Bipolar Disorder | Comparative Efficacy and Acceptability of Antimanic Drugs in Acute Mania
Bipolar Disorder research study
What is the primary objective of this study?
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.
Who is eligible to participate?
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
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:LithiumLithium is used as a mood stabiliser
Drug:ValproateValproate is used as a mood stabiliser
Drug:OxcarbazepineOxcarbazepine is used as a mood stabiliser
Drug:QuetiapineQuetiapine is used as a mood stabiliser
Drug:OlanzapineOlanzapine is used as a mood stabiliser.
Drug:ZiprasidoneZiprasidone is used as a mood stabiliser
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
ValproateName: Valproate; dosage form: tablet, 250mg; dosage and frequency: 800mg-- 1200mg/d; duration: 6 weeks.
OxcarbazepineName: Oxcarbazepine, dosage form: 300mg, tablet; dosage and frequency: 600-1200mg/d; duration: 6 weeks
Quetiapinename: Quetiapine, dosage form: 200mg,tablet; dosage and frequency: 600mg-- 800mg/d; duration: 6 weeks
OlanzapineName: Olanzapine, dosage form: 5mg tablet; dosage and frequency: 10mg--20mg/d; duration: 6 weeks
ZiprasidoneName: Ziprasidone, dosage form: 10mg tablet; dosage and frequency: 80mg—160mmg/d; duration: 6 weeks
Lithiumname: lithium; dosage form: 250mg Tablet; dosage and frequency: 750mg—2000mg/d;serum Li level: 0.6mmol—1.2mmol/L; duration: 6 weeks
Start Date: September 2013
Completed Date: December 2015
Phase: Phase 4
Primary Outcome: Change from baseline in Young Mania Rating Scale at 2 weeks and 6 weeks
Secondary Outcome: Clinical Global Impressions (CGI) Scale
Study sponsors, principal investigator, and references
Principal Investigator: Guinyun Xu, M.D
Lead Sponsor: Guiyun Xu
Collaborator: The University of Hong Kong
Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet. 1997 May 17;349(9063):1436-42.