Schlögelhofer Monika, Lin Ashleigh, Markulev Connie, Schäfer Miriam R, McGorry Patrick D, Nelson Barnaby, Street Rebekah, Mossaheb Nilufar, Smesny Stefan, Hickie Ian B, Berger Gregor, Chen Eric Yh, de Haan Lieuwe, Nieman Dorien H, Nordentoft Merete, Riecher-Rössler Anita, Verma Swapna, Thompson Andrew, Yung Alison R, Amminger G Paul
Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria.
BioPsyC-Biopsychosocial Corporation, Non-Profit Association for Research Funding Ltd., Vienna, Austria.
Aust N Z J Psychiatry. 2025 Aug 25;59(10):48674251361758. doi: 10.1177/00048674251361758.
Non-adherence is an important factor in clinical trials, which has not been investigated in people at ultra-high risk (UHR) of developing a first episode of psychosis.
Exploratory analysis of data from NEURAPRO, a multicenter, placebo-controlled trial of long-chain omega-3 polyunsaturated fatty acids (omega-3 PUFAs) in 304 individuals at UHR. We examined correlates of non-adherence with study medication (omega-3 PUFAs or placebo), including patient, illness and treatment factors, plus transition to psychosis. Non-adherence was defined as <75% study medication intake over 6 months and, post hoc, by the number of returned pills.
Of 285 randomized participants with baseline fatty acid data, 163 (57.2%) were non-adherent. In univariate analyses, non-adherence was associated with baseline omega-3 index, pre-baseline duration of untreated symptoms, smoking, cannabis use, lower baseline Social and Occupational Functioning Assessment Scale, Global Functioning: Social and Role Scale scores and transition to psychosis. Transition to psychosis risk was significantly lower in the adherent than non-adherent group (4.2%, 95% CI = 0.7-7.7% vs 17.3%, 95% CI = 10.4-24.2%), Kaplan-Meier Log-rank test, chi-square = 10.675, = 0.001), independent of omega-3 PUFA treatment status. Similarly, Cox regression analysis, covarying for the aforementioned factors significantly associated with non-adherence, also revealed non-adherence as an independent predictor of transition to psychosis ( = 1.452, = 0.005). Finally, non-adherence was also significantly associated with transition to psychosis, even when defining non-adherence by number of returned pills.
Non-adherence predicted a higher risk of progressing to psychosis in UHR individuals. Further studies are needed to better understand factors contributing to non-adherence and how non-adherence is related to transition to psychosis.
在临床试验中，不依从是一个重要因素，而在首次发作精神病超高风险（UHR）人群中尚未对此进行研究。
对NEURAPRO试验数据进行探索性分析，该试验是一项多中心、安慰剂对照试验，研究对象为304名UHR个体，使用长链ω-3多不饱和脂肪酸（ω-3 PUFAs）进行治疗。我们研究了与研究药物（ω-3 PUFAs或安慰剂）不依从相关的因素，包括患者、疾病和治疗因素，以及向精神病的转变情况。不依从被定义为6个月内研究药物摄入量<75%，事后通过返还药片数量进行定义。
在285名有基线脂肪酸数据的随机参与者中，163人（57.2%）不依从。在单变量分析中，不依从与基线ω-3指数、基线前未治疗症状的持续时间、吸烟、大麻使用、较低的基线社会和职业功能评估量表、总体功能：社会和角色量表得分以及向精神病的转变有关。依从组向精神病转变的风险显著低于不依从组（4.2%，95%CI = 0.7 - 7.7% 对比 17.3%，95%CI = 10.4 - 24.2%），Kaplan - Meier对数秩检验，卡方 = 10.675，P = 0.001），与ω-3 PUFA治疗状态无关。同样，在对上述与不依从显著相关的因素进行协变量调整的Cox回归分析中，也显示不依从是向精神病转变的独立预测因素（P = 1.452，P = 0.005）。最后，即使通过返还药片数量定义不依从，不依从也与向精神病的转变显著相关。
不依从预示着UHR个体发展为精神病的风险更高。需要进一步研究以更好地理解导致不依从的因素以及不依从与向精神病转变之间的关系。
