Major Depressive Disorders
Conditions
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
Interventions
For the assessment of drug-metabolizing enzyme activity, the patients will be given the cocktail probe drugs, by oral route, one time during the study: * 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
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Criteria for rating medication trials for antidepressant failure and level of resistance | 20, 40, 70 days | — |
| MARS Score | 20, 40, 70 days | — |
| Tobacco use | 20, 40, 70 days | Fagerstrom test |
| FISBER score | 20, 40, 70 days | — |
| PRISE-M score | 20, 40, 70 days | — |
| Mood disorder | 20, 40, 70 days | — |
| Anxiety scale Tyrer | 20, 40, 70 days | — |
| QIDS-SR16 | 20, 40, 70 days | — |
Countries
France
Contacts
Primary Contactcelia Lloret-Linares, MD
Outcome results
None listed