An interventional study of Pharmacogenomic Testing and Antidepressant Agents in Depression / Major Depressive Disorder, sponsored by The Fourth Affiliated Hospital of Zhejiang University School of Medicine. Not yet recruiting. Open to participants aged 14 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-07-31.
Sponsored by The Fourth Affiliated Hospital of Zhejiang University School of Medicine · Not applicable, Interventional, and Treatment
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.
(2) Conventional group: Buccal swabs are collected but not analyzed (sham procedure to maintain blinding balance). Clinicians prescribe antidepressants following Chinese depression treatment guidelines, based on symptom profiles, prior medication history, and clinical judgment. Both groups allow dose adjustments during follow-up, with all changes documented.
4. Data Acquisition and Multi-Dimensional Biomarker Assessment All participants (including healthy controls) undergo baseline assessments: (1) Demographics and clinical history; (2) Peripheral blood for inflammatory markers (CRP, IL-6), endocrine function (thyroid panel: TSH, FT3, FT4), neurotrophic factor (BDNF), and routine biochemistry (liver/kidney function, glucose, lipids); (3) Urine and stool samples for future metabolomic and gut microbiome analyses; (4) Resting-state fMRI scanning, with primary extraction of voxel-mirrored homotopic connectivity (VMHC), and optional exploration of ALFF and FCD; (5) Scale assessments: HAMD-17, HAMA, and TESS. Follow-up visits (Weeks 4, 8, 12) for patient groups include only scale assessments and adverse event recording, without repeated blood draws or imaging.
5. Outcome Definitions Primary outcome: 12-week response rate, defined as the proportion of patients with ≥50% reduction in HAMD-17 total score from baseline (χ² test between groups).
Secondary outcomes: (1) 12-week remission rate (HAMD-17 ≤7); (2) Trajectory of depressive symptoms across time points (repeated-measures ANOVA); (3) Incidence of treatment-emergent adverse events (TESS); (4) Dropout rate due to adverse events; (5) Concordance between initial drug choice and PGx recommendations (descriptive, intervention group only); (6) Time to reach stable effective dose (survival analysis); (7) Frequency of medication adjustments (Mann-Whitney U test).
Exploratory outcomes: (1) Efficacy differences across distinct metabolic phenotypes; (2) Correlations of baseline VMHC and blood biomarkers with 12-week efficacy; (3) Case-control comparisons of all biomarker dimensions; (4) Construction of a comprehensive predictive model integrating clinical, imaging, blood, and genomic features using multivariate logistic regression or machine learning (e.g., random forest, SVM), with cross-validation for performance evaluation (AUC, sensitivity, specificity).
6. Sample Size Justification Sample size is calculated for the primary outcome (two independent proportions, χ² test) using PASS 15.0. Parameters: α=0.05 (two-sided), power 1-β=0.80. Based on published literature, the 12-week response rate for conventional treatment is estimated at 50% (P₁), and the PGx-guided group is expected to achieve 70% (P₂), an absolute difference of 20%. The required sample size is 86 per group. Accounting for a 20% dropout rate, the adjusted sample size is 107.5 per group, rounded up to 110 per group, yielding a total of 220 patients to ensure adequate statistical power.
7. Statistical Analysis Plan Analyses will be performed using SPSS 26.0 and R 4.0. Efficacy analysis follows the intention-to-treat (ITT) principle with multiple imputation for missing data; per-protocol analysis serves as a sensitivity check. Baseline comparisons use t-tests or Mann-Whitney U tests for continuous variables and χ² or Fisher's exact tests for categorical variables. Repeated measures are analyzed using mixed-effects models or repeated-measures ANOVA, adjusting for baseline values. Biomarker exploration: Case-control comparisons use ANCOVA (adjusting for age, sex, etc.); correlation analyses use Pearson/Spearman coefficients. Predictive modeling: Candidate variables with P\<0.10 in univariate analysis enter multivariate logistic regression (forward stepwise) or machine learning algorithms. Internal validation employs 5-fold cross-validation, with AUC assessing discrimination and calibration curves assessing goodness-of-fit.
8. Data Management and Quality Control Data are recorded in an electronic data capture (EDC) system with double-entry verification. Biological samples are aliquoted, coded, and stored at -80°C with routine quality checks. MRI data are processed independently by two blinded neuroradiologists. All adverse events are assessed for severity and causality by study physicians and reported to the ethics committee. Independent monitoring audits are conducted periodically.
9. Ethical Approval and Informed Consent This study has been approved by the Ethics Committee of the Fourth Affiliated Hospital of Zhejiang University School of Medicine. Written informed consent is obtained from all patient participants (or their legal guardians) prior to any study procedures. For healthy controls, data are derived from an anonymized health check-up database archived before January 31, 2026; original consent covered research use, and the ethics committee granted a waiver of re-consent.
10. Study Timeline The total study duration is 36 months from ethics approval: 6 months for preparation and training, 24 months for enrollment and 12-week follow-up completion, and 6 months for data cleaning, statistical analysis, and final reporting.
8,577 studies on the registry are indexed under Depression; 1,720 are open to participants now.
This study's planned enrollment of 220 is above the median of 81 across 7,063 interventional studies indexed under Depression.
Browse Depression studies →The Fourth Affiliated Hospital of Zhejiang University School of Medicine is the lead sponsor of 92 studies on the registry; 78 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
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
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
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.
Time frame: From baseline to Week 12.
12-Week Remission Rate Defined by HAMD-17 Total Score
Unit: percent. The proportion of participants achieving remission, defined as a HAMD-17 total score of 7 or less. Assessments are conducted by trained psychiatrists blinded to group allocation.
Time frame: Week 12.
Longitudinal Trajectory of Depressive Symptoms Assessed by HAMD-17 Over 12 Weeks
Unit: score (0-52 scale points). Change in depressive symptom severity over time assessed by the Hamilton Depression Rating Scale (HAMD-17).
Time frame: Baseline, Week 4, Week 8, and Week 12.
Incidence of Treatment-Emergent Adverse Events Assessed by the TESS Scale
Unit: percent. The incidence of treatment-emergent adverse events assessed by the Treatment Emergent Symptom Scale (TESS).
Time frame: From randomization through Week 12.
Proportion of Participants Withdrawing Due to Adverse Drug Reactions
Unit: percent. The proportion of participants who discontinue the study due to adverse drug reactions.
Time frame: From randomization through Week 12.
Time to Reach Stable Effective Antidepressant Dose
Unit: days. Time required from treatment initiation to reaching a stable and effective antidepressant dose.
Time frame: From randomization through Week 12.
Concordance Between PGx Recommendations and Prescribed Medication
Unit: percent. The percentage of prescriptions that are concordant with pharmacogenomic recommendations.
Time frame: Baseline (time of first prescription).
Frequency of Antidepressant Regimen Adjustments Within 12 Weeks
Unit: count. The total number of antidepressant regimen adjustments made during the study period.medication adjustments (including dose changes, drug switches, or addition of adjunctive therapy) made during the 12-week treatment period due to either insufficient therapeutic response or unacceptable adverse effects. This outcome reflects the clinical practicality and stability of the treatment strategy in each arm. The adjustment frequency is compared between the pharmacogenomics-guided therapy group and the conventional treatment group using the Mann-Whitney U test. Descriptive statistics (median, interquartile range) will be reported for each group.
Time frame: From randomization through Week 12.
Incidence of Clinically Significant Laboratory Abnormalities
Unit: percent. Proportion of participants developing clinically significant laboratory abnormalities.
Time frame: Baseline to Week 12.
Amplitude of Low-Frequency Fluctuation (ALFF) Levels
Unit: z-score. Comparison of ALFF z-scores between MDD patients and healthy controls using ANCOVA.
Time frame: Baseline
Functional Connectivity Density (FCD)
Unit: z-score. Comparison of baseline FCD z-scores between groups.
Time frame: Baseline
Correlation Between Baseline VMHC and Change in HAMD-17 Score at 12 Weeks
Unit: Pearson correlation coefficient (r). Correlation analysis between baseline voxel-mirrored homotopic connectivity (VMHC) and change in HAMD-17 score.
Time frame: Baseline VMHC with Week 12 HAMD-17 change
Serum C-Reactive Protein (CRP) Concentration
Unit: mg/L Description: Case-control t-test/Mann-Whitney; within-patients, Pearson correlation with baseline HAMD-17 and Week-12 % change.
Time frame: Baseline
Serum Interleukin-6 (IL-6) Concentration
Unit: pg/mL
Time frame: Baseline
Serum Brain-Derived Neurotrophic Factor (BDNF) Concentration
Unit: ng/mL Description: Same as #14.
Time frame: Baseline
Serum Thyroid-Stimulating Hormone (TSH) Concentration
Unit: mIU/L Description: Same case-control and correlation analyses.
Time frame: Baseline
Serum Free Triiodothyronine (FT3) Concentration
Unit: pmol/L Description: Same case-control and correlation analyses.
Time frame: Baseline
Serum Free Thyroxine (FT4) Concentration
Unit: pmol/L Description: Same case-control and correlation analyses.
Time frame: Baseline
Multimodal Integrated Predictive Model Performance for 12-Week Response
Unit: Area under ROC curve (AUC), sensitivity (percent), specificity (percent). Performance of the logistic regression model integrating clinical, PGx, VMHC, and blood biomarkers.
Time frame: Baseline predictors with Week 12 outcome
Genotype-Phenotype Associations with 12-Week Clinical Outcomes
Unit: Odds ratio (OR). Association of CYP2D6/CYP2C19 metabolizer phenotypes with response, remission, and adverse events.Description: Compare response/remission/AE rates across CYP2D6/CYP2C19 metabolizer phenotypes. Chi-square/Fisher's for categorical; ANOVA/Kruskal-Wallis for continuous % reduction.
Time frame: Baseline genotyping; outcomes at Week 12
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