Andrea Cipriani, Karen Barros Parron Fernandes, Benoit H. Mulsant, Orestis Efthimiou, Nicola Williams, Sam Mort, Rania Elgarf, Qiang Liu, Nyla Haque, J. Manning Potts, Roger Ede, Robin Lane Fox, Marcos Liboni, Diego A. Nesi Cavicchioli, Judit Simon, Katharine Smith, Caroline Zangani, Zhenpeng Li, Ursula Taylor, M. Ishrat Husain, Maddalena Cipriani, Paulo V. Carpaneze Dalaqua, Eduardo Fernandes Leite, Gustavo Aliano Gâmbaro, Diogo Nabhan Silveira, Luísa Manfredin Vila, Fernanda Liboni Cavicchioli, Toshi A. Furukawa, Huseyin Naci, Edoardo G. Ostinelli, PETRUSHKA Team, Arradea Triesty Adinda, Nadeem Ahmed, Rosario Aronica, Eduarda Batista, Jithen Benjamin, Ian Binnian, Ruth Carson, Helen Collins, Johanna Cook, Rachel Delahay, Franco De Crescenzo, Lazarina Engonidou, Simon Gilbody, James S. W. Hong, Owen Hughes, Matt Jaquiery, Benjamin Johnston, Gemma Lewis, Andrea Paggi, Nicola Rizzopesci, Pippa Sealy, Neetul Shah, Rachel Shaw, Ilina Singh, Katherine Stevens, Jaimini Tanna, Anneka Tomlinson, Laurence Wainwright, Nick Wooding, Ly-Mee Yu, Stefan Kloiber, Daniel Mueller, Helena K. Kim, Brett D. M. Jones, Abigail Ortiz, Daniel Blumberger, Georgia Salanti, Stéphanie P. Araújo, Paulo R. Bignardi, Bruna G. Camargo, Andréa N. Colado Simões, João Pedro de Vasconcelos, Bianca B. P. Fernandes, Isadora L. Gobbi, Rafael S. A. Haber, Renato C. Jacovetti, Augusto Borges Liboni, Caio C. S. Martins, Amanda P. Oliveira, Giulia G. A. Ramos, Carolina B. N. Rodrigues, Raul H. M. Santos, Letícia F. R. Silva, Gabriela G. Tassi, Vitor F. Tomazini
Importance: Antidepressants for moderate to severe major depressive disorder may be discontinued prematurely because the prescribed antidepressant is not always the most appropriate medication for an individual. Guidelines have recommended more precise targeting of antidepressant treatment. Objective: To evaluate the efficacy of a web-based tool to personalize antidepressant treatment. Design, Setting, and Participants: This multicenter, randomized clinical trial included persons between the ages of 18 and 74 years with major depressive disorder. The trial was conducted at 47 sites in 3 countries (Brazil, Canada, and the UK). The first participant was screened on November 29, 2022, and the last follow-up visit occurred on January 15, 2025. Intervention: A total of 540 participants were randomized (1:1) to an evidence-based clinical decision-support system (PETRUSHKA tool; n = 271) or usual care (n = 269). Main Outcomes and Measures: The primary outcome was treatment discontinuation due to any cause at 8 weeks. The secondary outcomes included treatment discontinuation up to 24 weeks due to adverse events and changes in depressive symptoms (measured with the 9-item Patient Health Questionnaire [PHQ-9]; range, 0-27; higher scores indicate more severe depression) and anxiety symptoms (measured with the 7-item Generalized Anxiety Disorder [GAD-7] questionnaire; range, 0-21; higher scores indicate more severe symptoms). Results: Of the 520 eligible participants, 493 were included in the primary analysis (median age, 35 [IQR, 25 to 48] years; 58% female; PHQ-9 mean score, 16.6 [SD, 5.1]; GAD-7 mean score, 11.5 [SD, 4.1]). At 8 weeks, 41 of 241 participants (17%) in the PETRUSHKA group discontinued the prescribed antidepressant due to any cause vs 69 of 252 (27%) in the usual care group (adjusted relative risk, 0.62 [95% CI, 0.44 to 0.88]; P = .007). At 8 weeks, 22 of 241 participants (9%) in the PETRUSHKA group discontinued the prescribed antidepressant due to adverse events vs 39 of 252 (16%) in the usual care group (adjusted relative risk, 0.59 [95% CI, 0.36 to 0.97]; P = .04). For the assessment of depressive symptoms at 24 weeks, the mean PHQ-9 score was 7.1 (SD, 5.4) in the PETRUSHKA group vs 9.2 (SD, 6.5) in the usual care group (n = 129 in each group; adjusted between-group mean difference, -1.92 [95% CI, -3.06 to -0.78]; P < .001). For the assessment of anxiety symptoms at 24 weeks, the mean GAD-7 score was 4.6 (SD, 4.1) in the PETRUSHKA group (n = 133) vs 5.8 (SD, 4.9) in the usual care group (n = 126) (adjusted between-group mean difference, -1.39 [95% CI, -2.26 to -0.52]; P = .002). Conclusions and Relevance: Compared with usual care, use of the PETRUSHKA tool increased the number of patients still taking their antidepressant at 8 weeks and improved depressive and anxiety symptoms at 24 weeks. However, lack of a double-blind design and the large amount of missing data limit the validity of these results. Trial Registration: ClinicalTrials.gov Identifier: NCT05608330.