A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials
Luca Sforzini, Courtney Worrell, Melisa Kose, Ian Anderson, Bruno Aouizerate, Volker Arolt, Michael Bauer, Bernhard T. Baune, Pierre Blier, Anthony J. Cleare, Philip J. Cowen, Timothy G. Dinan, Andrea Fagiolini, I. Nicol Ferrier, Ulrich Hegerl, Andrew D. Krystal, Marion Leboyer, R. Hamish McAllister‐Williams, Roger S. McIntyre, Andreas Meyer‐Lindenberg, Andrew H. Miller, Charles B. Nemeroff, Claus Normann, David Nutt, Stefano Pallanti, Luca Pani, Brenda W.J.H. Penninx, Alan F. Schatzberg, Richard C. Shelton, Lakshmi N. Yatham, Allan H. Young, Roland Zahn, Georgios Aislaitner, Florence Butlen‐Ducuing, Christine Fletcher, Marion Haberkamp, Thomas Laughren, Fanni-Laura Mäntylä, Koen Schruers, Andrew Thomson, Gara Arteaga-Henríquez, Francesco Benedetti, Lucinda Cash‐Gibson, Woo Ri Chae, Heidi De Smedt, Stefan M. Gold, Witte J.G. Hoogendijk, Valeria Jordán Mondragón, Eduard Maron, Jadwiga Martynowicz, Elisa Melloni, Christian Otte, Gabriela Pérez-Fuentes, Sara Poletti, Mark E. Schmidt, Edwin van de Ketterij, Katherine Woo, Yanina Flossbach, Josep Antoni Ramos‐Quiroga, Adam Savitz, Carmine M. Pariante
Abstract
Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.