Pharmacogenetics in Psychiatry

Mental illness represents a major health issue both at the individual and at the socioeconomical level. This is partly due to the current suboptimal treatment options: existing psychotropic medications, including antidepressants, antipsychotics, and mood stabilizers, are effective only in a subset of patients or produce partial response and they are often associated with debilitating side effects that discourage adherence. Pharmacogenetics is the study of how genetic information impacts on drug response/side effects with the goal to provide tailored treatments, thereby maximizing efficacy and tolerability. The first pharmacogenetic studies focused on candidate genes, previously known to be relevant to the pharmacokinetics and pharmacodynamics of psychotropic drugs. Results were mainly inconclusive, but some replicated candidates were identified and included as pharmacogenetic biomarkers in drug labeling and in some commercial kits. With the advent of the genomic revolution, it became possible to study the genetic variation on an unprecedented scale, throughout the whole genome with no need of a priori hypothesis. This may lead to the personalized prescription of existing medications and potentially to the development of innovative ones, thanks to new insights into the genetics of mental illness. Promising findings were obtained, but methods for the generation and analysis of genome-wide and sequencing data are still in evolution. Future pharmacogenetic tests may consist of hundreds/thousands of polymorphisms throughout the genome or selected pathways in order to take into account the complex interactions across variants in a number of genes.