Xin Qianqian, Wei Huafeng, Paudel Dhirendra, Hu Nengyuan, Zhao Yuhan, Feng Yuan, Luo Xian, Su Meilei, Xue Xiang, Huang Haokang, Lv Zhihong, Tang Chong, Zhao Yongzhi, Tan Miaoqin, Luo Xinyou, Yang Yun, Liu Qiuqu, Huang Minghong, Cheng Yihong, Gao Tianming, Zhang Bin
Department of Psychiatry, Sleep Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Key Laboratory of Mental Health of the Ministry of Education, Guangzhou, Guangdong, China.
BMJ Open. 2025 Aug 28;15(8):e098281. doi: 10.1136/bmjopen-2024-098281.
Major depressive disorder (MDD) is the most prevalent mental illness. Antidepressants with rapid efficacy and acceptable tolerance have been investigated for many years. A preclinical study performed by our group revealed that the dysregulation of extracellular ATP is related to the pathophysiology of depression and that the medial prefrontal cortex-lateral habenula pathway is a potential cellular and neural circuit target for ATP involvement in depression-like behaviour. Moreover, through small-sample clinical trials, the group has preliminarily discovered the antidepressant effect of ATP. However, the antidepressant effects of and neural circuit mechanisms underlying ATP in depressed patients remain largely unexplored. This study pioneers the intravenous use of escitalopram in combination with oral escitalopram for the treatment of MDD, thus representing a new direction in antidepressant research.
This clinical study is a single-centre, randomised, double-blind, placebo-controlled, superiority trial involving 120 MDD patients evenly divided into two groups. The experimental group will receive an intravenous injection of 10 mL ATP in 100 mL normal saline (NS) two times per day (BD) for 2 weeks, whereas the control group will receive 110 mL NS BD for 2 weeks. All of the participants will take 10 mg of oral escitalopram daily for 4 weeks, with flexible adjustment thereafter based on clinical response. Our primary outcome will be the change in the Hamilton Depression Rating Scale 24 (HAMD-24) score from baseline to 2 and 4 weeks. The secondary outcomes assessment (at 1, 2, 4, 12 and 24 weeks) will be done by the Montgomery-Asberg Depression Rating Scale, HAMD-24, Hamilton Anxiety Scale, Beck Depression Inventory, Snaith-Hamilton Pleasure Scale, Clinical Global Impression, Insomnia Severity Index, Columbia-Suicide Severity Rating Scale, Side Effect Rating Scale of Asberg, MRI, cognitive function and cytokine level analyses.
The study protocol and all of the related materials were approved by the Institutional Ethics Committee of Nanfang Hospital, Southern Medical University (No. NFEC-2024-070, NFEC-2020-153, Guangzhou, China). Results will be disseminated through peer-reviewed publications and conference presentations.
NCT06266715.
重度抑郁症（MDD）是最常见的精神疾病。多年来一直在研究具有快速疗效和可接受耐受性的抗抑郁药。我们团队进行的一项临床前研究表明，细胞外ATP的失调与抑郁症的病理生理学有关，并且内侧前额叶皮质-外侧缰核通路是ATP参与抑郁样行为的潜在细胞和神经回路靶点。此外，通过小样本临床试验，该团队初步发现了ATP的抗抑郁作用。然而，ATP在抑郁症患者中的抗抑郁作用及其神经回路机制在很大程度上仍未得到探索。本研究率先采用静脉注射艾司西酞普兰联合口服艾司西酞普兰治疗MDD，从而代表了抗抑郁研究的一个新方向。
本临床研究是一项单中心、随机、双盲、安慰剂对照的优效性试验，涉及120例MDD患者，平均分为两组。实验组将每天两次（bid）静脉注射10 mL ATP于100 mL生理盐水中（NS），共2周，而对照组将每天两次静脉注射110 mL NS，共2周。所有参与者每天口服10 mg艾司西酞普兰，共4周，此后根据临床反应进行灵活调整。我们的主要结局将是汉密尔顿抑郁量表24项（HAMD-24）评分从基线到第2周和第4周的变化。次要结局评估（在第1、2、4、12和24周）将通过蒙哥马利-阿斯伯格抑郁量表、HAMD-24、汉密尔顿焦虑量表、贝克抑郁量表、斯奈斯-汉密尔顿愉悦量表、临床总体印象、失眠严重程度指数、哥伦比亚自杀严重程度评定量表、阿斯伯格副作用评定量表、MRI、认知功能和细胞因子水平分析来进行。
研究方案及所有相关材料均经南方医科大学南方医院机构伦理委员会批准（编号：NFEC-2024-070，NFEC-2020-153，中国广州）。研究结果将通过同行评审出版物和会议报告进行传播。
NCT06266715。
