Randomized Controlled Trial

. 2025 Jul 7;51(4):1082-1091.

doi: 10.1093/schbul/sbae186.

Effectiveness of Omega-3 Fatty Acids Versus Placebo in Subjects at Ultra-High Risk for Psychosis: The PURPOSE Randomized Clinical Trial

Inge Winter-van Rossum^{1

2}, Margot I E Slot¹, Hendrika H van Hell¹, Matthijs G Bossong¹, Gregor Berger³, Harald Aschauer⁴, Arija Maat^{1

5}, Susanne Walitza³, Orly Lavan⁶, Inmaculada Baeza^{7

8}, Montserrat Dolz^{9

10}, Elena Monducci¹¹, Paolo Fiori Nastro¹², Rune Andreas Kroken^{13

14}, Stephen M Lawrie¹⁵, Covadonga Martinez Díaz-Caneja¹⁶, Tobias Renner^{17

18}, Monika Schlögelhofer⁴, Christian Scharinger^{4

19}, Gianfranco Spalletta²⁰, Nerisa Banaj²⁰, Soraya Otero²¹, Maria Schipper²², Dorieke Brink- Kwakkel²²; PURPOSE Study Group; Rene S Kahn^{1

2}

Collaborators, Affiliations

Affiliations

¹ Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands.
² Department of Psychiatry, Icahn School of Medicine, Mount Sinai, NY, United States.
³ Department of Child and Adolescent Psychiatry and Psychotherapy of the Psychiatric University Hospital, University of Zurich, Zurich, Switzerland.
⁴ BioPsyC Biopsychosocial Corporation, Non-profit association for Research Funding Ltd., Vienna, Austria.
⁵ Department of Psychiatry, Spaarne Gasthuis Haarlem, Haarlem, The Netherlands.
⁶ Department of Psychological Medicine, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
⁷ Child and Adolescent Psychiatry and Psychology Department, SGR2021-01319, Hospital Clínic de Barcelona, Barcelona, Spain.
⁸ FCRB-IDIBAPS, CIBERSAM-ISCIII, Institute of Neurosciences, Universitat de Barcelona, Barcelona, Spain.
⁹ Child and Adolescent Mental Health Research Group, Institut de Recerca Sant Joan de Déu, Barcelona, Spain.
¹⁰ Child and Adolescent Psychiatry and Psychology Department, Hospital Sant Joan de Déu of Barcelona, Barcelona, Spain.
¹¹ Human Neuroscience, Child and Adolescent Neuropsychiatry, Sapienza University of Rome, Rome, Italy.
¹² Department of Human Neuroscience, U.O.D. of Psychotherapy "Villa Tiburtina," Sapienza University of Rome, Rome, Italy.
¹³ Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
¹⁴ Department of Clinical Medicine, University of Bergen, Bergen, Norway.
¹⁵ Division of Psychiatry, University of Edinburgh, Edinburgh, Scotland.
¹⁶ Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), CIBERSAM, ISCIII, School of Medicine, Universidad Complutense, Madrid, Spain.
¹⁷ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Tuebingen, Center for Mental Health, University Hospital of Tuebingen, Tuebingen, Germany.
¹⁸ German Center for Mental Health (DZPG), Partner Site Tuebingen, Tuebingen, Germany.
¹⁹ Department of Child and Youth Psychiatry, Medical University of Vienna, Vienna, Austria.
²⁰ Laboratory of Neuropsychiatry, Santa Lucia Foundation IRCCS, Rome, Italy.
²¹ Child and Adolescent Psychiatry and Psychology Unit, University Hospital Marques de Valdecilla, Institute of Research Valdecilla Hospital IDIVAL, Santander, Spain.
²² Department of Datascience and Biostatistics, Julius Center, University Medical Center Utrecht, Utrecht, The Netherlands.

PMID: 39450759
PMCID: PMC12236319
DOI: 10.1093/schbul/sbae186

Randomized Controlled Trial

Effectiveness of Omega-3 Fatty Acids Versus Placebo in Subjects at Ultra-High Risk for Psychosis: The PURPOSE Randomized Clinical Trial

Inge Winter-van Rossum et al. Schizophr Bull. 2025.

. 2025 Jul 7;51(4):1082-1091.

doi: 10.1093/schbul/sbae186.

Authors

Affiliations

¹ Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands.
² Department of Psychiatry, Icahn School of Medicine, Mount Sinai, NY, United States.
³ Department of Child and Adolescent Psychiatry and Psychotherapy of the Psychiatric University Hospital, University of Zurich, Zurich, Switzerland.
⁴ BioPsyC Biopsychosocial Corporation, Non-profit association for Research Funding Ltd., Vienna, Austria.
⁵ Department of Psychiatry, Spaarne Gasthuis Haarlem, Haarlem, The Netherlands.
⁶ Department of Psychological Medicine, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
⁷ Child and Adolescent Psychiatry and Psychology Department, SGR2021-01319, Hospital Clínic de Barcelona, Barcelona, Spain.
⁸ FCRB-IDIBAPS, CIBERSAM-ISCIII, Institute of Neurosciences, Universitat de Barcelona, Barcelona, Spain.
⁹ Child and Adolescent Mental Health Research Group, Institut de Recerca Sant Joan de Déu, Barcelona, Spain.
¹⁰ Child and Adolescent Psychiatry and Psychology Department, Hospital Sant Joan de Déu of Barcelona, Barcelona, Spain.
¹¹ Human Neuroscience, Child and Adolescent Neuropsychiatry, Sapienza University of Rome, Rome, Italy.
¹² Department of Human Neuroscience, U.O.D. of Psychotherapy "Villa Tiburtina," Sapienza University of Rome, Rome, Italy.
¹³ Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
¹⁴ Department of Clinical Medicine, University of Bergen, Bergen, Norway.
¹⁵ Division of Psychiatry, University of Edinburgh, Edinburgh, Scotland.
¹⁶ Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), CIBERSAM, ISCIII, School of Medicine, Universidad Complutense, Madrid, Spain.
¹⁷ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Tuebingen, Center for Mental Health, University Hospital of Tuebingen, Tuebingen, Germany.
¹⁸ German Center for Mental Health (DZPG), Partner Site Tuebingen, Tuebingen, Germany.
¹⁹ Department of Child and Youth Psychiatry, Medical University of Vienna, Vienna, Austria.
²⁰ Laboratory of Neuropsychiatry, Santa Lucia Foundation IRCCS, Rome, Italy.
²¹ Child and Adolescent Psychiatry and Psychology Unit, University Hospital Marques de Valdecilla, Institute of Research Valdecilla Hospital IDIVAL, Santander, Spain.
²² Department of Datascience and Biostatistics, Julius Center, University Medical Center Utrecht, Utrecht, The Netherlands.

PMID: 39450759
PMCID: PMC12236319
DOI: 10.1093/schbul/sbae186

Abstract

Background and hypotheses: In the past 2 decades, substantial effort has been put into research on therapeutic options for people at ultra-high risk (UHR) for developing a first episode of psychosis (FEP), focusing on omega-3 polyunsaturated fatty acids (PUFAs) in preventing transition to psychosis. Despite an initial positive finding, subsequent studies failed to find a beneficial effect. The current study aimed to further investigate the effect of omega-3 PUFAs in UHR, to determine whether this line of research is worth pursuing.

Study design: A double-blind, randomized, placebo-controlled study testing the efficacy of 6-month treatment with omega-3 PUFAs in 135 subjects at UHR for FEP, aged 13 to 20 years on the prevention of a transition to psychosis, followed up for 18 months post-treatment. The trial was conducted at 16 general hospitals and psychiatric specialty centers located in 8 European countries and Israel.

Study results: There was no beneficial effect of treatment with omega-3 PUFAs compared to placebo; the rate of transition over 2 years did not differ between treatment arms nor was there a difference in change in symptom severity after 6-month treatment. Dropout rates and serious adverse events were similar across the groups.

Conclusions: This is the third study that fails to replicate the original finding on the protective effect of omega-3 PUFAs in UHR subjects for transition to psychosis. The accumulating evidence therefore suggests that omega-3 PUFAs do not reduce transition rates to psychosis in those at increased risk at 2 years follow-up.

Clinical trials: This trial is registered with ClinicalTrials.gov (NCT02597439; Study Details | Placebo-controlled Trial in Subjects at Ultra-high Risk for Psychosis With Omega-3 Fatty Acids in Europe | ClinicalTrials.gov).

Keywords: nutrition; psychosis prevention; treatment.

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Conflict of interest statement

I.Wv.R., M.S., H.Hv.H., M.G.B., H.A., A.M., O.L., E.M., P.F.N., R.A.K., S.M.L., M.S., C.S., G.S., N.B., S.O., M.S., D.B.K., and R.S.K. have no conflicts to report. H.A. has received grant support from European Cooperation in Science and Technology (COST), Brussels (Action Nr. BM0905), European Cooperation in Science and Technology (COST), Brussels (Action Nr. CA16210), European Cooperation in Science and Technology (COST), Brussels (Action Nr. CA17130), Medical Scientific Fund of the Mayor of the City of Vienna (Project Nr. COVID021). GB In the last 5 years G.B. has speaker’s honorary fee from AntiStress AG (Burgerstein), Forum Suizidprävention Zürich, Spital Thurgau, Stadt Zürich, Foederatio Medicorum Helveticorum FMH, Bildungsdirektion Zürich, Salmon Pharma, Schlupfhus Zürich, Psychiatrie Baselland, Zürcher Hochschule für angewandte Wissenschaften ZHAW, Swiss Life AG, KOOP Soziale Fachdienstleistungen AG, Forum für medizinische Fortbildung und University of Basel. His work has been supported by the Swiss National Science Foundation (SNF), EU FP7s, University of Zurich, Switzerland, Hartmann Müller, Gertrud Thalmann and Heuberg Foundations as well as by Gesundheitsförderung Schweiz (Health Promotion Switzerland). IB has received honoraria or travel support to attend conferences from Angelini and Lundbeck, and grants from Spanish Ministry of Health, Instituto de Salud Carlos III (PI18/0242, INT19/00021, and PI21/0391, co-funded by the European Union), the Alicia Koplowitz Foundation, Pons-Bartran legacy (FCRB_IPB2_2023) and National Drugs Plan (2022I053). CDC has received grant support from Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (PI17/00481, PI20/00721, PI23/00625, JR19/00024), honoraria from Angelini and Viatris, and travel support from Janssen and Angelini. SW has received in the last 5 years royalties from Thieme, Hogrefe, Kohlhammer, Springer, Beltz. In 2024 she will receive speakers honorary from Takeda and Medice (topic ADHD).

Figures

**Figure 1.**
CONSORT subject flowchart PURPOSE trial.

**Figure 2.**
The rate of transition to psychosis was compared between subjects treated with omega-3 Polyunsaturated Fatty Acids (PUFA) and placebo, applying a strict definition of transition (A) and an extended definition of transition (B).

See this image and copyright information in PMC

References

1. Modinos G, McGuire P.. The prodromal phase of psychosis. Curr Opin Neurobiol. 2015;30:100–105. - PubMed
1. McHugh MJ, McGorry PD, Yuen HP, et al. The ultra-high-risk for psychosis groups: Evidence to maintain the status quo. Schizophr Res. 2018;195:543–548. - PubMed
1. Anderson KK, Norman R, MacDougall A, et al. Effectiveness of early psychosis intervention: comparison of service users and nonusers in population-based health administrative data. Am J Psychiatry. 2018;175:443–452. - PubMed
1. Devoe DJ, Farris M, Townes P, Addington J.. Interventions and transition in youth at risk of psychosis: a systematic review and meta-analyses. J Clin Psychiatry. 2020;81:17r12053. - PubMed
1. Fusar-Poli P, Davies C, Solmi M, et al. Preventive treatments for psychosis: Umbrella Review (Just the Evidence). Front Psychiatry. 2019;10:764. - PMC - PubMed

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Effectiveness of Omega-3 Fatty Acids Versus Placebo in Subjects at Ultra-High Risk for Psychosis: The PURPOSE Randomized Clinical Trial

Collaborators

Affiliations

Effectiveness of Omega-3 Fatty Acids Versus Placebo in Subjects at Ultra-High Risk for Psychosis: The PURPOSE Randomized Clinical Trial

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

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Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

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