Clinical outcomes in individuals at clinical high risk of psychosis who do not transition to psychosis: A meta-Analysis

Gonzalo Salazar De Pablo, Livia Soardo, Anna Cabras, Joana Pereira, Simi Kaur, Filippo Besana, Vincenzo Arienti, Francesco Coronelli, Jae Il Shin, Marco Solmi, Natalia Petros, Andre F. Carvalho, Philip McGuire, Paolo Fusar-Poli

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Abstract Aims The clinical outcomes of individuals at clinical high risk of psychosis (CHR-P) who do not transition to psychosis are heterogeneous and inconsistently reported. We aimed to comprehensively evaluate longitudinally a wide range of outcomes in CHR-P individuals not developing psychosis. Methods Preferred Reporting Items for Systematic reviews and Meta-Analyses and Meta-Analysis Of Observational Studies in Epidemiology-compliant meta-Analysis (PROSPERO: CRD42021229212) searching original CHR-P longitudinal studies in PubMed and Web of Science databases up to 01/11/2021. As primary analysis, we evaluated the following outcomes within CHR-P non-Transitioning individuals: (a) change in the severity of attenuated psychotic symptoms (Hedge's g); (b) change in the severity of negative psychotic symptoms (Hedge's g); (c) change in the severity of depressive symptoms (Hedge's g); (d) change in the level of functioning (Hedge's g); (e) frequency of remission (at follow-up). As a secondary analysis, we compared these outcomes in those CHR-P individuals who did not transition vs.Those who did transition to psychosis at follow-up. We conducted random-effects model meta-Analyses, sensitivity analyses, heterogeneity analyses, meta-regressions and publication bias assessment. The risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale (NOS). Results Twenty-eight studies were included (2756 CHR-P individuals, mean age = 20.4, 45.5% females). The mean duration of follow-up of the included studies was of 30.7 months. Primary analysis: Attenuated psychotic symptoms [Hedges' g = 1.410, 95% confidence interval (CI) 1.002-1.818]; negative psychotic symptoms (Hedges' g = 0.683, 95% CI 0.371-0.995); depressive symptoms (Hedges' g = 0.844, 95% CI 0.371-1.317); and functioning (Hedges' g = 0.776, 95% CI 0.463-1.089) improved in CHR-P non-Transitioning individuals; 48.7% remitted at follow-up (95% CI 39.3-58.2%). Secondary analysis: Attenuated psychotic symptoms (Hedges' g = 0.706, 95% CI 0.091-1.322) and functioning (Hedges' g = 0.623, 95% CI 0.375-0.871) improved in CHR-P individuals not-Transitioning compared to those transitioning to psychosis, but there were no differences in negative or depressive symptoms or frequency of remission (p > 0.05). Older age was associated with higher improvements of attenuated psychotic symptoms (β = 0.225, p = 0.012); publication years were associated with a higher improvement of functioning (β =-0.124, p = 0.0026); a lower proportion of Brief Limited Intermittent Psychotic Symptoms was associated with higher frequencies of remission (β =-0.054, p = 0.0085). There was no metaregression impact for study continent, the psychometric instrument used, the quality of the study or proportion of females. The NOS scores were 4.4 ± 0.9, ranging from 3 to 6, revealing the moderate quality of the included studies. Conclusions Clinical outcomes improve in CHR-P individuals not transitioning to psychosis but only less than half remit over time. Sustained clinical attention should be provided in the longer term to monitor these outcomes.

Original languageEnglish
Article numbere9
JournalEpidemiology and Psychiatric Sciences
Publication statusPublished - 2022 Jan 19

Bibliographical note

Publisher Copyright:
Copyright © The Author(s), 2022. Published by Cambridge University Press.

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Public Health, Environmental and Occupational Health
  • Psychiatry and Mental health


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