INTEGRATE: international guidelines for the algorithmic treatment of schizophrenia

doi:10.1016/S2215-0366(25)00031-8

Review

. 2025 May;12(5):384-394.

doi: 10.1016/S2215-0366(25)00031-8. Epub 2025 Mar 31.

INTEGRATE: international guidelines for the algorithmic treatment of schizophrenia

Robert A McCutcheon¹, Toby Pillinger², Ioana Varvari³, Sean Halstead⁴, Olatunde O Ayinde⁵, Nicolás A Crossley⁶, Christoph U Correll⁷, Margaret Hahn⁸, Oliver D Howes⁹, John M Kane¹⁰, Thomas Kabir¹¹, Åsa Konradsson-Geuken¹², Belinda Lennox³, Christy Lai Ming Hui¹³, Susan L Rossell¹⁴, Marco Solmi¹⁵, Iris E Sommer¹⁶, Heidi Taipale¹⁷, Hiroyuki Uchida¹⁸, Ganesan Venkatasubramanian¹⁹, Nicola Warren⁴; INTEGRATE Advisory Group; Dan Siskind⁴

Collaborators, Affiliations

Collaborators

INTEGRATE Advisory Group:
Ofer Agid, Celso Arango, Andrea de Bartolomeis, Robert A Bittner, Rodrigo A Bressan, Robert W Buchanan, Giacomo Cecere, Eric Y H Chen, Leslie Citrome, Sonia Dollfus, Serdar M Dursun, Bjørn H Ebdrup, Helio Elkis, Robin Emsley, Emilio Fernandez-Egea, Wolfgang Fleischhacker, Oliver Freudenreich, Ary Gadelha, Shiral S Gangadin, Fiona Gaughran, Jaime Eduardo Cecilio Hallak, Alkomiet Hasan, Philipp Homan, Sameer Jauhar, Stefan Kaiser, Jun Soo Kwon, Jimmy Lee, Stefan Leucht, Jan Libiger, Markus F Leweke, James H MacCabe, Stephen R Marder, Tiago Reis Marques, Ingrid Melle, Armida Mucci, Shinichiro Nakajima, Brian O'Donoghue, Akin Ojagbemi, Benjamin I Perry, J L Roos, Jose M Rubio, Janusz K Rybakowski, Gabriele Sachs, Cynthia O Siu, Takefumi Suzuki, David M Taylor, Hiroyoshi Takeuchi, Jagadisha Thirthalli, Neil Thomas, Alp Üçok, Shivarama Varambally, Octavian Vasiliu, Elias Wagner

Affiliations

¹ Department of Psychiatry, University of Oxford, Oxford, UK; Oxford Health NHS Foundation Trust, Oxford, UK; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Electronic address: robert.mccutcheon@psych.ox.ac.uk.
² Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; South London and Maudsley NHS Foundation Trust, London, UK.
³ Department of Psychiatry, University of Oxford, Oxford, UK; Oxford Health NHS Foundation Trust, Oxford, UK.
⁴ Medical School, The University of Queensland, Brisbane, QLD, Australia; Addiction and Mental Health Service, Metro South Health, Brisbane, QLD, Australia.
⁵ Department of Psychiatry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
⁶ Department of Psychiatry, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
⁷ Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempsted, NY, USA; The Feinstein Institute for Medical Research, Northwell Health, New Hyde Park, NY, USA; Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁸ Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁹ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
¹⁰ Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempsted, NY, USA; The Feinstein Institute for Medical Research, Northwell Health, New Hyde Park, NY, USA.
¹¹ Department of Psychiatry, University of Oxford, Oxford, UK.
¹² Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden; Swedish Schizophrenia Association, Stockholm, Sweden.
¹³ Department of Psychiatry, University of Hong Kong, Hong Kong Special Administrative Region, China.
¹⁴ Centre for Mental Health, Swinburne University of Technology, Melbourne, VIC, Australia.
¹⁵ SCIENCES Lab, University of Ottawa, Ottawa, ON, Canada; Champlain First Episode Psychosis Program, The Ottawa Hospital, Ottawa, ON, Canada; Ottawa Hospital Research Institute, Ottawa, ON, Canada; Department of Child and Adolescent Psychiatry, Charité - Universitätsmedizin Berlin, Berlin, Germany.
¹⁶ University Medical Center Groningen, Groningen, Netherlands.
¹⁷ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Niuvanniemi Hospital, Kuopio, Finland.
¹⁸ Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
¹⁹ Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, India.

PMID: 40179920
DOI: 10.1016/S2215-0366(25)00031-8

Review

INTEGRATE: international guidelines for the algorithmic treatment of schizophrenia

Robert A McCutcheon et al. Lancet Psychiatry. 2025 May.

. 2025 May;12(5):384-394.

doi: 10.1016/S2215-0366(25)00031-8. Epub 2025 Mar 31.

Authors

Collaborators

INTEGRATE Advisory Group:
Ofer Agid, Celso Arango, Andrea de Bartolomeis, Robert A Bittner, Rodrigo A Bressan, Robert W Buchanan, Giacomo Cecere, Eric Y H Chen, Leslie Citrome, Sonia Dollfus, Serdar M Dursun, Bjørn H Ebdrup, Helio Elkis, Robin Emsley, Emilio Fernandez-Egea, Wolfgang Fleischhacker, Oliver Freudenreich, Ary Gadelha, Shiral S Gangadin, Fiona Gaughran, Jaime Eduardo Cecilio Hallak, Alkomiet Hasan, Philipp Homan, Sameer Jauhar, Stefan Kaiser, Jun Soo Kwon, Jimmy Lee, Stefan Leucht, Jan Libiger, Markus F Leweke, James H MacCabe, Stephen R Marder, Tiago Reis Marques, Ingrid Melle, Armida Mucci, Shinichiro Nakajima, Brian O'Donoghue, Akin Ojagbemi, Benjamin I Perry, J L Roos, Jose M Rubio, Janusz K Rybakowski, Gabriele Sachs, Cynthia O Siu, Takefumi Suzuki, David M Taylor, Hiroyoshi Takeuchi, Jagadisha Thirthalli, Neil Thomas, Alp Üçok, Shivarama Varambally, Octavian Vasiliu, Elias Wagner

Affiliations

¹ Department of Psychiatry, University of Oxford, Oxford, UK; Oxford Health NHS Foundation Trust, Oxford, UK; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Electronic address: robert.mccutcheon@psych.ox.ac.uk.
² Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; South London and Maudsley NHS Foundation Trust, London, UK.
³ Department of Psychiatry, University of Oxford, Oxford, UK; Oxford Health NHS Foundation Trust, Oxford, UK.
⁴ Medical School, The University of Queensland, Brisbane, QLD, Australia; Addiction and Mental Health Service, Metro South Health, Brisbane, QLD, Australia.
⁵ Department of Psychiatry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
⁶ Department of Psychiatry, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
⁷ Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempsted, NY, USA; The Feinstein Institute for Medical Research, Northwell Health, New Hyde Park, NY, USA; Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁸ Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁹ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
¹⁰ Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempsted, NY, USA; The Feinstein Institute for Medical Research, Northwell Health, New Hyde Park, NY, USA.
¹¹ Department of Psychiatry, University of Oxford, Oxford, UK.
¹² Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden; Swedish Schizophrenia Association, Stockholm, Sweden.
¹³ Department of Psychiatry, University of Hong Kong, Hong Kong Special Administrative Region, China.
¹⁴ Centre for Mental Health, Swinburne University of Technology, Melbourne, VIC, Australia.
¹⁵ SCIENCES Lab, University of Ottawa, Ottawa, ON, Canada; Champlain First Episode Psychosis Program, The Ottawa Hospital, Ottawa, ON, Canada; Ottawa Hospital Research Institute, Ottawa, ON, Canada; Department of Child and Adolescent Psychiatry, Charité - Universitätsmedizin Berlin, Berlin, Germany.
¹⁶ University Medical Center Groningen, Groningen, Netherlands.
¹⁷ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Niuvanniemi Hospital, Kuopio, Finland.
¹⁸ Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
¹⁹ Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, India.

PMID: 40179920
DOI: 10.1016/S2215-0366(25)00031-8

Erratum in

Correction to Lancet Psychiatry 2025; 12: 384-94.
[No authors listed] [No authors listed] Lancet Psychiatry. 2025 Jun;12(6):e9. doi: 10.1016/S2215-0366(25)00131-2. Epub 2025 Apr 28. Lancet Psychiatry. 2025. PMID: 40311644 No abstract available.

Abstract

Schizophrenia is a mental illness involving multiple symptom domains and is often associated with substantial physical health comorbidities. Guidelines exist, but these tend to be country-specific and are often missing a concise yet comprehensive algorithmic approach. From May 1, 2023, to Jan 1, 2025, International Guidelines for Algorithmic Treatment (INTEGRATE) authors from all UN regions collaborated to develop a consensus guideline focused on the pharmacological treatment of schizophrenia. Following an umbrella review of the literature, input from expert workshops, a consensus survey, and lived experience focus groups, a consensus algorithmic guideline and associated digital tool were developed. Key recommendations include a focus on metabolic health from treatment initiation, timely assessment and management of non-response, symptom domain-specific interventions, mitigation of side-effects, and the prompt use of clozapine in cases of treatment resistance.

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Conflict of interest statement

Declaration of interests RAM has received speaker or consultancy fees, or both, from Boehringer Ingelheim, Janssen, Karuna, Lundbeck, Newron, Otsuka, and Viatris, and co-directs a company that designs digital resources to support treatment of mental ill health. TP has contributed to educational and advisory meetings organised by Recordati, Lundbeck, Otsuka, Janssen, CNX Therapeutics, Sunovion, ROVI Biotech, Schwabe Pharma, and Lecturing Minds Stockholm. He receives book royalties from Wiley Blackwell. He co-directs a company that designs digital resources to support treatment of mental ill health. CUC has been a consultant and advisor to or has received honoraria from AbbVie, Alkermes, Allergan, Angelini, Aristo, Boehringer Ingelheim, Bristol Meyers Squibb, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Delpor, Denovo, Eli Lilly, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Jamjoom Pharma, Johnson & Johnson Innovative Medicine (formerly Janssen), Karuna, LB Pharma, Lundbeck, MedInCell, MedLink, Merck, Mindpax, Mitsubishi Tanabe Pharma, Maplight, Mylan, Neumora Therapeutics, Neurocrine, Neurelis, Newron, Noven, Novo Nordisk, Otsuka, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Saladax, Sanofi, Seqirus, Servier, Sumitomo Pharma America, Sunovion, Sun Pharma, Supernus, Tabuk, Takeda, Teva, Terran, Tolmar, Vertex, Viatris, and Xenon Pharmaceuticals. He provided expert testimony for Janssen, Lundbeck, and Otsuka. He served on a Data safety monitoring board for Compass Pathways, IntraCellular Therapies, Relmada, Reviva, and Rovi. He has received grant support from Boehringer-Ingelheim, Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Kuleon Biosciences, LB Pharma, Medlink, Mindpax, Quantic, Terran. MH has received consultant and speaker fees from Alkermes and consultant fees from Merck. ODH has received investigator-initiated research funding from or participated in advisory or speaker meetings organised by AbbVie, Alkermes, Angellini, Autifony, Biogen, Boehringer Ingelheim, Delix, Eli Lilly, Elysium, Heptares, Global Medical Education, Invicro, Janssen, Karuna, Lundbeck, Merck, Neumora, Neurocrine, Ontrack and Pangea, Otsuka, Sunovion, Teva, Recordati, Roche, Rovi, and Mylan (a subsidiary of Viatris); was previously a part-time employee of Lundbeck. JMK has received a research grant and manages the funds from Lundbeck, Otsuka, Janssen, and Sunovion; receives ownership interest from Vanguard Research Group (private), LB Pharmaceuticals (private), North Shore Therapeutics (private), HealthRhythms (private), Cerevel (public), and Karuna (public); and receives consulting fees from Click Therapeutics, Karuna, Lundbeck, Merck, Newron, Novartis, Otsuka, Sumitomo, Alkermes, Allergan, Boehringer Ingelheim, Cerevel, Dainippon Sumitomo, Lundbeck, HealthRhythms, HLS Therapeutics, Indivior, Intracellular Therapies, Janssen Pharmaceutical, Johnson and Johnson, Karuna Therapeutics, LB Pharmaceuticals, Merck, Minerva, Neurocrine, NW PharmaTech, Otsuka, Roche, Saladax, Sunovion, and Teva. BL has received funding from Johnson and Johnson, ArgenX, Takeda, and Arialys for scientific advice. MS has received honoraria and has been a consultant for Angelini, AbbVie, Boehringer Ingelheim, Lundbeck, and Otsuka. HT has participated in research projects funded by grants from Janssen to their employing institution; and has received personal fees from Gedeon Richter, Janssen, Lundbeck, and Otsuka. HU has received grants from Daiichi Sankyo, Eisai, Mochida, Otsuka, and Sumitomo Pharma, has received speaker fees from Eisai, Lundbeck, Meiji Seika Pharma, Otsuka, Boehringer Ingelheim Japan, Merck Sharp & Dohme, and Sumitomo Pharma, and has received advisory board fees from Lundbeck, Sumitomo Pharma, Takeda Pharmaceutical Company, and Boehringer Ingelheim Japan for the past 3 years. SLR has received honoraria for advising and consulting from Boehringer Ingelheim. All other authors declare no competing interests.

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INTEGRATE: international guidelines for the algorithmic treatment of schizophrenia

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INTEGRATE: international guidelines for the algorithmic treatment of schizophrenia

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