Abstract
PURPOSE: Major depressive disorder (MDD) has a high incidence and high risk of suicide. Electroconvulsive therapy (ECT) is a highly effective and rapid physical therapy for MDD but limited by adverse effects. Ketamine/esketamine are new emerging rapid antidepressants, which can synergize the efficacy and safety of ECT but come with other side effects. Binaural beat music (BBM) is a non-invasive somatopsychic therapy with the potential to improve mood and assist the efficacy of (es)ketamine. Purpose of this study is to investigate the modification of BBM on effects of (esketamine combined with) ECT for MDD, and the probable interaction between BBM and esketamine, aiming to provide insights for optimizing ECT and improving outcomes of patients with MDD. PATIENTS AND METHODS: This study is a 2×2 factorial, prospective, randomized, controlled, blinded clinical trial that recruiting 476 patients with MDD who require ECT treatments. These participants are randomly 1:1:1:1 allocated to the following groups (119 in each group): ① Group B0E0 (blank sound and normal saline); ② Group B0E1 (blank sound and esketamine); ③ Group B1E0 (BBM and normal saline); ④ group B1E1 (BBM and esketamine). The primary outcome is the response rate of patients to ECT treatment, assessed using the Hamilton depression scale (HAMD). Secondary outcomes include remission rate of depression and remission of suicidal ideation (assessed using HAMD), accompanied psychotic symptoms assessed using the Brief Psychiatric Rating Scale, cognitive function assessed using the Montreal Cognitive Assessment Scale, parameters of ECT, perianesthesia vital signs and anesthesia-related indices, blood biomarkers, and side effects. DISCUSSION: This study provides the first clinical evidence of the effects of BBM alone or interacted with esketamine in patients with MDD undergoing ECT. Our data are expected to suggest BBM's potential for developing better ECT therapeutic strategies, optimizing treatments for MDD and promoting prognosis.