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An Observational Study of Venlafaxine and CYP2D6 in Clinical Practice
- Source :
- Università degli Studi del Piemonte Orientale-IRIS
- Publication Year :
- 2014
- Publisher :
- Clinical Laboratory Publications, 2014.
-
Abstract
- BACKGROUND: Venlafaxine (V) is a serotonin-norepinephrine selective reuptake inhibitor, mainly metabolized by cytochrome P4502D6 (CYP2D6). CYP2D6 polymorphisms result in a variety of phenotypes: poor (PMs), intermediate (IMs), extensive (EMs), and ultrarapid metabolizers (UMs). PMs usually show poor tolerance to drugs metabolized by CYP2D6, while UMs need greater doses. The aim of this study was to evaluate the impact of CYP2D6 genotype on V dosage, therapeutic response, and side effects in a clinical outpatient setting. METHODS: 47 patients with Major Depressive Disorder, treated with V 75 - 300 mg/day, underwent CYP2D6 genotyping using the INFINITI-CYP2D6 assay. Duration of treatment and clinical outcome (Clinical Global Impression [CGI] effectiveness index) were assessed. RESULTS: CGI assessment was performed after 6 weeks, 6 months, and 1 year of treatment with a V median dose of 150 mg/day. CYP2D6 genotyping resulted in 1 PM, 3 IMs, 42 EMs, and 1 UM. The UM took the greatest V dose (375 mg) without side effects; IMs/PMs took moderate/high doses of V (150 - 300 mg) without adverse effects; EMs displayed high response variability. CONCLUSIONS: PM/IM patients responded to V differently than expected according to genotype. However, the UM patient responded to a dosage higher than the usual therapeutic range and without developing side effects, suggesting an association between CYP2D6 gene duplication and the therapeutic efficacy of venlafaxine. The CYP2D6 genotyping may thus provide clinicians with a potential explanation for those patients requiring greater doses of CYP2D6 substrates in order to obtain the same therapeutic efficacy.
- Subjects :
- Adult
Male
CYP2D6
medicine.medical_specialty
Venlafaxine
digestive system
General Biochemistry, Genetics and Molecular Biology
Therapeutic index
Internal medicine
medicine
Humans
Practice Patterns, Physicians'
skin and connective tissue diseases
Adverse effect
Genotyping
Aged
Depressive Disorder, Major
business.industry
Venlafaxine Hydrochloride
Middle Aged
Cyclohexanols
medicine.disease
Phenotype
Cytochrome P-450 CYP2D6
Clinical Global Impression
Major depressive disorder
Female
Reuptake inhibitor
business
medicine.drug
Subjects
Details
- ISSN :
- 14336510
- Volume :
- 60
- Database :
- OpenAIRE
- Journal :
- Clinical Laboratory
- Accession number :
- edsair.doi.dedup.....528cb2f371f3f08479a23e3c8b9dec21