MetAbolism vaRiability of VEnLafaxine
- Conditions
- Major Depressive Disorders
- Interventions
- Drug: cocktail probe drugs
- Registration Number
- NCT02590185
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
Regarding the direct costs and the social value of depression, the decision of an antidepressant treatment prescription must be optimized as much as possible. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence burden and costs of affective disorders.
There is hope that biomarkers will be found to guide treatment selection. It might be of decisive interest to be able to assess an individual's metabolism activity. We propose here to explore the relationship between the activity of drug-metabolizing enzymes (DME) and transporters- assessed by a phenotypic approach and the efficacy of antidepressants. We will focus on venlafaxine (V) that provides a reasonable second-step choice for patients with depression and is used extensively in psychiatric practice, and the metabolism of which involves several cytochromes (CYP) P450 enzymes and the transporter P-gp.
Thus, the primary objective of this study is to study the correlation between the concentration of V and its metabolite ODesmethylV (V+ODV) and drug metabolism variability assessed by a phenotypic approach, in patients with major depressive disorder and MADRS ≥ 20 despite 4 weeks of V at 150mg or less
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 205
- Patient (Hospitalized or outpatient) with major depressive disorder and MADRS ≥ 20 at visit of selection
- Patients non responders to V after 4 weeks of V at 150mg or less
- Decision of the psychiatrist to increase the dose of V at visit of selection
- Understanding of French language and able to give a written inform consent.
- Informed consent signed to participate to the study
- Individuals covered by social security regimen
- Patients treated by more than one antidepressant
- Patients currently treated with one of the drug substrate of the cocktail
- Sensitivity or contra-indication to any of the substrate drugs used
- Current pregnancy, desire to get pregnant, or breastfeeding
- Bipolar disorder and schizophrenia
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description cocktail probe drugs cocktail probe drugs * A capsule of omeprazole ABBOTT® 10mg * 10 mg of an oral liquid formulation of Dextrométhorphane bromhydrate (Drill Pierre FABRE MEDICAMENT® 5mg/5mL, syrup) * 1 mg of an injectable solution of Midazolam for oral administration (Midazolam Panpharma® 1mg/mL, injectable solution) * A tablet of fexofenadine Zentiva® 120mg
- Primary Outcome Measures
Name Time Method The CYP2C19 activity 2 hours 5-hydroxyomeprazole/omeprazole
The CYP2D6 activity 2 hours dextrorphan/dextromethorphan ratio
The CYP3A4 activity 2 hours 1-hydroxymidazolam/ midazolam ratio
The P-gp activity 2, 3 and 6 hours Fexofenadine AUC based on fexofenadine concentrations
- Secondary Outcome Measures
Name Time Method Mood disorder 20, 40, 70 days PRISE-M score 20, 40, 70 days FISBER score 20, 40, 70 days QIDS-SR16 20, 40, 70 days Tobacco use 20, 40, 70 days Fagerstrom test
MARS Score 20, 40, 70 days Criteria for rating medication trials for antidepressant failure and level of resistance 20, 40, 70 days Anxiety scale Tyrer 20, 40, 70 days
Trial Locations
- Locations (2)
Fernand Widal hospital
🇫🇷Paris, France
Lariboisiere hospital
🇫🇷Paris, France