Current issue

Objectives. Discussion on the clinical significance of genotyping and phenotyping variants of the cytochrome P450 (CYP) enzyme system in the pharmacotherapy of mental disorders.

Literature review. Drug resistance is one of the biggest challenges in the pharmacotherapy of mental disorders; however, hypersensitivity to drugs is also a major problem. Doses of drugs in such cases are selected individually based on clinical response. This usually takes a long time and adversely affects the effects of treatment. Despite this, knowledge of individual cytochrome P450 enzyme activity is still not used. In clinical practice, CYP2D6, CYP2C19, CYP3A4, CYP1A2, and CYP2C9 isoenzymes are particularly important. Neither genotyping nor phenotyping are used as a standard of therapeutic management whereas a pharmacogenetic test once in a lifetime is sufficient to determine one’s genotype. Knowing this can be useful not only in the field of psychiatry but also in all other fields, including oncology. Human population shows great variability in the CYP enzyme activity. In the case of the CYP2D6 isoenzyme, about 6.5% of the Caucasian population are so-called poor metabolisers (PM), about 90% of the population are intermediate and normal metabolisers (IM+NM) who generally tolerate drugs well, while ultrafast metabolisers (UM) make up 3% of the population. It’s also worth knowing that concomitant drug intake can change the EM (extensive metaboliser) genotype to a PM phenotype, which means that non-genetic factors can influence the change in the enzyme activity, a phenomenon known as phenoconversion.

Conclusions. Determining both the patient’s CYP genotype and phenotype is advisable in order to optimise the safety and efficacy of treatment — this should certainly be done in patients who are resistant or hypersensitive to a number of drugs.