Double-blind, Placebo-Controlled Divalproex Sodium ER in Bipolar I or Bipolar II Depression

Double-Blind, Placebo-Controlled Divalproex Sodium ER in Bipolar I or Bipolar II Depression Previously Diagnosed and Treated as Recurrent Major Depression: This study recruits males and females aged 18 - 70 who currently meet diagnostic criteria for bipolar I or bipolar II disorder and are currently experiencing an episode of major depression. Patients are randomized to double-blind treatment with divalproex sodium ER or placebo and remain in the study for up to six weeks. This six-week double-blind treatment period is followed by an open-label treatment period of six months duration. This study is sponsored by Abbott Laboratories.

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder
• Intervention / Treatment: Drug: Divalproex Sodium ER; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 65 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject must give consent to participate in the study and sign and date the IRB approved written informed consent form prior to the initiation of any study procedures
• Subject must be between the ages of 18 and 70
• Subject must have a diagnosis of bipolar I or II.
• Subject must be currently depressed as confirmed by the Mini-International Neuropsychiatric Interview (MINI)
• Subject must have a baseline Montgomery-Asberg Depression Scale (MADRS) score of >19 and Young Mania Rating Scale (YMRS) score of <12
• Women of childbearing potential must be nonpregnant/nonlactating and using adequate contraception if sexually active
• Subject must not be using any concomitant psychotropic medications during the acute phase except prn benzodiazepines

Exclusion Criteria:

• Subjects lacks the capacity to provide informed consent
• Subject has currently or previously used divalproex or Dvpx-ER
• Subject is a serious suicide risk or has medically unstable conditions as judged by the investigators
• Subject has any alcohol, cocaine, or cannabis dependence within 3 months of study entry
• Subject has any cocaine, hallucinogens, opiates, crystal methamphetamine, or MMDA abuse within 3 months of study entry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; . Tablets will be available in 250mg and 500mg strengths. Divalproex will be titrated to a minimum blood level of 50 mg/L. However, the investigators will titrate divalproex to the maximum tolerable dose with an expected average dose of 2000mg per day. By dosing in this manner, all subjects will have a minimum blood level of 50 mg/L, but the mean level is likely to be considerably higher.
EXPERIMENTAL: Divalproex Sodium ER	Drug: Divalproex Sodium ER; Tablets will be available in 250mg and 500mg strengths. Divalproex will be titrated to a minimum blood level of 50 mg/L. However, the investigators will titrate divalproex to the maximum tolerable dose with an expected average dose of 2000mg per day. By dosing in this manner, all subjects will have a minimum blood level of 50 mg/L, but the mean level is likely to be considerably higher.; Other Names: Depakote ER

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	MADRS total scores range from 0-60, where higher scores are indicative of more depression.	Acute phase (week0-week6)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Young Mania Rating Scale (YMRS) Total Score	YMRS Scores range from 0 to 60 where higher scores are indicative of more mania.	Acute phase (week0-week6)
Change in General Behavior Inventory (GBI) Depression Scale Score	GBI Depression Scale Scores range from 46-184, where higher scores are indicative of more depression.	Acute phase (week0-week6)
Change in General Behavior Inventory (GBI) Hypomanic/Biphasic Scale Score	GBI Hypomanic/Biphasic Scale scores range from 28-112, where higher scores are indicative of more hypomanic/manic symptoms.	Acute phase (week0-week6)
Change in Short Form Health Survey (SF-36) Physical Component Summary Score	SF-36 Physical Component Summary scores range from 0-100, with a higher score indicating better physical health.	Acute phase (week0-week6)
Change in Short Form Health Survey (SF-36) Mental Component Summary Score	SF-36 Mental Component Summary scores range from 0-100, with a higher score indicating better mental health.	Acute phase (week0-week6)
Change in Hamilton Anxiety Rating Scale (HAMA) Total Score	HAMA Scores range from 0 to 56 where higher scores are indicative of more anxiety.	Acute phase (week0-week6)

Collaborators and Investigators

• Sponsor: University Hospitals Cleveland Medical Center
• Collaborators: Abbott

Publications and helpful links

General Publications

• Muzina DJ, Gao K, Kemp DE, Khalife S, Ganocy SJ, Chan PK, Serrano MB, Conroy CM, Calabrese JR. Acute efficacy of divalproex sodium versus placebo in mood stabilizer-naive bipolar I or II depression: a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry. 2011 Jun;72(6):813-9. doi: 10.4088/JCP.09m05570gre. Epub 2010 Aug 24.

Study record dates

Study Major Dates

• Study Start: September 1, 2004
• Primary Completion (ACTUAL): October 1, 2007
• Study Completion (ACTUAL): February 1, 2008

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (ESTIMATE): September 19, 2005

Study Record Updates

• Last Update Posted (ACTUAL): July 17, 2019
• Last Update Submitted That Met QC Criteria: May 3, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Tranquilizing Agents; Psychotropic Drugs; GABA Agents; Anticonvulsants; Antimanic Agents; Valproic Acid
• Other Study ID Numbers: UHHS 08-03-07