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VA Cooperative Studies Program (CSP)

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CSP #576: VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D)


Investigator Access

What's Available


Check with the study contact and publications for information on a public dataset, data archive, data enclave, or website where data might be available.

Available Documentation

Dates Data are Available

Access Criteria

Study Characteristics


To determine the relative effectiveness and safety of 3 common alternate treatments for major depressive disorder.

Era of Service



Patients within the VA health care system (85.2% men) diagnosed with major depressive disorder.

Study Design

Multisite randomized, single-blind, parallel-assignment clinical trial


  • Switch to a different antidepressant, bupropion (switch group)
  • Augment current treatment with bupropion (augment-bupropion group)
  • Augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group)

Time Period

December 2012 – May 2015




1,522 participants

Response Rate

7,234 VHA patients were screened, 1,861 (25.7%) patients consented to participate and, of these, 1,522 (81.8%) were randomized.

Recruitment Method

  • Patients who were diagnosed with nonpsychotic major depressive disorder
  • Unresponsive to at least 1 antidepressant course
  • Met minimal standards for treatment dose and duration were recruited from 35 VA medical centers



Data Collected

Primary outcome

  • Remission of symptoms of major depression during the acute treatment phase 

Secondary outcomes

  • Relapse in symptoms of major depression
  • Response measured as reduction in symptom score for major depression
  • Clinical assessment of a participant's level of depression and treatment response assessed by the Clinical Global Impression - Improvement (CGI -I) Scale

Additional outcomes

  • Suicidal ideation and behaviors
  • Anxiety
  • Quality of life
  • Health-related costs and cost-effectiveness
  • Medication adherence and satisfaction

Data Collection Methods

  • Physician and participant interview and self-report questionnaires
  • Vital sign and laboratory reports
  • Medical record review

Funding Sources

  • VA Cooperative Studies Program (CSP)
  • Bristol-Myers Squibb


Principal Investigator: Somaia Mohamed, PhD
Study Chairs: Somaia Mohamed, PhD and Sidney Zisook, MD


Elizabeth Jobes,

Selected Publications

Zisook S, Tal I, Weingart K, Hicks P, Davis LL, Chen P, Yoon J, Johnson GR, Vertrees JE, Rao S, Pilkinton PD, Wilcox JA, Sapra M, Iranmanesh A, Huang GD, Mohamed S. Characteristics of U.S. Veteran Patients with Major Depressive Disorder who require "next-step" treatments: A VAST-D report. J Affect Disord. 2016 Dec;206:232-240.

Mohamed S, Johnson GR, Chen P, Hicks PB, Davis LL, Yoon J, Gleason TC, Vertrees JE, Weingart K, Tal I, Scrymgeour A, Lawrence DD, Planeta B, Thase ME, Huang GD, Zisook S; and the VAST-D Investigators, Rao SD, Pilkinton PD, Wilcox JA, Iranmanesh A, Sapra M, Jurjus G, Michalets JP, Aslam M, Beresford T, Anderson KD, Fernando R, Ramaswamy S, Kasckow J, Westermeyer J, Yoon G, D'Souza DC, Larson G, Anderson WG, Klatt M, Fareed A, Thompson SI, Carrera CJ, Williams SS, Juergens TM, Albers LJ, Nasdahl CS, Villarreal G, Winston JL, Nogues CA, Connolly KR, Tapp A, Jones KA, Khatkhate G, Marri S, Suppes T, LaMotte J, Hurley R, Mayeda AR, Niculescu AB 3rd, Fischer BA, Loreck DJ, Rosenlicht N, Lieske S, Finkel MS, Little JT. Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial. JAMA. 2017 Jul 11;318(2):132-145.

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.

More Information

Study site Identifier: NCT01421342