Applying cytochrome P450 2D6 and 2C19 genotyping to clinical practice: Impact of genotypes and plasma levels on therapeutic decisions during antidepressant treatment

Genetic polymorphisms in alleles of the cytochrome P450 enzymes (CYP) 2D6 and 2C19 can result in intermediate (IM) or poor metabolizer (PM) status which may affect the plasma levels of antidepressants. We investigated a case series focussing on the connection between CYP genotypes and plasma levels of antidepressants and report whether this information was helpful for the pharmacological decision. Plasma levels of psychopharmacological substances were examined in 22 subjects treated with mainly escitalopram, mirtazapine or both in order to discover drug levels out of therapeutic range as a reason for lack of improvement or increased side effects. Genotyping results for CYP 2D6 (*3,*4,*5,*6) or CYP 2C19 (*2) were examined for interpretation of drug levels. For example, mirtazapine drug levels were diminished in one patient showing *3 CYP 2D6 heterozygosity which would have rather lead to IM status and therefore elevated plasma levels. This was a patient suffering from colitis ulcerosa, which may have led to insufficient uptake of mirtazapine from the bowel. The change from mirtazapine capsule to a disintegrating tablet of mirtazapine led to a sufficient increase in plasma levels and to remission of the patient. The cases demonstrate the high impact of therapeutic drug monitoring in order to evaluate shortcomings in therapeutic response. CYP genotyping can be of clinical relevance during therapy if additional clinical and pharmacokinetic information is taken into account.