Condition category
Mental and Behavioural Disorders
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status
Results overdue

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Dr Lakshmi N. Yatham


Contact details

Mood Disorders Centre
University of British Columbia
2255 Westbrook Mall
Rm 2C7
British Columbia
V6T 2A1
+1 604 822 7325

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Atypical antipsychotics for continuation and maintenance treatment after an acute manic episode: a randomised controlled trial


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


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet


Bipolar disorder


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



Not Applicable

Drug names

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 trial start date


Overall trial end date


Reason abandoned (if study stopped)


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


Age group




Target number of participants


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


Recruitment end date



Countries of recruitment


Trial participating centre

Mood Disorders Centre
Vancouver, British Columbia
V6T 2A1

Sponsor information


University of British Columbia (Canada)

Sponsor details

2075 Wesbrook Mall
British Columbia
V6T 1Z1

Sponsor type




Funder type


Funder name

Canadian Institutes of Health Research (CIHR) (Canada) - (ref: MCT-53576)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

Janssen-Ortho Canada, Inc. (Canada)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

Eli Lilly Canada, Inc. (Canada)

Alternative name(s)

Funding Body Type

Funding Body Subtype


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

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes