Comparative Efficacy and Acceptability of Antimanic Drugs in Acute Mania

NCT01893229 | Unknown Phase 4 DMC

• 1 other identifier: 20120509
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

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.

Conditions

Bipolar Disorder

Keywords

Bipolar disorder; Comparative Effectiveness Research; Therapeutics; Patient Dropouts

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (6)

• Clinical Global Impressions (CGI) Scale

  baseline, 2 weeks, 4 weeks, and 6 weeks

• Brief Psychiatric Rating Scale

  baseline, 2, 3, 4 and 6 weeks

• Global Assessment Scale

  baseline, 2, 3, 4 and 6 weeks

• Treatment Emergent Symptom Scale

  2, 3, 4 and 6 weeks

• Hamilton Anxiety Rating Scale

  baseline, 2, 3, 4, and 6 weeks

Study Arms (6)

Valproate

EXPERIMENTAL

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

Drug: Valproate

Oxcarbazepine

EXPERIMENTAL

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

Drug: Oxcarbazepine

Quetiapine

EXPERIMENTAL

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

Drug: Quetiapine

Olanzapine

EXPERIMENTAL

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

Drug: Olanzapine

Ziprasidone

EXPERIMENTAL

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

Drug: Ziprasidone

Lithium

EXPERIMENTAL

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

Drug: Lithium

Interventions

Lithium DRUG

Lithium is used as a mood stabiliser

Also known as: lithium Carbonate

Lithium

Valproate DRUG

Valproate is used as a mood stabiliser

Also known as: Depakote

Valproate

Oxcarbazepine DRUG

Oxcarbazepine is used as a mood stabiliser

Also known as: Trileptal

Oxcarbazepine

Quetiapine DRUG

Quetiapine is used as a mood stabiliser

Also known as: SEROquel

Quetiapine

Olanzapine DRUG

Olanzapine is used as a mood stabiliser.

Also known as: Zyprexa；

Olanzapine

Ziprasidone DRUG

Ziprasidone is used as a mood stabiliser

Also known as: Geodon

Ziprasidone

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• with a diagnosis of bipolar I disorder, manic or mixed phase
• equal or more than 18 scores in Young Mania Rating Scale (YMRS)

You may not qualify if:

• 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

Sponsors & Collaborators

• Guiyun Xu: lead
• The University of Hong Kong: collaborator

Study Sites (2)

Guangzhou Psychiatric Hospital

Guangzhou, Guangdong, 510370, China

ENROLLING BY INVITATION

Guangzhou Psychiatric Hospital

Guangzhou, Guangdong, 510370, China

RECRUITING

Related Publications (6)

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  PMID: 9164317 BACKGROUND

• 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.

  PMID: 21145595 BACKGROUND

• 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.

  PMID: 20402706 BACKGROUND

• 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.

  PMID: 21851976 BACKGROUND

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

  BACKGROUND

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

  PMID: 20622947 BACKGROUND

MeSH Terms

Conditions

Bipolar Disorder; Patient Dropouts

Interventions

Lithium; Lithium Carbonate; Valproic Acid; Oxcarbazepine; Quetiapine Fumarate; Olanzapine; ziprasidone

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals; Carbonates; Alkalies; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Carbamazepine; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring

Study Officials

• Guinyun Xu, M.D

  Guangzhou Psychiatric Hospital

  PRINCIPAL INVESTIGATOR

• Kangguang Lin, M.D

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guiyun Xu, MD

CONTACT

86(02081891425); xuguiyun2908@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 2, 2013
• First Posted: July 8, 2013
• Study Start: September 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: March 17, 2015

Record last verified: 2015-03

Locations

CN (2)