Clinical trial NCT02438072: Drug Metabolism and Antidepressant
Official title: Cocktail Phenotypic Approach to Explore Antidepressant Pharmacokinetic Variability: a Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Depression
Keywords: antidepressive agent
drug metabolism
CYP450
P-glycoprotein
Phenotypic study
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
First posted: 2015-05-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: 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: * 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

Eligibility criteria: Inclusion Criteria:

1. 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
2. Male and female aged from 18 to 70 years
3. Volunteers to participate to the study
4. 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

Primary outcomes:
measure: CYP1A2 activity
timeFrame: >two hours after an oral intake of the cocktail probe drugs
measure: CYP2B6 activity
timeFrame: >two hours after an oral intake of the cocktail probe drugs
measure: CYP2D6 activity
timeFrame: >two hours after an oral intake of the cocktail probe drugs
measure: CYP2C9 activity
timeFrame: >two hours after an oral intake of the cocktail probe drugs
measure: CYP2C19 activity
timeFrame: >two, three and six hours after an oral intake of the cocktail probe drugs
measure: CYP3A4 activity
timeFrame: >two hours after an oral intake of the cocktail probe drugs
measure: P-gp activity
timeFrame: >two, three and six hours after an oral intake of the cocktail probe drugs
Secondary outcomes:
measure: Antidepressant Concentration
timeFrame: almost 6 weeks after the last treatment change
measure: Antidepressant tolerance
timeFrame: almost 6 weeks after the last treatment change
measure: Antidepressant efficacy
timeFrame: almost 6 weeks after the last treatment change
Other outcomes:
Locations:
city: Genève
country: Switzerland
facility: Hôpitaux Universitaires de Genève
Study officials:
affiliation: University Hospital, Geneva
name: Celia Lloret-Linares, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bosilkovska M, Samer CF, Deglon J, Rebsamen M, Staub C, Dayer P, Walder B, Desmeules JA, Daali Y. Geneva cocktail for cytochrome p450 and P-glycoprotein activity assessment using dried blood spots. Clin Pharmacol Ther. 2014 Sep;96(3):349-59. doi: 10.1038/clpt.2014.83. Epub 2014 Apr 10.
citation: Hall-Flavin DK, Winner JG, Allen JD, Carhart JM, Proctor B, Snyder KA, Drews MS, Eisterhold LL, Geske J, Mrazek DA. Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting. Pharmacogenet Genomics. 2013 Oct;23(10):535-48. doi: 10.1097/FPC.0b013e3283649b9a.
citation: Lloret-Linares C, Bosilkovska M, Daali Y, Gex-Fabry M, Heron K, Bancila V, Michalopoulos G, Perroud N, Richard-Lepouriel H, Aubry JM, Desmeules J, Besson M. Phenotypic Assessment of Drug Metabolic Pathways and P-Glycoprotein in Patients Treated With Antidepressants in an Ambulatory Setting. J Clin Psychiatry. 2018 Mar/Apr;79(2):16m11387. doi: 10.4088/JCP.16m11387.