Department of Psychiatry and Psychotherapy, Semmelweis University, Balassa 6, Budapest, 1083, Hungary.
Department of Cognitive Science, Faculty of Natural Sciences, Budapest University of Technology and Economics, Budapest, Hungary.
Trials. 2024 Apr 17;25(1):269. doi: 10.1186/s13063-024-08106-9.
Treatment effects of conventional approaches with antipsychotics or psychosocial interventions are limited when it comes to reducing negative and cognitive symptoms in schizophrenia. While there is emerging clinical evidence that new, augmented protocols based on theta-burst stimulation can increase rTMS efficacy dramatically in depression, data on similar augmented therapies are limited in schizophrenia. The different patterns of network impairments in subjects may underlie that some but not all patients responded to given stimulation locations.
Therefore, we propose an augmented theta-burst stimulation protocol in schizophrenia by stimulating both locations connected to negative symptoms: (1) the left dorsolateral prefrontal cortex (DLPFC), and (2) the vermis of the cerebellum. Ninety subjects with schizophrenia presenting negative symptoms and aging between 18 and 55 years will be randomized to active and sham stimulation in a 1:1 ratio. The TBS parameters we adopted follow the standard TBS protocols, with 3-pulse 50-Hz bursts given every 200 ms (at 5 Hz) and an intensity of 100% active motor threshold. We plan to deliver 1800 stimuli to the left DLPFC and 1800 stimuli to the vermis daily in two 9.5-min blocks for 4 weeks. The primary endpoint is the change in negative symptom severity measured by the Positive and Negative Syndrome Scale (PANSS). Secondary efficacy endpoints are changes in cognitive flexibility, executive functioning, short-term memory, social cognition, and facial emotion recognition. The difference between study groups will be analyzed by a linear mixed model analysis with the difference relative to baseline in efficacy variables as the dependent variable and treatment group, visit, and treatment-by-visit interaction as independent variables. The safety outcome is the number of serious adverse events.
This is a double-blind, sham-controlled, randomized medical device study to assess the efficacy and safety of an augmented theta-burst rTMS treatment in schizophrenia. We hypothesize that social cognition and negative symptoms of patients on active therapy will improve significantly compared to patients on sham treatment.
The study protocol is registered at "ClinicalTrials.gov" with the following ID: NCT05100888. All items from the World Health Organization Trial Registration Data Set are registered. Initial release: 10/19/2021.
在减少精神分裂症的阴性和认知症状方面，传统的抗精神病药物治疗或心理社会干预的治疗效果有限。虽然有新的临床证据表明，基于θ爆发刺激的新增强协议可以显著提高 rTMS 在抑郁症中的疗效，但在精神分裂症中，类似增强治疗的数据有限。受试者中不同的网络损伤模式可能是以下原因：一些但不是所有患者对特定刺激部位有反应。
因此，我们提出了一种精神分裂症的增强型θ爆发刺激协议，刺激与阴性症状相关的两个部位：（1）左侧背外侧前额叶皮层（DLPFC），（2）小脑蚓部。将 90 名有阴性症状的精神分裂症患者，年龄在 18 至 55 岁之间，按 1:1 的比例随机分为活性刺激和假刺激组。我们采用的 TBS 参数遵循标准 TBS 协议，以 3 脉冲 50Hz 爆发，每 200ms （5Hz）给予一次，强度为 100%主动运动阈值。我们计划每天在两个 9.5 分钟的时间段内向左侧 DLPFC 给予 1800 次刺激，向小脑蚓部给予 1800 次刺激，持续 4 周。主要终点是阳性和阴性综合征量表（PANSS）测量的阴性症状严重程度的变化。次要疗效终点是认知灵活性、执行功能、短期记忆、社会认知和面部情绪识别的变化。采用线性混合模型分析，以疗效变量相对于基线的差异作为因变量，以治疗组、访视和治疗-访视交互作用作为自变量，分析研究组之间的差异。安全性结局是严重不良事件的数量。
这是一项双盲、假对照、随机医疗器械研究，旨在评估增强型θ爆发 rTMS 治疗精神分裂症的疗效和安全性。我们假设与假治疗组相比，接受活性治疗的患者的社会认知和阴性症状将显著改善。
该研究方案在“ClinicalTrials.gov”上注册，注册号为：NCT05100888。世界卫生组织试验注册数据集的所有项目均已注册。初始发布日期：2021 年 10 月 19 日。
