Analysis of genetic polymorphisms, adverse drug reactions and targeted treatment

Introduction Bipolar disorders (BD) are chronic and recurrent psychopathological conditions characterized by therapeutic failures (TFs), regardless of the initial choice of psychiatric medication with a high prevalence of adverse drug reactions (ADRs). Cytochrome P450(CYP)2D6 genetics has been recently suggested to have a role in the response to treatment and extra-pyramidal symptoms (EPS) across several psychiatric conditions. Objectives To evaluate interindividual differences in CYP2D6 enzyme activities, TFs and ADRs rates in BDs patients. Aims To tailor psychiatric medication choice and dose based on pharmacogenetic test. Methods We analyzed 16 clinical relevant polymorphisms CYP2D6 genotype in Psychiatric Unit of Foggia using the InfinitiTM Analyzer; the Simpson Angus Scale (SAS) was used to measure drug-induced EPS and Brief Psychiatric Rating Scale-24 (BPRS-24) response to treatment. Results Ten drug-resistant patients were consecutively enrolled, and six of these experience major ADR during therapy with worsening of symptoms before screening for CYP polymorphism: BM (*2A/*5 genotype, BPRS-24 T 0 : 63, T 14 : 51), SR (*2A/*4, BPRS-24 T 0 : 66, T 14 : 59), LT (*4/*17 BPRS-24 T 0 : 72, T 14 : 64), DC (*2A/*4A BPRS-24 T 0 : 69, T 14 : 54), AL (*2A/*2A, BPRS-24 T 0 : 72, T 14 : 64), PA (*2A/*2A BPRS-24 T 0 : 52, T 14 : 46). Conclusions According to the specific CYP2D6 polymorphism, we personalized patients’ treatment considering that poor and extensive metabolizers have different rates of ADR and responses to treatment. CYP2D6 genotype's knowledge is useful for the reduction of therapeutic attempt during patient clinical history, thus reducing admission time and costs, and to guide clinicians toward a better patient management.