{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T23:03:22Z","timestamp":1782342202485,"version":"3.54.5"},"reference-count":47,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T00:00:00Z","timestamp":1724976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Janssen Korea Ltd.","award":["54135419DEP4009"],"award-info":[{"award-number":["54135419DEP4009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>This study assesses the early effectiveness of esketamine nasal spray (ESK) in adults with treatment-resistant depression (TRD) 1 day after the first administration, as monitored through self-assessment via the mobile application, Esketamine Continuing Assessment for Relapse Prevention (EsCARe). In this multi-center, open-label, single-arm study, adults aged 18\u201365 years diagnosed with TRD after failing at least two antidepressant therapies were enrolled from five tertiary hospitals in South Korea. During the induction period, participants self-administered ESK twice weekly and used the EsCARe app daily to record mood, sleep, and somatic symptoms. Key clinical assessments, the Patient Health Questionnaire-9 (PHQ-9), the Hamilton Depression Rating Scale (HAMD), and the Generalized Anxiety Disorder Scale (GAD-7), were measured at baseline and at weeks 2 and 4. The reliability and validity of EsCARe was assessed. The treatment results indicated significant improvements in depressive and anxiety symptoms, with notable reductions in the PHQ-9 and the GAD-7 by week 2, and the HAMD by week 4. The EsCARe app reliably and validly monitored depressive symptoms and demonstrated a significant reduction in depressive symptoms 1 day after the first administration of ESK. Using ESK, complemented by mobile self-monitoring, effectively reduces the symptoms of TRD early in the treatment course. Integrating mobile health technology into the therapeutic regimen highlights a significant advancement in managing TRD, offering patients and clinicians immediate feedback on treatment efficacy.<\/jats:p>","DOI":"10.3390\/ph17091143","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T06:46:29Z","timestamp":1725000389000},"page":"1143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Multi-Center, Open-Label, Single-Arm Study to Investigate the Early Effectiveness of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression Using a Mobile Self-Monitoring Application"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7123-9535","authenticated-orcid":false,"given":"Junhyung","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul 03181, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5341-0933","authenticated-orcid":false,"given":"Seung-Hoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Korea University Guro Hospital, College of Medicine, Korea University, Seoul 08308, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheolmin","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Korea University Ansan Hospital, Korea University College of Medicine, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu-Man","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine, Seoul 02475, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6981-0931","authenticated-orcid":false,"given":"Sung Joon","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul 03181, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3781-9939","authenticated-orcid":false,"given":"Narei","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Hallym University Sacred Heart Hospital, Anyang 14068, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4021-8907","authenticated-orcid":false,"given":"Changsu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Korea University Guro Hospital, College of Medicine, Korea University, Seoul 08308, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S0006-3223(03)00231-2","article-title":"Diagnosis and Definition of Treatment-Resistant Depression","volume":"53","author":"Fava","year":"2003","journal-title":"Biol. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1176\/ajp.2006.163.11.1905","article-title":"Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report","volume":"163","author":"Rush","year":"2006","journal-title":"Am. J. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.biopsych.2015.10.018","article-title":"Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study","volume":"80","author":"Singh","year":"2016","journal-title":"Biol. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1001\/jamapsychiatry.2017.3739","article-title":"Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression: A Randomized Clinical Trial","volume":"75","author":"Daly","year":"2018","journal-title":"JAMA Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1176\/appi.ajp.2018.17060720","article-title":"Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study","volume":"175","author":"Canuso","year":"2018","journal-title":"Am. J. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1176\/appi.ajp.2019.19020172","article-title":"Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined with a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study","volume":"176","author":"Popova","year":"2019","journal-title":"Am. J. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1017\/S1092852924000105","article-title":"Effects of Esketamine Nasal Spray on Depressive Symptom Severity in Adults with Treatment-Resistant Depression and Associations Between the Montgomery-\u00c5sberg Depression Rating Scale and the 9-Item Patient Health Questionnaire","volume":"29","author":"Naranjo","year":"2024","journal-title":"CNS Spectr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.2217\/cer-2022-0149","article-title":"Safety and Effectiveness of Intranasal Esketamine for Treatment-Resistant Depression: A Real-World Retrospective Study","volume":"11","author":"Brendle","year":"2022","journal-title":"J. Comp. Eff. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.jad.2022.09.043","article-title":"Real-World Experience of Esketamine Use to Manage Treatment-Resistant Depression: A Multicentric Study on Safety and Effectiveness (REAL-ESK Study)","volume":"319","author":"Martinotti","year":"2022","journal-title":"J. Affect. Disord."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/wps.21120","article-title":"Treatment-Resistant Depression: Definition, Prevalence, Detection, Management, and Investigational Interventions","volume":"22","author":"McIntyre","year":"2023","journal-title":"World Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez de Le\u00f3n, B., del Pino-Sede\u00f1o, T., Serrano-P\u00e9rez, P., Rodr\u00edguez \u00c1lvarez, C., Bejarano-Quisoboni, D., and Trujillo-Mart\u00edn, M.M. (2022). Effectiveness of Interventions to Improve Medication Adherence in Adults With Depressive Disorders: A Meta-Analysis. BMC Psychiatry, 22.","DOI":"10.1186\/s12888-022-04120-w"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s12991-020-00306-2","article-title":"How to Improve Adherence to Antidepressant Treatments in Patients with Major Depression: A Psychoeducational Consensus Checklist","volume":"19","author":"Albert","year":"2020","journal-title":"Ann. Gen. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/BF02686921","article-title":"Mood Variability and the Intensity of Depressive States","volume":"14","author":"McConville","year":"1996","journal-title":"Curr. Psychol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1037\/1528-3542.6.3.383","article-title":"Diurnal Mood Variation in Major Depressive Disorder","volume":"6","author":"Peeters","year":"2006","journal-title":"Emotion"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.copsyc.2015.01.002","article-title":"Ecological Momentary Assessment (EMA) of Depression-Related Phenomena","volume":"4","author":"Armey","year":"2015","journal-title":"Curr. Opin. Psychol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Colombo, D., Fern\u00e1ndez-\u00c1lvarez, J., Patan\u00e9, A., Semonella, M., Kwiatkowska, M., Garc\u00eda-Palacios, A., Cipresso, P., Riva, G., and Botella, C. (2019). Current State and Future Directions of Technology-Based Ecological Momentary Assessment and Intervention for Major Depressive Disorder: A Systematic Review. J. Clin. Med., 8.","DOI":"10.3390\/jcm8040465"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.jpsychires.2016.01.011","article-title":"Ecological Momentary Assessment Versus Standard Assessment Instruments for Measuring Mindfulness, Depressed Mood, and Anxiety Among Older Adults","volume":"75","author":"Moore","year":"2016","journal-title":"J. Psychiatr. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e14179","DOI":"10.2196\/14179","article-title":"Ecological Momentary Assessment Using Smartphones in Patients With Depression: Feasibility Study","volume":"5","author":"Maatoug","year":"2021","journal-title":"JMIR Form. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jad.2009.06.019","article-title":"A 4-Item Measure of Depression and Anxiety: Validation and Standardization of the Patient Health Questionnaire-4 (PHQ-4) in the General Population","volume":"122","author":"Wahl","year":"2010","journal-title":"J. Affect. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Urtasun, M., Daray, F.M., Teti, G.L., Coppolillo, F., Herlax, G., Saba, G., Rubinstein, A., Araya, R., and Irazola, V. (2019). Validation and Calibration of the Patient Health Questionnaire (PHQ-9) in Argentina. BMC Psychiatry, 19.","DOI":"10.1186\/s12888-019-2262-9"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1093\/ijnp\/pyz039","article-title":"Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1)","volume":"22","author":"Fedgchin","year":"2019","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1001\/jamapsychiatry.2019.1189","article-title":"Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients with Treatment-Resistant Depression: A Randomized Clinical Trial","volume":"76","author":"Daly","year":"2019","journal-title":"JAMA Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association. [5th ed.].","DOI":"10.1176\/appi.books.9780890425596"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s10194-015-0583-8","article-title":"Validation of the Generalized Anxiety Disorder-7 (GAD-7) and GAD-2 in Patients with Migraine","volume":"16","author":"Seo","year":"2015","journal-title":"J. Headache Pain"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"210","DOI":"10.3988\/jcn.2014.10.3.210","article-title":"Validation of a Korean Version of the Insomnia Severity Index","volume":"10","author":"Cho","year":"2014","journal-title":"J. Clin. Neurol."},{"key":"ref_26","first-page":"456","article-title":"Validity and Reliability of the Korean Version of the Hamilton Depression Rating Scale (K-HDRS)","volume":"44","author":"Yi","year":"2005","journal-title":"J Korean Neuropsychiatr. Assoc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.kjms.2014.11.001","article-title":"Dimensional Approach to Symptom Factors of Major Depressive Disorder in Koreans, Using the Brief Psychiatric Rating Scale: The Clinical Research Center for Depression of South Korea Study","volume":"31","author":"Park","year":"2015","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1097\/00003643-200706001-00097","article-title":"Validity of the Modified Observer\u2019s Assessment of Alertness\/Sedation Scale (MOAA\/S) During Low Dose Propofol Sedation: 3AP6-3","volume":"24","author":"Kowalski","year":"2007","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1093\/occmed\/kqv043","article-title":"The Hamilton Rating Scale for Depression","volume":"65","author":"Sharp","year":"2015","journal-title":"Occup. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Johnson, S.U., Ulvenes, P.G., \u00d8ktedalen, T., and Hoffart, A. (2019). Psychometric Properties of the General Anxiety Disorder 7-Item (GAD-7) Scale in a Heterogeneous Psychiatric Sample. Front. Psychol., 10.","DOI":"10.3389\/fpsyg.2019.01713"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1093\/sleep\/34.5.601","article-title":"The Insomnia Severity Index: Psychometric Indicators to Detect Insomnia Cases and Evaluate Treatment Response","volume":"34","author":"Morin","year":"2011","journal-title":"Sleep"},{"key":"ref_32","first-page":"153","article-title":"The Prevalence and Clinical Characteristics Associated with Diagnostic and Statistical Manual Version-5-Defined Anxious Distress Specifier in Adults with Major Depressive Disorder: Results from the International Mood Disorders Collaborative Project","volume":"7","author":"McIntyre","year":"2016","journal-title":"J. Affect. Disord."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1002\/da.22968","article-title":"Defining Treatment-Resistant Depression","volume":"37","author":"Gaynes","year":"2020","journal-title":"Depress Anxiety"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1080\/13651501.2022.2030757","article-title":"Esketamine Nasal Spray in Patients with Treatment-Resistant Depression: The Real-World Experience in the French Cohort Early-Access Programme","volume":"26","author":"Samalin","year":"2022","journal-title":"Int. J. Psychiatry Clin. Pract."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Pepe, M., Bartolucci, G., Marcelli, I., Pesaresi, F., Brugnami, A., Caso, R., Fischetti, A., Grisoni, F., Mazza, M., and Camardese, G. (2023). The Patient\u2019s Perspective on the Effects of Intranasal Esketamine in Treatment-Resistant Depression. Brain Sci., 13.","DOI":"10.3390\/brainsci13101494"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1097\/BCR.0b013e31822ac7d1","article-title":"The Effect of Ketamine Administration on Nocturnal Sleep Architecture","volume":"32","author":"Gottschlich","year":"2011","journal-title":"J. Burn. Care Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/164_2017_51","article-title":"Ketamine-Induced Glutamatergic Mechanisms of Sleep and Wakefulness: Insights for Developing Novel Treatments for Disturbed Sleep and Mood","volume":"253","author":"Duncan","year":"2017","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.jad.2024.01.003","article-title":"Hypersomnia as a Predictor of Response to Intravenous Ketamine\/Intranasal Esketamine in Treatment-Resistant Depression","volume":"349","author":"Pazdernik","year":"2024","journal-title":"J. Affect. Disord."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e22890","DOI":"10.2196\/22890","article-title":"Smartphone-Delivered Ecological Momentary Interventions Based on Ecological Momentary Assessments to Promote Health Behaviors: Systematic Review and Adapted Checklist for Reporting Ecological Momentary Assessment and Intervention Studies","volume":"9","author":"Dao","year":"2021","journal-title":"JMIR Mhealth Uhealth"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1037\/h0087036","article-title":"Review of Psychological Testing: A Practical Approach to Design and Evaluation","volume":"46","author":"McKelvie","year":"2005","journal-title":"Can. Psychol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"110970","DOI":"10.1016\/j.jpsychores.2022.110970","article-title":"Validation of the Patient Health Questionnaire-4 (PHQ-4) to Screen for Depression and Anxiety in the Greek General Population","volume":"160","author":"Christodoulaki","year":"2022","journal-title":"J. Psychosom. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"104","DOI":"10.9758\/cpn.2021.19.1.104","article-title":"Standardization of the Korean Version of the Patient Health Questionnaire-4 (PHQ-4)","volume":"19","author":"Kim","year":"2021","journal-title":"Clin Psychopharmacol. Neurosci."},{"key":"ref_43","unstructured":"Kline, T. (2014). Psychological Testing: A Practical Approach to Design and Evaluation, SAGE Publications, Inc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1192\/bjp.180.5.461","article-title":"The Work and Social Adjustment Scale: A Simple Measure of Impairment in Functioning","volume":"180","author":"Mundt","year":"2002","journal-title":"Br. J. Psychiatry"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev.clinpsy.3.022806.091415","article-title":"Ecological Momentary Assessment","volume":"4","author":"Shiffman","year":"2008","journal-title":"Annu. Rev. Clin. Psychol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/BF02310555","article-title":"Coefficient Alpha and the Internal Structure of Tests","volume":"16","author":"Cronbach","year":"1951","journal-title":"Psychometrika"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"563","DOI":"10.5664\/jcsm.27351","article-title":"Relationships Between the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Clinical\/Polysomnographic Measures in a Community Sample","volume":"4","author":"Buysse","year":"2008","journal-title":"J. Clin. Sleep Med."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/9\/1143\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:45:41Z","timestamp":1760111141000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/9\/1143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,30]]},"references-count":47,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ph17091143"],"URL":"https:\/\/doi.org\/10.3390\/ph17091143","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,30]]}}}