Effectiveness of Lithium and Valproate in Treating High-Risk Bipolar Disorder

April 30, 2012 updated by: New York State Psychiatric Institute

Pharmacotherapy of High-Risk Bipolar Disorder

This study will evaluate the effectiveness of two different mood stabilizing medications, lithium and valproate, in treating people with bipolar disorder and suicidal behavior.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Bipolar disorder, also called manic-depressive illness, is a brain disorder that causes dramatic changes in a person's mood and energy. Bipolar disorder normally forms in late adolescence or early adulthood and requires treatment for the rest of a person's life. People with bipolar disorder undergo periods of extreme happiness and extreme sadness, known as episodes of mania and depression. Symptoms of mania can include increased energy, euphoric moods, mind racing, aggressive behavior, substance abuse, and poor decision making. Symptoms of depression can include persistent feelings of anxiety, guilt, or hopelessness; irregular sleep and appetite patterns; lethargy; disinterest in previously enjoyed activities; excessive irritability and restlessness; and inability to concentrate. Some people with bipolar disorder also become suicidal. Suicidal behaviors are more likely to occur at the onset of the illness, making it vital to recognize and treat the disorder early on. Current treatments include mood stabilizing medications and psychotherapy. This study will evaluate the effectiveness of two different mood stabilizing medications, lithium and valproate, in treating people with bipolar disorder and suicidal behavior.

Participants in this double-blind study will be randomly assigned to take one of two medications, either lithium or valproate. In the first 2 to 6 months, depending on clinical condition, participants may also be required to take the antidepressant paroxetine and/or the medication olanzapine. Participants will attend regular visits to a psychiatrist or a psychologist at the Neuroscience Clinic. A blood sample will be taken at each visit to monitor medication blood levels. Participants will also undergo periodic routine laboratory and urine tests to assure their safety.

If the psychiatrist feels improvement has occurred by the end of the 2- to 6-month period, participants will be gradually taken off paroxetine and/or olanzapine over a 2-week period. They will then continue taking the assigned lithium or valproate for the remainder of the study. If the psychiatrist feels the condition has worsened, participants will be prescribed new medications as needed. These medications include other antidepressants (bupropion or venlafaxine) or other antimanic or antipsychotic drugs (perphenazine or haloperidol). Once these participants have achieved at least 2 weeks of normal moods, they will be gradually taken off all other prescribed medications and will remain taking the assigned lithium or valproate. Participants who do not achieve at least 2 weeks of normal moods will stop study participation but will still be offered clinical treatment. The remaining participants taking only lithium or valproate will continue their regular visits with a psychiatrist for the last 6 months of the study. The entire study will last 12 months.

Study Type

Interventional

Enrollment (Actual)

98

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • New York State Psychiatric Institute/Columbia University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Current major depressive episode or mixed episode
  • Bipolar disorder
  • History of suicidal behavior

Exclusion Criteria:

  • Requires detoxification from alcohol or other substances
  • Blood pressure greater than 160/90 mm Hg
  • Active medical problems
  • Requires long-term antipsychotic maintenance
  • Becomes manic on mood stabilizers and antidepressants
  • Contraindication to the use of lithium 1 or valproate (including failure to respond)
  • Failure to respond to adequate trials of paroxetine, bupropion, and venlafaxine in the 2 years prior to study entry
  • Failure to respond to adequate trials of olanzapine, haloperidol, and perphenazine in the 2 years prior to study entry
  • Unable or unwilling to consent to treatment
  • Pregnant or lactating

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Participants will take lithium for 12 months
Drug: Lithium
Participants may also be required to take the antidepressant paroxetine and/or the medication olanzapine for a portion of the study.
Experimental: 2
Participants will take valproate for 12 months
Drug: Valproic acid
Participants may also be required to take the antidepressant paroxetine and/or the medication olanzapine for a portion of the study.
Other Names:
  • Sodium valproate or valproic acid (Depakote)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Severity of depression and mania by SADS-C (Schedule for Affective Disorders and Schizophrenia, Change) and LIFE (Longitudinal Interval Follow-up Evaluation)
Time Frame: Measured between Months 2 and 6 and at Month 12
Measured between Months 2 and 6 and at Month 12
Suicide history form and Scale for Suicidal Ideation
Time Frame: Measured between Months 2 and 6 and at Month 12
Measured between Months 2 and 6 and at Month 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

New York State Psychiatric Institute

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Maria A. Oquendo, MD, Columbia University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2001

Primary Completion (Actual)

September 1, 2008

Study Completion (Actual)

October 1, 2008

Study Registration Dates

First Submitted

November 23, 2007

First Submitted That Met QC Criteria

November 23, 2007

First Posted (Estimate)

November 27, 2007

Study Record Updates

Last Update Posted (Estimate)

May 1, 2012

Last Update Submitted That Met QC Criteria

April 30, 2012

Last Verified

April 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • #4973R
  • DSIR 83-ATP (NCT00719979)
  • R01MH059710 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe