Objective: Early-onset psychosis (EOP) refers to the development of psychosis before the age of 18 years. We aimed to summarize, for the fi rst time, the meta-analytical evidence in the fi eld 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 metaanalytically in neuroimaging markers but not in oxidative stress and in fl ammatory response markers. In all, 60.1% of EOP individuals had a poor prognosis. Clozapine was the antipsychotic with the highest eff i cacy 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 eff i cacious 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. Plain language summary: This umbrella review summarized the meta-analytical knowledge from 30 meta-analyses on early-onset psychosis. Earlyonset psychosis refers to the development of psychosis before the age of 18 years and is associated with cognitive impairment, hospitalization, and poor prognosis. Individuals with early-onset psychosis show more cognitive impairments and abnormalities compared with controls. Clozapine was the antipsychotic with the highest eff i cacy for positive, negative, and overall symptoms and should be considered in individuals with early-onset psychosis.
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