高精度经颅直流电刺激联合抗抑郁药治疗伴焦虑痛苦特征抑郁症的探索性随机对照研究

High-definition transcranial direct current stimulation combined with antidepressants in the treatment of major depressive disorder with anxious distress:a pilot randomized controlled trial

目的探讨联合高精度经颅直流电刺激(high-definition transcranial direct current stimulation,HD-tDCS)治疗对伴焦虑痛苦特征抑郁症患者临床疗效、不良反应和可行性。方法招募镇江市精神卫生中心收治的伴焦虑痛苦特征抑郁症患者60例,按照随机数字表法分为真刺激组与伪刺激组,每组各30例,2组均在抗抑郁药基础上使用HD-tDCS刺激患者左侧背外侧前额叶。真刺激组采用2 mA的电流刺激20 min,伪刺激组仅在刺激开始与结束的30 s内有电流通过。每周5次,连续2周。在治疗前、治疗2周末、治疗4周末、治疗6周末,分别采用HAMD_(17)和蒙哥马利抑郁量表(Montgomery-Asberg Depression Rating Scale,MARDS)以及HAMA和贝克焦虑量表(Beck Anxiety Inventory,BAI)评估患者的抑郁、焦虑症状。采用重复测量方差分析和简单效应分析比较2组临床症状变化的差异。采用Fisher确切概率法比较2组有效率、缓解率以及不良反应率等。结果(1)HAMD_(17)、BAI评分时间与分组存在交互效应(F=3.29、2.99,均P<0.05);HAMD_(17)、BAI、MARDS、HAMA评分组别主效应(F=4.40~7.94)以及不同治疗时间主效应(F=35.42~247.59)均有统计学意义(均P<0.05)。(2)简单效应分析显示治疗前、治疗2周末2组HAMD_(17)评分以及治疗前、治疗2周末、治疗6周末时BAI评分差异均无统计学意义。真刺激组治疗4周末、治疗6周末时的HAMD_(17)评分以及治疗4周末时BAI评分均显著低于伪刺激组(均P<0.05)。(3)真刺激组在治疗4周末时缓解比例(16/20)以及有效比例(19/20)均高于伪刺激组(9/19和13/19),真刺激组在治疗6周末时缓解比例(18/20)也高于伪刺激组(11/19),差异均有统计学意义(均P<0.05);2组治疗6周末时有效比例差异无统计学意义。(4)2组无严重不良事件发生,无躁狂或轻躁狂发生。2组脱落率以及皮肤刺痛、痒感、头痛等不良反应差异无统计学意义。结论HD-tDCS治疗抑郁症伴焦虑痛苦特征患者疗效显著且起效迅速,安全性较好,但仍需大样本量的临床研究进行验证。

Objective To explore the efficacy,adverse reactions,and feasibility of high-definition transcranial direct current stimulation(HD-tDCS)treating major depressive disorder(MDD)patients with anxious distress.Methods Sixty cases of MDD with anxious distress admitted to Zhenjiang Mental Health Center were recruited as participants.All patients were allocated into either the active treatment group or the sham group based on the random number table method.HD-tDCS was utilized in both groups to stimulate the left dorsolateral prefrontal cortex on the basis of conventional antidepressant treatment.In the active group,2mA current stimulation was used for 20 min,and in the sham group,a 30-sceond stimulation was adopted at the beginning and the end of the stimulation.Participants in both group were treated once a day,five times a week for two consecutive weeks.Anxiety and depression symptoms of the patients were assessed respectively by the Hamilton depression scale(HAMD_(17)),the Montgomery-Asberg Depression Rating Scale(MARDS),the Hamilton Anxiety Scale(HAMA),and the Beck Anxiety Inventory(BAI)at the baseline,2nd,4th,and the 6th weekend of the treatment.The differences between active treatment and sham groups were analyzed by repetitive measure analysis of variance and simple effect analysis.Fisher′s exact probability test was used to compare the effective rate,remission rate and adverse reaction rate between the two groups.Results(1)The interaction of times and groups was significant in HAMD_(17)(F=3.29,P<0.05)and BAI(F=2.99,P<0.05).In all measurement instruments,the main effects of groups(F=4.40-7.94)and times(F=35.42-247.59)were significant(P<0.05).(2)Findings from the simple effect analysis showed that:there were no significant differences in the scores of HAMD_(17) at baseline and the 2nd assessment between the two groups.Similarly,no significant differences were found in BAI at baseline,the 2nd and the 6th weekend of the treatment between two groups(P>0.05).(3)The scores of HAMD_(17) at the 4th and the 6th week,BAI at the 4th weekend of the treatment in the active group were significantly lower than that in the sham group(P<0.05).(4)At the 4th weekend of the treatment,the active group had a remission rate of 16/20 and a response rates of 19/20,which were higher than 9/19 and 13/19,respectively,in the sham group(P<0.05).Also,the remission rate(18/20)in the active group was higher than that in the sham group(11/19)at the 6th weekend of the treatment.(P<0.05).As for the response rates,differences were not found between the two groups at the 6th weekend of the treatment.(5)The overall dropout rate had no significant differences in-between(P>0.05).As for the safety outcome,the rate of adverse events(e.g.,itching,tingling and headache)showed no significant differences between the two groups.Additionally,no severe adverse events or mania was reported.Conclusions This study indicated that HD-tDCS has significant efficacy and high safety in the treatment among MDD patient with anxious distress.Nevertheless,further large sample clinical studies are warranted to confirm the findings of the current investigation.