TY - JOUR
T1 - An observational study of venlafaxine and CYP2D6 in clinical practice
AU - Rolla, R.
AU - Gramaglia, Carla
AU - Dalò, Valentina
AU - Ressico, Francesca
AU - Prosperini, Pierluigi
AU - Vidali, Matteo
AU - Meola, Silvia
AU - Pollarolo, Paola
AU - Bellomo, Giorgio
AU - Torre, Eugenio
AU - Zeppegno, Patrizia
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - CYP450 2D6
KW - DNA microarrays
KW - Serotonin-norepinephrine reuptake inhibitor antidepressant
KW - Side effects
KW - Treatment effectiveness
KW - Venlafaxine
UR - http://www.scopus.com/inward/record.url?scp=84895780904&partnerID=8YFLogxK
U2 - 10.7754/Clin.Lab.2013.130141
DO - 10.7754/Clin.Lab.2013.130141
M3 - Article
SN - 1433-6510
VL - 60
SP - 225
EP - 231
JO - Clinical Laboratory
JF - Clinical Laboratory
IS - 2
ER -