Mohamed, Somaia; Johnson, Gary R.; Chen, Peijun; Hicks, Paul B.; Davis, Lori L.; Yoon, Jean; Gleason, Theresa C.; Vertrees, Julia E.; Weingart, Kimberly; Tal, Ilanit; Scrymgeour, Alexandra; Lawrence, David D.; Planeta, Beata; Thase, Michael E.; Huang, Grant D.; Zisook, Sidney; and the VAST-D Investigators; Rao, Sanjai D.; Pilkinton, Patricia D.; Wilcox, James A.; Iranmanesh, Ali; Sapra, Mamta; Jurjus, George; Michalets, James P.; Aslam, Muhammed; Beresford, Thomas; Anderson, Keith D.; Fernando, Ronald; Ramaswamy, Sriram; Kasckow, John; Westermeyer, Joseph; Yoon, Gihyun; D’Souza, D. Cyril; Larson, Gunnar; Anderson, William G.; Klatt, Mary; Fareed, Ayman; Thompson, Shabnam I.; Carrera, Carlos J.; Williams, Solomon S.; Juergens, Timothy M.; Albers, Lawrence J.; Nasdahl, Clifford S.; Villarreal, Gerardo; Winston, Julia L.; Nogues, Cristobal A.; Connolly, K. Ryan; Tapp, Andre; Jones, Kari A.; Khatkhate, Gauri; Marri, Sheetal; Suppes, Trisha; LaMotte, Joseph; Hurley, Robin; Mayeda, Aimee R.; Niculescu, Alexander B.; Fischer, Bernard A.; Loreck, David J.; Rosenlicht, Nicholas; Lieske, Steven; Finkel, Mitchell S.; Little, John T.
OBJECTIVE To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. Editorial page 126 Supplemental content CME Quiz at jamanetwork.com/learning 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 Յ5 at 2 consecutive visits). Secondary outcomes included response (Ն50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. RESULTS Among1522randomizedpatients(meanage,54.4years;men,1296[85.2%]),1137(74.7%) completedtheacutetreatmentphase.Remissionratesat12weekswere22.3%(n = 114)fortheswitch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augmentaripiprazole 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 augmentaripiprazolegroup[n = 84];and22.5%inaugment-bupropiongroup[n = 114]).Adverseeffectsmore 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.
