Ascorbic Acid for Major Depressive Disorder Treated With Modified Electroconvulsive Therapy: A Randomized Controlled Trial Protocol

Background: Major depressive disorder is marked by high prevalence and elevated suicide risk. Modified electroconvulsive therapy (MECT) is a well-established, effective, and fast-acting method for treating major depressive disorder with acute suicide control, though its application is constrained by adverse effects. Enhancing the therapeutic effectiveness and/or reducing the adverse effects of MECT holds clinical practical value. Ascorbic acid (AA) can enhance the effectiveness of some antidepressants, yet its effects on depressed patients undergoing MECT lack clinical evidence. This study investigates whether AA augments the antidepressant effects of MECT in patients with major depressive disorder. Methods and Analysis: This is a prospective, randomized, double-blind, placebo-controlled trial. We will enroll 240 patients with major depressive disorder scheduled for MECT. Participants will be treated either with intravenous AA (500 mg, n = 120) or with intravenous normal saline (n = 120), administered immediately before each MECT session, just prior to induction of general anesthesia. The primary outcome is the treatment response rate, defined as the proportion of patients with a ≥50% reduction in the 24-item Hamilton Depression Rating Scale (HAMD-24) score. Secondary outcomes include remission rate, presence of psychotic symptoms, cognition, and adverse effects. This study is expected to provide an evidence based, safe, and cost effective strategy for optimizing MECT protocols, as well as potential directions for future mechanistic investigations. Ethics and Dissemination: The study will adhere to the principles of the Declaration of Helsinki. It received approval from the Institutional Review Board of the First Affiliated Hospital of Chongqing Medical University, China (Approval No. 2024-235-01). Written informed consent will be obtained from all participants. Results will be disseminated through peer reviewed publications and conference presentations. This study will offer the first clinical evidence of the effects of AA on patients diagnosed with major depressive disorder undergoing MECT. The findings may indicate the potential of AA for refining MECT based therapeutic strategies, optimizing depression treatment protocols, and improving clinical prognosis. Clinical Trial Registration: The study has been registered on https://www.chictr.org.cn/index.html (registration number: ChiCTR2500095678; registration link: https://www.chictr.org.cn/showproj.html?proj=248072).