Towards the implementation ofCYP2D6andCYP2C19genotypes in clinical practice: Update and report from a pharmacogenetic service clinic

Abstract

Genetic testing may help to improve treatment outcomes in order to avoid non-response or severe side effects to psychotropic medication. Most robust data have been obtained for gene variants in CYP2D6 and CYP2C19 enzymes for antipsychotics and antidepressant treatment. We reviewed original articles indexed in PubMed from 2008-2013 on CYP2D6 and CYP2C19 gene variants and treatment outcome to antidepressant or antipsychotic medication. We have started providing CYP2D6 and CYP2C19 genotype information to physicians and conducted a survey where preliminary results are reported. Studies provided mixed results regarding the impact of CYP2D6 and CYP2C19 gene variation on treatment response. Plasma levels were mostly found associated with CYP metabolizer status. Higher occurrence/severity of side effects were reported in non-extensive CYP2D6 or CYP2C19 metabolizers. Results showed that providing genotypic information is feasible and generally well accepted by both patients and physicians. Although currently available studies are limited by small sample sizes and infrequent plasma drug level assessment, research to date indicates that CYP2D6 and CYP2C19 testing may be beneficial particularly for non-extensive metabolizing patients. In summary, clinical assessment of CYP2D6 and CYP2C19 metabolizer status is feasible, well accepted and optimizes drug treatment in psychiatry.

Personalized therapies in psychiatry: promises, pitfalls and perspectives

“…Although CYP pharmacogenetic testing has already become available in some clinical settings (cf. Müller et al 2013), such services are not established yet as common practice. Therefore, the present papers may further inform on the potential value and clinical applicability of CYP gene testing.…”

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

“…Those who carry one normal and one non-functional allele are categorized as intermediate metabolizers (IM); those with two nonfunctional alleles are known as poor metabolizers (PM). Finally, individuals with duplicate copies of alleles are categorized as ultra-rapid metabolizers (UM) (11).…”

“…By knowing the metabolizer status, dose adjustments can be made or alternative medications can be selected (11).…”

“…Furthermore, both enzymes can be inhibited or induced by drugs and diet and create phenocopies (11). An example of a phenocopy would be the conversion of a CYP2D6 EM to a CYP2D6 PM after exposure to a potent CYP2D6 inhibitor such as paroxetine (19).…”

“…Response to APs depends partially on demographic and clinical factors (1). However, the literature has shown substantial evidence for a genetic component in individuals' outcomes to APs which include variation in drug metabolism and side effects (11).…”