VA Augmentation and Switching Treatments for Improving Depression Outcomes

Summary

The overall purpose is to determine research based 'next-steps' for outpatients with major depressive disorder who have not had satisfactory outcomes to standard 'first-step' treatments. The primary objective is to compare the acute (up to 12 weeks) treatment effectiveness of augmenting an antidepressant with aripiprazole or with bupropion-slow release (SR) vs. switching treatment to bupropion-SR monotherapy on symptom remission in Veterans with Major Depressive Disorder (MDD) who have not achieved optimal response after an adequate trial on antidepressant (a selective serotonin reuptake inhibitor \[SSRI\] or serotonin and norepinephrine reuptake inhibitor \[SNRI\] or mirtazapine) monotherapy. The secondary objectives are to compare the acute (up to 12 weeks) and long term (up to 36 weeks) efficacy, safety, effects on functioning, suicidality, quality of life, anxiety and other associated symptoms, costs and cost-effectiveness of each of the three treatments.

Conditions

• Major Depressive Disorder

Interventions

DRUG

Switching: Bupropion-SR

Bupropion-SR (Dose: 150 mg - 400 mg taken per day orally for up to 36 weeks): Initiating with bupropion-SR dose of 150 mg, then increasing dose per protocol up to 400 mg (200 mg BID), maintaining or decreasing dose for up to 36 weeks depending on response and side effect profile through the acute and continuation phases.

DRUG

Augmenting: Antidepressant + Bupropion-SR

Current antidepressant (either a SSRI or a SNRI or mirtazapine): Continue the dose prescribed at time of enrollment, or adjust depending on response or side effect profile for up to 36 weeks. And Bupropion-SR (Dose: 150 mg - 400 mg taken per day orally for up to 36 weeks): Initiating with bupropion-SR dose of 150 mg, then increasing dose per protocol up to 400 mg (200 mg BID), maintaining or decreasing dose for up to 36 weeks depending on response and side effect profile through the acute and continuation phases.

DRUG

Augmenting: Antidepressant + Aripiprazole

Current antidepressant (either a SSRI or a SNRI or mirtazapine): Continue the dose prescribed at time of enrollment or adjust depending on response or side effect profile for up to 36 weeks. And Aripiprazole (Dose: 2 mg - 15 mg taken orally once per day for up to 36 weeks): Initiating with aripiprazole dose of 2 mg for one week, then increasing dose per protocol up to 15 mg, maintaining or decreasing dose for up to 36 weeks depending on response and side effect profile through the acute and continuation phases.

Sponsors & Collaborators

• VA Office of Research and Development

  lead FED

Principal Investigators

• Somaia Mohamed, PhD · VA Connecticut Healthcare System West Haven Campus, West Haven, CT

• Sidney Zisook, MD · VA San Diego Healthcare System, San Diego, CA

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-12-31

Primary Completion

2015-08-31

Completion

2016-06-30

Countries

• United States

Study Locations