Accurate Clinical Study of Medication in Patients With Depression Via Pharmacogenomics (PGx) and Therapeutic Drug Monitoring (TDM) of Venlafaxine

Study Overview
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Brief Summary
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This study evaluates the efficacy of PGx-guided medication in patients with depression treated with Venlafaxine and the efficacy of the combination of PGx and TDM in patients with depression treated with Venlafaxine. Half of participants will receive PGx-guided treatment, while the other half will receive routine treatment. After the 8th week, the PGx-guided treatment group would be randomly divided into two groups. Of which, half of participants will receive the combination of PGx and TDM, and the other half will receive PGx -guided medication only.

Detailed Description
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The current clinical medication is based on Trial and Error, while the traditional medication is mainly based on experience. The study mainly optimizes the treatment path from two perspectives: to help clinicians select drugs accurately through the detection of PGx; to help clinicians monitor the whole process of drug use through TDM and adjust the dosage in time to achieve better treatment. PGx tests take the information of metabolic, transporting and target genetic factors into account comprehensively. Furthermore, clinical effects depend on blood concentration rather than dose concentration. TDM aims to monitor blood concentration, which is related to drug efficacy and toxicity. Venlafaxine is an antidepressant drugs of the 5-hydroxytryptamine selective seratonin re-uptake inhibitors (SSRIs), which has been approved by FDA for the treatment of depressive disorders, depressive disorders with anxiety symptoms, generalized anxiety disorders and social anxiety disorders since 1994.

Official Title
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Accurate Clinical Study of Medication in Patients With Depression Via Pharmacogenomics (PGx) and Therapeutic Drug Monitoring (TDM) of Venlafaxine

Conditions
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Depression

Intervention / Treatment
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* Diagnostic Test: pharmacogenomics
* Diagnostic Test: pharmacogenomics & therapeutic drug monitoring
* Drug: Venlafaxine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with endogenous depression, with any of the following 4 symptoms: ① Interest Loss; ② Hypothymia; ③ Early awakening; ④ Serious in the morning and relieved at night; ⑤ Hysteresis or agitation of movement of Spirit; ⑥ Appetite loss; ⑦ Weight loss; ⑧ Loss of libido; Scores of 17 items in Hamilton Depression Scale (HAM-D17): over 17 points; First-episode patients or relapsed patients without taking any antidepressant drugs in the recent 3 months; No significant abnormalities are shown in physical examination (temperature, pulse, blood pressure, head and neck, chest and abdomen). No obvious abnormalities in laboratory examination (Thyroid Function). Informed patient consent. Exclusion Criteria: Those diagnosed with mental disorders other than major depressive disorders (with the exception of combination of anxiety disorders); non-endogenous depressive disorders; Patients with stroke, brain tumor and other brain organic diseases; Patients receiving combined drugs (but there is no need to exclude patients receving drugs against sleep disorders, such as Eszopiclone, alprazolam or estazolam); History of drug allergy; Pregnant and lying-in women; Patients with serious suicidal tendencies.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A group: Routine treatment group<br>Routine dosage of venlafaxine during the first 4 weeks. | Drug: Venlafaxine<br>* Venlafaxine hydrochloride sustained-release capsules 75mg x 14 tablets x 1 case 75-225mg/morning<br>|
| Experimental: B group: PGx-guided group<br>The PGx test results guide the dosage of venlafaxine during the first 4 weeks. | Diagnostic Test: pharmacogenomics<br>* pharmacogenomics<br>Drug: Venlafaxine<br>* Venlafaxine hydrochloride sustained-release capsules 75mg x 14 tablets x 1 case 75-225mg/morning<br>|
| Active Comparator: C group: Routine PGx-guided group<br>The PGx test results guide the dosage of venlafaxine between 4th and 8th weeks. | Diagnostic Test: pharmacogenomics<br>* pharmacogenomics<br>Drug: Venlafaxine<br>* Venlafaxine hydrochloride sustained-release capsules 75mg x 14 tablets x 1 case 75-225mg/morning<br>|
| Active Comparator: D group: The combination of PGx and TDM group<br>The PGx and TDM test results guide the dosage of venlafaxine between 4th and 8th weeks. | Diagnostic Test: pharmacogenomics<br>* pharmacogenomics<br>Diagnostic Test: pharmacogenomics & therapeutic drug monitoring<br>* pharmacogenomics & therapeutic drug monitoring<br>Drug: Venlafaxine<br>* Venlafaxine hydrochloride sustained-release capsules 75mg x 14 tablets x 1 case 75-225mg/morning<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score reduction rate of Hamilton Depression Rating Scale | Reduction Rate=[(total score before treatment-total score after treatment)/total score before treatment] *100% Healed: reduction rate ≥ 75%; Significant Effective: reduction rate≥50％and <75％; ③Effective: reduction rate≥25％ and <50％; ④Invalid: Reduction rate < 25% | 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PGx, pharmacogenomics, therapeutic drug monitoring, TDM, Venlafaxine, depression