Pharmacogenomics: A focus on antidepressants and atypical antipsychotics

Abstract

The study of pharmacogenomics is rapidly growing, particularly in the field of mental health. Understanding pharmacogenomic principles can be a challenge for many clinicians. Most mental health genomic data concentrates on variability (response, side effects) with antidepressants and atypical antipsychotics. Current pharmacogenomic practice and research primarily focuses on two areas: pharmacodynamics and pharmacokinetics. Based on the current literature, genetic polymorphisms of pharmacodynamics and pharmacokinetics parameters likely influence medication efficacy, therefore affecting the therapeutic benefit. Additionally, certain pharmacodynamic and pharmacokinetic polymorphisms have been linked to an elevated risk of side effects and adverse events with these medications. In this review, specific pharmacodynamic and pharmacokinetic polymorphisms related to antidepressants and atypical antipsychotics will be discussed, as well as the potential clinical effect these genomic abnormalities have within psychiatric care.

Psychopharmacological Treatment of Obsessive-Compulsive Disorder (OCD)

“…The continuous and rapid development of genomic testing and related studies focused on predictive factors, association studies, and pharmacoeconomy will prove or disprove the validity of the personalised approach in mental health. An important question regarding timing (i.e., when a psychiatrist should indicate a pharmacogenomic test) is still unclear [320].…”

Towards personalized pharmacology: Antipsychotics and schizophrenia

“…Pharmacogenetics is the study of the influence of genotype on the variability of response to a treatment [35]. Concerning psychotropic drugs, the most suitable analysis is testing for genetic polymorphism of CYP2D6 and CYP2C19 [36]. These tests enable the documentation of situations for which there is no clinical efficacy or there are recurrent ADRs, by identifying patients who are extreme metabolizers (poor or ultra-rapid).…”

“…The impact of genetic polymorphisms that modulate dopaminergic and serotoninergic activities on the response to antipsychotic treatment is currently under study [36]. The main genes of interest are those coding for dopamine receptors (DRD2) and for serotonin receptors and transporters (HTR2A, SLC6A) [39].…”

Genetic Risk Assessment in Psychiatry

“…The second is to inform the treatment and management of an affected individual. Currently available pharmacogenetic testing (Lister 2016;Routhieaux et al 2018) aims to predict medication efficacy and risk of side effects and adverse events. Specific panels are available to inform psychotropic medication selection, such as the Assurex GeneSight Psychotropic Test (https://genesight.com/).…”

“…A systematic review (Health Quality Ontario 2017) of the Assurex panel found improved patient response to depression treatment and greater response in measures of depression, but no differences in rates of complete remission (based on low to very-low quality evidence). The optimal timing of pharmacogenetic testing and extent to which results should inform treatment recommendations are still under debate (Lister 2016;Routhieaux et al 2018). The American Psychiatric Association recently concluded that there is insufficient data to support the widespread use of pharmacogenetic testing (Zeier et al 2018).…”