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Depakote ER in Bipolar Depression

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ClinicalTrials.gov Identifier: NCT00186186
Recruitment Status : Completed
First Posted : September 16, 2005
Results First Posted : April 12, 2017
Last Update Posted : April 12, 2017
National Alliance for Research on Schizophrenia and Depression
Information provided by (Responsible Party):
Terrence Ketter, Stanford University

Brief Summary:
The purpose of this study is to examine the safety and efficacy of Depakote ER in bipolar depression and to evaluate metabolic and GABA changes with Depakote ER administration using PET and MRI/MRS brain imaging techniques.

Condition or disease Intervention/treatment Phase
Depression, Bipolar Drug: Depakote ER Phase 4

Detailed Description:

Mood disorders are important public health problems. Bipolar disorder is a major psychiatric disorder characterized by mood cycles alternating between mania and depression and affects approximately 1% of the population. Most patients are treated beginning in the early twenties and then embark on a course marked by multiple recurrences, hospitalizations, and encounters with legal authorities. These disorders inflict substantial morbidity which yields important deficits in occupational and interpersonal function. The risk of suicide in mood disorders may be as high as 10%.

Although the outlook for recovery from acute manic or depressive episodes is generally excellent, the long-term prognosis of the disorder varies tremendously across the patient population. The introduction of lithium, anticonvulsants and atypical antipsychotics significantly changes the outlook for bipolar disorder, with some individuals on chronic treatment attaining complete remission and indefinite prophylaxis against mood episodes. However, such optimum outcomes may be limited to as few as one-third to one-half of all treated patients. The remaining experiences various combinations of breakthrough mood episodes, including chronic mood instability, persistent depression, and rapid cycling.

Very little research has been conducted with bipolar disorder, and no medications have an FDA indication to treat bipolar depression. Previous studies suggest that Depakote is promising in the treatment of mixed and depressed episodes of bipolar disorder. This study utilizes the extended release formulation of divalproex sodium, with demonstrated increased tolerability.

We propose investigating safety, tolerability and efficacy of Depakote ER monotherapy in Bipolar I, II or NOS depression, and monitoring associated changes in brain GABA levels. In addition, we intend to evaluate and assess the differences between brain metabolic rate and GABA levels in bipolar disorder patients and healthy volunteers.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Depakote ER in Bipolar Depression
Study Start Date : January 2004
Actual Primary Completion Date : January 2009
Actual Study Completion Date : January 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Depakote ER
Depakote ER up to 1500 mg/day
Drug: Depakote ER
Depakote ER

Primary Outcome Measures :
  1. Montgomery Asberg Depression Rating Scale (MADRS) [ Time Frame: Baseline, 7 weeks ]

    The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders.

    Higher MADRS score indicates more severe depression the overall score ranges from 0 to 60.

    Usual cutoff points are:

    0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression.

Secondary Outcome Measures :
  1. Response to the Divalproex-ER in Acute Bipolar 2 Depression. [ Time Frame: 7 weeks ]
    A reduction greater than or equal to 50% in MADRS total score from baseline to the endpoint.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Bipolar I, II or NOS currently suffering from depression
  • Both: both female and male participants are being studied
  • Adults 18 years and older of any race

Exclusion Criteria:

  • Schizophrenia or schizoaffective disorder and other disorders excluded at the discretion of the investigator's discretion
  • Substance dependence within the past 3 months and abuse within the past 2 weeks prior to study.
  • Positive screen for psychoactive drugs, stimulants or drugs of abuse (excluding marijuana, as long as dependence and abuse are ruled out according to DSM-IV)
  • Significant risk harm to self or others based on history and mental status exam
  • Clinically significant or unstable medical condition
  • Unstable thyroid pathology and treatment initiated or altered within the past 3 months
  • Clinically significant abnormal laboratory test results, vital signs, as judged by the investigators
  • Women pregnant or nursing, or WOCBP who do not use adequate contraception or who are judged to be unreliable in their use of contraception
  • Subjects who failed (because of inefficacy or adverse effects) an adequate trial of Depakote; eligible patient's may not have received Depakote within 30 days of screen

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00186186

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United States, California
Stanford University Bipolar Disorders Clinic
Stanford, California, United States, 94305-5723
Sponsors and Collaborators
Stanford University
National Alliance for Research on Schizophrenia and Depression
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Study Director: Terence A. Ketter, MD Stanford University, Department of Psychiatry and Behavioral Sciences
Publications of Results:
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Responsible Party: Terrence Ketter, Professot, Stanford University
ClinicalTrials.gov Identifier: NCT00186186    
Other Study ID Numbers: 79130
First Posted: September 16, 2005    Key Record Dates
Results First Posted: April 12, 2017
Last Update Posted: April 12, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Depressive Disorder
Bipolar Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Bipolar and Related Disorders
Valproic Acid
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