Efficacy and Mechanisms of Escitalopram in Drug-Naïve First-Episode Major Depressive Disorder

The goal of this project is to quantify the effectiveness and safety of escitalopram oxalate oral solution in the treatment of first-episode, drug-naïve patients with major depressive disorder, and to explore the mechanisms underlying its antidepressant effects using multi-omics approaches. By integrating clinical, cognitive, laboratory, imaging, genetic, and environmental data, the study aims to identify patient subgroups who are most likely to benefit from escitalopram, thereby promoting individualized and precision treatment for depression.

This multicenter, prospective, single-arm intervention study will enroll 200 adults aged 18-65 years with major depressive disorder, who will receive escitalopram oxalate oral solution for 8 weeks. Depressive symptoms, cognitive function, and adverse events will be assessed at baseline, during treatment, and after 8 weeks of treatment to evaluate efficacy and safety. Escitalopram blood concentrations will be measured at week 4 to monitor treatment adherence and support safety evaluation. Through comprehensive data collection and multimodal analysis, this project seeks to clarify the biological mechanisms of escitalopram and provide evidence to guide more precise clinical use of antidepressant therapy.

Study Overview

• Status: Recruiting
• Conditions: Depression - Major Depressive Disorder
• Intervention / Treatment: Drug: Escitalopram (Oral antidepressant)

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Weihua Yue; Phone Number: 86-010-82805307; Email: dryue@bjmu.edu.cn
• Study Contact Backup: Name: Tong Yu; Phone Number: 86-010-82805307; Email: tongyu@bjmu.edu.cn

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100191
      • Recruiting
      • Peking University Sixth Hostipal
      • Contact: Weihua Yue; Phone Number: 010-82805307; Email: dryue@bjmu.edu.cn
      • Contact: Tong Yu; Phone Number: 010-82805307; Email: tongyu@bjmu.edu.cn
  • Hebei
    • Baoding, Hebei, China, 071000
      • Recruiting
      • Hebei Provincial Mental Health Center
      • Contact: Yunshu Zhang; Phone Number: +86 15533222271; Email: yunshucoffee@sina.com
    • Shijiazhuang, Hebei, China, 050031
      • Recruiting
      • The First Hospital of Hebei Medical University
      • Contact: Xueyi Wang; Phone Number: 0311-87155488; Email: ydyywxy@163.com
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • Recruiting
      • The First Affiliated Hospital of China Medical University
      • Contact: Gang Zhu; Phone Number: +86 13940252095; Email: gzhu@cmu.edu.cn
  • Shandong
    • Jinan, Shandong, China, 250014
      • Recruiting
      • Shandong Mental Health Center
      • Contact: Yuandong Gong; Phone Number: 0531-86336687; Email: 525882199@qq.com
      • Contact: Yuanyuan Dai; Phone Number: 0531-86336621; Email: 412882716@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18-65 years (including 18 and 65), no gender restriction, Han Chinese ethnicity.
2. Meets the diagnostic criteria for depressive disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), confirmed by the Mini-International Neuropsychiatric Interview, version 5.0 (MINI).
3. Outpatients or inpatients; Hamilton Depression Rating Scale-17 items (HAMD-17) score ≥17; Hypomania Checklist-32 (HCL-32) score ≤13; and Clinical Global Impressions-Severity (CGI-S) score ≥4.
4. First depressive episode (duration ≤3 months), with no use of antidepressants or other psychotropic medications in the past 3 months.
5. Written informed consent obtained from the patient.

Exclusion Criteria:

1. Meet DSM-IV diagnostic criteria other mental disorders, including schizophrenia spectrum and other psychotic disorders, bipolar and related disorders, obsessive-compulsive disorder, etc..
2. Individuals with intellectual disabilities or who are unable to cooperate for other reasons, or those lacking or having incomplete civil capacity during the onset of illness;
3. Suffering from neurological or organic brain diseases (such as stroke, cerebral hemorrhage, brain tumors, Parkinson's disease, epilepsy, etc.) and a history of severe traumatic brain injury;
4. Have attempted suicide within the past 3 months, or currently present a high suicide risk, defined as a Montgomery-Åsberg Depression Rating Scale (MADRS) item 10 score ≥5.
5. Are pregnant or breastfeeding, cannot use reliable contraception during the study, or plan to conceive (or impregnate a partner) within 3 months after study initiation.
6. Have known allergies to escitalopram oxalate or its excipients.
7. Are currently taking medications that may interfere with the evaluation of escitalopram efficacy.
8. Have participated in another drug clinical trial within the past 3 months.
9. Have contraindications to MRI scanning, such as metal implants or claustrophobia.
10. Considered unsuitable for study participation by the investigators for any other reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Escitalopram; Participants will receive escitalopram oral solution as open-label monotherapy.	Drug: Escitalopram (Oral antidepressant); Participants will receive escitalopram oral solution as open-label monotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Hamilton Depression Rating Scale (HAMD)	The outcome is assessed by 17-item Hamilton Depression Rating Scale (HAMD-17) Scale. Total HAMD scores range from 0 to 24, with higher scores indicating more severe depressive symptoms. The change of HAMD from baseline to 8-week (after intervention) was used as the primary outcome.	Week 4 and 8 of treatment duration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain imaging features	Acquisition was performed by magnetic resonance imaging	Week 0 and 8 of treatment duration
Escitalopram Therapeutic drug monitoring		Week 4 of treatment duration
Change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS)	Change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The MADRS consists of 10 clinician-rated items with a total score ranging from 0 to 60. Higher scores indicate more severe depressive symptoms.	Week 4 and 8 of treatment duration
Response to treatment	Treatment response is defined as a ≥50% reduction from baseline in either the 17-item Hamilton Depression Rating Scale (HAMD-17) total score or the Montgomery-Åsberg Depression Rating Scale (MADRS) total score.	Week 4 and 8 of treatment duration
Clinical Global Impression-Severity of Illness (CGI-S)	The Clinical Global Impression-Severity of Illness (CGI-S) scale is a clinician-rated measure of illness severity ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Higher scores indicate greater illness severity.	Baseline; Week 4 and 8 of treatment duration
Change from baseline in C-BCT score	Change from baseline in the Cognitive Bias Questionnaire (C-BCT) T-score. The C-BCT score is standardized as a T-score ranging from 0 to 100. Higher T-scores indicate greater cognitive function.	Week 4 and 8 of treatment duration
Change from baseline in Hamilton Anxiety Rating Scale (HAMA)	Change from baseline in the Hamilton Anxiety Rating Scale (HAMA) total score. The HAMA contains 14 items with a total score ranging from 0 to 56. Higher scores indicate more severe anxiety symptoms.	Week 4 and 8 of treatment duration
Treatment Emergent Symptom Scale (TESS)	The Treatment Emergent Symptom Scale (TESS) is used to assess adverse events during treatment. The total score ranges from 0 to 350 (please specify according to the version used). Higher scores indicate greater severity of treatment-emergent adverse effects.	Baseline; Week 4 and 8 of treatment duration
Change from baseline in Snaith-Hamilton Pleasure Scale (SHAPS)	Change from baseline in the Snaith-Hamilton Pleasure Scale (SHAPS) total score. The SHAPS consists of 14 items with a total score ranging from 0 to 56. Higher scores indicate greater anhedonia.	Week 4 and 8 of treatment duration
The Temporal Experience of Pleasure Scale (TEPS)	Change from baseline in the Temporal Experience of Pleasure Scale (TEPS) total score. The score ranges from 0 to 100 depending on the version used. Higher scores indicate greater hedonic capacity.	Week 4 and 8 of treatment duration
Childhood Trauma Questionnaire (CTQ)	The Childhood Trauma Questionnaire (CTQ) assesses childhood maltreatment experiences. The total score ranges from 28 to 140. Higher scores indicate more severe childhood trauma.	Baseline
Change from baseline in Ruminative Responses Scale (RRS)	Change from baseline in the Ruminative Responses Scale (RRS) total score. The total score ranges from 22 to 88. Higher scores indicate greater rumination.	Week 4 and 8 of treatment duration
Change from baseline in Pittsburgh Sleep Quality Index (PSQI)	Change from baseline in the Pittsburgh Sleep Quality Index (PSQI) global score. The total score ranges from 0 to 21. Higher scores indicate poorer sleep quality.	Week 4 and 8 of treatment duration
Change from baseline in Connor-Davidson Resilience Scale (CD-RISC)	Change from baseline in the Connor-Davidson Resilience Scale (CD-RISC) total score. The total score ranges from 0 to 100 (25-item version). Higher scores indicate greater psychological resilience.	Week 4 and 8 of treatment duration
Change from baseline in liver function biomarkers	Change from baseline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Both biomarkers are measured in IU/L.	Baseline, Week 4, and Week 8 of treatment duration
Change from baseline in lipid biomarkers	Change from baseline in total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). All biomarkers are measured in mmol/L.	Baseline, Week 4, and Week 8 of treatment duration
Change from baseline in fasting blood glucose	Change from baseline in fasting blood glucose, measured in mmol/L.	Baseline, Week 4, and Week 8 of treatment duration
Change from baseline in glycated hemoglobin (HbA1c)	Change from baseline in glycated hemoglobin (HbA1c), measured as percentage (%).	Baseline, Week 4, and Week 8 of treatment duration

Collaborators and Investigators

• Sponsor: Peking University
• Collaborators: First Hospital of China Medical University; The First Hospital of Hebei Medical University; Shandong Mental Health Center; Hebei Provincial Mental Health Center

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 14, 2026
• First Submitted That Met QC Criteria: March 14, 2026
• First Posted (Actual): March 18, 2026

Study Record Updates

• Last Update Posted (Actual): August 20, 2026
• Last Update Submitted That Met QC Criteria: August 18, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: depression; antidepressant
• Additional Relevant MeSH Terms: Behavioral Symptoms; Behavior; Depression; Psychotropic Drugs; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Amines; Nitriles; Central Nervous System Agents; Propylamines; Benzofurans; Escitalopram; Antidepressive Agents
• Other Study ID Numbers: 2025-109 (Unidade Local de Saúde Lisboa Ocidental (ULSLO))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No