Fenoy Albert J, Schulz Paul E, Sanches Marsal, Selvaraj Sudhakar, Burrows Christina L, Asir Bashar, Conner Christopher R, Quevedo Joao, Soares Jair C
Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, TX, USA.
Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, (UT Health), Houston, TX, USA.
Mol Psychiatry. 2022 May;27(5):2546-2553. doi: 10.1038/s41380-022-01504-y. Epub 2022 Mar 14.
Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB) has emerged as a quite efficacious therapy for treatment resistant depression (TRD), leading to rapid antidepressant effects. In this study, we complete our assessment of our first 10 enrolled patients throughout one year post-implantation, showing sustained antidepressant effect up to 5 years. The primary outcome measure was a 50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score, which was interpreted as a response. Deterministic fiber tracking was used to individually map the target area. An insertional effect was seen during the 4-week sham stimulation phase (29% mean MADRS reduction, p = 0.02). However, after 2 weeks of initiating stimulation, five patients met response criteria (47% mean MADRS reduction, p < 0.001). One patient withdrew from study participation at 6 weeks. Twelve weeks after initiating stimulation, six of nine remaining patients had a >50% decrease in MADRS scores relative to baseline (52% mean MADRS reduction, p = 0.001); these same six patients continued to meet response criteria at 52 weeks (63% overall mean MADRS reduction, p < 0.001). Four of five patients who achieved the 5-year time point analysis continued to be responders (81% mean MADRS reduction, p < 0.001). Evaluation of modulated fiber tracts reveals significant common prefrontal/orbitofrontal connectivity to the target region in all responders. Key points learned from this study that we can incorporate in future protocols to better elucidate the effect of this therapy are a longer blinded sham stimulation phase and use of scheduled discontinuation concomitant with functional imaging.
对内侧前脑束（MFB）的上外侧分支进行深部脑刺激（DBS）已成为治疗难治性抑郁症（TRD）的一种非常有效的疗法，可产生快速抗抑郁效果。在本研究中，我们完成了对首批10名入组患者植入后一年的评估，结果显示抗抑郁效果可持续长达5年。主要结局指标是蒙哥马利-阿斯伯格抑郁评定量表（MADRS）评分降低50%，这被视为有反应。使用确定性纤维束追踪技术对目标区域进行个体化映射。在为期4周的假刺激阶段观察到一种插入效应（平均MADRS降低29%，p = 0.02）。然而，在开始刺激2周后，5名患者达到反应标准（平均MADRS降低47%，p < 0.001）。一名患者在6周时退出研究。开始刺激12周后，其余9名患者中有6名相对于基线的MADRS评分降低了>50%（平均MADRS降低52%，p = 0.001）；这6名患者在52周时继续符合反应标准（总体平均MADRS降低63%，p < 0.001）。在达到5年时间点分析的5名患者中，有4名继续保持有反应（平均MADRS降低81%，p < 0.001）。对调节后的纤维束进行评估发现，所有有反应者的前额叶/眶额叶与目标区域之间存在显著的共同连接。从本研究中获得的、可纳入未来方案以更好地阐明该疗法效果的关键点是延长盲法假刺激阶段以及在功能成像的同时使用计划停药。
