Prevention of Psychosis Advances in Detection, Prognosis, and Intervention

Paolo Fusar-Poli*, Gonzalo Salazar de Pablo, Christoph U. Correll, Andreas Meyer-Lindenberg, Mark J. Millan, Stefan Borgwardt, Silvana Galderisi, Andreas Bechdolf, Andrea Pfennig, Lars Vedel Kessing, Therese van Amelsvoort, Dorien H. Nieman, Katharina Domschke, Marie-Odile Krebs, Nikolaos Koutsouleris, Philip McGuire, Kim Q. Do, Celso Arango

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

196 Citations (Web of Science)


Importance Detection, prognosis, and indicated interventions in individuals at clinical high risk for psychosis (CHR-P) are key components of preventive psychiatry. Objective To provide a comprehensive, evidence-based systematic appraisal of the advancements and limitations of detection, prognosis, and interventions for CHR-P individuals and to formulate updated recommendations. Evidence Review Web of Science, Cochrane Central Register of Reviews, and Ovid/PsychINFO were searched for articles published from January 1, 2013, to June 30, 2019, to identify meta-analyses conducted in CHR-P individuals. MEDLINE was used to search the reference lists of retrieved articles. Data obtained from each article included first author, year of publication, topic investigated, type of publication, study design and number, sample size of CHR-P population and comparison group, type of comparison group, age and sex of CHR-P individuals, type of prognostic assessment, interventions, quality assessment (using AMSTAR [Assessing the Methodological Quality of Systematic Reviews]), and key findings with their effect sizes. Findings In total, 42 meta-analyses published in the past 6 years and encompassing 81 outcomes were included. For the detection component, CHR-P individuals were young (mean [SD] age, 20.6 [3.2] years), were more frequently male (58%), and predominantly presented with attenuated psychotic symptoms lasting for more than 1 year before their presentation at specialized services. CHR-P individuals accumulated several sociodemographic risk factors compared with control participants. Substance use (33% tobacco use and 27% cannabis use), comorbid mental disorders (41% with depressive disorders and 15% with anxiety disorders), suicidal ideation (66%), and self-harm (49%) were also frequently seen in CHR-P individuals. CHR-P individuals showed impairments in work (Cohen d = 0.57) or educational functioning (Cohen d = 0.21), social functioning (Cohen d = 1.25), and quality of life (Cohen d = 1.75). Several neurobiological and neurocognitive alterations were confirmed in this study. For the prognosis component, the prognostic accuracy of CHR-P instruments was good, provided they were used in clinical samples. Overall, risk of psychosis was 22% at 3 years, and the risk was the highest in the brief and limited intermittent psychotic symptoms subgroup (38%). Baseline severity of attenuated psychotic (Cohen d = 0.35) and negative symptoms (Cohen d = 0.39) as well as low functioning (Cohen d = 0.29) were associated with an increased risk of psychosis. Controlling risk enrichment and implementing sequential risk assessments can optimize prognostic accuracy. For the intervention component, no robust evidence yet exists to favor any indicated intervention over another (including needs-based interventions and control conditions) for preventing psychosis or ameliorating any other outcome in CHR-P individuals. However, because the uncertainty of this evidence is high, needs-based and psychological interventions should still be offered. Conclusions and Relevance This review confirmed recent substantial advancements in the detection and prognosis of CHR-P individuals while suggesting that effective indicated interventions need to be identified. This evidence suggests a need for specialized services to detect CHR-P individuals in primary and secondary care settings, to formulate a prognosis with validated psychometric instruments, and to offer needs-based and psychological interventions.

Question What is the status of current clinical knowledge in the detection, prognosis, and interventions for individuals at risk of psychosis? Findings In this review of 42 meta-analyses encompassing 81 outcomes, detecting individuals at risk for psychosis required knowledge of their specific sociodemographic, clinical, functional, cognitive, and neurobiological characteristics, and predicting outcomes was achieved with good accuracy provided that assessment tools were used in clinical samples. Evidence for specific effective interventions for this patient population is currently insufficient. Meaning Findings of this review suggest that, although clinical research knowledge for psychosis prevention is substantial and detecting and formulating a prognosis in individuals at risk for psychosis are possible, further research is needed to identify specific effective interventions in individuals with sufficient risk enrichment.

This review synthesizes research findings from 42 meta-analyses that assessed detection, prognosis, and interventions for the prevention of psychosis and offers updated practice recommendations.

Original languageEnglish
Pages (from-to)755-765
Number of pages11
JournalJAMA Psychiatry
Issue number7
Publication statusPublished - Jul 2020



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