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Relapse in schizophrenia: a systematic review of criteria for clinical studies and international consensus guidelines to improve them : reviews and overviews

Objective: - Relapse prevention is a major goal of schizophrenia treatment. However, there is no standard definition of relapse. To address this, the authors reviewed recent approaches and developed consensus criteria to operationally define relapse. - Methods: - To evaluate current criteria, a syst...

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Main Authors: Howes, Oliver D. (Author) , Bukala, Bernard R. (Author) , Chen, Eric Y.H. (Author) , Correll, Christoph U. (Author) , Hasan, Alkomiet (Author) , Honer, William G. (Author) , Kane, John M. (Author) , Leucht, Stefan (Author) , Siafis, Spyridon (Author) , Agid, Ofer (Author) , Akena, Dickens (Author) , Arango, Celso (Author) , Atwoli, Lukoye (Author) , Barnes, Thomas R.E. (Author) , Birnbaum, Michael L. (Author) , Bitter, Istvan (Author) , Breier, Alan (Author) , Buchanan, Robert W. (Author) , Citrome, Leslie (Author) , Cotter, David R. (Author) , Crossley, Nicolas (Author) , Davidson, Michael (Author) , de Bartolomeis, Andrea (Author) , DeLisi, Lynn E. (Author) , Dollfus, Sonia (Author) , Dursun, Serdar M. (Author) , Ebdrup, Bjørn H. (Author) , Elkis, Helio (Author) , Emsley, Robin (Author) , Falkai, Peter (Author) , Fernández-Egea, Emilio (Author) , Fleischhacker, Wolfgang (Author) , Freudenreich, Oliver (Author) , Gadelha, Ary (Author) , Gaebel, Wolfgang (Author) , Graff-Guerrero, Ariel (Author) , Gridley, Ad (Author) , Hallak, Jaime E.C. (Author) , Homan, Philipp (Author) , Kahn, René S. (Author) , Kaiser, Stefan (Author) , Kapi, Maria (Author) , Kennedy, James L. (Author) , Kim, Euitae (Author) , Kinon, Bruce J. (Author) , Soo Kwon, Jun (Author) , Lawrie, Stephen M. (Author) , Lee, Jimmy (Author) , Leweke, F. Markus (Author) , Li, Tao (Author) , Libiger, Jan (Author) , Marder, Stephen R. (Author) , Melle, Ingrid (Author) , Meltzer, Herbert (Author) , Mucci, Armida (Author) , Naber, Dieter (Author) , Nakajima, Shinchiro (Author) , Nielsen, Jimmi (Author) , O’Brien, Oisín (Author) , Ojagbemi, Akin (Author) , Omlor, Wolfgang (Author) , Pantelis, Christos (Author) , Peuskens, Jozef (Author) , Raedler, Thomas J. (Author) , Ran, Mao-Sheng (Author) , Marques, Tiago Reis (Author) , Remington, Gary (Author) , Rossell, Susan (Author) , Rubio, Jose M. (Author) , Sachs, Gabriele (Author) , Scott, James (Author) , Si, Tianmei (Author) , Siskind, Dan (Author) , Siu, Cynthia O. (Author) , Sommer, Iris E. (Author) , Suzuki, Takefumi (Author) , Takeuchi, Hiroyoshi (Author) , Tandon, Rajiv (Author) , Taylor, David (Author) , Teferra, Solomon (Author) , Thomas, Neil (Author) , Tiihonen, Jari (Author) , Uchida, Hiroyoki (Author) , Ucok, Alp (Author) , Umbricht, Daniel (Author) , Venkatasubramanian, Ganesan (Author) , Wagner, Elias (Author) , Walters, James T.R. (Author) , Wang, Chuanyue (Author) , Weiser, Mark (Author) , Wright, Charlie (Author) , Yu, Xin (Author) , McCutcheon, Robert A. (Author)
Format: Article (Journal)
Language:English
Published: November 01, 2025
In: The American journal of psychiatry
Year: 2025, Volume: 182, Issue: 11, Pages: 969-983
ISSN:1535-7228
DOI:10.1176/appi.ajp.20241040
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1176/appi.ajp.20241040
Verlag, lizenzpflichtig, Volltext: https://psychiatryonline-org.ezproxy.medma.uni-heidelberg.de/doi/10.1176/appi.ajp.20241040
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Author Notes:Oliver D. Howes, Ph.D., Bernard R. Bukala, M.A., B.M.B.Ch., Eric Y.H. Chen, M.D., Christoph U. Correll, M.D., Alkomiet Hasan, M.D., William G. Honer, M.D., John M. Kane, M.D., Stefan Leucht, M.D., Spyridon Siafis, M.D., Ofer Agid, M.D., Dickens Akena, M.D., Celso Arango, Ph.D., Lukoye Atwoli, Ph.D., Thomas R.E. Barnes, D.Sc., Michael L. Birnbaum, M.D., Istvan Bitter, Ph.D., Alan Breier, M.D., Robert W. Buchanan, M.D., Leslie Citrome, M.D., David R. Cotter, Ph.D., Nicolas Crossley, Ph.D., Michael Davidson, M.D., Andrea de Bartolomeis, Ph.D., Lynn E. DeLisi, M.D., Sonia Dollfus, Ph.D., Serdar M. Dursun, F.R.C.P.C., Bjørn H. Ebdrup, M.D., Ph.D., Helio Elkis, Ph.D., Robin Emsley, D.Sc., Peter Falkai, Ph.D., Emilio Fernández-Egea, Ph.D., Wolfgang Fleischhacker, M.D., Oliver Freudenreich, M.D., Ary Gadelha, Ph.D., Wolfgang Gaebel, M.D., Ariel Graff-Guerrero, M.D., Ad Gridley, Jaime E.C. Hallak, Ph.D., Philipp Homan, Ph.D., René S. Kahn, Ph.D., Stefan Kaiser, M.D., Maria Kapi, Ph.D., James L. Kennedy, F.R.S.C., Euitae Kim, Ph.D., Bruce J. Kinon, M.D., Jun Soo Kwon, Ph.D., Stephen M. Lawrie, F.R.C.Psych., Jimmy Lee, M.B.B.S., F. Markus Leweke, M.D., Tao Li, M.D., Jan Libiger, M.D., Stephen R. Marder, M.D., Ingrid Melle, Ph.D., Herbert Meltzer, M.D., Armida Mucci, Ph.D., Dieter Naber, M.D., Shinchiro Nakajima, Ph.D., Jimmi Nielsen, M.D., Oisín O’Brien, M.B.B.Ch., Akin Ojagbemi, Ph.D., Wolfgang Omlor, Ph.D., Christos Pantelis, F.R.A.N.Z.C.P., Jozef Peuskens, Ph.D., Thomas J. Raedler, M.D., Mao-Sheng Ran, M.D., Ph.D., Tiago Reis Marques, Ph.D., Gary Remington, Ph.D., Susan Rossell, Ph.D., Jose M. Rubio, Ph.D., Gabriele Sachs, Ph.D., James Scott, B.M.B.S., Tianmei Si, M.D., Dan Siskind, Ph.D., Cynthia O. Siu, Ph.D., Iris E. Sommer, Ph.D., Takefumi Suzuki, Ph.D., Hiroyoshi Takeuchi, Ph.D., Rajiv Tandon, M.D., David Taylor, Ph.D., Solomon Teferra, Ph.D., Neil Thomas, D.Clin.Psy., Jari Tiihonen, Ph.D., Hiroyoki Uchida, Ph.D., Alp Ucok, M.D., Daniel Umbricht, M.D., Ganesan Venkatasubramanian, Ph.D., Elias Wagner, M.D., James T.R. Walters, Ph.D., Chuanyue Wang Ph.D., Mark Weiser, Ph.D., Charlie Wright, Xin Yu, M.D., Robert A. McCutcheon, Ph.D
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Summary:Objective: - Relapse prevention is a major goal of schizophrenia treatment. However, there is no standard definition of relapse. To address this, the authors reviewed recent approaches and developed consensus criteria to operationally define relapse. - Methods: - To evaluate current criteria, a systematic review was performed of randomized controlled trials of relapse conducted from 2012 to 2024. To develop consensus criteria, the authors used a multiphase Delphi approach involving over 100 experts from 37 countries, including people with lived experience of relapse. - Results: - The review showed only two pairs of studies that used the same criteria. Clinical judgment alone was sufficient to define relapse in 85% of studies, and 58% used relative symptom change. The recommended criteria cover the pre-baseline, baseline, and relapse components with optimum and minimum criteria and provide a reporting checklist. The recommendations include using standardized, validated measures that can be applied across settings, and using absolute symptom change. The authors also identify criteria that should not be used and make reporting recommendations, including for specific symptom domains (positive, negative, or cognitive) and across symptom domains, hospitalization, home treatment, and risky, violent, or suicidal behavior. - Conclusions: - There are limitations and heterogeneity in current definitions of relapse, which limit study comparisons, potentially bias meta-analyses, and question the validity of some studies. Adopting the consensus recommendations for a standardized approach should improve the validity and reliability of study outcomes, facilitate cross-study comparisons, and also standardize research into risk factors for relapse.
Item Description:Online veröffentlicht: 8. Oktober 2025
Gesehen am 27.01.2026
Physical Description:Online Resource
ISSN:1535-7228
DOI:10.1176/appi.ajp.20241040

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