Maintenance Treatment of Bipolar Depression - Full Text View

Purpose

This study will compare two different antidepressant treatment regimens to determine which is more effective in reducing symptoms of bipolar depression.

Condition	Intervention	Phase
Bipolar Disorder Depression	Drug: Lamotrigine (LAM) Drug: Divalproex (DIV) Drug: Placebo	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Eight-Month Maintenance Treatment of Bipolar Depression With Lamotrigine or Lamotrigine Plus Divalproex Combination

Resource links provided by NLM:

MedlinePlus related topics: Antidepressants Bipolar Disorder Depression

Drug Information available for: Valproic acid Valproate sodium Divalproex sodium Lamotrigine

U.S. FDA Resources

Further study details as provided by The University of Texas Health Science Center at San Antonio:

Primary Outcome Measures:

Rates of response to treatment regimen [ Time Frame: Measured at Week 32 ] [ Designated as safety issue: Yes ]

Enrollment:	164
Study Start Date:	December 2004
Study Completion Date:	April 2009
Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Participants will take active lamotrigine and active divalproex	Drug: Lamotrigine (LAM) If the participant is naive to LAM, LAM will be started at 25 mg every day for the first 2 weeks, then 50 mg per day for the next 2 weeks. The dose of LAM can be increased to 100 mg at week 5 and increased to maximum of 200 mg at week 6 based on symptoms, tolerability, and ratings of the rating scales. If the participant is already taking LAM, the dose will be increased to up to 200 mg using the same guide lines. Upon randomization the participant in the placebo comparator will have their dosage titrated to doubled since the potentiating effect of the Divalproex will no longer exist. It will remain at this dosage until the end of the study with the possibility of one adjustment for side effects. Other Name: Lamictal Drug: Divalproex (DIV) If the participant is naive to DIV and if LAM was initiated before the start of treatment with DIV, DIV can be started at any point of time in the study provided the participant has been on LAM for at least 2 weeks. DIV will be started at 500 mg and titrated by increments of 500 mg every 3 to 4 days until a therapeutic blood level is attained up to 2500 mg. Other Names: Depakote Divalproic Acid
Placebo Comparator: 2 Participants will take active lamotrigine and placebo	Drug: Lamotrigine (LAM) If the participant is naive to LAM, LAM will be started at 25 mg every day for the first 2 weeks, then 50 mg per day for the next 2 weeks. The dose of LAM can be increased to 100 mg at week 5 and increased to maximum of 200 mg at week 6 based on symptoms, tolerability, and ratings of the rating scales. If the participant is already taking LAM, the dose will be increased to up to 200 mg using the same guide lines. Upon randomization the participant in the placebo comparator will have their dosage titrated to doubled since the potentiating effect of the Divalproex will no longer exist. It will remain at this dosage until the end of the study with the possibility of one adjustment for side effects. Other Name: Lamictal Drug: Placebo During the randomized phase participants randomized to placebo comparator group will discontinue DIV and will start taking the placebo in the same fasion.

Arms

Assigned Interventions

Active Comparator: 1

Participants will take active lamotrigine and active divalproex

Drug: Lamotrigine (LAM)

If the participant is naive to LAM, LAM will be started at 25 mg every day for the first 2 weeks, then 50 mg per day for the next 2 weeks. The dose of LAM can be increased to 100 mg at week 5 and increased to maximum of 200 mg at week 6 based on symptoms, tolerability, and ratings of the rating scales. If the participant is already taking LAM, the dose will be increased to up to 200 mg using the same guide lines. Upon randomization the participant in the placebo comparator will have their dosage titrated to doubled since the potentiating effect of the Divalproex will no longer exist. It will remain at this dosage until the end of the study with the possibility of one adjustment for side effects.

Other Name: Lamictal

Drug: Divalproex (DIV)

If the participant is naive to DIV and if LAM was initiated before the start of treatment with DIV, DIV can be started at any point of time in the study provided the participant has been on LAM for at least 2 weeks. DIV will be started at 500 mg and titrated by increments of 500 mg every 3 to 4 days until a therapeutic blood level is attained up to 2500 mg.

Other Names:

Depakote
Divalproic Acid

Placebo Comparator: 2

Participants will take active lamotrigine and placebo

Drug: Lamotrigine (LAM)

If the participant is naive to LAM, LAM will be started at 25 mg every day for the first 2 weeks, then 50 mg per day for the next 2 weeks. The dose of LAM can be increased to 100 mg at week 5 and increased to maximum of 200 mg at week 6 based on symptoms, tolerability, and ratings of the rating scales. If the participant is already taking LAM, the dose will be increased to up to 200 mg using the same guide lines. Upon randomization the participant in the placebo comparator will have their dosage titrated to doubled since the potentiating effect of the Divalproex will no longer exist. It will remain at this dosage until the end of the study with the possibility of one adjustment for side effects.

Other Name: Lamictal

Drug: Placebo

During the randomized phase participants randomized to placebo comparator group will discontinue DIV and will start taking the placebo in the same fasion.

Detailed Description:

Depression is a serious condition that is often difficult to diagnosis and treat. Bipolar disorder-related depression is especially complex because of the presence of mania symptoms. Lamotrigine and divalproex are commonly prescribed medications for depression. However, their effectiveness in treating bipolar depression has not been thoroughly evaluated. Studies have shown that combining lamotrigine with another antidepressant may be more effective in reducing depressive symptoms than lamotrigine alone. This study will provide participants with either lamotrigine alone or in combination with divalproex and will determine which regimen is more effective in reducing symptoms of bipolar depression.

Participants will be randomly assigned to a daily regimen of either lamotrigine and divalproex or lamotrigine and placebo for 8 months. Participants will be assessed at study entry, at two unspecified times during the study, and at the end of the study. During each assessment, participants will undergo a brief interview and complete a questionnaire about their depressive symptoms, any physical manifestations of their depression, and their overall level of functioning in daily activities.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of bipolar disorder I or II
Experiencing symptoms of depression at study entry OR have experienced symptoms of depression within 6 months prior to study entry
Willing to use acceptable methods of contraception
Parent or guardian willing to provide informed consent, if applicable

Exclusion Criteria:

History of liver disease
History of substance abuse
Previous treatment with lamotrigine or divalproex
Lamotrigine or divalproex intolerance

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00183469

Sponsors and Collaborators

The University of Texas Health Science Center at San Antonio

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:

Charles L. Bowden, MD

210-567-5405

More Information

Publications:

Bowden CL, Singh V, Weisler R, Thompson P, Chang X, Quinones M, Mintz J. Lamotrigine vs. lamotrigine plus divalproex in randomized, placebo-controlled maintenance treatment for bipolar depression. Acta Psychiatr Scand. 2012 Nov;126(5):342-50. doi: 10.1111/j.1600-0447.2012.01890.x. Epub 2012 Jun 18.

Responsible Party:	Charles L. Bowden, Professor, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier:	NCT00183469 History of Changes
Other Study ID Numbers:	P20 MH68662, 5P20MH068662, DSIR 83-ATSO
Study First Received:	September 13, 2005
Last Updated:	December 7, 2012
Health Authority:	United States: Federal Government

Keywords provided by The University of Texas Health Science Center at San Antonio:

Lamotrigine
Divalproex
Antidepressant

Additional relevant MeSH terms:

Bipolar Disorder
Depression
Depressive Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Behavioral Symptoms
Lamotrigine
Valproic Acid
Anticonvulsants
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
Calcium Channel Blockers
Membrane Transport Modulators
Cardiovascular Agents

ClinicalTrials.gov processed this record on May 19, 2013