Atypical Antipsychotics for Continuation and Maintenance Treatment After an Acute Manic Episode
Primary Purpose
Bipolar I Disorder
Status
Completed
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Valproate
Lithium
Risperidone
Olanzapine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Bipolar I Disorder
Eligibility Criteria
Inclusion Criteria:
- Patients who were recently (within the last 12 weeks) commenced on treatment for a Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) manic or mixed episode with a combination of lithium and risperidone, lithium and olanzapine, valproate and risperidone, or valproate and olanzapine;
- Patients on 1 to 6 mg of risperidone or 5 to 25 mg of olanzapine
- Patients who are in remission from mania for at least 2 weeks but no more than 6 weeks and have maintained remission for 2 consecutive weeks;
- Patients must not be taking any other psychotropic medication (with the exception of benzodiazepines) or treatments including bromocriptine, omega 3 fatty acids, Axid or EMPower;
- Patients aged 17 and above.
Exclusion Criteria:
- Any subjects who do not meet the above inclusion criteria will be excluded from the study.
- In order for the findings to be generalizable to clinically representative patients with bipolar disorder, any patients with a history of co-morbid substance abuse or medical illnesses will not be excluded.
Sites / Locations
- University of British Columbia
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Active Comparator
Arm Label
Mood stabilizer & Placebo
'24 week " arm
"52 week" arm
Arm Description
Patients will receive lithium or valproate plus placebo for 52 weeks (risperidone or olanzapine tapering will begin on the day of randomization with discontinuation of the drug within 2 weeks).
Continuation of the lithium or valproate plus risperidone or olanzapine for 24 weeks followed by mood stabilizer plus placebo for another 28 weeks. Dosages: 1 to 6 mg of risperidone, 5 to 20 mg olanzapine.
Continuation of the atypical antipsychotic, risperidone or olanzapine, plus lithium or valproate for 52 weeks.
Outcomes
Primary Outcome Measures
The primary outcome measure is the time to any mood episode (depressive or manic episode).
A mood episode is defined as 1) Young Mania Rating Scale (YMRS) score of 15 or greater 2)Hamilton Rating Scale for Depression (HAM-D) 21-item score of 15 or greater or a HAM-D suicide item score of 3 or greater 3)A Clinical Global Impression -Severity (CGI-S) score of 3 or greater 4) a patient requiring hospitalization for treatment of mood symptoms or 5) a patient who makes a suicide attempt or commits suicide during the study.
Secondary Outcome Measures
Time to manic episode.
Time to occurrence of a manic episode measured by Young Mania Rating Scale (YMRS) score of 15 or greater .
Time to depressive episode
Time to occurrence of a depressive episode measured by Hamilton Rating Scale for Depression (HAM-D) 21-item score of 15 or greater or a HAM-D suicide item score of 3 or greater.
Full Information
NCT ID
NCT01977300
First Posted
October 22, 2013
Last Updated
November 19, 2015
Sponsor
University of British Columbia
Collaborators
Canadian Institutes of Health Research (CIHR), Eli Lilly and Company, Janssen-Ortho Inc., Canada
1. Study Identification
Unique Protocol Identification Number
NCT01977300
Brief Title
Atypical Antipsychotics for Continuation and Maintenance Treatment After an Acute Manic Episode
Official Title
Atypical Antipsychotics for Continuation and Maintenance Treatment After an Acute Manic Episode
Study Type
Interventional
2. Study Status
Record Verification Date
October 2013
Overall Recruitment Status
Completed
Study Start Date
January 2003 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of British Columbia
Collaborators
Canadian Institutes of Health Research (CIHR), Eli Lilly and Company, Janssen-Ortho Inc., Canada
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Hypothesis: Continuation of an atypical antipsychotic medication in combination with a Mood Stabilizer, following remission from an acute manic episode, lowers the rates of relapse and recurrence of mood episodes compared to discontinuing the antipsychotics within days of resolution of manic symptoms.
Detailed Description
This is a randomised, double-blind, placebo controlled trial over 52 weeks. Patients will be on one of four combinations of medications at the time of entry into the study: a) lithium and risperidone, b) lithium and olanzapine, c) valproate and risperidone, or d) valproate and olanzapine. After obtaining informed consent, patients will be randomised to one of three groups 1)"0" week group: patients will receive lithium or valproate plus placebo for 52 weeks (risperidone or olanzapine tapering will begin on the day of randomisation with discontinuation of the drug within 2 weeks), 2) continuation of the same atypical antipsychotic, risperidone or olanzapine, plus lithium or valproate for 24 weeks (tapering of the antipsychotic begins at the end of 24 weeks and completed within 2 weeks) followed by the same mood stabilizer plus placebo for another 28 weeks, and 3) continuation of the atypical antipsychotic, risperidone or olanzapine, plus lithium or valproate for 52 weeks. The duration of the double-blind phase of the study will be 52 weeks and all patients will continue on the mood stabilizer, lithium or valproate, they had been on during the acute mania for the full duration of the study. The serum level of the mood stabilizer will be maintained within the therapeutic range (0.6 to 1.2 mmol/L for lithium and 50 to 125 ug/L for valproate) throughout the 52 weeks as determined by blood tests. The dose and the type of atypical antipsychotic (ie risperidone or olanzapine) each patient will receive during the double-blind period will be the same that the patient had been on at the time of entry into the double-blind phase. All patients, irrespective of which treatment arm they are in, will receive active psychoeducation and counselling regarding sleep hygiene, healthy daily routines and rhythms, alcohol and substance abuse, anxiety management, conflict resolution and problem solving as clinically indicated in routine clinical practice. Patients who withdraw from or meet a primary end point of the study will be treated actively as done in regular clinical practice.
Patients will not be allowed to receive any other psychotropic medication with the exception of benzodiazepines for sedation and anti-parkinsonian medication for extrapyramidal side effects. The doses of these will be recorded.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar I Disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
159 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Mood stabilizer & Placebo
Arm Type
Placebo Comparator
Arm Description
Patients will receive lithium or valproate plus placebo for 52 weeks (risperidone or olanzapine tapering will begin on the day of randomization with discontinuation of the drug within 2 weeks).
Arm Title
'24 week " arm
Arm Type
Experimental
Arm Description
Continuation of the lithium or valproate plus risperidone or olanzapine for 24 weeks followed by mood stabilizer plus placebo for another 28 weeks. Dosages: 1 to 6 mg of risperidone, 5 to 20 mg olanzapine.
Arm Title
"52 week" arm
Arm Type
Active Comparator
Arm Description
Continuation of the atypical antipsychotic, risperidone or olanzapine, plus lithium or valproate for 52 weeks.
Intervention Type
Drug
Intervention Name(s)
Valproate
Other Intervention Name(s)
Valproic Acid
Intervention Description
serum level of 50 to 125 ug/L
Intervention Type
Drug
Intervention Name(s)
Lithium
Other Intervention Name(s)
Lithium Carbonate
Intervention Description
serum levels of 0.6 to 1.2 mmol/L
Intervention Type
Drug
Intervention Name(s)
Risperidone
Other Intervention Name(s)
Risperdal
Intervention Description
1 to 6 mg/day
Intervention Type
Drug
Intervention Name(s)
Olanzapine
Other Intervention Name(s)
Zyprexa
Intervention Description
5 to 25 mg/day
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sugar Pill
Intervention Description
manufactured to mimic risperidone and olanzapine
Primary Outcome Measure Information:
Title
The primary outcome measure is the time to any mood episode (depressive or manic episode).
Description
A mood episode is defined as 1) Young Mania Rating Scale (YMRS) score of 15 or greater 2)Hamilton Rating Scale for Depression (HAM-D) 21-item score of 15 or greater or a HAM-D suicide item score of 3 or greater 3)A Clinical Global Impression -Severity (CGI-S) score of 3 or greater 4) a patient requiring hospitalization for treatment of mood symptoms or 5) a patient who makes a suicide attempt or commits suicide during the study.
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Time to manic episode.
Description
Time to occurrence of a manic episode measured by Young Mania Rating Scale (YMRS) score of 15 or greater .
Time Frame
52 weeks
Title
Time to depressive episode
Description
Time to occurrence of a depressive episode measured by Hamilton Rating Scale for Depression (HAM-D) 21-item score of 15 or greater or a HAM-D suicide item score of 3 or greater.
Time Frame
52 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients who were recently (within the last 12 weeks) commenced on treatment for a Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) manic or mixed episode with a combination of lithium and risperidone, lithium and olanzapine, valproate and risperidone, or valproate and olanzapine;
Patients on 1 to 6 mg of risperidone or 5 to 25 mg of olanzapine
Patients who are in remission from mania for at least 2 weeks but no more than 6 weeks and have maintained remission for 2 consecutive weeks;
Patients must not be taking any other psychotropic medication (with the exception of benzodiazepines) or treatments including bromocriptine, omega 3 fatty acids, Axid or EMPower;
Patients aged 17 and above.
Exclusion Criteria:
Any subjects who do not meet the above inclusion criteria will be excluded from the study.
In order for the findings to be generalizable to clinically representative patients with bipolar disorder, any patients with a history of co-morbid substance abuse or medical illnesses will not be excluded.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lakshmi N Yatham, Dr.
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Serge Beaulieu, Dr.
Organizational Affiliation
McGill University, Montreal
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Andree Daigneault, Dr.
Organizational Affiliation
Clinique des Maladies Affectives, Montreal
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Verinder Sharma, Dr.
Organizational Affiliation
Regional Mental Health Care London, Ont.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Hubert Wong, Dr.
Organizational Affiliation
University of British Columbia
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Ayal Schaffer, Dr.
Organizational Affiliation
Sunnybrook Health Sciences Centre, Toronto, Ont.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Sagar Parikh, Dr.
Organizational Affiliation
Centre for Addiction and Mental Health, Toronto, Ont.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Philippe Baruch, Dr.
Organizational Affiliation
Clinique des troubles de l'humeur, Quebec
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Peter Silverstone, Dr.
Organizational Affiliation
University of Alberta
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Roumen Milev, Dr.
Organizational Affiliation
Providence Continuing Care, Kingston, Ont.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Ram Veluri, Dr.
Organizational Affiliation
Northern Health Research Inc., Sudbury, Ont.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Pablo Cervantes, Dr.
Organizational Affiliation
Montreal General, Quebec
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Claire O'Donovan, Dr.
Organizational Affiliation
Mental Health Services, Halifax, NS
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Flavio Kapczinski, Dr.
Organizational Affiliation
Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Benny Lafer, Dr.
Organizational Affiliation
Instituto de Psiquiatria do Hospital das Clínicas, Sao Paulo, Brazil
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Angelo B Miralha da Cunha, Dr.
Organizational Affiliation
Santa Maria, Brazil
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Joao Quevedo, Dr.
Organizational Affiliation
Casa de Saude do Rio Maina Ltda, Criciuma, Brazil
Official's Role
Study Director
Facility Information:
Facility Name
University of British Columbia
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6T 2A1
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
26460229
Citation
Yatham LN, Beaulieu S, Schaffer A, Kauer-Sant'Anna M, Kapczinski F, Lafer B, Sharma V, Parikh SV, Daigneault A, Qian H, Bond DJ, Silverstone PH, Walji N, Milev R, Baruch P, da Cunha A, Quevedo J, Dias R, Kunz M, Young LT, Lam RW, Wong H. Optimal duration of risperidone or olanzapine adjunctive therapy to mood stabilizer following remission of a manic episode: A CANMAT randomized double-blind trial. Mol Psychiatry. 2016 Aug;21(8):1050-6. doi: 10.1038/mp.2015.158. Epub 2015 Oct 13.
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Atypical Antipsychotics for Continuation and Maintenance Treatment After an Acute Manic Episode
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