VA Augmentation and Switching Treatments for Improving Depression Outcomes - Full Text View

Purpose

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-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 (SSRI or 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.

Condition	Intervention	Phase
Major Depressive Disorder	Drug: Augmenting: Antidepressant + Aripiprazole Drug: Augmenting: Antidepressant + Bupropion-SR Drug: Switching: Bupropion-SR	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	CSP #576 - VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D)

Resource links provided by NLM:

MedlinePlus related topics: Antidepressants

Drug Information available for: Bupropion

U.S. FDA Resources

Further study details as provided by VA Office of Research and Development:

Primary Outcome Measures:

Remission of symptoms of major depressive disorder [ Time Frame: During acute phase (12 weeks) ]
Remission of symptoms of major depression during the acute treatment phase (12 weeks) defined as a sustained clinician-rated Quick Inventory of Depressive Symptoms (QIDS-C16) of <= 5 for two consecutive visits.

Secondary Outcome Measures:

Relapse in symptoms of major depression [ Time Frame: During acute phase (up to 12 weeks) and continuation phase (from 12 weeks up to 36 weeks) ]
Relapse in symptoms of major depression defined as a QIDS-C16 => 11 after remission in the acute phase, and QIDS-C16 >= 11 for participants who enter into the continuation phase and had not remitted.
Response in symptoms of major depression [ Time Frame: During acute phase (up to 12 weeks) and continuation phase (from 12 weeks up to 36 weeks) ]
Response in symptoms of major depression defined as: 1. a reduction in QIDS-C16 of 50% or greater, or 2. as a separate measure of response, improvement in the Clinical Global Impressions (CGI) Improvement score (much improved or very much improved)
Onset or cessation of akathisia [ Time Frame: During acute phase (up to 12 weeks) and continuation phase (from 12 weeks up to 36 weeks) ]
Onset or cessation of akathisia, or change in symptom proclivity to as measured by the Barnes Akathisia Scale (Barnes 1989).
Onset or cessation of anxiety [ Time Frame: During acute phase (up to 12 weeks) and continuation phase (from 12 weeks up to 36 weeks) ]
Anxiety will be assessed by Beck Anxiety Inventory (BAI) (Beck, Epstein et al. 1988).
Onset or cessation of suicide ideation [ Time Frame: During acute phase (up to 12 weeks) and continuation phase (from 12 weeks up to 36 weeks) ]
Suicide ideation and behaviors will be assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS).
Change in Clinical Global Impression Scale [ Time Frame: During acute phase (up to 12 weeks) and continuation phase (from 12 weeks up to 36 weeks) ]
Clinical assessment of a participant's level of depression and treatment response assessed by the Clinical Global Impression - Severity (CGI -S) Scale, a 7-point clinician rating scale of the severity of depression and the Clinical Global Impression - Improvement (CGI -I) Scale, a 7-point clinician rating scale of improvement from baseline in severity of depression (Guy 1976).
Emergence of adverse experiences [ Time Frame: During acute phase (up to 12 weeks) and continuation phase (from 12 weeks up to 36 weeks) ]
Side effects, tolerability and discontinuation of medications will be assessed by the patient-rated Frequency and Intensity of Side Effects Rating/Global Rating of Side-Effect Burden (FIBSER) (Wisniewski, Rush et al. 2006) and by recording the occurrence of commonly reported side effects of antidepressant and atypical -psychotic medications, and the occurrence of serious or unexpected adverse experiences.
Cost and Cost-Effectiveness [ Time Frame: During acute phase (up to 12 weeks) and continuation phase (from 12 weeks up to 36 weeks) ]
Costs will be assessed by costs of care and health care utilization, and cost-effectiveness assessed by the ratio of costs to quality-adjusted life years.


Estimated Enrollment:	1518
Study Start Date:	December 2012
Estimated Study Completion Date:	April 2016
Primary Completion Date:	August 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm 1 Augmenting: Antidepressant + Aripiprazole	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.
Active Comparator: Arm 2 Augmenting: Antidepressant + Bupropion-SR	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.
Active Comparator: Arm 3 Switching: Bupropion-SR	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.

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Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

DSM-IV diagnosis of single or recurrent, non-psychotic, major depressive disorder
Currently taking a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) or mirtazapine for major depressive disorder
Need for "next-step" treatment based on documented suboptimal outcome from current antidepressant treatment for major depressive episode (at least 6 weeks treatment with a QIDS-C16 >= 16 or at least 8 weeks with a QIDS-C16 >= 11; and at least 3 weeks at a stable "optimal" dose
Age: 18 years of age or older

Exclusion Criteria:

Prior inadequate response after an adequate treatment trial or clear cut intolerance to either of the study medications (aripiprazole or bupropion)
Current treatment with bupropion, aripiprazole or any other antipsychotic agent
Lifetime history of bipolar disorder, schizophrenia, schizoaffective disorder, or psychosis not otherwise specified
Current diagnosis of Dementia
Current diagnosis of an eating disorder or a seizure disorder
High suicide risk currently requiring acute intervention (other than outpatient treatment of depression)
Unstable, serious medical condition or one requiring acute medical treatment, or anticipation of hospitalization for extended care
Requiring immediate hospitalization for psychiatric disorders
Physiologic substance dependence requiring detoxification (excluding nicotine) in the past 30 days (substance abuse is not an exclusion criteria)
Taking any concomitant medication that contraindicates any of treatment options or augmenting agents known to have an antidepressant effect
Concurrent or recent participation (within the last 30 days) in another conflicting clinical trial with a mental health, investigational drug, or medical device intervention
Female - pregnant or lactating or planning to become pregnant
Patient was not able or willing to provide informed consent; or changed mind about participating prior to randomization
Patient was not referred to the study

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01421342

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Sponsors and Collaborators

VA Office of Research and Development

Investigators


Study Chair:	Somaia Mohamed, PhD	VA Connecticut Healthcare System West Haven Campus, West Haven, CT
Study Chair:	Sidney Zisook, MD	VA San Diego Healthcare System, San Diego, CA

More Information

Publications:

Mohamed S, Johnson GR, Vertrees JE, Guarino PD, Weingart K, Young IT, Yoon J, Gleason TC, Kirkwood KA, Kilbourne AM, Gerrity M, Marder S, Biswas K, Hicks P, Davis LL, Chen P, Kelada A, Huang GD, Lawrence DD, LeGwin M, Zisook S. The VA augmentation and switching treatments for improving depression outcomes (VAST-D) study: Rationale and design considerations. Psychiatry Res. 2015 Oct 30;229(3):760-70. doi: 10.1016/j.psychres.2015.08.005. Epub 2015 Aug 6.


Responsible Party:	VA Office of Research and Development
ClinicalTrials.gov Identifier:	NCT01421342 History of Changes
Other Study ID Numbers:	576
Study First Received:	August 5, 2011
Last Updated:	April 19, 2016

Keywords provided by VA Office of Research and Development:


Mood Disorder Depression Depressive Disorder Depressive Disorder, Major Bupropion Aripiprazole Remission	Relapse Cost-Effectiveness Atypical Antipsychotic Antidepressant Augmentation Veterans Mental Health

Additional relevant MeSH terms:


Depression Depressive Disorder Depressive Disorder, Major Behavioral Symptoms Mood Disorders Mental Disorders Antidepressive Agents Bupropion Aripiprazole Psychotropic Drugs Antipsychotic Agents Tranquilizing Agents	Central Nervous System Depressants Physiological Effects of Drugs Antidepressive Agents, Second-Generation Dopamine Uptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Dopamine Agents Neurotransmitter Agents Cytochrome P-450 CYP2D6 Inhibitors Cytochrome P-450 Enzyme Inhibitors Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 17, 2017

VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D)