Data_Sheet_1_A Clinical Rationale for Assessing the Impact of Childhood Sexual Abuse on Adjunctive Subcutaneous Esketamine for Treatment-Resistant Depression.docx

Background: A history of child sexual abuse (CSA) is related to higher suicide rates and poor treatment outcomes in depressed adult patients. Twenty years after the first study investigating the effects of ketamine/esketamine on depression and suicide, there is a lack of data on the CSA effects on this emerging treatment. Here, we assess the impact of CSA on adjunctive subcutaneous (SC) esketamine for treatment-resistant depression (TRD).Methods: A directed acyclic graphic (DAG) was designed to identify clinical confounders between CSA and esketamine predictors of response. The confounders were applied in a statistical model to predict depression symptom trajectory in a sample of 67 TRD outpatients.Results: The patient sample had a relatively high prevalence rate of CSA (35.82%). Positive family history of first-degree relatives with alcohol use disorder and sex were clinical mediators of the effects of esketamine in a CSA adult population. Overall, the presence of at least one CSA event was unrelated to esketamine symptom reduction.Conclusions: Unlike responses to conventional antidepressants and psychotherapy, CSA does not appear to predict poor response to esketamine.

背景：儿童性虐待（CSA）与抑郁成年患者自杀率升高和治疗效果不佳有关。自首次研究氯胺酮/艾斯氯胺酮对抑郁和自杀的影响以来，已有二十年，然而关于CSA对此新兴治疗方法的影响数据仍然匮乏。本研究旨在评估CSA对难治性抑郁症（TRD）患者辅助性皮下（SC）艾斯氯胺酮治疗的影响。方法：设计了一个有向无环图（DAG），以识别CSA与艾斯氯胺酮治疗反应预测因子之间的临床混杂因素。将这些混杂因素应用于统计模型中，以预测67例TRD门诊患者的抑郁症状轨迹。结果：患者样本中CSA的患病率相对较高（35.82%）。一级亲属中存在酒精使用障碍和性别方面的阳性家族史是CSA成年人群中艾斯氯胺酮治疗效果的临床中介因素。总体而言，至少一次CSA事件的存在与艾斯氯胺酮症状的减轻无关。结论：与对传统抗抑郁药和心理治疗的反应不同，CSA似乎并不能预测对艾斯氯胺酮的较差反应。