Abstract
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. "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). 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. 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.
Highlights
Indicated prevention in individuals at clinical high risk for psychosis (CHR-P) is one of the most promising primary preventive approaches in psychiatry (Fusar-Poli et al, 2017b)
We investigated the influence of the following factors: continent (Europe vs. North America vs. Other); type of psychometric instrument (CAARMS vs. SIPS vs. Other); quality of the study (NOS total score); CHR-P subgroups: (a) proportion of Attenuated Psychosis Symptoms (APS), (b) proportion of Brief and Limited Intermittent Psychotic Symptoms (BLIPS), (c) proportion of Genetic Risk and Deterioration syndrome (GRD), (d) proportion of Basic Symptoms (BS); mean age; sex (% female); year of publication; duration of untreated attenuated psychotic symptoms; International Classification of Diseases (ICD) or DSM-defined comorbidity; exposure to baseline interventions
We showed that negative symptom improvements in CHR-P individuals who do not transition are of similar magnitude to those observed in individuals with schizophrenia (ES = 0.66) (Savill et al, 2015)
Summary
Indicated prevention in individuals at clinical high risk for psychosis (CHR-P) is one of the most promising primary preventive approaches in psychiatry (Fusar-Poli et al, 2017b). CHR-P individuals are young and they accumulate risk factors such as living alone or being unemployed (Fusar-Poli et al, 2017e; Radua et al, 2018; Oliver et al, 2019) that enrich their level of risk for psychosis (Fusar-Poli et al, 2016c). The distress associated with these experiences can prompt CHR-P individuals to seek help (Falkenberg et al, 2015) at specialised mental health clinics (Kotlicka-Antczak et al, 2020; Salazar de Pablo et al, 2021a). In these clinics, the prognosis is formulated reaching very good accuracy using psychometric instruments (Fusar-Poli et al, 2015a). Longitudinal research comparing individuals who develop psychosis with those who do not is overall inconsistent (Fusar-Poli et al, 2013)
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