SOURCE: Brain. 145(1):83-91, 2022 Mar 29.

AUTHORS: Wang H; Wang K; Xue Q; Peng M; Yin L; Gu X; Leng H; Lu J; Liu H; Wang D; Xiao J; Sun Z; Li N; Dong K; Zhang Q; Zhan S; Fan C; Min B; Zhou A; Xie Y; Song H; Ye J; Liu A; Gao R; Huang L; Jiao L; Song Y; Dong H; Tian Z; Si T; Zhang X; Li X; Kamiya A; Cosci F; Gao K; Wang Y

ABSTRACT: Treatment of depression with antidepressants is partly effective. Transcranial alternating current stimulation can provide a non-pharmacological alternative for adult patients with major depressive disorder. However, no study has used the stimulation to treat first-episode and drug-na?ve patients with major depressive disorder. We used a randomized, double-blind, sham-controlled design to examine the clinical efficacy and safety of the stimulation in treating first-episode drug-na?ve patients in a Chinese Han population. From 4 June 2018 to 30
December 2019, 100 patients were recruited and randomly assigned to receive 20 daily 40-min, 77.5 Hz, 15 mA, one forehead and two mastoid sessions of active or sham stimulation (n = 50 for each group) in four consecutive weeks (Week 4), and were followed for additional 4-week efficacy/safety assessment without stimulation (Week 8). The primary outcome was a remission rate defined as the 17-item Hamilton Depression Rating Scale (HDRS-17) score <= 7 at Week 8. Secondary analyses were response rates (defined as a reduction of >= 50% in the HDRS-17), changes in depressive symptoms and severity from baseline to Week 4 and Week 8, and rates of adverse events. Data were analysed in an intention-to-treat sample. Forty-nine in the active and 46 in the sham completed the study. Twenty-seven of 50 (54%) in the active treatment group and 9 of 50 (18%) in the sham group achieved remission at the end of Week 8. The remission rate was significantly higher in the active group compared to that in the sham group with a risk ratio of 1.78 (95% confidence interval, 1.29, 2.47). Compared with the sham, the active group had a significantly higher remission rate at Week 4, response rates at Weeks 4 and 8, and a larger reduction in depressive symptoms from baseline to Weeks 4 and 8. Adverse events were similar between the groups. In conclusion, the stimulation on
the frontal cortex and two mastoids significantly improved symptoms in first-episode drug-na?ve patients with major depressive disorder and may be considered as a non-pharmacological intervention for them in an outpatient setting.