Preventing psychosis in people at clinical high risk: an updated meta-analysis by the World Psychiatric Association Preventive Psychiatry section

Minichino, A; Davies, C; Karpenko, O; Christodoulou, N; Ramalho, R; Nandha, S; Damiani, S; Provenzani, U; Esposito, CM; Mensi, MM; Borgatti, R; Stefana, A; McGuire, P; Fusar-Poli, P

Neuroscience & Neuroimaging Research Collection

Journal article : Review

Preventing psychosis in people at clinical high risk: an updated meta-analysis by the World Psychiatric Association Preventive Psychiatry section

Abstract:: Recently published large-scale randomised controlled trials (RCTs) have questioned the efficacy of preventive interventions in individuals at clinical high risk for psychosis (CHR-P). We conducted a systematic review and meta-analysis to include this new evidence and provide future directions for the field. We followed the PRISMA guidelines and a pre-registered protocol, with a literature search conducted from inception to November 2023. We included RCTs that collected data on psychosis transition (the primary outcome) in CHR-P. Secondary outcomes were symptoms severity and functioning. Investigated time points were 6,12,24,36, and +36 months. We used odd ratios (ORs) and standardised mean differences (SMD) as summary outcomes. Heterogeneity was estimated with the Higgins I2. Twenty-four RCTs, involving 3236 CHR-P individuals, were included. Active interventions were Cognitive Behavioural Therapy (CBT), family-focused therapy, Integrated Psychological Therapy, antipsychotics, omega-3 fatty acids, CBT plus risperidone, minocycline, and other non-pharmacological approaches (cognitive remediation, sleep-targeted therapy, brain stimulation). Results showed no evidence that any of the investigated active interventions had a sustained and robust effect on any of the investigated outcomes in CHR-P, when compared to control interventions, including CBT on transition to psychosis at 12 months (9 RCTs; OR: 0.64; 95% CI: 0.39–1.06; I2: 21%; P = 0.08). These results highlight the need for novel treatment approaches in CHR-P. Future studies should consider the heterogeneity of this clinical population and prioritise stratification strategies and bespoke treatments.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Minichino, A., Davies, C., Karpenko, O., Christodoulou, N., Ramalho, R., Nandha, S., Damiani, S., Provenzani, U., Esposito, C., Mensi, M., Borgatti, R., Stefana, A., McGuire, P., & Fusar-Poli, P. (2025). Preventing psychosis in people at clinical high risk: an updated meta-analysis by the World Psychiatric Association Preventive Psychiatry section. Molecular Psychiatry, 30(6), 2773–2782.

MLA Style

Minichino, A., et al. “Preventing Psychosis in People at Clinical High Risk: An Updated Meta-Analysis by the World Psychiatric Association Preventive Psychiatry Section.” Molecular Psychiatry, vol. 30, no. 6, 2025, pp. 2773–82.

Chicago Style

Minichino, A., C. Davies, O. Karpenko, et al. 2025. “Preventing Psychosis in People at Clinical High Risk: An Updated Meta-Analysis by the World Psychiatric Association Preventive Psychiatry Section.” Molecular Psychiatry 30 (6): 2773–82.
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