Clinical impact of CYP2D6 polymorphism on the therapy with antidepressants and antipsychotics -: case reports of CYP2D6 poor metabolisers

CYP2D6 is one of the best characterised cytochrome P450 isozyme with broad substrate specificity which is involved in the oxidative metabolism of more than 40 commonly prescribed drugs including several antipsychotics and antidepressants. With respect to these drugs, the genetic polymorphism of CYP2D6 has become an important target in psychopharmacology research, since an association was found between the interindividual variation of CYP2D6 function and the degree of oxidative metabolism. CYP2D6 deficiency occurs in 5 to 10% Caucasians who lack CYP2D6 enzyme activity and therefore are impaired in their metabolic capacity. For these subjects, the poor metabolisers (PM), high plasma drug concentrations and prolonged elimination half-lives of CYP2D6 substrates are to be expected. We analysed phenotype, genotype and plasma drug concentrations of 160 psychiatric inpatients taking different psychotropic drugs at admission to the department of psychiatry. Out of these, 13 (8.1%) patients presented with PM status. We performed detailed drug history for each PM including all available clinical data; 10 PMs showed high or toxic plasma concentrations of CYP2D6 substrates or non-compliance because of adverse drug effects. Our results indicate that the determination of the CYP2D6 status-if possible prior to drug treatment-identifies patients at risk for concentration-dependent adverse drug effects and, combined with long-term TDM dose recommendations, optimises individual psychopharmacotherapy.