Efficacy of Quetiapine XR Versus Divalproex on Clinical Outcome Quality of Sleep and Quality of Life in Bipolar Depression

Quetiapine is one of atypical antipsychotics with good efficacy and better side effect profiles than conventional antipsychotics, so it is being widely used beyond the treatment of schizophrenia. Recently, the BOLDER I and II study showed that quetiapine monotherapy is an effective and well-tolerated treatment for depressive episodes in bipolar disorder. However, most c1inicians did not have confidence with quetiapine monotherapy yet, and most practice guidelines recommend the monotherapy with mood stabilizer as the first-line treatment. The Korean medication algorithm for bipolar disorder published in 2006 also recommend the monotherapy with lithium, divalproex, or lamotrigine in the treatment of mild to moderate depressive episode of bipolar disorder.

Therefore, the aim of this study is investigating the efficacy and safety of quetiapine monotherapy when compared with mood stabilizer monotherapy. In addition, the investigators are going to reveal the quality of sleep and quality of life, of the two groups of patients.

Study Overview

• Status: Withdrawn
• Conditions: Bipolar Depression
• Intervention / Treatment: Drug: Quetiapine fumarate; Drug: Divalproex sodium

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Jeollanam-do
    • Naju, Jeollanam-do, Korea, Republic of
      • Naju National Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of written informed consent
• A diagnosis of Bipolar depression by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV)
• Females and males aged 20 to 65 years
• Female patients of childbearing potential must be using a reliable method of contraception and have a negative urine human chorionic gonadotropin (HCG) test at enrollment
• Able to understand and comply with the requirements of the study
• HAM-D score at Visit 0 and Visit 1 should be above 20.
• Willingness to adhere to the schedule of assessments
• Able and willing to comply with self-administration of study drug, or have consistent help or support available

Exclusion Criteria:

• Pregnancy or lactation
• Any DSM-IV Axis 1 disorder not defined in the inclusion criteria
• Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others
• Known intolerance or lack of response to quetiapine fumarate or divalproex, as judged by the investigator
• Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrollment including but not limited to: ketoconazole, itraconazole, fluconazole, erγthromycin， clarithromycin, troleandomycin, indinavir, nelfinavir，ritonavir, fluvoxamine and saquinavir
• Use of any of the following cytochrome P450 3A4 inducers in the 14 days preceding enrollment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin， St. John's Wort, and glucocorticoids
• Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation
• Substance or alcohol dependence at enrollment (except dependence in full remission,and except for caffeine or nicotine dependence) ， as defined by DSM-IV criteria
• Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 8 weeks prior to enrollment
• Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment
• Unstable or inadequately treated medical illness (e,g, congestive heart failure,angina pectoris, hypertension) as judged by the investigator Invo1vement in the planning and conduct of the study
• Previous enrollment or randomisation of treatment in the present study.
• Participation in another drug trial within 8 weeks prior enrollment into this study or longer in accordance with local requirements

A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria:

• Unstable DM defined as enrolment glycosylated hemoglobin (HbAlc) > 8.5%
• Admitted to hospital for treatment of DM or DM related illness in past 12 weeks
• Not under physician care for DM
• Physician responsib1e for patient's DM care has not indicated that patient's DM is controlled
• Physician responsible for patient's DM care has not approved patient's participation in the study
• Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to randomisation. For thiazolidinediones (glitazones) this period should not be less than 8 Weeks

• Taking insulin whose daily dose on one occasion in the past 4 weeks has been more than 10% above or below their mean dose in the preceding 4 weeks Note: If a diabetic patient meets one of these criteria, the patient is to be excluded even if the treating physician believes that the patient is stable and can participate in the study

  • An absolute neutrophil count (ANC) of s 1.5 x 109 per liter

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Quetiapine fumarate	Drug: Quetiapine fumarate; Efficacy of Quetiapine XR vs. Divalproex on Clinical Outcome, Quality of Sleep and Quality of Life in Bipolar Depression; Other Names: Seroquel XR, Quetiapine fumarate
Active Comparator: Divalproex sodium	Drug: Divalproex sodium; Efficacy of Quetiapine XR vs. Divalproex on Clinical Outcome, Quality of Sleep and Quality of Life in Bipolar Depression; Other Names: Depakote XR, Divalproex sodium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In between the two drugs at baseline MADRS score change at 8 weeks comparison.	Quetiapine fumarate XR vs. Divalproex sodium treatment compared clinical outcomes in bipolar depression.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement compared with the Number of subjects responding to drug and reliability, and tolerability between the two drugs, quality of sleep and quality of life	Improvement compared with the Number of subjects responding to drug and reliability, and tolerability between the two drugs, quality of sleep and quality of life.	one year

Collaborators and Investigators

• Sponsor: Bo-Hyun Yoon
• Investigators: Principal Investigator: Bo-Hyun Yoon, Doctor, Naju National Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Anticipated): September 1, 2011

Study Registration Dates

• First Submitted: April 25, 2012
• First Submitted That Met QC Criteria: April 26, 2012
• First Posted (Estimate): April 27, 2012

Study Record Updates

• Last Update Posted (Estimate): April 27, 2012
• Last Update Submitted That Met QC Criteria: April 26, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Bipolar and Related Disorders; Depression; Depressive Disorder; Bipolar Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; GABA Agents; Anticonvulsants; Antimanic Agents; Valproic Acid; Quetiapine Fumarate
• Other Study ID Numbers: D1443L00059