Case report: application of pharmacogenetics in the personalized treatment of an elderly patient with a major depressive episode

Abstract

Background: Pharmacogenetic analyses can predict interpersonal differences in response to psychopharmacotherapy, which greatly facilitates the selection of the most effective medication at optimal doses. By personalizing therapy in this way, we can minimize adverse drug reactions (ADR) and prevent polypharmacy. Most psychotropic medications are metabolized by the cytochrome P450 enzymes CYP2D6, CYP2C19, and CYPA3A4, which influence drug metabolism and concentration, affecting both efficacy and the occurrence of ADR. The relationships between genetic variations and enzymatic activity allow pharmacogenetic analysis to provide important data for optimal drug selection. The following case report illustrates the impact of pharmacogenetic analysis on the course of pharmacologic treatment in an elderly patient with a major depressive episode.

Methods: We present a case of a 79-year-old patient treated for severe depression with psychotic symptoms. We collected data on treatment selection and response to treatment before and after pharmacogenetic analysis. For pharmacogenetic analysis, common functional variants in CYP1A2, CYP3A4, CYP2B6, CYP2C19, and CYP2D6 were genotyped, and corresponding evidence-based treatment recommendations were prepared.

Results: The patient suffered from lack of efficacy and serious ADR of several medications, resulting in worsening depression and treatment resistance over the course of several months of treatment. Pharmacogenetic analysis provided important insights into the patient's pharmacokinetic phenotype and allowed us to personalize treatment and achieve remission of the depressive episode.

Conclusion: In the case presented, we have shown how consideration of pharmacogenetic characteristics in an individual patient can improve treatment outcome and patient well-being. Knowledge of the patient's pharmacogenetic characteristics helped us to personalize treatment, resulting in complete remission of psychopathology. Due to the complexity of psychiatric disorders, the efficacy of combinations of different medications, which are often required in individual patients, cannot be clearly explained. Therefore, it is of great importance to conduct further pharmacokinetic and pharmacogenetic studies to better assess gene-drug interactions in psychopharmacotherapy.

Keywords: antidepressants; antipsychotics; case report; cytochrome P450 enzymes; depression; personalized therapy; pharmacogenetics.