Disclosures: Salazar de Pablo reports honoraria from Janssen-Cilag and grants from the Alicia Koplowitz Foundation outside the submitted work. Please see the study for all other authors’ relevant financial disclosures.
July 16, 2021
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25% of people at clinical high risk for psychosis develop the disorder within 3 years

Disclosures: Salazar de Pablo reports honoraria from Janssen-Cilag and grants from the Alicia Koplowitz Foundation outside the submitted work. Please see the study for all other authors’ relevant financial disclosures.
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One-fourth of people at clinical high risk for psychosis developed psychosis within 3 years, according to results of an updated meta-analysis published in JAMA Psychiatry.

“Risk of transition to psychosis in individuals at [clinical high risk for psychosis] as estimated by our earlier meta-analysis (including studies until January 2011) was 18% at 6 months, 22% at 1 year, 29% at 2 years and 36% at 3 years,” Gonzalo Salazar de Pablo, MD, of the Institute of Psychiatry, Psychology & Neuroscience in the department of psychosis studies at King’s College London in the U.K., and colleagues wrote. “After a decade, many more studies have been published at rapid pace, which makes the periodic review of prognostic knowledge essential. This meta-analysis fills this gap by estimating the updated risk for transition to psychosis in individuals at [clinical high risk for psychosis].”

infographic with 25% visual to represent number of people at clinical high risk for psychosis who developed the disorder within 3 years
Infographic data derived from: Salazar de Pablo G, et al. JAMA Psychiatry. 2021;doi:10.1001/jamapsychiatry.2021.0830.          

Specifically, the researchers aimed to quantitatively assess the consistency and magnitude of transition to psychosis risk among this patient population. They analyzed two databases until Nov. 1, 2020, and conducted a manual search of references from prior articles. They included 130 longitudinal studies that reported transition risks among a total of 9,222 individuals at clinical high risk for psychosis (mean age, 20.3 years; 55.3% men). Cumulative risk for transition to psychosis at 0.5, 1, 1.5, 2, 2.5, 3, 4 and more than 4 years’ follow-up according to estimates of the number of individuals at clinical high risk for psychosis who transitioned to psychosis at each time point served as the primary effect size. The researchers also calculated meta-analytical Kaplan-Meier curves and speed of transition to psychosis and conducted random-effects meta-analysis, between-study heterogeneity analysis, study quality assessment and meta-regressions.

Results showed a cumulative transition risk of 0.09 (95% CI, 0.07-0.1; n = 6,485) at 0.5 years, 0.15 (95% CI, 0.13-0.16; n = 7,907) at 1 year, 0.2 (95% CI, 0.17-0.22; n = 5,488) at 1.5 years, 0.19 (95% CI, 0.17-0.22; n = 7,351) at 2 years, 0.25 (95% CI, 0.21-0.29; n = 3,114) at 2.5 years, 0.25 (95% CI, 0.22-0.29; n = 4,029) at 3 years, 0.27 (95% CI, 0.23-0.3; n = 2,926) at 4 years and 0.28 (95% CI, 0.2-0.37; n = 2,301) at more than 4 years. The researchers reported cumulative Kaplan-Meier transition risk of 0.08 (95% CI, 0.08-0.09; n = 4,860) at 0.5 years, 0.14 (95% CI, 0.13-0.15; n = 3,408) at 1 year, 0.17 (95% CI, 0.16-0.19; n = 2,892) at 1.5 years, 0.2 (95% CI, 0.19-0.21; n = 2,357) at 2 years, 0.25 (95% CI, 0.23-0.26; n = 1,444) at 2.5 years, 0.27 (95% CI, 0.25-0.28; n = 1,029) at 3 years, 0.28 (95% CI, 0.26-0.29; n = 808) at 3.5 years, 0.29 (95% CI, 0.27-0.3; n = 737) at 4 years and 0.35 (95% CI, 0.32-0.38; n = 114) at 10 years, with the hazard rate having plateaued only at 4 years’ follow-up.

According to meta-regressions, a lower proportion of female individuals (beta = 0.02; 95% CI, 0.04 to 0.01) and a higher proportion of brief limited intermittent psychotic symptoms (beta = 0.02; 95% CI, 0.01-0.03) were linked to an increase in transition risk. The researchers noted high heterogeneity across the studies.

“Extended clinical monitoring and preventive care may be beneficial in this patient group,” Salazar de Pablo and colleagues wrote.