CYP2D6-Genotyping in clinical practice: Impact of Genotyp on serum concentrations of psychiatric relevant CYP2D6-substrates

We established CYP2D6-genotyping as a routine examination for psychiatric practice. Patients over / not reacting to various antidepressants were genotyped employing a CYP2D6 PCR method. Serum concentrations of possible CYP2D6 substrates were analyzed under steady-state conditions. We identified 9 poor metabolizer (PM) out of 20 patients over reacting to various antidepressants and 1 ultrarapid metabolizer (UM) with a functional duplication of the CYP2D6 gene out of 26 patients with insufficient drug response. Identified PMs developed elevated serum concentrations under treatment with imipramine (n=2), amitriptyline (n=1) and sertraline (n=1), whereas treatment of PMs with citalopram (n=4), mirtazapine (n=2) and paroxetine (n=1) was well tolerated and did not produce elevated serum concentrations. The UM developed therapeutic serum concentrations under treatment with citalopram but not with doxepine at standard clinical doses. Our results clearly emphasize the usefulness to characterize drug metabolism in identified PMs and UMs in order to individualize psychiatric pharmacotherapy.