Orygen, Melbourne, Victoria, Australia.
Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
JAMA Psychiatry. 2023 Sep 1;80(9):875-885. doi: 10.1001/jamapsychiatry.2023.1947.
Clinical trials have not established the optimal type, sequence, and duration of interventions for people at ultrahigh risk of psychosis.
To determine the effectiveness of a sequential and adaptive intervention strategy for individuals at ultrahigh risk of psychosis.
DESIGN, SETTING, AND PARTICIPANTS: The Staged Treatment in Early Psychosis (STEP) sequential multiple assignment randomized trial took place within the clinical program at Orygen, Melbourne, Australia. Individuals aged 12 to 25 years who were seeking treatment and met criteria for ultrahigh risk of psychosis according to the Comprehensive Assessment of At-Risk Mental States were recruited between April 2016 and January 2019. Of 1343 individuals considered, 342 were recruited.
Step 1: 6 weeks of support and problem solving (SPS); step 2: 20 weeks of cognitive-behavioral case management (CBCM) vs SPS; and step 3: 26 weeks of CBCM with fluoxetine vs CBCM with placebo with an embedded fast-fail option of ω-3 fatty acids or low-dose antipsychotic medication. Individuals who did not remit progressed through these steps; those who remitted received SPS or monitoring for up to 12 months.
Global Functioning: Social and Role scales (primary outcome), Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Montgomery-Åsberg Depression Rating Scale, quality of life, transition to psychosis, and remission and relapse rates.
The sample comprised 342 participants (198 female; mean [SD] age, 17.7 [3.1] years). Remission rates, reflecting sustained symptomatic and functional improvement, were 8.5%, 10.3%, and 11.4% at steps 1, 2, and 3, respectively. A total of 27.2% met remission criteria at any step. Relapse rates among those who remitted did not significantly differ between SPS and monitoring (step 1: 65.1% vs 58.3%; step 2: 37.7% vs 47.5%). There was no significant difference in functioning, symptoms, and transition rates between SPS and CBCM and between CBCM with fluoxetine and CBCM with placebo. Twelve-month transition rates to psychosis were 13.5% (entire sample), 3.3% (those who ever remitted), and 17.4% (those with no remission).
In this sequential multiple assignment randomized trial, transition rates to psychosis were moderate, and remission rates were lower than expected, partly reflecting the ambitious criteria set and challenges with real-world treatment fidelity and adherence. While all groups showed mild to moderate functional and symptomatic improvement, this was typically short of remission. While further adaptive trials that address these challenges are needed, findings confirm substantial and sustained morbidity and reveal relatively poor responsiveness to existing treatments.
ClinicalTrials.gov Identifier: NCT02751632.
临床试验尚未确定针对精神病超高风险人群的干预措施的最佳类型、顺序和持续时间。
确定针对精神病超高风险个体的序贯和适应性干预策略的有效性。
设计、地点和参与者：分期治疗早期精神病（STEP）序贯多分配随机试验在澳大利亚墨尔本 Orygen 的临床项目中进行。12 至 25 岁的个体正在寻求治疗，并根据风险精神状态综合评估标准符合精神病超高风险标准。2016 年 4 月至 2019 年 1 月期间共招募了 1343 名符合条件的参与者，其中 342 名被招募。
第 1 步：6 周的支持和解决问题（SPS）；第 2 步：20 周的认知行为案例管理（CBCM）与 SPS 相比；第 3 步：26 周的 CBCM 加氟西汀与 CBCM 加安慰剂，具有快速失败选项ω-3 脂肪酸或低剂量抗精神病药物。未缓解的个体通过这些步骤进行治疗；缓解的个体接受 SPS 或监测，最长可达 12 个月。
总体功能：社会和角色量表（主要结局）、简明精神病评定量表、阴性症状评定量表、蒙哥马利-阿斯伯格抑郁评定量表、生活质量、向精神病转变以及缓解和复发率。
样本包括 342 名参与者（198 名女性；平均[标准差]年龄 17.7[3.1]岁）。缓解率反映了持续的症状和功能改善，分别为第 1、2 和 3 步的 8.5%、10.3%和 11.4%。共有 27.2%的人在任何一步都符合缓解标准。缓解者的复发率在 SPS 和监测之间没有显著差异（第 1 步：65.1%比 58.3%；第 2 步：37.7%比 47.5%）。SPS 和 CBCM 之间以及氟西汀加 CBCM 和安慰剂加 CBCM 之间的功能、症状和转化率没有显著差异。12 个月向精神病转变的发生率为 13.5%（整个样本）、3.3%（曾经缓解的人）和 17.4%（无缓解的人）。
在这项序贯多分配随机试验中，向精神病转变的发生率中等，缓解率低于预期，部分反映了设定的严格标准以及现实世界治疗一致性和依从性的挑战。尽管所有组都表现出轻度至中度的功能和症状改善，但这通常达不到缓解标准。虽然需要进一步的适应性试验来解决这些挑战，但研究结果证实了大量持续的发病率，并揭示了对现有治疗方法的相对较差反应。
ClinicalTrials.gov 标识符：NCT02751632。
