Comparative Efficacy and Acceptability of Antimanic Drugs in Acute Mania

Summary

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.

Conditions

• Bipolar Disorder

Interventions

DRUG

Lithium

Lithium is used as a mood stabiliser

DRUG

Valproate

Valproate is used as a mood stabiliser

DRUG

Oxcarbazepine

Oxcarbazepine is used as a mood stabiliser

DRUG

Quetiapine

Quetiapine is used as a mood stabiliser

DRUG

Olanzapine

Olanzapine is used as a mood stabiliser.

DRUG

Ziprasidone

Ziprasidone is used as a mood stabiliser

Sponsors & Collaborators

• The University of Hong Kong

  collaborator OTHER

• Guiyun Xu

  lead OTHER_GOV

Principal Investigators

• Guinyun Xu, M.D · Guangzhou Psychiatric Hospital

• Kangguang Lin, M.D · The University of Hong Kong

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-09-30

Primary Completion

2015-12-31

Completion

2015-12-31

Countries

• China

Study Locations