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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.
During the visit V0 with an investigator: patients will be included:
During the visit V1, will take place:
Phenotypic study
Genetic study
Dosage of current antidepressant drug
Clinical evaluation: efficacy and tolerance
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Overall population | Other |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Omeprazole (10 mg, A02BC01) | Drug | 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 |
| 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 |
| 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 |
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Inclusion Criteria:
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
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Celia Lloret-Linares, MD, PhD | Contact | 0041 79 55 36 389 | Celia.LloretLinares@hcuge.ch |
| Name | Affiliation | Role |
|---|---|---|
| Celia Lloret-Linares, MD, PhD | University Hospital, Geneva | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpitaux Universitaires de Genève | Recruiting | Geneva | 1205 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24722393 | Background | 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. | |
| 24018772 | Result | 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. |
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| ID | Term |
|---|---|
| D003863 | Depression |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D009853 | Omeprazole |
| D005480 | Flurbiprofen |
| D003915 | Dextromethorphan |
| D008874 | Midazolam |
| C093230 | fexofenadine |
| D016642 | Bupropion |
| D002110 | Caffeine |
| ID | Term |
|---|---|
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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|
| Antidepressant efficacy | Tests: MADRS, Hamilton, QIDS-16 | almost 6 weeks after the last treatment change |
| 29570971 | Derived | 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. |
| D011725 |
| Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D011422 | Propionates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D011427 | Propiophenones |
| D007659 | Ketones |
| D014970 | Xanthines |
| D011688 | Purinones |
| D011687 | Purines |