Veraart Jolien Ke, Smith-Apeldoorn Sanne Y, van der Meij Annemarie, Spijker Jan, Schoevers Robert A, Kamphuis Jeanine
Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Psychiatry, PsyQ Haaglanden, Parnassia Psychiatric Institute, The Hague, The Netherlands.
J Psychopharmacol. 2025 Jun;39(6):559-570. doi: 10.1177/02698811251332831. Epub 2025 Apr 25.
Oral esketamine for patients with treatment-resistant depression (TRD) could offer certain advantages over other routes, such as intravenous or intranasal, but it has not been systematically studied in a real-world setting.
Here we present results from a relatively large naturalistic study to evaluate the effectiveness, tolerability, and safety of oral esketamine in patients with TRD.
One hundred eighty-five adults with severe TRD (average of 8.1 antidepressant trials plus electroconvulsive therapy in 63% without beneficial outcome) received oral esketamine treatment twice-weekly for 6 weeks with individually titrated doses ranging from 0.5 to 3 mg/kg. Outcome measures included change from baseline to week 6 on the Hamilton Depression Rating Scale (HDRS), Minimal Clinically Important Difference (MCID), response, remission, self-reported symptom improvement, functioning, and side effects.
Oral esketamine treatment improved depressive symptom severity on the HDRS from 21.2 to 15.8 ( < 0.001). MCID, response, and remission rates were 47.1%, 26.8% and 15.6% respectively. In 45.9% of participants, treatment was continued after 6 weeks to maintain initial positive effects. Side effects were reported frequently but were overall well tolerated. The drop-out rate was 7.6%. We found no significant adverse effects associated with urinary tract or cognition.
Repeated treatment with oral esketamine is effective in improving depressive symptom severity in highly treatment-resistant depressive patients. It is safe, well tolerated, and patient-friendly. Considering the level of treatment resistance, outcomes were in the range of studies investigating other routes of (es)ketamine administration.
对于难治性抑郁症（TRD）患者，口服艾氯胺酮相较于其他给药途径（如静脉注射或鼻内给药）可能具有某些优势，但尚未在实际临床环境中进行系统研究。
在此，我们展示一项相对大型的自然主义研究结果，以评估口服艾氯胺酮治疗TRD患者的有效性、耐受性和安全性。
185名患有严重TRD的成年人（平均接受8.1次抗抑郁药物试验，63%的患者接受过电休克治疗但无有益效果），每周接受两次口服艾氯胺酮治疗，持续6周，剂量根据个体情况进行滴定，范围为0.5至3mg/kg。疗效指标包括从基线到第6周汉密尔顿抑郁量表（HDRS）的变化、最小临床重要差异（MCID）、缓解、痊愈、自我报告的症状改善、功能状况及副作用。
口服艾氯胺酮治疗使HDRS抑郁症状严重程度从21.2降至15.8（<0.001）。MCID、缓解率和痊愈率分别为47.1%、26.8%和15.6%。45.9%的参与者在6周后继续接受治疗以维持初始积极效果。副作用报告频繁，但总体耐受性良好。脱落率为7.6%。我们未发现与尿路或认知相关的显著不良反应。
口服艾氯胺酮重复治疗对高度难治性抑郁症患者改善抑郁症状严重程度有效。它安全、耐受性良好且对患者友好。考虑到难治程度，其结果与研究其他（艾）氯胺酮给药途径的研究结果范围相当。
