Minichino Amedeo, Davies Cathy, Karpenko Olga, Christodoulou Nikos, Ramalho Rodrigo, Nandha Sunil, Damiani Stefano, Provenzani Umberto, Esposito Cecilia Maria, Mensi Martina Maria, Borgatti Renato, Stefana Alberto, McGuire Philip, Fusar-Poli Paolo
Department of Psychiatry, University of Oxford, Oxford, UK.
EPIC Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Mol Psychiatry. 2025 Jun;30(6):2773-2782. doi: 10.1038/s41380-025-02902-8. Epub 2025 Feb 14.
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 I. 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; I: 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.
最近发表的大规模随机对照试验（RCT）对针对临床高危精神病个体（CHR-P）的预防性干预措施的疗效提出了质疑。我们进行了一项系统评价和荟萃分析，纳入这一新证据，并为该领域提供未来方向。我们遵循PRISMA指南和预先注册的方案，从开始到2023年11月进行文献检索。我们纳入了收集CHR-P精神病转变数据（主要结局）的随机对照试验。次要结局是症状严重程度和功能。研究的时间点为6、12、24、36和+36个月。我们使用比值比（OR）和标准化均数差（SMD）作为汇总结局。用Higgins I估计异质性。纳入了24项随机对照试验，涉及3236名CHR-P个体。积极干预措施包括认知行为疗法（CBT）、以家庭为中心的疗法、综合心理疗法、抗精神病药物、ω-3脂肪酸、CBT加利培酮、米诺环素以及其他非药物方法（认知康复、针对睡眠的疗法、脑刺激）。结果显示，与对照干预措施相比，没有证据表明任何一种被研究的积极干预措施对CHR-P的任何一项被研究结局有持续且显著的效果，包括在12个月时CBT对精神病转变的影响（9项随机对照试验；OR：0.64；95%CI：0.39-1.06；I：21%；P = 0.08）。这些结果凸显了CHR-P需要新的治疗方法。未来的研究应考虑这一临床人群的异质性，并优先采用分层策略和定制治疗。
