Comparative Efficacy and Acceptability of Antimanic Drugs in Acute Mania

NCT ID: NCT01893229

Last Updated: 2015-03-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-09-30

Study Completion Date

2015-12-31

Brief Summary

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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

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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.

Conditions

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Bipolar Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Valproate

Name: Valproate; dosage form: tablet, 250mg; dosage and frequency: 800mg-- 1200mg/d; duration: 6 weeks.

Group Type EXPERIMENTAL

Valproate

Intervention Type DRUG

Valproate is used as a mood stabiliser

Oxcarbazepine

Name: Oxcarbazepine, dosage form: 300mg, tablet; dosage and frequency: 600-1200mg/d; duration: 6 weeks

Group Type EXPERIMENTAL

Oxcarbazepine

Intervention Type DRUG

Oxcarbazepine is used as a mood stabiliser

Quetiapine

name: Quetiapine, dosage form: 200mg,tablet; dosage and frequency: 600mg-- 800mg/d; duration: 6 weeks

Group Type EXPERIMENTAL

Quetiapine

Intervention Type DRUG

Quetiapine is used as a mood stabiliser

Olanzapine

Name: Olanzapine, dosage form: 5mg tablet; dosage and frequency: 10mg--20mg/d; duration: 6 weeks

Group Type EXPERIMENTAL

Olanzapine

Intervention Type DRUG

Olanzapine is used as a mood stabiliser.

Ziprasidone

Name: Ziprasidone, dosage form: 10mg tablet; dosage and frequency: 80mg-160mmg/d; duration: 6 weeks

Group Type EXPERIMENTAL

Ziprasidone

Intervention Type DRUG

Ziprasidone is used as a mood stabiliser

Lithium

name: lithium; dosage form: 250mg Tablet; dosage and frequency: 750mg-2000mg/d;serum Li level: 0.6mmol-1.2mmol/L; duration: 6 weeks

Group Type EXPERIMENTAL

Lithium

Intervention Type DRUG

Lithium is used as a mood stabiliser

Interventions

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Lithium

Lithium is used as a mood stabiliser

Intervention Type DRUG

Valproate

Valproate is used as a mood stabiliser

Intervention Type DRUG

Oxcarbazepine

Oxcarbazepine is used as a mood stabiliser

Intervention Type DRUG

Quetiapine

Quetiapine is used as a mood stabiliser

Intervention Type DRUG

Olanzapine

Olanzapine is used as a mood stabiliser.

Intervention Type DRUG

Ziprasidone

Ziprasidone is used as a mood stabiliser

Intervention Type DRUG

Other Intervention Names

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lithium Carbonate Depakote Trileptal SEROquel Zyprexaï¼› Geodon

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The University of Hong Kong

OTHER

Sponsor Role collaborator

Guiyun Xu

OTHER_GOV

Sponsor Role lead

Responsible Party

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Guiyun Xu

Associate Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Guinyun Xu, M.D

Role: PRINCIPAL_INVESTIGATOR

Guangzhou Psychiatric Hospital

Kangguang Lin, M.D

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

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Guangzhou Psychiatric Hospital

Guangzhou, Guangdong, China

Site Status ENROLLING_BY_INVITATION

Guangzhou Psychiatric Hospital

Guangzhou, Guangdong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Guiyun Xu, MD

Role: CONTACT

86(02081891425) ext. 8111

Facility Contacts

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Guiyun Xu, M.D

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 9164317 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21145595 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20402706 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21851976 (View on PubMed)

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

Reference Type BACKGROUND

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

Reference Type BACKGROUND
PMID: 20622947 (View on PubMed)

Other Identifiers

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20120509

Identifier Type: -

Identifier Source: org_study_id

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