Updated: 2016-11-07

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

49 participants

Primary outcome timeframe

Baseline and Week 28

Results posted on

2016-11-07

Participant Flow

The study was conducted by the Mood Disorders Program at Case Western Reserve University/University Hospitals Case Medical Center (Cleveland, OH, USA) from August 2002 to June 2007.

Participant milestones

Participant milestones
Measure	Lithium + Divalproex + Lamotrigine 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. 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. 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).	Lithium + Divalproex + Placebo 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. Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 mEq/L.
Overall Study STARTED	23	26
Overall Study COMPLETED	19	22
Overall Study NOT COMPLETED	4	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Combination Therapy for the Treatment of Bipolar Disorders

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lithium + Divalproex + Lamotrigine n=23 Participants 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. 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. Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 mEq/L.	Lithium + Divalproex + Placebo n=26 Participants 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. Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 mEq/L.	Total n=49 Participants Total of all reporting groups
Age, Continuous	35.7 years STANDARD_DEVIATION 11.0 • n=5 Participants	43.0 years STANDARD_DEVIATION 9.6 • n=7 Participants	37.9 years STANDARD_DEVIATION 11.1 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	15 Participants n=7 Participants	27 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants	24 Participants n=7 Participants	45 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Bipolar Subtype Bipolar I disorder	11 participants n=5 Participants	16 participants n=7 Participants	27 participants n=5 Participants
Bipolar Subtype Bipolar II disorder	12 participants n=5 Participants	10 participants n=7 Participants	22 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 28

Outcome measures

Outcome measures
Measure	Lithium + Divalproex + Lamotrigine n=23 Participants 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. 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. Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 mEq/L.	Lithium + Divalproex + Placebo n=26 Participants 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. Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 mEq/L.
The Proportion of Patients Who Experience a Marked and Persistent Bimodal Response	7 participants	8 participants

Adverse Events

Lithium + Divalproex + Lamotrigine

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Lithium + Divalproex + Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Lithium + Divalproex + Lamotrigine n=23 participants at risk 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. 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. Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 mEq/L.	Lithium + Divalproex + Placebo n=26 participants at risk 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. Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 mEq/L.
Skin and subcutaneous tissue disorders Itching	4.3% 1/23 • Number of events 1	3.8% 1/26 • Number of events 1
Skin and subcutaneous tissue disorders Rash	4.3% 1/23 • Number of events 1	0.00% 0/26

Additional Information

Dr. Keming Gao

University Hospitals Case Medical Center

Phone: 216-844-2865

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place