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

Bipolar Disorder Clinical Trial

Official title:

A Single-Blind, Randomized, Naturalistic Pilot Study, Comparison of Divalproex ER and Quetiapine for Adults With Acute Mania or Mixed Episodes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00397020
• Other study ID #: Bipolar Mania
• Status: Completed
• Phase: Phase 4
• Start date: December 2006
• Est. completion date: December 2008

Study information

• Verified date: August 2019
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

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

Locations

Country	Name	City	State
United States	UCSD Medical Center	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Diego	Abbott

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Measure: Young Mania Rating Scale (YMRS) Primary Endpoint: Day 7	Minimum: 0 Maximum: 60 Higher scores indicate worse outcome	Day 7
Secondary	Young Mania Rating Scale (YMRS) Secondary Endpoints		weekly - Day 3, 14, 21
Secondary	Clinical Global Impression: Severity (CGI:S)		each visit
Secondary	Clinical Global Impression: Improvement (CGI:I)		each week/visit
Secondary	Readiness to Discharge Questionnaire (RDQ)		each week/visit in the hospital
Secondary	Montgomery-Asberg Depression Rating Scale (MADRS)		each week/visit
Secondary	Behavioral Activity Rating Scale (BARS)		each week/visit
Secondary	Extrapyramidal Symptoms Rating Scale (ESRS)		each week/visit