Pharmacogenetics in psychiatry: translating research into clinical practice

Abstract

Pharmacogenetic/pharmacogenomic (PGx) approaches to psychopharmacology aim to identify clinically meaningful predictors of drug efficacy and/or side-effect burden. To date, however, PGx studies in psychiatry have not yielded compelling results, and clinical utilization of PGx testing in psychiatry is extremely limited. In this review, the authors provide a brief overview on the status of PGx studies in psychiatry, review the commercialization process for PGx tests and then discuss methodological considerations that may enhance the potential for clinically applicable PGx tests in psychiatry. The authors focus on design considerations that include increased ascertainment of subjects in the earliest phases of illness, discuss the advantages of drug-induced adverse events as phenotypes for examination and emphasize the importance of maximizing adherence to treatment in pharmacogenetic studies. Finally, the authors discuss unique aspects of pharmacogenetic studies that may distinguish them from studies of other complex traits. Taken together, these data provide insights into the design and methodological considerations that may enhance the potential for clinical utility of PGx studies.

Conflict of interest statement

Conflict of interest

The authors declare no conflict of interest.

Figures

Figure 1

Effect of phenotypic rating reliability on statistical power given a fixed sample size (n = 100; red line, left axis) and required sample size to attain 80% power (blue line, right axis), given a fixed ‘true’ effect size (d = 0.4; adapted from Perkins et al.). ICC, intraclass correlation coefficient.

Figure 2

Proportion of clozapine-induced agranulocytosis cases and controls in patients with and without the HLA-DQB1 marker (data extracted from Athanasiou et al.).

Figure 3

Weight gain observed after 12 weeks of exposure to second-generation antipsychotics in drug-naive youth (adapted from Correll et al.).

Figure 4

Effect of medication nonadherence rate on statistical power as a function of sample size in a simulated pharmacogenetic study of antipsychotic-induced weight gain, assuming risk genotype frequency of 20% and true effect size of 0.50.