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JAMA. 2017 Jul 11;318(2):132-145. doi: 10.1001/jama.2017.8036.

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

Author information

1
Veterans Affairs (VA) New England Mental Illness Research, Education, and Clinical Center, VA Connecticut Healthcare System, West Haven2Yale University School of Medicine, West Haven, Connecticut.
2
Cooperative Studies Program Coordinating Center, VA Connecticut Healthcare System, West Haven.
3
Louis Stokes VA Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio.
4
Central Texas Veterans Healthcare System and Department of Psychiatry and Behavioral Science, Texas A&M Health Science Center College of Medicine, Temple6Central Texas Veterans Healthcare System, Temple.
5
Tuscaloosa VA Medical Center, Tuscaloosa, Alabama8University of Alabama School of Medicine, Birmingham.
6
Health Economics Resource Center, VA Palo Alto, Menlo Park, California.
7
Department of Veterans Affairs, Office of Research and Development, Washington, DC.
8
Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, New Mexico.
9
VA San Diego Healthcare System, San Diego, California13University of California, San Diego.
10
VA San Diego Healthcare System, San Diego, California.
11
Philadelphia VA Medical Center, Philadelphia, Pennsylvania.
12
Cooperative Studies Program Central Office, Department of Veterans Affairs Office of Research and Development, Washington, DC.
13
Tuscaloosa VA Medical Center, Tuscaloosa, Alabama.
14
Southern Arizona VA Healthcare System, Tucson.
15
Salem VA Medical Center, Salem, Virginia.
16
Charles George VA Medical Center, Asheville, North Carolina.
17
Cincinnati VA Medical Center, Cincinnati, Ohio.
18
VA Eastern Colorado Healthcare System, Denver.
19
Kansas City VA Medical Center, Kansas City, Missouri.
20
VA Loma Linda Healthcare System, Loma Linda, California.
21
VA Nebraska Western Iowa Healthcare System, Omaha.
22
VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.
23
Minneapolis VA Health Care System, Minneapolis, Minnesota.
24
Veterans Affairs (VA) New England Mental Illness Research, Education, and Clinical Center, VA Connecticut Healthcare System, West Haven.
25
Clement J. Zablocki VA Medical Center, Milwaukee, Wisconsin.
26
Atlanta VA Medical Center, Atlanta, Georgia.
27
Phoenix VA Health Care System, Phoenix, Arizona.
28
Central Texas Veterans Healthcare System, Temple.
29
William S. Middleton Veterans Hospital, Madison, Wisconsin.
30
Long Beach VA Healthcare System, Long Beach, California.
31
Memphis VA Medical Center, Memphis, Tennessee.
32
New Mexico VA Healthcare System, Albuquerque.
33
James A Haley VA Hospital, Tampa, Florida.
34
Bruce W. Carter VA Medical Center, Miami, Florida.
35
VA Puget Sound Health Care System, American Lake/Tacoma, Washington.
36
Edward Hines Jr VA Hospital, Hines, Illinois.
37
VA Palo Alto Healthcare System, Palo Alto, California.
38
W.G. Hefner VA Medical Center, Salisbury, North Carolina.
39
Richard L Roudebush VA Medical Center, Indianapolis, Indiana.
40
VA Maryland Healthcare System, Baltimore.
41
San Francisco VA Health Care System, San Francisco, California.
42
Louis A. Johnson VA Medical Center, Clarksburg, West Virginia.
43
Washington DC VA Medical Center.

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.

Trial Registration:

clinicaltrials.gov Identifier: NCT01421342.

PMID:
28697253
PMCID:
PMC5817471
DOI:
10.1001/jama.2017.8036
[Indexed for MEDLINE]
Free PMC Article

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