Comparative Efficacy and Acceptability of Antimanic Drugs in Acute Mania

• ClinicalTrials.gov Identifier: NCT01893229
• Recruitment Status: Unknown
• First Posted: July 8, 2013
• Last Update Posted: March 17, 2015
• Sponsor: Guiyun Xu
• Collaborator: The University of Hong Kong
• Information provided by (Responsible Party): Guiyun Xu, Guangzhou Psychiatric Hospital

Tracking Information

• First Submitted Date: July 2, 2013
• First Posted Date: July 8, 2013
• Last Update Posted Date: March 17, 2015
• Study Start Date: September 2013
• Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 17, 2014)

• 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
• 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

Original Primary Outcome Measures (submitted: July 2, 2013)

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

Current Secondary Outcome Measures (submitted: January 17, 2014)

• 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
• Brief Psychiatric Rating Scale [ Time Frame: baseline, 2, 3, 4 and 6 weeks ]
  Brief Psychiatric Rating Scale is used to assess psychotic symptoms.
• 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.
• 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.
• Hamilton Anxiety Rating Scale [ Time Frame: baseline, 2, 3, 4, and 6 weeks ]
  Hamilton Anxiety Rating Scale is used to assess anxious symptoms
• Hamilton Depression Rating Scale [ Time Frame: baseline, 2, 3, 4, and 6 weeks ]
  Hamilton Depression Rating Scale is used to assess the depressive symptoms

Original Secondary Outcome Measures (submitted: July 2, 2013)

• rate of dropout (treatment discontinuation) [ Time Frame: 6 weeks ]
  to compare the rates of treatment discontinuation of different drugs because of side effect or effectiveness
• 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
• Brief Psychiatric Rating Scale [ Time Frame: baseline, 2, 3, 4 and 6 weeks ]
  Brief Psychiatric Rating Scale is used to assess psychotic symptoms.
• 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.
• 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.
• Hamilton Anxiety Rating Scale [ Time Frame: baseline, 2, 3, 4, and 6 weeks ]
  Hamilton Anxiety Rating Scale is used to assess anxious symptoms
• Hamilton Depression Rating Scale [ Time Frame: baseline, 2, 3, 4, and 6 weeks ]
  Hamilton Depression Rating Scale is used to assess the depressive symptoms

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Comparative Efficacy and Acceptability of Antimanic Drugs in Acute Mania
• Official Title: Comparative Efficacy and Acceptability of Lithium, Valproate, Oxcarbazepine, Quetiapine, Olanzapine, and Ziprasidone in Bipolar I Disorder, Manic or Mixed Phase

Brief 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.

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
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: Bipolar Disorder

Intervention

• Drug: Lithium
  Lithium is used as a mood stabiliser
  Other Name: lithium Carbonate
• Drug: Valproate
  Valproate is used as a mood stabiliser
  Other Name: Depakote
• Drug: Oxcarbazepine
  Oxcarbazepine is used as a mood stabiliser
  Other Name: Trileptal
• Drug: Quetiapine
  Quetiapine is used as a mood stabiliser
  Other Name: SEROquel
• Drug: Olanzapine
  Olanzapine is used as a mood stabiliser.
  Other Name: Zyprexa；
• Drug: Ziprasidone
  Ziprasidone is used as a mood stabiliser
  Other Name: Geodon

Study Arms

• Experimental: Valproate
  Name: Valproate; dosage form: tablet, 250mg; dosage and frequency: 800mg-- 1200mg/d; duration: 6 weeks.
  Intervention: Drug: Valproate
• Experimental: Oxcarbazepine
  Name: Oxcarbazepine, dosage form: 300mg, tablet; dosage and frequency: 600-1200mg/d; duration: 6 weeks
  Intervention: Drug: Oxcarbazepine
• Experimental: Quetiapine
  name: Quetiapine, dosage form: 200mg,tablet; dosage and frequency: 600mg-- 800mg/d; duration: 6 weeks
  Intervention: Drug: Quetiapine
• Experimental: Olanzapine
  Name: Olanzapine, dosage form: 5mg tablet; dosage and frequency: 10mg--20mg/d; duration: 6 weeks
  Intervention: Drug: Olanzapine
• Experimental: Ziprasidone
  Name: Ziprasidone, dosage form: 10mg tablet; dosage and frequency: 80mg-160mmg/d; duration: 6 weeks
  Intervention: Drug: Ziprasidone
• 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
  Intervention: Drug: Lithium

Publications *

• 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. doi: 10.1016/S0140-6736(96)07495-8.
• Tarr GP, Glue P, Herbison P. Comparative efficacy and acceptability of mood stabilizer and second generation antipsychotic monotherapy for acute mania--a systematic review and meta-analysis. J Affect Disord. 2011 Nov;134(1-3):14-9. doi: 10.1016/j.jad.2010.11.009. Epub 2010 Dec 9.
• Correll CU, Sheridan EM, DelBello MP. Antipsychotic and mood stabilizer efficacy and tolerability in pediatric and adult patients with bipolar I mania: a comparative analysis of acute, randomized, placebo-controlled trials. Bipolar Disord. 2010 Mar;12(2):116-41. doi: 10.1111/j.1399-5618.2010.00798.x.
• Cipriani A, Barbui C, Salanti G, Rendell J, Brown R, Stockton S, Purgato M, Spineli LM, Goodwin GM, Geddes JR. Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis. Lancet. 2011 Oct 8;378(9799):1306-15. doi: 10.1016/S0140-6736(11)60873-8. Epub 2011 Aug 16.
• American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. text revision. Washington (DC): American Psychiatric Association; 2000.
• Zhang L, Ning Y. Guangzhou psychiatric hospital: the oldest psychiatric hospital in china. Psychiatry (Edgmont). 2010 Jun;7(6):53-4.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: January 17, 2014): 120
• Original Estimated Enrollment (submitted: July 2, 2013): 480
• Estimated Study Completion Date: December 2015
• Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT01893229
• Other Study ID Numbers: 20120509
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Guiyun Xu, Guangzhou Psychiatric Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Guiyun Xu
• Original Study Sponsor: Same as current
• 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

• PRS Account: Guangzhou Psychiatric Hospital
• Verification Date: March 2015