Drug Metabolism and Antidepressant

Study Overview
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Brief Summary
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We propose here to explore systematically the association between drug-metabolizing enzymes activity assessed by a phenotypical approach and antidepressant plasma concentration, efficacy and tolerance in the clinical setting. During one year, patients receiving antidepressant will be included in tis prospective clinical, naturalistic and descriptive pilot study.

Detailed Description
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Objectives To describe drug metabolism variability in depressive patients using a phenotypic approach Study design Prospective, clinical, naturalistic, descriptive study During a consultation with their clinician, depressive patients will receive information. During the visit V0 with an investigator: patients will be included: Verification of inclusion and non inclusion criteria Reminder participation conditions Inclusion, signature of consent Collection of clinical and demographic features Between V0 and V1, for patients with change in antidepressant therapy, will take place telephone interviews every two weeks, conducted by the clinician to evaluate treatment depression response (tolerance and efficacy) During the visit V1, will take place: Phenotypic study Genetic study Dosage of current antidepressant drug Clinical evaluation: efficacy and tolerance Number of patients During one year, the protocol will be proposed to all patients with depression and decision of change in antidepressant therapy, and all patients with stability od prescription since almost 6 weeks. The inclusion of approximately 100 patients is expected. Name of the finished product Zyban®, Froben®, Antra®, Bexine®, Dormicum® Telfast® Name of the active substance Omeprazole (10 mg, A02BC01) Caffeine (50 mg, N06BC01) Flurbiprofen (10 mg, M01AE09) Dextromethorphan (10 mg, R05DA09) Midazolam (1 mg, N05CD08) Fexofenadine (25mg, R06AX26 ) Bupropion (20 mg, N06AX12) Duration of treatment One time during the study, one day (Visit 1) Time plan of research -Duration for the patient: The study will stop when the patient has performed the V1 study Minimal delay between V0 and V1: 6 weeks (5-7 weeks) : for patient with decision to change the treatment, 5 days for patients with stability of treatment since almost 6 weeks. Maximal delay of participation for the patient: 4 months even when V1 was not performed -Overall duration of inclusion: one year Maximal overall duration of the study: 12 months+4 months= 16 months Maximal duration for the analytical study since the beginning of the study= 16 months+6 months: 22 months. Maximal delay for communication of the results: 2 years after the beginning of the study

Official Title
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Cocktail Phenotypic Approach to Explore Antidepressant Pharmacokinetic Variability: a Pilot Study

Conditions
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Depression

Intervention / Treatment
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* Drug: Omeprazole (10 mg, A02BC01)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with clinical diagnosis of depression and decision to change antidepressant therapy (augmentation or switch) OR Patients with clinical diagnosis of depression and stability of prescription since almost 6 weeks Male and female aged from 18 to 70 years Volunteers to participate to the study Understanding of French language and able to give a written inform consent. Exclusion Criteria: Renal or hepatic impairment (Clearance below 60mL/min, AST or ALT over 3N) Sensitivity to any of the substrate drugs used ECG showing long QT interval (>0.46sec) No antidepressant dosage available Current pregnancy or desire to get pregnant Criteria to perform V1 Sufficient compliance between V0 and V1 Six weeks period without change in antidepressant therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Overall population<br> | Drug: Omeprazole (10 mg, A02BC01)<br>* The cocktail of drug substrates will be given one time, one day during the study, to explore the activity of CYP 1A2, 2B6, 2C9, 2C19, 3A4, 2D6, and the P-gp<br>* Other names: Caffeine (50 mg, N06BC01);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CYP1A2 activity | paraxanthine/caffeine | >two hours after an oral intake of the cocktail probe drugs | 
| CYP2B6 activity | 4-hydroxybupropion/ bupropion | >two hours after an oral intake of the cocktail probe drugs | 
| CYP2D6 activity | dextrorphan / dextromethorphan | >two hours after an oral intake of the cocktail probe drugs | 
| CYP2C9 activity | 4-hydroxyflurbiprofen/ flurbiprofen | >two hours after an oral intake of the cocktail probe drugs | 
| CYP2C19 activity | 5-hydroxyomeprazole/ omeprazole | >two, three and six hours after an oral intake of the cocktail probe drugs | 
| CYP3A4 activity | 1-hydroxymidazolam/ midazolam | >two hours after an oral intake of the cocktail probe drugs | 
| P-gp activity | Limited sampling fexofenadine AUC | >two, three and six hours after an oral intake of the cocktail probe drugs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antidepressant Concentration |  | almost 6 weeks after the last treatment change | 
| Antidepressant tolerance | FISBER test | almost 6 weeks after the last treatment change | 
| Antidepressant efficacy | Tests: MADRS, Hamilton, QIDS-16 | almost 6 weeks after the last treatment change | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antidepressive agent, drug metabolism, CYP450, P-glycoprotein, Phenotypic study