The Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto (Kaster, Knyahnytska, Daskalakis, Blumberger); the Department of Psychiatry (Kaster, Downar, Giacobbe, Kennedy, Daskalakis, Blumberger), the Institute of Medical Science (Downar, Giacobbe, Kennedy, Daskalakis, Blumberger), and the Dalla Lana School of Public Health (Thorpe), University of Toronto, Toronto; the MRI-Guided rTMS Clinic, Toronto Western Hospital, Toronto (Downar); the Krembil Research Institute, University Health Network, Toronto (Downar, Kennedy); the Department of Psychiatry, University of British Columbia, Vancouver (Vila-Rodriguez, Lam); the Non-Invasive Neurostimulation Therapies Laboratory, University of British Columbia, Vancouver (Vila-Rodriguez); the Shalvata Mental Health Center, Hod-Hasharon, Israel, and the Sackler School of Medicine, Tel Aviv University, Tel Aviv (Feffer); the Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo (Noda); the Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto (Giacobbe); and the Li Ka Shing Knowledge Institute, Saint Michael's Hospital, Toronto (Kennedy).
Am J Psychiatry. 2019 May 1;176(5):367-375. doi: 10.1176/appi.ajp.2018.18091096. Epub 2019 Feb 15.
Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for refractory major depressive disorder, yet no studies have characterized trajectories of rTMS response. The aim of this study was to characterize response trajectories for patients with major depression undergoing left dorsolateral prefrontal cortex rTMS and to determine associated baseline clinical characteristics.
This was a secondary analysis of a randomized noninferiority trial (N=388) comparing conventional 10-Hz rTMS and intermittent theta burst stimulation (iTBS) rTMS. Participants were adult outpatients who had a primary diagnosis of major depressive disorder, had a score ≥18 on the 17-item Hamilton Depression Rating Scale (HAM-D), and did not respond to one to three adequate antidepressant trials. Treatment was either conventional 10-Hz rTMS or iTBS rTMS applied to the dorsolateral prefrontal cortex, 5 days/week over 4-6 weeks (20-30 sessions). Group-based trajectory modeling was applied to identify HAM-D response trajectories, and regression techniques were used to identify associated characteristics.
Four trajectories were identified: nonresponse (N=43, 11%); rapid response (N=73, 19%); higher baseline symptoms, linear response (N=118, 30%); and lower baseline symptoms, linear response (N=154, 40%). Significant differences in response and remission rates between trajectories were detectable by week 1. There was no association between treatment protocol and response trajectory. Higher baseline scores on the HAM-D and the Quick Inventory of Depression Symptomatology-Self-Report (QIDS-SR) were associated with the nonresponse trajectory, and older age, lower QIDS-SR score, and lack of benzodiazepine use were associated with the rapid response trajectory.
Major depression shows distinct response trajectories to rTMS, which are associated with baseline clinical characteristics but not treatment protocol. These response trajectories with differential response to rTMS raise the possibility of developing individualized treatment protocols.
重复经颅磁刺激（rTMS）是治疗难治性重度抑郁症的有效方法，但目前尚无研究对 rTMS 反应轨迹进行特征描述。本研究旨在描述接受左侧背外侧前额叶皮层 rTMS 治疗的重度抑郁症患者的反应轨迹，并确定相关的基线临床特征。
这是一项比较常规 10Hz rTMS 和间歇性 theta 爆发刺激（iTBS）rTMS 的随机非劣效性试验（N=388）的二次分析。参与者为成年门诊患者，主要诊断为重度抑郁症，汉密尔顿抑郁量表（HAM-D）的得分为≥18 分，且对 1-3 次充分的抗抑郁治疗反应不佳。治疗为常规 10Hz rTMS 或 iTBS rTMS，应用于背外侧前额叶皮层，每周 5 天，持续 4-6 周（20-30 次）。采用基于群组的轨迹建模来识别 HAM-D 反应轨迹，并采用回归技术来识别相关特征。
共确定了 4 种反应轨迹：无反应（N=43，11%）；快速反应（N=73，19%）；基线症状较高，线性反应（N=118，30%）；基线症状较低，线性反应（N=154，40%）。通过第 1 周可检测到不同反应轨迹之间的反应率和缓解率存在显著差异。治疗方案与反应轨迹之间无关联。HAM-D 和贝克抑郁自评量表（BDI）基线评分较高与无反应轨迹相关，而年龄较大、BDI 评分较低和不使用苯二氮䓬类药物与快速反应轨迹相关。
重度抑郁症对 rTMS 显示出明显的反应轨迹，这些轨迹与基线临床特征有关，但与治疗方案无关。这些对 rTMS 有不同反应的反应轨迹提示有可能制定个体化的治疗方案。
