Maintenance Treatment of Bipolar Depression - Full Text View

Sponsored by:	National Institute of Mental Health (NIMH)
Information provided by:	National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:	NCT00183469

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 IV

MedlinePlus related topics: Bipolar Disorder Depression

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

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Eight-Month Maintenance Treatment of Bipolar Depression With Lamotrigine or Lamotrigine Plus Divalproex Combination

Further study details as provided by National Institute of Mental Health (NIMH):

Primary Outcome Measures:

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

Estimated Enrollment:	170
Study Start Date:	December 2004
Estimated Study Completion Date:	June 2008
Estimated Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator 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. 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.
2: Placebo Comparator 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. 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

1: Active Comparator

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.

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.

2: Placebo Comparator

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.

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

Contacts

Contact: Martha L. Dahl, RN

210-567-5501

dahlml@uthscsa.edu

Locations

United States, Texas
Department of Psychiatry, University of Texas Health Science Center	Recruiting
San Antonio, Texas, United States, 78229
Contact: Martha Dahl, RN 210-567-5501 dahlm@uthscsa.edu
Contact: Charles L. Bowden, MD 210-567-5405 bowdenc@uthscsa.edu
Sub-Investigator: Vivek Singh, MD

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:

Charles L. Bowden, MD

210-567-5405

More Information

Responsible Party:	University of Texas Health Science Center at SanAntonio ( Charles L. Bowden )
Study ID Numbers:	P20 MH68662, DSIR 83-ATSO
Study First Received:	September 13, 2005
Last Updated:	February 12, 2008
ClinicalTrials.gov Identifier:	NCT00183469
Health Authority:	United States: Food and Drug Administration; United States: Federal Government

Keywords provided by National Institute of Mental Health (NIMH):

Lamotrigine
Divalproex
Antidepressant

Study placed in the following topic categories:

Calcium, Dietary
Affective Disorders, Psychotic
Depression
Mental Disorders
Bipolar Disorder
Lamotrigine

Mood Disorders
Psychotic Disorders
Depressive Disorder
Valproic Acid
Behavioral Symptoms

Additional relevant MeSH terms:

Neurotransmitter Agents
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Psychotropic Drugs
Calcium Channel Blockers
Central Nervous System Depressants
Enzyme Inhibitors

Cardiovascular Agents
Antimanic Agents
Pharmacologic Actions
Membrane Transport Modulators
Therapeutic Uses
GABA Agents
Central Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on January 30, 2009