1. 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
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Trisha Suppes, Shabnam I. Thompson, William G. Anderson, Carlos J. Carrera, Muhammed Aslam, Sanjai D. Rao, Julia E. Vertrees, David Lawrence, Mitchell S. Finkel, Timothy M. Juergens, Sidney Zisook, James Wilcox, Joseph Westermeyer, Paul B. Hicks, John Kasckow, Gerardo Villarreal, Sriram Ramaswamy, Ilanit Tal, Clifford S. Nasdahl, Kari A. Jones, Gihyun Yoon, David Loreck, Steven Lieske, K. Ryan Connolly, Somaia Mohamed, James P. Michalets, Gauri Khatkhate, Nicholas Rosenlicht, Patricia Pilkinton, Mamta Sapra, Gary R. Johnson, Michael E Thase, Gunnar Larson, Lori L. Davis, Mary Klatt, Jean Yoon, Thomas P. Beresford, Cristobal A. Nogues, Grant D. Huang, Aimee R. Mayeda, Peijun Chen, Lawrence J. Albers, Julia L. Winston, John T. Little, Solomon S. Williams, Bernard A. Fischer, George Jurjus, Andre Tapp, Ronald Fernando, Beata Planeta, Joseph M. LaMotte, Theresa Gleason, Ali Iranmanesh, D. Cyril D’Souza, Keith D. Anderson, Alexander B. Niculescu, Ayman Fareed, Alexandra Scrymgeour, Sheetal Marri, Kimberly R. Weingart, and Robin A. Hurley
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.drug_class ,Aripiprazole ,Drug Resistance ,Atypical antipsychotic ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,health services administration ,Internal medicine ,mental disorders ,Medicine ,Humans ,Adverse effect ,Psychiatry ,Bupropion ,Original Investigation ,Veterans ,Depressive Disorder ,Depressive Disorder, Major ,Depression ,business.industry ,Drug Substitution ,Remission Induction ,Drug Synergism ,General Medicine ,Middle Aged ,medicine.disease ,Antidepressive Agents ,United States ,030227 psychiatry ,Relative risk ,behavior and behavior mechanisms ,Clinical Global Impression ,Major depressive disorder ,Drug Therapy, Combination ,Female ,business ,psychological phenomena and processes ,030217 neurology & neurosurgery ,medicine.drug ,Antipsychotic Agents - 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-C 16 ] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C 16 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
- Published
- 2017