Atypical antipsychotics for continuation and maintenance treatment after an acute manic episode

ISRCTN	ISRCTN76555175
DOI	https://doi.org/10.1186/ISRCTN76555175
Secondary identifying numbers	MCT-53576

Submission date: 01/09/2005
Registration date: 01/09/2005
Last edited: 24/02/2009

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Mental and Behavioural Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Lakshmi N. Yatham
Scientific

Mood Disorders Centre
University of British Columbia
2255 Westbrook Mall, Rm 2C7
Vancouver, British Columbia
V6T 2A1
Canada

Phone	+1 604 822 7325
Email	yatham@interchange.ubc.ca

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Prevention
Scientific title	Atypical antipsychotics for continuation and maintenance treatment after an acute manic episode: a randomised controlled trial
Study objectives	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(s)	University of Western Ontario, Office of Research Ethics gave approval on the 31st May 2005
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Risperidone, olanzapine, lithium, valproate
Primary outcome measure	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 study start date	01/04/2002
Completion date	30/03/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	540
Key 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)
Key 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.
Date of first enrolment	01/04/2002
Date of final enrolment	30/03/2007

Locations

Countries of recruitment

Canada

Study participating centre

Mood Disorders Centre

Vancouver, British Columbia
V6T 2A1
Canada

Sponsor information

University of British Columbia (Canada)
University/education

2075 Wesbrook Mall
Vancouver, British Columbia
V6T 1Z1
Canada

Website	http://www.ubc.ca/
"ROR"	https://ror.org/03rmrcq20

Funders

Funder type

Other

Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-53576)

No information available

Janssen-Ortho Canada, Inc. (Canada)

No information available

Eli Lilly Canada, Inc. (Canada)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan