Biomarkers and Pharmacogenomics for Precision Depression Therapy

NCT07738497 | Not Yet Recruiting DMC

• 1 other identifier: KY-2025-327
• Study Type: interventional
• Target: 220
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: The clinical management of major depressive disorder (MDD) is hampered by the lack of objective biomarkers and high inter-individual variability in drug response, with conventional antidepressants achieving only a 50% response rate. Objective and Design: This prospective, randomized, parallel-controlled trial aims to enroll 220 MDD patients, who will be allocated 1:1 to either a pharmacogenomics (PGx)-guided therapy group (treatment selection based on genetic testing) or a conventional treatment group (treatment as usual per guidelines), with a 12-week follow-up. Additionally, a matched healthy control cohort will be included for cross-sectional biomarker comparisons. Intervention and Outcomes: Patients in the PGx group undergo buccal swab testing for key genetic polymorphisms (e.g., CYP2D6, CYP2C19) to inform antidepressant type and dosage. The primary outcome is the 12-week response rate (≥50% reduction in HAMD-17 score from baseline). Secondary outcomes include remission rate, incidence of adverse drug reactions, and medication adjustment frequency. Exploratory Aims: Multidimensional baseline data-including resting-state fMRI (VMHC), peripheral blood biomarkers (inflammatory cytokines, thyroid function, BDNF), urinary metabolites, and gut microbiome-will be integrated to construct a predictive model for treatment efficacy and to identify novel MDD biomarkers. Scientific Significance: This study seeks to validate the clinical utility of PGx-guided prescribing and to advance the shift from symptom-based diagnosis towards a biological-characteristic-based precision medicine framework for depression.

Conditions

Depression / Major Depressive Disorder

Keywords

Pharmacogenetics; Personalized Medicine; Biomarkers; Inflammation; Antidepressive Agents; Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (1)

• Title: 12-Week Response Rate Defined by HAMD-17 Score Reduction

  Unit: percent. The proportion of participants achieving a clinical response, defined as a reduction in HAMD-17 score of 50% or greater from baseline.

  From baseline to Week 12.

Secondary Outcomes (8)

• 12-Week Remission Rate Defined by HAMD-17 Total Score

  Week 12.

• Longitudinal Trajectory of Depressive Symptoms Assessed by HAMD-17 Over 12 Weeks

  Baseline, Week 4, Week 8, and Week 12.

• Incidence of Treatment-Emergent Adverse Events Assessed by the TESS Scale

  From randomization through Week 12.

• Proportion of Participants Withdrawing Due to Adverse Drug Reactions

  From randomization through Week 12.

• Time to Reach Stable Effective Antidepressant Dose

  From randomization through Week 12.

Other Outcomes (11)

• Amplitude of Low-Frequency Fluctuation (ALFF) Levels

  Baseline

• Functional Connectivity Density (FCD)

  Baseline

• Correlation Between Baseline VMHC and Change in HAMD-17 Score at 12 Weeks

  Baseline VMHC with Week 12 HAMD-17 change

Study Arms (2)

Pharmacogenomics-Guided Antidepressant Therapy

EXPERIMENTAL

Patients receive pharmacogenomic testing via buccal swab at baseline. The test detects polymorphisms in CYP2D6, CYP2C19, CYP3A4/5, CYP1A2, CYP2B6, CYP2C9, HTR2A, and SLC6A4. Clinicians select antidepressant type and starting dosage based on the genotype report (metabolizer phenotype) to optimize efficacy and minimize adverse drug reactions.

Diagnostic Test: Pharmacogenomic Testing

Guideline-Based Conventional Antidepressant Therapy

ACTIVE COMPARATOR

Patients undergo a sham buccal swab procedure without genetic analysis. Clinicians prescribe antidepressants following the Chinese Depression Prevention and Treatment Guidelines, based on clinical experience, symptom profiles, prior medication history, and physical condition. Medication adjustments are allowed during the 12-week follow-up.

Drug: Antidepressant Agents

Interventions

Pharmacogenomic Testing DIAGNOSTIC_TEST

Buccal swab collection for targeted genotyping of polymorphisms in CYP2D6, CYP2C19, CYP3A4/5, CYP1A2, CYP2B6, CYP2C9, HTR2A, and SLC6A4. The assay classifies patients into ultrarapid, normal, intermediate, or poor metabolizer phenotypes for CYP450 enzymes, and provides response/risk predictions for SSRIs (escitalopram, sertraline, fluoxetine, paroxetine, fluvoxamine, citalopram), SNRIs (venlafaxine, duloxetine, milnacipran), mirtazapine, and bupropion. A written report with genotype-based drug and dosage recommendations is issued to the clinician.

Also known as: PGx Genotyping, CYP450 Genotyping Panel, Antidepressant Genetic Test

Pharmacogenomics-Guided Antidepressant Therapy

Antidepressant Agents DRUG

Oral administration of first-line or second-line antidepressants approved for major depressive disorder, including selective serotonin reuptake inhibitors (SSRIs: escitalopram, sertraline, fluoxetine, paroxetine, fluvoxamine, citalopram), serotonin-norepinephrine reuptake inhibitors (SNRIs: venlafaxine, duloxetine, milnacipran), noradrenergic and specific serotonergic antidepressants (NaSSA: mirtazapine), and bupropion. Dosing follows clinical guidelines. In the experimental arm, selection and initial dosage are guided by the pharmacogenomic test report; in the conventional arm, selection and dosage are determined by physician expertise and standard care guidelines. Dose adjustments are permitted at Weeks 4, 8, and 12 based on efficacy and tolerability.

Also known as: SSRIs, SNRIs, Mirtazapine, Bupropion

Guideline-Based Conventional Antidepressant Therapy

Eligibility Criteria

• Age: 14 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Clinical diagnosis of Major Depressive Disorder (MDD) according to DSM-5 criteria
• Age between 18 and 60 years
• Baseline HAMD-17 total score ≥ 17
• Ability to provide written informed consent

You may not qualify if:

• History of other psychiatric disorders (e.g., bipolar disorder, schizophrenia)
• Presence of severe physical illnesses or major central nervous system diseases
• History of sedative-hypnotic, alcohol, or substance abuse
• Pregnancy, lactation, or planning to become pregnant during the study
• Significant abnormalities in ECG, complete blood count, or liver/kidney/thyroid function tests

Sponsors & Collaborators

• The Fourth Affiliated Hospital of Zhejiang University School of Medicine: lead

MeSH Terms

Conditions

Depression; Depressive Disorder, Major; Inflammation

Interventions

Pharmacogenomic Testing; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Mirtazapine; Bupropion

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services; Psychotropic Drugs; Central Nervous System Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Propiophenones; Ketones; Organic Chemicals

Central Study Contacts

Haiyan XIE, MD

CONTACT

+86 0579-89935006; 8015138@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2026
• First Posted: July 31, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): January 19, 2029
• Study Completion (Estimated): January 19, 2029
• Last Updated: July 31, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share