Atypical Antipsychotics for Continuation and Maintenance Treatment After an Acute Manic Episode

Bipolar I Disorder Clinical Trial

Official title:

Atypical Antipsychotics for Continuation and Maintenance Treatment After an Acute Manic Episode

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01977300
• Other study ID #: H02-70188
• Secondary ID: V02-0130
• Status: Completed
• Phase: Phase 3
• First received: October 22, 2013
• Last updated: November 19, 2015
• Start date: January 2003
• Est. completion date: August 2011

Study information

• Verified date: October 2013
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 159
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 17 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar I Disorder

Intervention

Drug:
• Valproate
serum level of 50 to 125 ug/L
• Lithium
serum levels of 0.6 to 1.2 mmol/L
• Risperidone
1 to 6 mg/day
• Olanzapine
5 to 25 mg/day

Other:
• Placebo
manufactured to mimic risperidone and olanzapine

Locations

Country	Name	City	State
Canada	University of British Columbia	Vancouver	British Columbia

Sponsors (4)

Lead Sponsor	Collaborator
University of British Columbia	Canadian Institutes of Health Research (CIHR), Eli Lilly and Company, Janssen-Ortho Inc., Canada

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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. 2015 Oct 13. doi: 10.1038/mp.2015.158. [Epub ahead of print] — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	52 weeks	Yes
Secondary	Time to manic episode.	Time to occurrence of a manic episode measured by Young Mania Rating Scale (YMRS) score of 15 or greater .	52 weeks	No
Secondary	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.	52 weeks	No