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.

Timeline

Start

2012-12

Primary completion

2015-08

Completion

2016-06

Publications

• Background 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.
• Results 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. doi: 10.1016/j.jad.2016.07.023. Epub 2016 Jul 26.
• Results 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. doi: 10.1001/jama.2017.8036.
• Zisook S, Johnson GR, Planeta B, Mohamed S. How Does Positive Mental Health Affect Next-Step Treatment Outcomes in Treatment-Resistant Depression? A VAST-D Report. J Clin Psychopharmacol. 2025 Sep-Oct 01;45(5):421-431. doi: 10.1097/JCP.0000000000002051. Epub 2025 Jul 31.
• Zisook S, Planeta B, Hicks PB, Chen P, Davis LL, Villarreal G, Sapra M, Johnson GR, Mohamed S. Childhood adversity and adulthood major depressive disorder. Gen Hosp Psychiatry. 2022 May-Jun;76:36-44. doi: 10.1016/j.genhosppsych.2022.03.008. Epub 2022 Mar 24.
• Zisook S, Johnson GR, Hicks P, Chen P, Beresford T, Michalets JP, Rao S, Thase ME, Wilcox J, Sevilimedu V, Mohamed S. Continuation phase treatment outcomes for switching, combining, or augmenting strategies for treatment-resistant major depressive disorder: A VAST-D report. Depress Anxiety. 2021 Feb;38(2):185-195. doi: 10.1002/da.23114. Epub 2020 Nov 22.
• Mohamed S, Johnson GR, Sevilimedu V, Rao SD, Hicks PB, Chen P, Lauro K, Jurjus G, Pilkinton P, Davis L, Wilcox JA, Iranmanesh A, Sapra M, Aslam M, Michalets J, Thase M, Zisook S; CSP#576 VAST-D Investigators. Impact of Concurrent Posttraumatic Stress Disorder on Outcomes of Antipsychotic Augmentation for Major Depressive Disorder With a Prior Failed Treatment: VAST-D Randomized Clinical Trial. J Clin Psychiatry. 2020 Jun 23;81(4):19m13038. doi: 10.4088/JCP.19m13038.
• Zisook S, Johnson GR, Tal I, Hicks P, Chen P, Davis L, Thase M, Zhao Y, Vertrees J, Mohamed S. General Predictors and Moderators of Depression Remission: A VAST-D Report. Am J Psychiatry. 2019 May 1;176(5):348-357. doi: 10.1176/appi.ajp.2018.18091079. Epub 2019 Apr 5.
• Yoon J, Zisook S, Park A, Johnson GR, Scrymgeour A, Mohamed S. Comparing Cost-Effectiveness of Aripiprazole Augmentation With Other "Next-Step" Depression Treatment Strategies: A Randomized Clinical Trial. J Clin Psychiatry. 2018 Dec 18;80(1):18m12294. doi: 10.4088/JCP.18m12294.

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