Mood Stabilizer (MS)+ Antidepressant vs MS + Placebo in Maintenance of Bipolar Disorder.

Summary

Patients with bipolar I disorder (BD) experience depression 3 times more frequently than mania, and antidepressants are prescribed as adjuncts to mood stabilizers in up to 70% of patients. However, no placebo-controlled trials have assessed the efficacy or safety of modern antidepressants in combination with mood stabilizers in the maintenance treatment of BD. The investigators propose a multicentre, randomized, double-blind clinical trial comparing mood stabilizer plus antidepressant (escitalopram or bupropion XL) to mood stabilizer plus placebo in the maintenance treatment of BD.

The investigators hypothesize that in clinically representative patients with bipolar disorder, who respond to acute treatment with a newer antidepressant medication in conjunction with a mood stabilizing medication, continuing the antidepressant for 12 months will reduce the risk of relapse into any mood episode, including depression, mania, and hypomania, compared to stopping the antidepressant after 8 weeks.

Conditions

• Bipolar I Disorder

Interventions

DRUG

Escitalopram

Escitalopram will be prescribed in the dose range 10-30 mg daily. In patients randomized to the "8-week group: * escitalopram will be tapered, discontinued, and replaced with placebo over a period of 2 weeks, beginning at the week 6 study visit. The dose of escitalopram (or matching placebo) may be decreased in 10 mg increments only in the case of intolerable side effects. The dose must remain within the protocol-defined range of 10-30 mg daily at all time points. Patients randomized to the "52 week arm" will continue treatment with their antidepressant medication for 52 weeks, or until withdrawal from the study.

DRUG

Bupropion XL

Bupropion XL will be prescribed in the dosage range 150-450 mg daily. In patients randomized to the "8-week group: * bupropion XL will be tapered, discontinued, and replaced with placebo over a period of 2 weeks, beginning at the week 6 study visit. The dose of bupropion XL (or matching placebo) may be decreased in 150 mg increments only in the case of intolerable side effects. The dose must remain within the protocol-defined range of 150-450 mg daily at all time points. Patients randomized to the "52 week arm" will continue treatment with their antidepressant medication for 52 weeks, or until withdrawal from the study.

Sponsors & Collaborators

• Canadian Institutes of Health Research (CIHR)

  collaborator OTHER_GOV

• GlaxoSmithKline

  collaborator INDUSTRY

• Lundbeck Canada Inc.

  collaborator INDUSTRY

• Lupin Limited

  collaborator INDUSTRY

• University of British Columbia

  lead OTHER

Principal Investigators

• Lakshmi Yatham, Dr. · University of British Columbia

• B. Frey, Dr. · St. Joseph's Healthcare, Hamilton, Ont.

• S. Beaulieu, Dr. · Douglas Mental Health University Institute, Montreal, Quebec

• A. Daigneault, Dr. · Douglas Mental Health University Institute, Montreal, Quebec

• A. Ravindran, Dr. · Centre for Addictions and Mental Health, Toronto, Ont.

• A. Schaffer, Dr. · Sunnybrook Health Sciences Centre, Toronto, Ont.

• R. Milev, Dr. · Queen's University, Kingston, Ontario

• P. Cervantes, Dr. · McGill University Health Centre, Montreal, Que

• T. H. Ha, Dr. · Seoul National University Bundang Hospital

• Y. M. Ahn, Dr. · Seoul National University Hospital

• Y. H. Joo, Dr. · Asan Medical Centre, Korea

• S. Won, Dr. · Kyungpook National University Hospital, Korea

• J. Y. Reddy, Dr. · National Institute of Mental Health and Neuro sciences, Bangalore, India

• P.S. Sharma, Dr. · Kasturba Medical College Manipal, India

• M.S. Reddy, Dr. · Asha Hospital, Hyderabad, India

• A.V. Mysore, Dr. · St. John's hospital, Bangalore, India

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-11-30

Primary Completion

2020-03-31

Completion

2020-05-20

Countries

• Canada

Study Locations