Clinical trial NCT01977300: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bipolar I Disorder
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Eli Lilly and Company
name: Janssen-Ortho Inc., Canada
First posted: 2013-11-06
Enrollment: 159
Sex: ALL
Minimum age (years): 17
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The primary outcome measure is the time to any mood episode (depressive or manic episode).
timeFrame: 52 weeks
Secondary outcomes:
measure: Time to manic episode.
timeFrame: 52 weeks
measure: Time to depressive episode
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Lakshmi N Yatham, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: McGill University, Montreal
name: Serge Beaulieu, Dr.
role: STUDY_DIRECTOR
affiliation: Clinique des Maladies Affectives, Montreal
name: Andree Daigneault, Dr.
role: STUDY_DIRECTOR
affiliation: Regional Mental Health Care London, Ont.
name: Verinder Sharma, Dr.
role: STUDY_DIRECTOR
affiliation: University of British Columbia
name: Hubert Wong, Dr.
role: STUDY_DIRECTOR
affiliation: Sunnybrook Health Sciences Centre, Toronto, Ont.
name: Ayal Schaffer, Dr.
role: STUDY_DIRECTOR
affiliation: Centre for Addiction and Mental Health, Toronto, Ont.
name: Sagar Parikh, Dr.
role: STUDY_DIRECTOR
affiliation: Clinique des troubles de l'humeur, Quebec
name: Philippe Baruch, Dr.
role: STUDY_DIRECTOR
affiliation: University of Alberta
name: Peter Silverstone, Dr.
role: STUDY_DIRECTOR
affiliation: Providence Continuing Care, Kingston, Ont.
name: Roumen Milev, Dr.
role: STUDY_DIRECTOR
affiliation: Northern Health Research Inc., Sudbury, Ont.
name: Ram Veluri, Dr.
role: STUDY_DIRECTOR
affiliation: Montreal General, Quebec
name: Pablo Cervantes, Dr.
role: STUDY_DIRECTOR
affiliation: Mental Health Services, Halifax, NS
name: Claire O'Donovan, Dr.
role: STUDY_DIRECTOR
affiliation: Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil
name: Flavio Kapczinski, Dr.
role: STUDY_DIRECTOR
affiliation: Instituto de Psiquiatria do Hospital das Clínicas, Sao Paulo, Brazil
name: Benny Lafer, Dr.
role: STUDY_DIRECTOR
affiliation: Santa Maria, Brazil
name: Angelo B Miralha da Cunha, Dr.
role: STUDY_DIRECTOR
affiliation: Casa de Saude do Rio Maina Ltda, Criciuma, Brazil
name: Joao Quevedo, Dr.
role: STUDY_DIRECTOR
References:
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.