The European physical journal. C, Particles and fields
Authors: Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, Brandstetter J, Brondolin E, Dragicevic M, Erö J, Flechl M, Friedl M, Frühwirth R, Ghete VM, Hartl C, Hörmann N, Hrubec J, Jeitler M, König A, Krätschmer I, Liko D, Matsushita T, Mikulec I, Rabady D, Rad N, Rahbaran B, Rohringer H, Schieck J, Strauss J, Waltenberger W, Wulz CE, Dvornikov O, Makarenko V, Mossolov V, Suarez Gonzalez J, Zykunov V, Shumeiko N, Alderweireldt S, De Wolf EA, Janssen X, Lauwers J, Van De Klundert M, Van Haevermaet H, Van Mechelen P, Van Remortel N, Van Spilbeeck A, Abu Zeid S, Blekman F, D'Hondt J, Daci N, De Bruyn I, Deroover K, Lowette S, Moortgat S, Moreels L, Olbrechts A, Python Q, Skovpen K, Tavernier S, Van Doninck W, Van Mulders P, Van Parijs I, Brun H, Clerbaux B, De Lentdecker G, Delannoy H, Fasanella G, Favart L, Goldouzian R, Grebenyuk A, Karapostoli G, Lenzi T, Léonard A, Luetic J, Maerschalk T, Marinov A, Randle-Conde A, Seva T, Vander Velde C, Vanlaer P, Vannerom D, Yonamine R, Zenoni F, Zhang F, Cornelis T, Dobur D, Fagot A, Gul M, Khvastunov I, Poyraz D, Salva S, Schöfbeck R, Tytgat M, Van Driessche W, Yazgan E, Zaganidis N, Bakhshiansohi H, Bondu O, Brochet S, Bruno G, Caudron A, De Visscher S, Delaere C, Delcourt M, Francois B, Giammanco A, Jafari A, Komm M, Krintiras G, Lemaitre V, Magitteri A, Mertens A, Musich M, Piotrzkowski K, Quertenmont L, Selvaggi M, Vidal Marono M, Wertz S, Beliy N, Aldá Júnior WL, Alves FL, Alves GA, Brito L, Hensel C, Moraes A, Pol ME, Rebello Teles P, Chagas EBBD, Carvalho W, Chinellato J, Custódio A, Da Costa EM, Da Silveira GG, De Jesus Damiao D, De Oliveira Martins C, De Souza SF, Guativa LMH, Malbouisson H, Matos Figueiredo D, Mora Herrera C, Mundim L, Nogima H, Prado Da Silva WL, Santoro A, Sznajder A, Tonelli Manganote EJ, Torres Da Silva De Araujo F, Vilela Pereira A, Ahuja S, Bernardes CA, Dogra S, Fernandez Perez Tomei TR, Gregores EM, Mercadante PG, Moon CS, Novaes SF, Padula SS, Romero Abad D, Ruiz Vargas JC, Aleksandrov A, Hadjiiska R, Iaydjiev P, Rodozov M, Stoykova S, Sultanov G, Vutova M, Dimitrov A, Glushkov I, Litov L, Pavlov B, Petkov P, Fang W, Ahmad M, Bian JG, Chen GM, Chen HS, Chen M, Chen Y, Cheng T, Jiang CH, Leggat D, Liu Z, Romeo F, Ruan M, Shaheen SM, Spiezia A, Tao J, Wang C, Wang Z, Zhang H, Zhao J, Ban Y, Chen G, Li Q, Liu S, Mao Y, Qian SJ, Wang D, Xu Z, Avila C, Cabrera A, Chaparro Sierra LF, Florez C, Gomez JP, González Hernández CF, Ruiz Alvarez JD, Sanabria JC, Godinovic N, Lelas D, Puljak I, Ribeiro Cipriano PM, Sculac T, Antunovic Z, Kovac M, Brigljevic V, Ferencek D, Kadija K, Mesic B, Susa T, Ather MW, Attikis A, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis PA, Rykaczewski H, Finger M, Finger M, Carrera Jarrin E, Ellithi Kamel A, Mahmoud MA, Radi A, Kadastik M, Perrini L, Raidal M, Tiko A, Veelken C, Eerola P, Pekkanen J, Voutilainen M, Härkönen J, Järvinen T, Karimäki V, Kinnunen R, Lampén T, Lassila-Perini K, Lehti S, Lindén T, Luukka P, Tuominiemi J, Tuovinen E, Wendland L, Talvitie J, Tuuva T, Besancon M, Couderc F, Dejardin M, Denegri D, Fabbro B, Faure JL, Favaro C, Ferri F, Ganjour S, Ghosh S, Givernaud A, Gras P, Hamel de Monchenault G, Jarry P, Kucher I, Locci E, Machet M, Malcles J, Rander J, Rosowsky A, Titov M, Abdulsalam A, Antropov I, Baffioni S, Beaudette F, Busson P, Cadamuro L, Chapon E, Charlot C, Davignon O, Granier de Cassagnac R, Jo M, Lisniak S, Miné P, Nguyen M, Ochando C, Ortona G, Paganini P, Pigard P, Regnard S, Salerno R, Sirois Y, Stahl Leiton AG, Strebler T, Yilmaz Y, Zabi A, Zghiche A, Agram JL, Andrea J, Bloch D, Brom JM, Buttignol M, Chabert EC, Chanon N, Collard C, Conte E, Coubez X, Fontaine JC, Gelé D, Goerlach U, Bihan AL, Van Hove P, Gadrat S, Beauceron S, Bernet C, Boudoul G, Carrillo Montoya CA, Chierici R, Contardo D, Courbon B, Depasse P, El Mamouni H, Fay J, Finco L, Gascon S, Gouzevitch M, Grenier G, Ille B, Lagarde F, Laktineh IB, Lethuillier M, Mirabito L, Pequegnot AL, Perries S, Popov A, et al
Volume 318 of Issue 2 | JAMA
Authors: 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, Fischer BA, Loreck DJ, Rosenlicht N, Lieske S, Finkel MS, Little JT
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.
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