Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment

The VAST-D Randomized Clinical Trial

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Importance Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. Objective To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. Design, Setting, and Participants From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. Interventions Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). Main Outcomes and Measures The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. Results Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain. Conclusions and Relevance Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach.

Original languageEnglish (US)
Pages (from-to)132-145
Number of pages14
JournalJAMA - Journal of the American Medical Association
Volume318
Issue number2
DOIs
StatePublished - Jul 11 2017

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Major Depressive Disorder
Bupropion
Antidepressive Agents
Therapeutics
Veterans Health
Aripiprazole
Recurrence
Psychomotor Agitation
United States Department of Veterans Affairs
Antipsychotic Agents
Weight Gain
Cost-Benefit Analysis
Anxiety
Outcome Assessment (Health Care)
Safety
Equipment and Supplies

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment. / The VAST-D Randomized Clinical Trial.

In: JAMA - Journal of the American Medical Association, Vol. 318, No. 2, 11.07.2017, p. 132-145.

Research output: Contribution to journalArticle

@article{b8ce669bb1274c42b905a6d633c42d6c,
title = "Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment",
abstract = "Importance Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. Objective To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. Design, Setting, and Participants From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. Interventions Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). Main Outcomes and Measures The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50{\%} reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. Results Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2{\%}]), 1137 (74.7{\%}) completed the acute treatment phase. Remission rates at 12 weeks were 22.3{\%} (n = 114) for the switch group, 26.9{\%} (n = 136)for the augment-bupropion group, and 28.9{\%} (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95{\%} CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3{\%}) than for either the switch group (62.4{\%}; RR, 1.19 [95{\%} CI, 1.09-1.29]) or the augment-bupropion group (65.6{\%}; RR, 1.13 [95{\%} CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3{\%} in the switch group [n = 124] vs 16.6{\%} in the augment-aripiprazole group [n = 84]; and 22.5{\%} in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain. Conclusions and Relevance Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach.",
author = "{The VAST-D Randomized Clinical Trial} and Somaia Mohamed and Johnson, {Gary R.} and Peijun Chen and Hicks, {Paul B.} and Davis, {Lori L.} and Jean Yoon and Gleason, {Theresa C.} and Vertrees, {Julia E.} and Kimberly Weingart and Ilanit Tal and Alexandra Scrymgeour and Lawrence, {David D.} and Beata Planeta and Thase, {Michael E.} and Huang, {Grant D.} and Sidney Zisook and Pilkinton, {Patricia D.} and Wilcox, {James A.} and {Ali Iranmanesh}, {A. I.} and Mamta Sapra and George Jurjus and Michalets, {James P.} and Muhammed Aslam and Thomas Beresford and Anderson, {Keith D.} and Ronald Fernando and Sriram Ramaswamy and John Kasckow and Joseph Westermeyer and Gihyun Yoon and {Cyril D’Souza}, D. and Gunnar Larson and Anderson, {William G.} and Mary Klatt and Ayman Fareed and Thompson, {Shabnam I.} and Carrera, {Carlos J.} and Williams, {Solomon S.} and Juergens, {Timothy M.} and Albers, {Lawrence J.} and Nasdahl, {Clifford S.} and Gerardo Villarreal and Winston, {Julia L.} and Nogues, {Cristobal A.} and {Ryan Connolly}, K. and Andre Tapp and Jones, {Kari A.} and Gauri Khatkhate and Sheetal Marri and Trisha Suppes",
year = "2017",
month = "7",
day = "11",
doi = "10.1001/jama.2017.8036",
language = "English (US)",
volume = "318",
pages = "132--145",
journal = "JAMA - Journal of the American Medical Association",
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TY - JOUR

T1 - Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment

AU - The VAST-D Randomized Clinical Trial

AU - Mohamed, Somaia

AU - Johnson, Gary R.

AU - Chen, Peijun

AU - Hicks, Paul B.

AU - Davis, Lori L.

AU - Yoon, Jean

AU - Gleason, Theresa C.

AU - Vertrees, Julia E.

AU - Weingart, Kimberly

AU - Tal, Ilanit

AU - Scrymgeour, Alexandra

AU - Lawrence, David D.

AU - Planeta, Beata

AU - Thase, Michael E.

AU - Huang, Grant D.

AU - Zisook, Sidney

AU - Pilkinton, Patricia D.

AU - Wilcox, James A.

AU - Ali Iranmanesh, A. I.

AU - Sapra, Mamta

AU - Jurjus, George

AU - Michalets, James P.

AU - Aslam, Muhammed

AU - Beresford, Thomas

AU - Anderson, Keith D.

AU - Fernando, Ronald

AU - Ramaswamy, Sriram

AU - Kasckow, John

AU - Westermeyer, Joseph

AU - Yoon, Gihyun

AU - Cyril D’Souza, D.

AU - Larson, Gunnar

AU - Anderson, William G.

AU - Klatt, Mary

AU - Fareed, Ayman

AU - Thompson, Shabnam I.

AU - Carrera, Carlos J.

AU - Williams, Solomon S.

AU - Juergens, Timothy M.

AU - Albers, Lawrence J.

AU - Nasdahl, Clifford S.

AU - Villarreal, Gerardo

AU - Winston, Julia L.

AU - Nogues, Cristobal A.

AU - Ryan Connolly, K.

AU - Tapp, Andre

AU - Jones, Kari A.

AU - Khatkhate, Gauri

AU - Marri, Sheetal

AU - Suppes, Trisha

PY - 2017/7/11

Y1 - 2017/7/11

N2 - Importance Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. Objective To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. Design, Setting, and Participants From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. Interventions Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). Main Outcomes and Measures The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. Results Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain. Conclusions and Relevance Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach.

AB - Importance Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. Objective To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. Design, Setting, and Participants From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. Interventions Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). Main Outcomes and Measures The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. Results Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain. Conclusions and Relevance Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach.

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