Umbrella Review: Atlas of the Meta-Analytical Evidence of Early-Onset Psychosis

Gonzalo Salazar de Pablo; Victoria Rodriguez; Filippo Besana; Serena Chiara Civardi; Vincenzo Arienti; Laura Maraña Garceo; P Andrés-Camazón; Ana Catalan; Maria Rogdaki; Chris Abbott; Marinos Kyriakopoulos; Paolo Fusar-Poli; Christoph U Correll; Celso Arango

doi:10.1016/j.jaac.2023.10.016

Umbrella Review: Atlas of the Meta-Analytical Evidence of Early-Onset Psychosis

J Am Acad Child Adolesc Psychiatry. 2024 Jan 25:S0890-8567(24)00006-6. doi: 10.1016/j.jaac.2023.10.016. Online ahead of print.

Authors

Affiliations

¹ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain; Child and Adolescent Mental Health Services, South London and Maudsley NHS Foundation Trust, London, United Kingdom. Electronic address: gonzalo.salazar_de_pablo@kcl.ac.uk.
² Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
³ University of Pavia, Pavia, Italy.
⁴ Donostia University Hospital.
⁵ Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain.
⁶ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Biobizkaia Health Research Institute. Basurto University Hospital, OSI Bilbao-Basurto, and the University of the Basque Country UPV/EHU. Centro de Investigación en Red de Salud Mental (CIBERSAM), Vizcaya, Spain.
⁷ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Francis Crick Institute, London, United Kingdom.
⁸ Child and Adolescent Mental Health Services, South London and Maudsley NHS Foundation Trust, London, United Kingdom.
⁹ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Child and Adolescent Mental Health Services, South London and Maudsley NHS Foundation Trust, London, United Kingdom; National and Kapodistrian University of Athens, Athens, Greece.
¹⁰ University of Pavia, Pavia, Italy; Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; LMU Munich, Munich, Germany; OASIS service, South London and Maudsley NHS Foundation Trust, London, UK; and National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, United Kingdom; Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University, Munich, Germany.
¹¹ Charité Universitätsmedizin, Berlin, Germany; The Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York; Zucker School of Medicine at Hofstra/ Northwell, Hempstead, New York; Center for Psychiatric Neuroscience, The Feinstein Institutes for Medical Research, Manhasset, New York; and the German Center for Mental Health (DZPG), partner site Berlin, Germany.

PMID: 38280414
DOI: 10.1016/j.jaac.2023.10.016

Abstract

Objective: Early-onset psychosis (EOP) refers to the development of psychosis before the age of 18 years. We aimed to summarize, for the first time, the meta-analytical evidence in the field of this vulnerable population and to provide evidence-based recommendations.

Method: We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant, pre-registered (PROSPERO: CRD42022350868) systematic review of several databases and registers to identify meta-analyses of studies conducted in EOP individuals to conduct an umbrella review. Literature search, screening, data extraction, and quality assessment were carried out independently. Results were narratively reported, clustered across core domains. Quality assessment was performed with the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool.

Results: A total of 30 meta-analyses were included (373 individual studies, 25,983 participants, mean age 15.1 years, 38.3% female). Individuals with EOP showed more cognitive impairments compared with controls and individuals with adult/late-onset psychosis. Abnormalities were observed meta-analytically in neuroimaging markers but not in oxidative stress and inflammatory response markers. In all, 60.1% of EOP individuals had a poor prognosis. Clozapine was the antipsychotic with the highest efficacy for overall, positive, and negative symptoms. Tolerance to medication varied among the evaluated antipsychotics. The risk of discontinuation of antipsychotics for any reason or side effects was low or equal compared to placebo.

Conclusion: EOP is associated with cognitive impairment, involuntary admissions, and poor prognosis. Antipsychotics can be efficacious in EOP, but tolerability and safety need to be taken into consideration. Clozapine should be considered in EOP individuals who are resistant to 2 non-clozapine antipsychotics. Further meta-analytical research is needed on response to psychological interventions and other prognostic factors.

Study preregistration information: Early Onset Psychosis: Umbrella Review on Diagnosis, Prognosis and Treatment factors; https://www.crd.york.ac.uk/PROSPERO/; CRD42022350868.

Keywords: early-onset psychosis; first-episode; meta-analysis; schizophrenia; umbrella review.

Publication types

Review