Longitudinal outcome of attenuated positive symptoms, negative symptoms, functioning and remission in people at clinical high risk for psychosis: a meta-analysis

Background: Little is known about clinical outcomes other than transition to psychosis in people at Clinical High-Risk for psychosis (CHR-P). Our aim was to comprehensively meta-analytically evaluate for the first time a wide range of clinical and functional outcomes beyond transition to psychosis in CHR-P individuals. Methods: PubMed and Web of Science were searched until November 2020 in this PRISMA compliant meta-analysis (PROSPERO:CRD42020206271). Individual longitudinal studies conducted in individuals at CHR-P providing data on at least one of our outcomes of interest were included. We carried out random-effects pairwise meta-analyses, meta-regressions, and assessed publication bias and study quality. Analyses were two-tailed with α=0.05. Findings: 75 prospective studies were included (n=5,288, age=20.0 years, females=44.5%). Attenuated positive symptoms improved at 12 (Hedges’ g=0.753, 95%CI=0.495-1.012) and 24 (Hedges’ g=0.836, 95%CI=0.463-1.209), but not ≥36 months (Hedges’ g=0.315. 95%CI=-0.176–0.806). Negative symptoms improved at 12 (Hedges’ g=0.496, 95%CI=0.315–0.678), but not 24 (Hedges’ g=0.499, 95%CI=-0.137–1.134) or ≥36 months (Hedges’ g=0.033, 95%CI=-0.439–0.505). Depressive symptoms improved at 12 (Hedges’ g=0.611, 95%CI=0.441–0.782) and 24 (Hedges’ g=0.583, 95%CI=0.364–0.803), but not ≥36 months (Hedges’ g=0.512 95%CI=-0.337–1.361). Functioning improved at 12 (Hedges’ g=0.711, 95%CI=0.488–0.934), 24 (Hedges’ g=0.930, 95%CI=0.553–1.306) and ≥36 months (Hedges’ g=0.392, 95%CI=0.117–0.667). Remission from CHR-P status occurred in 33.4% (95%CI=22.6–44.1%) at 12 months, 41.4% (95%CI=32.3–50.5%) at 24 months and 42.4% (95%CI=23.4–61.3%) at ≥36 months. Heterogeneity across the included studies was significant and ranged from I2=53.6% to I2=96.9%. The quality of the included studies (mean±SD) was 4.6±1.1 (range=2-8). Interpretation: CHR-P individuals improve on symptomatic and functional outcomes over time, but these improvements are not maintained in the longer term, and less than half fully remit. Prolonged duration of care may be needed for this patient population to optimize outcomes. Funding: None