Clinical trial NCT02590185: MetAbolism vaRiability of VEnLafaxine
Official title: Xploring Venlafaxine Pharmacokinetic Variability by a Phenotyping Approach
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Major Depressive Disorders
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2015-10-28
Enrollment: 205
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: The CYP2C19 activity
timeFrame: 2 hours
measure: The CYP2D6 activity
timeFrame: 2 hours
measure: The CYP3A4 activity
timeFrame: 2 hours
measure: The P-gp activity
timeFrame: 2, 3 and 6 hours
Secondary outcomes:
measure: Tobacco use
timeFrame: 20, 40, 70 days
measure: Mood disorder
timeFrame: 20, 40, 70 days
measure: Anxiety scale Tyrer
timeFrame: 20, 40, 70 days
measure: QIDS-SR16
timeFrame: 20, 40, 70 days
measure: Criteria for rating medication trials for antidepressant failure and level of resistance
timeFrame: 20, 40, 70 days
measure: MARS Score
timeFrame: 20, 40, 70 days
measure: PRISE-M score
timeFrame: 20, 40, 70 days
measure: FISBER score
timeFrame: 20, 40, 70 days
Other outcomes:
Locations:
city: Paris
country: France
facility: Fernand Widal hospital
city: Paris
country: France
facility: Lariboisiere hospital
Study officials:
affiliation: APHP
name: Celia Lloret-Linares, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lloret-Linares C, Daali Y, Chevret S, Nieto I, Moliere F, Courtet P, Galtier F, Richieri RM, Morange S, Llorca PM, El-Hage W, Desmidt T, Haesebaert F, Vignaud P, Holtzmann J, Cracowski JL, Leboyer M, Yrondi A, Calvas F, Yon L, Le Corvoisier P, Doumy O, Heron K, Montange D, Davani S, Deglon J, Besson M, Desmeules J, Haffen E, Bellivier F. Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study). BMC Pharmacol Toxicol. 2017 Nov 7;18(1):70. doi: 10.1186/s40360-017-0173-2.