Naturalistic Study, Comparison of Divalproex Extended Release (ER) and Quetiapine for Adults With Acute Mania or Mixed Episodes

NCT ID: NCT00397020

Last Updated: 2019-09-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2008-12-31

Brief Summary

The primary objective of this study is to compare the efficacy and tolerability of quetiapine versus divalproex extended-release administered in a rapid oral loading fashion in the treatment of acute episodes of mania or mixed mania in bipolar disorder. Three hypotheses will be tested:

Hypothesis 1: treatment ( 3 weeks) of divalproex extended-release is similar to quetiapine in the symptomatic control of mania or mixed mania

Hypothesis 2: divalproex extended-release orally loaded may produce significant improvements in symptoms of mania sooner than quetiapine

Hypothesis 3: divalproex extended-release may produce significantly less sedation

Detailed Description

This will be a rater-blinded, head-to-head comparison (no placebo) of divalproex ER and quetiapine in patients with symptoms of an active manic or mixed mania (symptoms of mania and depression). Forty subjects are expected to be enrolled. After screening for eligibility, eligible subjects will be randomized while hospitalized in a 1:1 ratio into 2 treatment groups: divalproex ER or quetiapine. Depakote® ER will be given orally at 30 mg/kg day initially taken at night and rounded up to nearest 500 mg dose with adjustments made through the trial as needed to obtain serum valproic acid levels of 85-125 mcg/ml. Quetiapine will be given orally at an initial dose of 200mg/day on Day 1, and titrate up to 800 mg/day. The duration of the study will be 21 days from baseline and the total number of visits including screening is five. Patients will be released from the hospital once stable and visits for the study will then take place on an outpatient basis.

Conditions

Bipolar Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

1 Divalproex ER

Divalproex ER

Group Type: EXPERIMENTAL

divalproex ER

Intervention Type: DRUG

Dose: 30mg per kg, rounded to nearest 500mg, dosed PO QHS. Adjustments made through trial to obtain serum valproic acid levels of 85-125 mcg/ml

2 Quetiapine Fumarate

quetiapine fumarate

Group Type: ACTIVE_COMPARATOR

quetiapine

Intervention Type: DRUG

Dose: 200mg PO QHS, titrated up to therapeutic dose of 600-800mg.

Interventions

divalproex ER

Dose: 30mg per kg, rounded to nearest 500mg, dosed PO QHS. Adjustments made through trial to obtain serum valproic acid levels of 85-125 mcg/ml

Intervention Type: DRUG

quetiapine

Dose: 200mg PO QHS, titrated up to therapeutic dose of 600-800mg.

Intervention Type: DRUG

Other Intervention Names

Depakote ER; Seroquel

Eligibility Criteria

Inclusion Criteria

For inclusion, patients must fulfill all of the following criteria at enrollment:

1. Provide written informed consent before initiation of any study-related procedures

2. A diagnosis of Bipolar I Disorder, Most Recent Episode Manic (296.4x), or Bipolar I Disorder, Most Recent Episode Mixed (296.5x), with or without psychotic features, as defined by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSMIV)

3. Male or female, at least 18 years old

4. YMRS score equal to or greater than 17 and a CGI of 4 (moderate) or greater.

5. Female patients of childbearing potential must be using a reliable method of contraception. Reliable methods of contraception include hormonal contraceptives (e.g., oral contraceptive or long-term injectable or implantable hormonal contraceptive), double-barrier methods (e.g., condom and diaphragm, condom and foam, condom and sponge), intrauterine devices, and tubal ligation.

Exclusion Criteria

1. Known intolerance or lack of response to quetiapine fumarate or Divalproex ER as judged by the investigator.

2. Unwilling or not able to provide informed consent

3. Positive urine toxicology result on screening for cocaine, phencyclidine (PCP), opiates or amphetamines that confirms the current manic/mixed episode is better accounted by a substance intoxication or withdrawal as judged by PI.

4. History of schizophrenia or schizoaffective disorder

5. Treatment with a depot antipsychotic within 1 treatment cycle

6. Unstable medical condition including hepatic, renal, gastroenterologic, neurologic, immunologic, or hematologic diseases that is deemed by the principle investigator to likely to result in hospitalization in 6 months or death within one year

7. A female subject who is pregnant or lactating

8. Lorazepam will be provided for agitation and insomnia as needed for rescue only. Not to exceed 6 mg in the first 7 days; Not to exceed 4 mg for the next 3 days and note to exceed 2 mg/day for the remainder of the study. Those that require a greater amount of Lorazepam will be excluded.

9. Hospitalized for more than 1 week for current episode at the screen

10. Substance or alcohol dependence at enrollment and within the three months prior to enrollment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria.

11. Known diagnosis of dementia or MCI

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Abbott

INDUSTRY

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

David Feifel

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David Feifel, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UCSD

Locations

UCSD Medical Center

San Diego, California, United States

Countries

United States

Other Identifiers

Bipolar Mania

Identifier Type: -

Identifier Source: org_study_id