Winter-van Rossum Inge, Slot Margot I E, van Hell Hendrika H, Bossong Matthijs G, Berger Gregor, Aschauer Harald, Maat Arija, Walitza Susanne, Lavan Orly, Baeza Inmaculada, Dolz Montserrat, Monducci Elena, Fiori Nastro Paolo, Kroken Rune Andreas, Lawrie Stephen M, Díaz-Caneja Covadonga Martinez, Renner Tobias, Schlögelhofer Monika, Scharinger Christian, Spalletta Gianfranco, Banaj Nerisa, Otero Soraya, Schipper Maria, Kwakkel Dorieke Brink-, Kahn Rene S
Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Psychiatry, Icahn School of Medicine, Mount Sinai, NY, United States.
Schizophr Bull. 2025 Jul 7;51(4):1082-1091. doi: 10.1093/schbul/sbae186.
In the past 2 decades, substantial effort has been put into research on therapeutic options for people at ultra-high risk (UHR) for developing a first episode of psychosis (FEP), focusing on omega-3 polyunsaturated fatty acids (PUFAs) in preventing transition to psychosis. Despite an initial positive finding, subsequent studies failed to find a beneficial effect. The current study aimed to further investigate the effect of omega-3 PUFAs in UHR, to determine whether this line of research is worth pursuing.
A double-blind, randomized, placebo-controlled study testing the efficacy of 6-month treatment with omega-3 PUFAs in 135 subjects at UHR for FEP, aged 13 to 20 years on the prevention of a transition to psychosis, followed up for 18 months post-treatment. The trial was conducted at 16 general hospitals and psychiatric specialty centers located in 8 European countries and Israel.
There was no beneficial effect of treatment with omega-3 PUFAs compared to placebo; the rate of transition over 2 years did not differ between treatment arms nor was there a difference in change in symptom severity after 6-month treatment. Dropout rates and serious adverse events were similar across the groups.
This is the third study that fails to replicate the original finding on the protective effect of omega-3 PUFAs in UHR subjects for transition to psychosis. The accumulating evidence therefore suggests that omega-3 PUFAs do not reduce transition rates to psychosis in those at increased risk at 2 years follow-up.
This trial is registered with ClinicalTrials.gov (NCT02597439; Study Details | Placebo-controlled Trial in Subjects at Ultra-high Risk for Psychosis With Omega-3 Fatty Acids in Europe | ClinicalTrials.gov).
在过去20年里，人们投入了大量精力研究针对超高风险（UHR）人群首次发作精神病（FEP）的治疗方案，重点关注ω-3多不饱和脂肪酸（PUFAs）在预防精神病转化方面的作用。尽管最初有积极发现，但后续研究未能发现有益效果。本研究旨在进一步探究ω-3 PUFAs对UHR人群的影响，以确定这一研究方向是否值得继续。
一项双盲、随机、安慰剂对照研究，测试135名年龄在13至20岁的UHR FEP受试者接受为期6个月的ω-3 PUFAs治疗对预防精神病转化的疗效，并在治疗后随访18个月。该试验在位于8个欧洲国家和以色列的16家综合医院和精神科专科中心进行。
与安慰剂相比，ω-3 PUFAs治疗没有有益效果；两组在2年期间的转化率没有差异，6个月治疗后症状严重程度的变化也没有差异。各治疗组的脱落率和严重不良事件相似。
这是第三项未能重复最初关于ω-3 PUFAs对UHR受试者预防精神病转化具有保护作用这一发现的研究。因此，越来越多的证据表明，在2年随访中，ω-3 PUFAs并不能降低高风险人群转化为精神病的比率。
本试验已在ClinicalTrials.gov注册（NCT02597439；研究详情 | 欧洲使用ω-3脂肪酸对超高风险精神病受试者进行的安慰剂对照试验 | ClinicalTrials.gov）。
