Burkhardt Gerrit, Kumpf Ulrike, Crispin Alexander, Goerigk Stephan, Andre Elisabeth, Plewnia Christian, Brendel Bettina, Fallgatter Andreas, Langguth Berthold, Abdelnaim Mohamed, Hebel Tobias, Normann Claus, Frase Lukas, Zwanzger Peter, Diemer Julia, Kammer Thomas, Schönfeldt-Lecuona Carlos, Kamp Daniel, Bajbouj Malek, Behler Nora, Wilkening Anja, Nenov-Matt Tabea, Dechantsreiter Esther, Keeser Daniel, Bulubas Lucia, Palm Ulrich, Blankenstein Christiane, Mansmann Ulrich, Falkai Peter, Brunoni Andre R, Hasan Alkomiet, Padberg Frank
Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Munich, Germany.
Ludwig-Maximilians-Universität Hospital, Institute for Medical Information Processing, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München, Munich, Germany.
Lancet. 2023 Aug 12;402(10401):545-554. doi: 10.1016/S0140-6736(23)00640-2. Epub 2023 Jul 3.
Transcranial direct current stimulation (tDCS) has been proposed as a feasible treatment for major depressive disorder (MDD). However, meta-analytic evidence is heterogenous and data from multicentre trials are scarce. We aimed to assess the efficacy of tDCS versus sham stimulation as an additional treatment to a stable dose of selective serotonin reuptake inhibitors (SSRIs) in adults with MDD.
The DepressionDC trial was triple-blind, randomised, and sham-controlled and conducted at eight hospitals in Germany. Patients being treated at a participating hospital aged 18-65 years were eligible if they had a diagnosis of MDD, a score of at least 15 on the Hamilton Depression Rating Scale (21-item version), no response to at least one antidepressant trial in their current depressive episode, and treatment with an SSRI at a stable dose for at least 4 weeks before inclusion; the SSRI was continued at the same dose during stimulation. Patients were allocated (1:1) by fixed-blocked randomisation to receive either 30 min of 2 mA bifrontal tDCS every weekday for 4 weeks, then two tDCS sessions per week for 2 weeks, or sham stimulation at the same intervals. Randomisation was stratified by site and baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score (ie, <31 or ≥31). Participants, raters, and operators were masked to treatment assignment. The primary outcome was change on the MADRS at week 6, analysed in the intention-to-treat population. Safety was assessed in all patients who received at least one treatment session. The trial was registered with ClinicalTrials.gov (NCT02530164).
Between Jan 19, 2016, and June 15, 2020, 3601 individuals were assessed for eligibility. 160 patients were included and randomly assigned to receive either active tDCS (n=83) or sham tDCS (n=77). Six patients withdrew consent and four patients were found to have been wrongly included, so data from 150 patients were analysed (89 [59%] were female and 61 [41%] were male). No intergroup difference was found in mean improvement on the MADRS at week 6 between the active tDCS group (n=77; -8·2, SD 7·2) and the sham tDCS group (n=73; -8·0, 9·3; difference 0·3 [95% CI -2·4 to 2·9]). Significantly more participants had one or more mild adverse events in the active tDCS group (50 [60%] of 83) than in the sham tDCS group (33 [43%] of 77; p=0·028).
Active tDCS was not superior to sham stimulation during a 6-week period. Our trial does not support the efficacy of tDCS as an additional treatment to SSRIs in adults with MDD.
German Federal Ministry of Education and Research.
经颅直流电刺激（tDCS）已被提议作为重度抑郁症（MDD）的一种可行治疗方法。然而，荟萃分析的证据存在异质性，且多中心试验的数据稀缺。我们旨在评估tDCS与假刺激相比，作为对MDD成年患者稳定剂量的选择性5-羟色胺再摄取抑制剂（SSRI）的辅助治疗的疗效。
DepressionDC试验是一项三盲、随机、假对照试验，在德国的八家医院进行。在参与试验的医院接受治疗的18 - 65岁患者，如果符合以下条件则 eligible：诊断为MDD，汉密尔顿抑郁量表（21项版本）得分至少为15分，在当前抑郁发作中对至少一次抗抑郁药试验无反应，且在纳入前至少4周以稳定剂量接受SSRI治疗；在刺激期间SSRI以相同剂量持续使用。患者通过固定区组随机化以1:1的比例分配，接受以下两种治疗之一：每周工作日进行30分钟2毫安的双额叶tDCS，共4周，然后每周进行两次tDCS治疗，共2周；或按相同间隔进行假刺激。随机化按地点和基线蒙哥马利 - 阿斯伯格抑郁量表（MADRS）得分（即<31或≥31）分层。参与者、评估者和操作者均对治疗分配不知情。主要结局是第6周时MADRS的变化，在意向性治疗人群中进行分析。在所有接受至少一次治疗的患者中评估安全性。该试验已在ClinicalTrials.gov注册（NCT02530164）。
在2016年1月19日至2020年6月15日期间，对3601人进行了资格评估。160名患者被纳入并随机分配接受活性tDCS（n = 83）或假tDCS（n = 77）。6名患者撤回同意书，4名患者被发现被错误纳入，因此对150名患者的数据进行了分析（89名[59%]为女性，61名[41%]为男性）。活性tDCS组（n = 77；-8.2，标准差7.2）和假tDCS组（n = 73；-8.0，9.3；差异0.3 [95% CI -2.4至2.9]）在第6周时MADRS的平均改善方面未发现组间差异。活性tDCS组（83名中的50名[60%]）出现一种或多种轻度不良事件的参与者明显多于假tDCS组（77名中的33名[43%]；p = 0.028）。
在6周期间，活性tDCS并不优于假刺激。我们的试验不支持tDCS作为MDD成年患者SSRI辅助治疗的疗效。
德国联邦教育与研究部。
