Transcutaneous electrical cranial‐auricular acupoint stimulation versus escitalopram for mild‐to‐moderate depression: An assessor‐blinded, randomized, non‐inferiority trial

Aim Transcutaneous electrical cranial‐auricular acupoint stimulation (TECAS) is a novel non‐invasive therapy that stimulates acupoints innervated by the trigeminal and auricular vagus nerves. An assessor‐blinded, randomized, non‐inferiority trial was designed to compare the efficacy of TECAS and escitalopram in mild‐to‐moderate major depressive disorder. Methods 468 participants received two TECAS sessions per day at home ( n = 233) or approximately 10–13 mg/day escitalopram ( n = 235) for 8 weeks plus 4‐week follow‐up. The primary outcome was clinical response, defined as a baseline‐to‐endpoint ≥50% reduction in Montgomery‐Åsberg Depression Rating Scale (MADRS) score. Secondary outcomes included remission rate, changes in the severity of depression, anxiety, sleep and life quality. Results The response rate was 66.4% on TECAS and 63.2% on escitalopram with a 3.2% difference (95% confidence interval [CI], −5.9% to 12.9%) in intention‐to‐treat analysis, and 68.5% versus 66.2% with a 2.3% difference (95% CI, −6.9% to 11.4%) in per‐protocol analysis. The lower limit of 95% CI of the differences fell within the prespecified non‐inferiority margin of −10% ( P ≤ 0.004 for non‐inferiority). Most secondary outcomes did not differ between the two groups. TECAS‐treated participants who experienced psychological trauma displayed a markedly greater response than those without traumatic experience (81.3% vs 62.1%, P = 0.013). TECAS caused much fewer adverse events than escitalopram. Conclusions TECAS was comparable to escitalopram in improving depression and related symptoms, with high acceptability, better safety profile, and particular efficacy in reducing trauma‐associated depression. It could serve an effective portable therapy for mild‐to‐moderate depression.