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Systematic Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Psychiatry | doi: 10.3389/fpsyt.2019.00764


  • 1King's College London, United Kingdom
  • 2University of Pavia, Italy
  • 3Medical University of Lodz, Poland
  • 4Yonsei University, South Korea

Indicated primary prevention in young people at Clinical High Risk for Psychosis (CHR-P) is a promising avenue for improving outcomes of the most severe mental disorders; their effectiveness has recently been questioned.

Umbrella review. A multi-step independent literature search of Web of Science until January 11th, 2019 identified interventional meta-analyses in CHR-P individuals. The individual RCTs that were analysed by the meta-analyses were extracted. A review of ongoing trials and a simulation of living meta-analysis complemented the analysis.

Seven meta-analyses investigating preventive treatments in CHR-P individuals were included. None of them produced pooled effect sizes across psychological, pharmacological or other types of interventions. The outcomes analysed encompassed: risk of psychosis onset, the acceptability of treatments, the severity of attenuated positive/negative psychotic symptoms, depression, symptom-related distress, social functioning, general functioning, and quality of life. These meta-analyses were based on 20 RCTs: the vast majority defined the prevention of psychosis onset as their primary outcome of interest and only powered to large effect sizes. There was no evidence to favour any preventive intervention over any other (or control condition) for improving any of these clinical outcomes. Caution is required when making clinical recommendations for the prevention of psychosis in CHR-P individuals.

Prevention of psychosis from a CHR-P state has been and should remain, the primary outcome of interventional research, refined and complemented by other clinically meaningful outcomes (severity of symptoms, functional status, recovery, quality of life). Stagnation of knowledge should promote innovative and collaborative research efforts, in line with the progressive and incremental nature of medical knowledge. Advancements will most likely be associated with the development of new experimental therapeutics that are ongoing, along with the ability to deconstruct the high CHR-P heterogeneity. This would require the estimation of treatment-specific effect sizes through living individual participant data meta-analyses, controlling risk enrichment during recruitment, statistical power and embedding precision medicine within youth mental health services that can accommodate sequential prognosis and advanced trial designs.

The evidence-based challenges and proposed solutions addressed by this umbrella review can inform the next generation of research into preventive treatments for psychosis.

Keywords: psychosis, Schizophrenia, prevention, risk, Evidence based medicine (EBM), Trial, Living meta-analysis

Received: 15 Mar 2019; Accepted: 23 Sep 2019.

Copyright: © 2019 Fusar-Poli, Davies, Solmi, Brondino, De Micheli, Kotlicka-Antczak, Shin and Radua. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Paolo Fusar-Poli, King's College London, London, United Kingdom,