A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials
Open accessAbstract
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.
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Limitations of the MGH-S include the lack of operationalization of 'failure' of trials; the arbitrary scores attributed to treatments; the fact that optimization of dose or duration of treatment is weighted equally as augmentation/combination strategies (which is not empirically supported); and the assignment of one point for each failed antidepressant, which may generate a very high total score.
“Limitations of the MGH- S include the lack of operationalization of 'failure' of trials; the arbitrary scores attributed to treatments; the fact that optimization of dose or dura tion of treatment is weighted equally as aug men tation/combination strategies (which is not empirically supported); and the assignment of one point for each failed antidepressant, which may generate a very high total”
From Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions (2023) · cites this paper as [63]
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References 74 · Cited by 214
Research works printed but not linked: 3
- [39]Trivedi MH Rush AJ Wisniewski SR Nierenberg AA Warden D Ritz L Evaluation of Outcomes With Citalopram for Depression Using Measurement-Based Care in STAR*D Implic Clin Pract 2006 163 28 40 16390886
- [40]McIntyre RS Rosenblat JD Nemeroff CB Sanacora G Murrough JW Berk M Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: Int Expert Opin Available Evid Implement 2021 178 383 99 PMC9635017 33726522
- [72]Montgomery SA Asberg M A new depression scale designed to be sensitive to change Br J Psychiatry 1979 134 382 9 10.1192/bjp.134.4.382 444788 · DOI · Paper page
- Authors
- Sforzini, L., Worrell, C., Kose, M., Anderson, I. M., Aouizerate, B., Arolt, V., Bauer, M., Baune, B. T., Blier, P., Cleare, A. J., Cowen, P. J., Dinan, T. G., Fagiolini, A., Ferrier, I. N., Hegerl, U., Krystal, A. D., Leboyer, M., McAllister-Williams, R. H., McIntyre, R. S., Meyer-Lindenberg, A., Miller, A. H., Nemeroff, C. B., Normann, C., Nutt, D., Pallanti, S., Pani, L., Penninx, B. W. J. H., Schatzberg, A. F., Shelton, R. C., Yatham, L. N., Young, A. H., Zahn, R., Aislaitner, G., Butlen-Ducuing, F., Fletcher, C., Haberkamp, M., Laughren, T., Mäntylä, F.-L., Schruers, K., Thomson, A., Arteaga-Henríquez, G., Benedetti, F., Cash-Gibson, L., Chae, W. R., De Smedt, H., Gold, S. M., Hoogendijk, W. J. G., Mondragón, V. J., Maron, E., Martynowicz, J., Melloni, E., Otte, C., Perez-Fuentes, G., Poletti, S., Schmidt, M. E., van de Ketterij, E., Woo, K., Flossbach, Y., Ramos-Quiroga, J. A., Savitz, A. J., & Pariante, C. M.
- Affiliations
- King's College London (GB)
- Manchester Academic Health Science Centre (GB)
- Université de Bordeaux (FR)
- University of Münster (DE)
- University Hospital Carl Gustav Carus (DE)
- The University of Melbourne (AU)
- University of Ottawa (CA)
- National Health Service (GB)
- University of Oxford (GB)
- University College Cork (IE)
- University of Siena (IT)
- Newcastle University (GB)
- Goethe University Frankfurt (DE)
- Duke University (US)
- Inserm (FR)
- University Health Network (CA)
- Emory University (US)
- The University of Texas at Austin (US)
- University of Freiburg (DE)
- Imperial College London (GB)
- Albert Einstein College of Medicine (US)
- University of Modena and Reggio Emilia (IT)
- Amsterdam University Medical Centers (NL)
- Stanford Medicine (US)
- University of Alabama at Birmingham (US)
- University of British Columbia (CA)
- Federal Institute for Drugs and Medical Devices (DE)
- GlaxoSmithKline (United Kingdom) (GB)
- Global Alliance of Mental Illness Advocacy Networks-Europe (BE)
- Maastricht University Medical Centre (NL)
- European Medicines Agency (NL)
- Universitat Autònoma de Barcelona (ES)
- Vita-Salute San Raffaele University (IT)
- Charité – Universitätsmedizin Berlin (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Erasmus MC (NL)
- Novartis (Switzerland) (CH)
- Janssen Research & Development (United States) (US)
- IRCCS Ospedale San Raffaele (IT)
- Janssen (Belgium) (BE)
- Corresponding author
- Sforzini, Luca
- ORCID
- Sforzini, Luca
- Worrell, Courtney
- Kose, Melisa
- Anderson, Ian M.
- Aouizerate, Bruno
- Arolt, Volker
- Bauer, Michael
- Baune, Bernhard T.
- Blier, Pierre
- Cleare, Anthony J.
- Cowen, Philip J.
- Dinan, Timothy G.
- Fagiolini, Andrea
- Ferrier, I. Nicol
- Hegerl, Ulrich
- Krystal, Andrew D.
- Leboyer, Marion
- McIntyre, Roger S.
- Miller, Andrew H.
- Nemeroff, Charles B.
- Normann, Claus
- Nutt, David
- Pallanti, Stefano
- Pani, Luca
- Penninx, Brenda W. J. H.
- Schatzberg, Alan F.
- Shelton, Richard C.
- Yatham, Lakshmi N.
- Young, Allan H.
- Zahn, Roland
- Aislaitner, Georgios
- Haberkamp, Marion
- Mäntylä, Fanni-Laura
- Schruers, Koen
- Thomson, Andrew
- Arteaga-Henríquez, Gara
- Benedetti, Francesco
- Chae, Woo Ri
- Gold, Stefan M.
- Hoogendijk, Witte J. G.
- Maron, Eduard
- Melloni, Elisa
- Otte, Christian
- Poletti, Sara
- Schmidt, Mark E.
- van de Ketterij, Edwin
- Ramos-Quiroga, J. Antoni
- Savitz, Adam J.
- Pariante, Carmine M.
- Venue
- Molecular Psychiatry
- Published
- 2021-12-15
- Volume
- 27
- Issue
- 3
- Pages
- 1286-1299
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC9095475
- OpenAlex
- W4200627112
- Cited by
- 214
- References
- 74
- Citations by year
- 2026: 42 · 2025: 47 · 2024: 52 · 2023: 48 · 2022: 25
- FWCI
- 18.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Molecular Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by)
- Pure Amsterdam UMC (acceptedVersion, cc-by)
- Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Lirias (submittedVersion, cc-by)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- HAL (submittedVersion, cc-by)
- Research Publications (Maastricht University) (submittedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion, cc-by)
- UWA Profiles and Research Repository (UWA) (submittedVersion, cc-by)
- Use Siena air (University of Siena) (submittedVersion, cc-by)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- Innovative Medicines Initiative (853966)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Sociology and Political Science › Delphi Technique in Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- treatment-resistant depression, major depressive disorder, diagnostic criteria, clinical trial design, regulatory guidelines, platform trials, depression classification, unmet needs
- MeSH terms
- Adaptive Clinical Trials as Topic, Depression, Major Depressive Disorder, Humans, Depressive Disorder, Treatment-Resistant
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