Comparative Efficacy and Acceptability of Antimanic Drugs in Acute Mania

March 14, 2015 updated by: Guiyun Xu

Comparative Efficacy and Acceptability of Lithium, Valproate, Oxcarbazepine, Quetiapine, Olanzapine, and Ziprasidone in Bipolar I Disorder, Manic or Mixed Phase

Background:

Bipolar disorder is one of the most common mental illnesses affecting 1%-4% of the population, and one of the leading causes of worldwide disability. Mania is a condition of excessively elevated mood, characterizes bipolar disorder, and usually is a main cause of hospitalization. Mood stabilisers and antipsychotic drugs have long been the maintenance treatment of acute mania with and without psychotic symptoms. Though clinical trails have been demonstrated that these drugs are individually more effective than placebo in the relatively long term (e.g 4, 8 weeks). However, in the pragmatic practice, patient at acute mania urgently want to see the effectiveness, and psychiatrist under great pressure and are in great need to evaluate the very short-term effectiveness (e.g one week). If the first attempted antimanic drug fails, psychiatrist need the evidence that which medication should be to added on or switch to.

Objectives:

one main aim is to rank the short-term ( e.g.one and two week) effectiveness and acceptability of the common anti-mania drugs, including Lithium, Valproate, Oxcarbazepine, Quetiapine, Olanzapine, or Ziprasidone. Secondary aim is to investigate which medication to add on for non-responders or switch to.

Methods:

The study setting: it is expected that 120 subjects with a diagnose of DSM-IV bipolar I disorder will be recruited from Guangzhou Psychiatric Hospital, the earliest psychiatric hospital in the history of China established by Dr.J. G. Kerr in 1898.

Design:This study is a randomized, controlled trial. Participants with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of bipolar I disorder, manic or mixed episode will be randomly assigned to a treatment of Lithium, Valproate, Oxcarbazepine, Quetiapine, Olanzapine, or Ziprasidone. In the following conditions, participants will take another antimanic drug as a combination medication: 1) those who have a reduction in YMRS scores less than 25% after one week of treatment; 2) those who have a reduction in YMRS scores less than 50% after two weeks of treatment; or 3) those who have a increase in YMRS more than 30% at day 4. An antipsychotic (Quetiapine, Olanzapine, and Ziprasidone) will be added on for those who use lithium, Valproate or Oxcarbazepine as a first attempted medication; while Lithium, Valproate, or Oxcarbazepine will be added on for those who use an antipsychotic as a first attempted medication. Those participants who are recognized as non-response/partial response to two combined medications after 6 weeks of treatment will switch to Modified Electroconvulsive Therapy (MECT).

Measures: Primary outcome measures are change scores on the Young Mania Rating Scale (YMRS) and dropout rates. Secondary outcome measures include Clinical Global Impressions (CGI) Scale, Global Assessment Scale (GAS), Treatment Emergent Symptom Scale (TESS), and Brief Psychiatric Rating Scale (BPRS).

Response criteria: <25% reduction in YMRS scores or >=4 scores of CGI is defined as non-response. 25-49% reduction in YMRS scores from baseline as well as <=3 scores of Clinical General Impression (CGI) is recognized as partial response.>= 50% reduction in YMRS as well as 1 (very much improved) or 2 scores (much improved) of CGI is recognized as response. Remission is defined as a YMRS score <=12 and CGI score equal to 1 or 2.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Background:

Bipolar disorder is one of the most common mental illnesses affecting 1%-4% of the population, and one of the leading causes of worldwide disability. Mania is a condition of excessively elevated mood, characterizes bipolar disorder, and usually is a main cause of hospitalization. Mood stabilisers and antipsychotic drugs have long been the maintenance treatment of acute mania with and without psychotic symptoms. Though clinical trails have been demonstrated that these drugs are individually more effective than placebo.However, in the pragmatic practice, patient at acute mania urgently want to see the effectiveness, and psychiatrist under great pressure and are in great need to evaluate the very short-term effectiveness (e.g one week). If the first attempted antimanic drug fails, psychiatrist need the evidence that which medication should be to added on or switch to.

Objectives:

one main aim is to rank the short-term ( e.g.one and two week) effectiveness and acceptability of the common anti-mania drugs, including Lithium, Valproate, Oxcarbazepine, Quetiapine, Olanzapine, or Ziprasidone. Secondary aim is to investigate which medication to add on for non-responders or switch to.

Methods:

The study setting: it is expected that 120 subjects with a diagnose of DSM-IV bipolar disorder will be recruited from Guangzhou Psychiatric Hospital, the earliest psychiatric hospital in the history of China established by Dr.J. G. Kerr in 1898.

Design:This study is a randomized, controlled trial, consisting two phase. 120 participants with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of bipolar I disorder, manic or mixed phase will be randomly assigned to a treatment of Lithium, Valproate, Oxcarbazepine, Quetiapine, Olanzapine, or Ziprasidone. The period from starting dose to effective dose for each drug is within 2 days, and the effective doses for these drugs are described as follow: Lithium, 750mg-2000mg/d, serum Li level: 0.6mmol-1.2mmol/L; Valproate, 800mg-- 1200mg/d, serum Valproate level: 70-120ug/ml; Oxcarbazepine, 600-1200mg/d; Quetiapine, 600mg--800mg/d; Olanzapine, 10mg-- 20mg/d; Ziprasidone, 80mg-160mmg/d.

In the following conditions, participants will take a another antimanic drug as a combination medication: 1) those who have a reduction in YMRS scores less than 25% after one week of treatment; 2) those who have a reduction in YMRS scores less than 50% after two weeks of treatment; or 3) those who have a increase in YMRS more than 30% at day 4. An antipsychotic (Quetiapine, Olanzapine, and Ziprasidone) will be added on for those who use lithium, Valproate or Oxcarbazepine as a first attempted medication; while Lithium, Valproate, or Oxcarbazepine will be added on for those who use an antipsychotic as a first attempted medication. Those participants who are recognized as non-response/partial response to two combined medications after 6 weeks of treatment will switch to Modified Electroconvulsive Therapy (MECT).

Measures: Primary outcome measures are change scores on the Young Mania Rating Scale (YMRS) and dropout rates. Secondary outcome measures include Clinical Global Impressions (CGI) Scale, Global Assessment Scale (GAS), Treatment Emergent Symptom Scale (TESS), and Brief Psychiatric Rating Scale (BPRS).

Response criteria: <25% reduction in YMRS scores or >=4 scores of CGI is defined as non-response. 25-49% reduction in YMRS scores from baseline as well as <=3 scores of Clinical General Impression (CGI) is recognized as partial response.>= 50% reduction in YMRS as well as 1 (very much improved) or 2 scores (much improved) of CGI is recognized as response. Remission is defined as a YMRS score <=12 and CGI score equal to 1 or 2.

Study Type

Interventional

Enrollment (Anticipated)

120

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510370
        • Enrolling by invitation
        • Guangzhou Psychiatric Hospital
      • Guangzhou, Guangdong, China, 510370
        • Recruiting
        • Guangzhou Psychiatric Hospital
        • Contact:
        • Principal Investigator:
          • Guiyun Xu, M.D

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • with a diagnosis of bipolar I disorder, manic or mixed phase
  • equal or more than 18 scores in Young Mania Rating Scale (YMRS)

Exclusion Criteria:

  • Serious general medical illness
  • pregnancy and lactation
  • given long-acting antipsychotic drug within the last two month
  • endocrine disease( e.g.Diabetes and thyrotoxicosis)
  • given thyroxine therapy within the last three months or is being given hormone therapy
  • sexually active and not using contraceptives

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Valproate
Name: Valproate; dosage form: tablet, 250mg; dosage and frequency: 800mg-- 1200mg/d; duration: 6 weeks.
Drug: Valproate
Valproate is used as a mood stabiliser
Other Names:
  • Depakote
Experimental: Oxcarbazepine
Name: Oxcarbazepine, dosage form: 300mg, tablet; dosage and frequency: 600-1200mg/d; duration: 6 weeks
Drug: Oxcarbazepine
Oxcarbazepine is used as a mood stabiliser
Other Names:
  • Trileptal
Experimental: Quetiapine
name: Quetiapine, dosage form: 200mg,tablet; dosage and frequency: 600mg-- 800mg/d; duration: 6 weeks
Drug: Quetiapine
Quetiapine is used as a mood stabiliser
Other Names:
  • SEROquel
Experimental: Olanzapine
Name: Olanzapine, dosage form: 5mg tablet; dosage and frequency: 10mg--20mg/d; duration: 6 weeks
Drug: Olanzapine
Olanzapine is used as a mood stabiliser.
Other Names:
  • Zyprexa；
Experimental: Ziprasidone
Name: Ziprasidone, dosage form: 10mg tablet; dosage and frequency: 80mg-160mmg/d; duration: 6 weeks
Drug: Ziprasidone
Ziprasidone is used as a mood stabiliser
Other Names:
  • Geodon
Experimental: Lithium
name: lithium; dosage form: 250mg Tablet; dosage and frequency: 750mg-2000mg/d;serum Li level: 0.6mmol-1.2mmol/L; duration: 6 weeks
Drug: Lithium
Lithium is used as a mood stabiliser
Other Names:
  • lithium Carbonate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in Young Mania Rating Scale at 2 weeks and 6 weeks
Time Frame: Baseline, 2 weeks and 6 weeks
Young Mania Rating Scale is used to assess hypomania/mania symptoms
Baseline, 2 weeks and 6 weeks
rate of dropout (treatment discontinuation)
Time Frame: 1,2,4,6 weeks
to compare the rates of treatment discontinuation of different drugs because of side effect or effectiveness
1,2,4,6 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Global Impressions (CGI) Scale
Time Frame: baseline, 2 weeks, 4 weeks, and 6 weeks
Clinical Global Impressions (CGI) Scale is used to assess the patient's global functioning prior to and after initiating a study medication. The CGI provides an overall clinician-determined summary measure, taking into account all available information, including a knowledge of the patient's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the patient's ability to function
baseline, 2 weeks, 4 weeks, and 6 weeks
Brief Psychiatric Rating Scale
Time Frame: baseline, 2, 3, 4 and 6 weeks
Brief Psychiatric Rating Scale is used to assess psychotic symptoms.
baseline, 2, 3, 4 and 6 weeks
Global Assessment Scale
Time Frame: baseline, 2, 3, 4 and 6 weeks
Global Assessment Scale is a numeric scale (1 through 100) used by mental health clinicians to rate the general functioning.
baseline, 2, 3, 4 and 6 weeks
Treatment Emergent Symptom Scale
Time Frame: 2, 3, 4 and 6 weeks
Treatment Emergent Symptom Scale is used to assess the adverse event of the drug.
2, 3, 4 and 6 weeks
Hamilton Anxiety Rating Scale
Time Frame: baseline, 2, 3, 4, and 6 weeks
Hamilton Anxiety Rating Scale is used to assess anxious symptoms
baseline, 2, 3, 4, and 6 weeks
Hamilton Depression Rating Scale
Time Frame: baseline, 2, 3, 4, and 6 weeks
Hamilton Depression Rating Scale is used to assess the depressive symptoms
baseline, 2, 3, 4, and 6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Guiyun Xu

Collaborators

The University of Hong Kong

Investigators

  • Principal Investigator: Guinyun Xu, M.D, Guangzhou Psychiatric Hospital
  • Principal Investigator: Kangguang Lin, M.D, The University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (Anticipated)

December 1, 2015

Study Completion (Anticipated)

December 1, 2015

Study Registration Dates

First Submitted

July 2, 2013

First Submitted That Met QC Criteria

July 2, 2013

First Posted (Estimate)

July 8, 2013

Study Record Updates

Last Update Posted (Estimate)

March 17, 2015

Last Update Submitted That Met QC Criteria

March 14, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20120509

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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