Comparative Efficacy and Acceptability of Antimanic Drugs in Acute Mania

Bipolar Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01893229
• Other study ID #: 20120509
• Status: Recruiting
• Phase: Phase 4
• First received: July 2, 2013
• Last updated: March 14, 2015
• Start date: September 2013
• Est. completion date: December 2015

Study information

• Verified date: March 2015
• Source: Guangzhou Psychiatric Hospital
• Contact: Guiyun Xu, MD
• Phone: 86(02081891425)
• Email: xuguiyun2908[@]hotmail.com
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

Drug:
• Lithium
Lithium is used as a mood stabiliser
• Valproate
Valproate is used as a mood stabiliser
• Oxcarbazepine
Oxcarbazepine is used as a mood stabiliser
• Quetiapine
Quetiapine is used as a mood stabiliser
• Olanzapine
Olanzapine is used as a mood stabiliser.
• Ziprasidone
Ziprasidone is used as a mood stabiliser

Locations

Country	Name	City	State
China	Guangzhou Psychiatric Hospital	Guangzhou	Guangdong
China	Guangzhou Psychiatric Hospital	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Guiyun Xu	The University of Hong Kong

Country where clinical trial is conducted

China, 

References & Publications (6)

American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. text revision. Washington (DC): American Psychiatric Association; 2000.

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

Zhang L, Ning Y. Guangzhou psychiatric hospital: the oldest psychiatric hospital in china. Psychiatry (Edgmont). 2010 Jun;7(6):53-4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in Young Mania Rating Scale at 2 weeks and 6 weeks	Young Mania Rating Scale is used to assess hypomania/mania symptoms	Baseline, 2 weeks and 6 weeks	No
Primary	rate of dropout (treatment discontinuation)	to compare the rates of treatment discontinuation of different drugs because of side effect or effectiveness	1,2,4,6 weeks	Yes
Secondary	Clinical Global Impressions (CGI) Scale	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	Yes
Secondary	Brief Psychiatric Rating Scale	Brief Psychiatric Rating Scale is used to assess psychotic symptoms.	baseline, 2, 3, 4 and 6 weeks	No
Secondary	Global Assessment Scale	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	No
Secondary	Treatment Emergent Symptom Scale	Treatment Emergent Symptom Scale is used to assess the adverse event of the drug.	2, 3, 4 and 6 weeks	Yes
Secondary	Hamilton Anxiety Rating Scale	Hamilton Anxiety Rating Scale is used to assess anxious symptoms	baseline, 2, 3, 4, and 6 weeks	No
Secondary	Hamilton Depression Rating Scale	Hamilton Depression Rating Scale is used to assess the depressive symptoms	baseline, 2, 3, 4, and 6 weeks	No

External Links

•   official organization website