Towards personalized medicine: the role of pharmacogenetics in the treatment of bipolar disorder

Abstract Background Bipolar disorder (BD) is a severe psychiatric disease characterized by mood swings between mania and depression, with a life-time prevalence of approximately 2.4%. Patients suffering from BD frequently present several problems due to drug-resistance and drug-drug interactions, rapid-cycling, and cognitive decline. Pharmacogenetic tests (PGTs) have been proposed as a method to determine the most efficacious treatment with the lowest side effects, recognizing individual variability in genetics as a key component of drug response. Nevertheless, PGTs have been occasionally used in clinical practice up to now and their clinical utility is an empirical question that has remained largely untested. This research project aims to evaluate the utility of PGT in routine clinical practice for the treatment of BD in terms of efficacy and cost saving; evaluate the attitude of psychiatrists towards the PGT use in clinical practice; review the literature dealing with lithium, the most common mood stabilizer used, to find any correlation among genes and tolerability/efficacy. Materials and methods The first phase of study evaluated 30 patients affected by BD type I or II who underwent the PGT Neurofarmagen® between March 2016 and March 2017. Second phase compares 12 months before the execution of the PGT versus 12 months after, in terms of number and days of hospitalization and accesses to emergency services. Secondarily, it gives an economic value to the data based on the diagnosis-related group (DRG). The third part of the study evaluates psychiatrists’ attitude towards the use of PGx into clinical practice; the last phase of study reviews the literature about lithium salts. Results In phase I At T0, 4 patients (13%) had an optimal therapy in line with the PGT suggestions. At 3-month followup, 13 patients (40%) had received a change of therapy consistent to the test, showing a significant statistical improvement in CGI-S score over time compared to those not having changes consistent with the test. Regarding AEs, at baseline 9 out of 10 (90%) of the patients who received a therapy modification according to the test presented AEs, and a significant within-group reduction was observed after 3 months (p = 0.031). At 12 months follow-up (T3) 93% of patients (n=28) received a therapy concordant to the test; the others (7%, n=2) had a therapy discordant to the test Phase II showed statistically significant differences in all the comparisons (p < 0.0001). Important cost saving emerged after the use of PGT (€148,920 the first year versus €39,048 the following year). Phase III showed a positive attitude of the 45 psychiatrists interviewed towards the use of PGX. All respondents 100% (N = 45) believe that pharmacogenetics can help in making decisions about psychopharmacological treatment. All respondents 100% (N = 45) believe that pharmacogenetics can help in setting up therapy, particularly regarding drug interactions. There were no significant differences between those who already had experience with PGTs and those who did not. Phase IV showed that the pharmacogenetics of Lithium appears to be a field still in its infancy, even though the advent of genome-wide association studies holds particular promise for future studies. Conclusion Despite the small sample size and lack of a control group this study shows promising data about the usefulness of PGT to support clinicians in reaching a more effective and tolerated treatment in the routine approach and the potential role of PGT in cost saving for the treatment of bipolar disorder. Also the attitude of clinicians seemed to be positive towards the use of PGT as a helpful tool into clinical practice. To confirm this result, larger and clinical trials are needed