Objective: To explore the efficacy, adverse reactions, feasibility, and acceptability of transcranial alternating current stimulation (tACS) treating drug-naive adult patients with major depressive disorder (MDD), and provide basis for further study with a large sample. Methods: The study was performed in the Neuromodulation laboratory, Department of Neurology of Xuanwu Hospital, Capital Medical University (Beijing, China) from July, 2017 to June, 2018. Thirty Eligible first-episode MDD outpatients were randomized 1∶1 to receive active tACS or sham intervention. The tACS was administered in a 40 minute, 77.5 Hz frequency, 15 mA session with one forehead (Fp1, Fpz, and Fp2, in the 10/20 international placement system, 4.45 cm×9.53 cm) and two mastoid (3.18 cm×3.81 cm) stimulation for 20 times in 4 consecutive weeks at fixed day time frame once daily from Monday through Friday, with weekends off (week 4), followed by 4 weeks with no tACS treatment (week 8). By utilizing the Hamilton rating scale for depression-17 item (HRSD-17) to assess the depressive severity of MDD patients, adverse events were administered by the treatment-emergent adverse events, the Young mania rating scale, and the self-made common questionnaire on cranial electrical stimulation. The primary efficacy outcome was the remission rate defined as HRSD-17 score ≤7 at week 8. Secondary outcomes included the rates of remission at week 4 and response at weeks 4 and 8. Safety was assessed by evaluation of adverse events. Also the proportions of participants accepting the intervention and this study procedure were evaluated at weeks 4 and 8. Results: Thirty MDD patients completed the study, and both groups had no statistical differences on their demographic characteristics (P>0.05). At week 8, the active group had a remission rate of 10/15, which was higher than 3/15 in the sham group (P<0.05). Also, the remission rate (14/15) in the active group was higher than 5/15 of the sham group at week 4 (P<0.05). For the response rates, significant differences were found between groups at week 8. For safety, both groups showed no severe adverse events and no mania/hypomania. One participant per group had 2 times of tinnitus cerebri during the intervention days. All patients accepted the intervention and the study procedure. Conclusions: The pilot study indicated that tACS with 77.5 Hz and 15 mA may have a therapeutic effect on depressive symptoms. It is well-tolerated and safe, as well as feasible and acceptable for adults with MDD.
目的： 初步探讨经颅交流电刺激干预抑郁症的疗效、不良反应及可行性，为进一步的研究提供基础资料。 方法： 本研究于2017年7月到2018年6月在首都医科大学宣武医院神经内科神经调控室完成。收集符合美国精神障碍诊断与统计手册（第4版）中从未药物治疗的抑郁症单次发作的患者30例，按简单随机法1∶1分配到真治疗组（真组）和伪治疗组（伪组）进行连续8周观察，其中前4周是干预期（第4周），后4周是随访期（第8周）。两组在干预期内给予相同的操作程序，伪组无电流发出。经颅交流电刺激是通过安放在前额部（Fp1、Fpz、Fp2，按国际10-20系统）1个电极片和双侧乳突部2个电极片总共3个电极发出77.5 Hz、15 mA的交流电。通过汉密尔顿抑郁量表-17项来评估受试者抑郁程度，通过生命体征、治疗中出现的不良事件、杨氏躁狂评定量表以及自编常见经颅电治疗不良反应问卷来评估不良事件。主要观察指标是第8周末缓解比例；次要观察指标是第4周末缓解比例和有效比例、第8周末有效比例，以及不良反应。并在第4周末和随访4周末时，评估受试者是否接受该项干预方法和试验过程。 结果： 两组受试者均完成了8周临床观察。两组基线资料的差异均无统计学意义（P>0.05）。真组第8周末的缓解比例高于伪组（真组10/15比伪组3/15，P<0.05）。第4周末的缓解比例真组高于伪组（真组14/15比伪组5/15，P<0.05），两组第4周末的有效比例差异无统计学意义（P>0.05），第8周末的有效比例差异有统计学意义（真组15/15比伪组10/15，P=0.042）。两组无严重不良事件发生，无躁狂或轻躁狂发生，每组各有1例受试者在tACS干预中出现过2次脑鸣。在干预4周末和随访4周末时两组受试者均能够接受该项干预方法和试验过程。 结论： 经颅交流电刺激可能具有减轻抑郁的效应，且未见明显的不良反应，该临床试验操作可行，患者接受度好。.
Keywords: Adverse event; Efficacy; Major depressive disorder; Transcranial alternating current stimulation.