Contact information
Type
Scientific
Primary contact
Dr Lakshmi N. Yatham
ORCID ID
Contact details
Mood Disorders Centre
University of British Columbia
2255 Westbrook Mall
Rm 2C7
Vancouver
British Columbia
V6T 2A1
Canada
+1 604 822 7325
yatham@interchange.ubc.ca
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
MCT-53576
Study information
Scientific title
Atypical antipsychotics for continuation and maintenance treatment after an acute manic episode: a randomised controlled trial
Acronym
Study hypothesis
We hypothesise that continuing risperidone or olanzapine for 6 or 12 months (along with a mood stabiliser) will lead to significantly lower rates of relapse or recurrence of mood episodes compared with mood stabiliser monotherapy for 12 months, in bipolar patients currently in remission but recently treated for an acute manic episode with a mood stabiliser and risperidone or olanzapine combination.
Ethics approval
University of Western Ontario, Office of Research Ethics gave approval on the 31st May 2005
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Prevention
Patient information sheet
Condition
Bipolar disorder
Intervention
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 stabiliser plus placebo for another 28 weeks
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 stabiliser, lithium or valproate, they had been on during the acute mania for the full duration of the study
Intervention type
Drug
Phase
Not Applicable
Drug names
Risperidone, olanzapine, lithium, valproate
Primary outcome measures
Time to any mood episode.
Secondary outcome measures
1. Time to premature discontinuation from the study for any clinical reason (dose change in medication, new intervention, side effects, etc.)
2. Time to manic episode
3. Time to depressive episode
4. Proportion of patients gaining more than 7% of body weight (this amount of weight gain is significant for cardiovascular morbidity)
5. Proportion of patients developing extrapyramidal symptoms, tardive dyskinesia, prolactin related side effects
6. Changes in YMRS, HAM-D 21, CGI-S, ESRS scores and weight during the study period
Overall trial start date
01/04/2002
Overall trial end date
30/03/2007
Reason abandoned
Eligibility
Participant inclusion criteria
1. Patients who were recently (within the last 12 weeks) commenced on treatment for a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) manic or mixed episode with a combination of lithium and risperidone, lithium and olanzapine, valproate and risperidone, or valproate and olanzapine
2. Patients who are in remission from mania for at least 2 weeks but no more than 6 weeks. Remission is defined as either:
2.1. A Clinical Global Impression - Severity (CGI-S) scale score of 2 (borderline mentally ill) or less (normal, not ill) for 2 consecutive weeks
2.2. A YMRS score of 8 or less (normal range) and a Hamilton Rating Scale for Depression (HAM-D) 21-item score of 8 or less (normal range) for 2 consecutive weeks
3. Must not be taking any other psychotropic medication with the exception of benzodiazepines (maximum of lorazepam 4 mg per day or its equivalent)
4. Patients aged 18 and above (efficacy of risperidone and olanzapine is not tested in those below 18 years of age), either sex
5. Patients on 1 to 6 mg risperidone or 5 to 25 mg olanzapine (these are the dose ranges commonly used in clinical practice, and are shown to be effective doses in acute mania trials)
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
540
Participant exclusion criteria
As we want the findings to be generalisable to clinically representative patients with bipolar disorder, we will not exclude any patients with a history of co-morbid substance abuse or medical illnesses. Any subjects who do not meet the above inclusion criteria will be excluded from the study.
Recruitment start date
01/04/2002
Recruitment end date
30/03/2007
Locations
Countries of recruitment
Canada
Trial participating centre
Mood Disorders Centre
Vancouver, British Columbia
V6T 2A1
Canada
Sponsor information
Organisation
University of British Columbia (Canada)
Sponsor details
2075 Wesbrook Mall
Vancouver
British Columbia
V6T 1Z1
Canada
Sponsor type
University/education
Website
Funders
Funder type
Other
Funder name
Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-53576)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Janssen-Ortho Canada, Inc. (Canada)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Eli Lilly Canada, Inc. (Canada)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary