Transition to psychosis in randomized clinical trials of individuals at clinical high risk of psychosis compared to observational cohorts: a systematic review and meta-analysis

Gonzalo Salazar de Pablo; Cathy Davies; Héctor de Diego; Marco Solmi; Jae Il Shin; Andre F Carvalho; Joaquim Radua; Paolo Fusar-Poli

doi:10.1192/j.eurpsy.2021.2222

Transition to psychosis in randomized clinical trials of individuals at clinical high risk of psychosis compared to observational cohorts: a systematic review and meta-analysis

Eur Psychiatry. 2021 Jul 28;64(1):e51. doi: 10.1192/j.eurpsy.2021.2222.

Authors

Gonzalo Salazar de Pablo^{1

2}, Cathy Davies¹, Héctor de Diego², Marco Solmi^{1

3}, Jae Il Shin⁴, Andre F Carvalho⁵, Joaquim Radua^{1

6

7}, Paolo Fusar-Poli^{1

8

9

10}

Affiliations

¹ Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
² Institute of Psychiatry and Mental Health, Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), CIBERSAM, Madrid, Spain Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
³ Department of Psychiatry, University of Ottawa, Department of Mental Health, The Ottawa Hospital.
⁴ Department of Paediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea.
⁵ IMPACT (Innovation in Mental and Physical Health and Clinical Treatment) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia.
⁶ Imaging of Mood- and Anxiety-Related Disorders (IMARD) Group, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), CIBERSAM, Barcelona, Spain.
⁷ Department of Clinical Neuroscience, Centre for Psychiatric Research and Education, Karolinska Institutet, Stockholm, Sweden.
⁸ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
⁹ OASIS service, South London and Maudsley NHS Foundation Trust, London, UK.
¹⁰ National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK.

Abstract

Background: Individuals at clinical high risk of psychosis (CHR-P) recruited in randomized clinical trials (RCTs) and observational cohorts may display a different enrichment and hence risk of transition to psychosis. No meta-analysis has ever addressed this issue.

Methods: "Preferred Reporting Items for Systematic reviews and Meta-Analyses" (PRISMA) and "Meta-analysis Of Observational Studies in Epidemiology" (MOOSE)-compliant meta-analysis. PubMed and Web of Science were searched until November 2020 (PROSPERO:CRD42021229223). We included nonoverlapping longitudinal studies (RCTs-control condition and observational cohorts) reporting the transition to psychosis in CHR-P individuals. The primary effect size measure was the cumulative risk of transition at 0.5, 1, and 2 years follow-up in RCTs compared to observational cohorts. Random effects meta-analyses, heterogeneity assessment, quality assessment, and meta-regressions were conducted.

Results: Ninety-four independent studies (24 RCTs, 70 observational cohorts) and 9,243 individuals (mean age = 20.1 ± 3.0 years; 43.7% females) were included. The meta-analytical risk of transitioning to psychosis from a CHR-P stage was 0.091 (95% confidence intervals [CI] = 0.068-0.121) at 0.5 years, 0.140 (95% CI = 0.101-0.191) at 1 year and 0.165 (95% CI = 0.097-0.267) at 2 years follow-up in RCTs, and 0.081 (95% CI = 0.067-0.099) at 0.5 years, 0.138 (95% CI = 0.114-0.167) at 1 year, and 0.174 (95% CI = 0.156-0.193) at 2 years follow-up in observational cohorts. There were no between-group differences in transition risks (p > 0.05). The proportion of CHR-P individuals with substance use disorders (excluding alcohol and cannabis) was higher in observational cohorts (16.8, 95% CI = 13.3-21.0%) than in RCTs (3.4, 95% CI = 0.8-12.7%; p = 0.018).

Conclusions: There is no meta-analytic evidence supporting sampling biases in RCTs of CHR-P individuals. Further RCTs are needed to detect effective interventions to prevent psychosis in this at-risk group.

Keywords: CHR; Meta-analysis; Psychosis; Transition; risk; schizophrenia.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Female
Humans
Male
Observational Studies as Topic
Psychotic Disorders* / epidemiology
Randomized Controlled Trials as Topic
Substance-Related Disorders*