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

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 provide evidence-based recommendations.

METHOD: 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: Thirty meta-analyses were included (373 individual studies, 25,983 participants, mean age 15.1 years, 38.3% females). 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. 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 two non-clozapine antipsychotics. Further meta-analytical research is needed on response to psychological interventions and other prognostic factors.