Psychiatria pre prax 2/2012

Is pharmacogenetic prediction of therapeutic efficacy of paroxetine possible?

Variability in antidepressant response may be linked to availability of the drug at the target side. P-glycoprotein (P-gp) located in the blood brain barrier is encoded by the multidrug resistance 1 (MDR1) gene and acts as a cellular efflux pump. We monitored the influence of G2677T polymorphism of MDR1 gene on therapeutic efficacy and tolerability of paroxetine (substrate of P-gp) in 50 depressive patients. PCR-restriction fragment length polymorphism was used for genotyping. Therapeutic response was evaluated using the Hamilton Rating Scale for Depression. A failure of therapeutic response was significantly more frequent in patients with G allele (G vs T: p=0,018; TT vs GG: p=0.009; Fisher exact or χ2test). We failed to show any evidence that G2677T polymorphism could influence the occurence of tested side effects of paroxetine. Our results demonstrate that G2677T/A polymorphism could play the role in inter-individual variability in therapeutic response to paroxetine.

Keywords: pharmacogenetics, P-glycoprotein, paroxetine, antidepressive therapy