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Ascorbic Acid and Esketamine for Mental Disorders in Women with Miscarriage: A Randomized Controlled Double-Blind Trial Protocol.

Zhaojuan Ke, Ying Zhang, Binyang Cai, Jie Luo, Yao Ma, Qibin Chen, Linya Deng

Neuropsychiatric Disease and Treatment 2025 DOI: 10.2147/NDT.S516355 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Double-blind Peer reviewed
Sample size 424
Population Women with miscarriage undergoing painless curettage
Interventions Ascorbic acid Esketamine
Duration 7-day follow-up for primary outcome
Topics Anxiety Depression Ketamine Esketamine
Keywords Pain Sleep disorders Vitamin c Pregnancy complications Alternative medicine Depression treatment Anxiety disorders Mental health
Citations 1
Key findings The trial aims to determine whether ascorbic acid alone or combined with esketamine prevents depression and other mental disorders after miscarriage curettage.

Abstract

Pregnancy leads to vulnerabilities and susceptibilities to mental disorders. Miscarriage, as an adverse pregnancy outcome, and following curettage for treatment, add the risks of further psychiatric disorders, including depression, anxiety, insomnia, etc., and current approaches to prevention are unsatisfactory. Ketamine and its S-enantiomer esketamine can prevent postpartum depression, and esketamine even treats depressive symptoms after miscarriage curettage, but their side effects bring limitations. Ascorbic acid (AA, Vitamin C) can modulate mood and enhance ketamine's antidepressant efficacy synergistically, reducing its dosages and adverse effects potentially. The purpose of this study is to clarify the beneficial modification of AA on esketamine for preventing depression and other mental disorders in patients with miscarriage after painless curettage, as well as the interaction between AA and esketamine. This study is a 2×2 factorial, double-blinded, randomized, controlled trial that will recruit women with miscarriage undergoing painless curettage. A total of 424 participants will be recruited and randomly 1:1:1:1 allocated to the following four groups (106 in each): Group A0K0 (normal saline and normal saline), Group A0K1 (normal saline and esketamine), Group A1K0 (AA and normal saline), and Group A1K1 (AA and esketamine). The primary outcome is the incidence of depression on postoperative day 7, assessed with the Edinburgh Postnatal Depression Scale (EPDS). The secondary outcomes include the EPDS score, assessments of anxiety, sleep, and pain, adverse events, perianesthetic data and patient satisfaction. This study provides the clinical trial-based evidence of the effects of AA alone or in combination/interacting with the emerging rapid-acting antidepressant esketamine on depression and other mental disorders in patients with miscarriage undergoing painless curettage. Our data are expected to suggest AA's potential application for optimizing strategies of promoting post-miscarriage mental health, and its possible adjunctive improvement of (es)ketamine's usage as antidepressants. One major limitation is that this study is a single-center study, and the results might be biased due to regional factors.

Comparable studies

Other randomized controlled trials on esketamine for anxiety, most cited first.

Study Year Design Participants
Meaningful Change in Depression Symptoms Assessed with the Patient Health Questionnaire (PHQ-9) and Montgomery-Åsberg Depression Rating Scale (MADRS) Among Patients with Treatment Resistant Depression in Two, Randomized, Double-blind, Active-controlled Trials of Esketamine Nasal Spray Combined With a New Oral Antidepressant Patients with treatment resistant depression 2020 Randomized controlled trial
Treatment Response With Esketamine Nasal Spray Plus an Oral Antidepressant in Patients With Treatment-Resistant Depression Without Evidence of Early Response Patients with treatment-resistant depression 2021 Pooled post hoc analysis of two phase 3, double-blind, active-controlled studies
Predictors of response and remission in patients with treatment-resistant depression: A post hoc pooled analysis of two acute trials of esketamine nasal spray Patients with treatment-resistant depression 2023 Post hoc analysis of two pooled phase 3 double-blind placebo- and active-controlled trials n = 518
Assessment of health-related quality of life and health status in patients with treatment-resistant depression treated with esketamine nasal spray plus an oral antidepressant Patients aged 18-64 years with treatment-resistant depression 2023 Phase 3, randomized, double-blind, short-term flexibly dosed study n = 223
The effect of esketamine on postoperative anxiety and depression in patients with thyroid cancer: A randomized, double-blind, placebo-controlled, parallel-group trial. Female patients with thyroid cancer scheduled for surgery under general anesthesia 2025 Randomized controlled trial n = 80

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