{
  "abstract": "Introduction 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.Methods and analysis 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.Ethics and dissemination 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.Trial registration number NCT06266715.",
  "authors": [
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Qianqian Xin"
    },
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Huafeng Wei"
    },
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Dhirendra Paudel"
    },
    {
      "affiliations": [
        "Key Laboratory of Mental Health of the Ministry of Education, Guangzhou, Guangdong, China",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China",
        "Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangzhou, Guangdong, China",
        "Guangdong Province Key Laboratory of Psychiatric Disorders, Guangzhou, Guangdong, China",
        "Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou, Guangdong, China",
        "State Key Laboratory of Organ Failure Research, Guangzhou, Guangdong, China",
        "Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Nengyuan Hu"
    },
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Yuhan Zhao"
    },
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Yuan Feng"
    },
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Xian Luo"
    },
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Meilei Su"
    },
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Xiang Xue"
    },
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Haokang Huang"
    },
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Zhihong Lv"
    },
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Chong Tang"
    },
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Yongzhi Zhao"
    },
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Miaoqin Tan"
    },
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Xinyou Luo"
    },
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Yun Yang"
    },
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Qiuqu Liu"
    },
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Minghong Huang"
    },
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Yihong Cheng"
    },
    {
      "affiliations": [
        "Key Laboratory of Mental Health of the Ministry of Education, Guangzhou, Guangdong, China",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China",
        "Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangzhou, Guangdong, China",
        "Guangdong Province Key Laboratory of Psychiatric Disorders, Guangzhou, Guangdong, China",
        "Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou, Guangdong, China",
        "State Key Laboratory of Organ Failure Research, Guangzhou, Guangdong, China",
        "Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Tianming Gao"
    },
    {
      "affiliations": [
        "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",
        "Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, China"
      ],
      "name": "Bin Zhang"
    }
  ],
  "title": "Intravenous administration of adenosine triphosphate combined with escitalopram in major depressive disorder: protocol for a randomised, double-blind, placebo-controlled trial",
  "uid": "8c47231b-2352-5e63-b53c-8da82ce7922f"
}