Pharmacogenomic Testing and Personalized Treatment of Depression

Abstract

BACKGROUND:There is wide variation in antidepressant efficacy and tolerability during the treatment of major depressive disorder, a brain disease associated with significant morbidity and mortality risk. The ability to rapidly identify optimal treatment, thereby shortening the time to symptomatic remission, could reduce these risks and associated costs.CONTENT: Up to 42% of variance in antidepressant response is associated with common genetic variation, and there are over 10 psychotropic medications for which the US Food and Drug Administrationapproved labeling reflects a genetic test. Most published studies have examined functional variations in genes of the cytochrome p450 system, relevant to metabolism of many antidepressants. However, there are few data supporting the clinical usefulness of specific pharmacogenetic tests. Randomized trials and costeffectiveness studies are emerging, but larger-scale studies are needed. Specific challenges in translating genetic association results to clinical practice include need for replication to address risk of type I error, overestimation of effect sizes, absence of data from generalizable cohorts, and absence of comparative data that would suggest one specific intervention over another. Several opportunities to accelerate development and validation of new tools for stratification remain, including integration of these tests with clinical data or other biomarkers and application of electronic health records for test development and investigation.

Pharmacogenetics of Antidepressants, A Review of Significant Genetic Variants in Different Populations

“…Genotyping for these polymorphisms is justified in clinical practice in order to optimize drug dosing for efficacy and prevention of side effects. However, many factors complicate the recommendations including patient compliance, environmental circumstances, and comorbidities [24]. Moreover, a patient that carries one polymorphism affecting antidepressant treatment response may also carry others.…”

NMR-based pharmacometabonomics: A new paradigm for personalised or precision medicine

“…[5] Thus, whilst the promise of pharmacogenomics to help deliver personalised medicine is clear, it has recently been shown to have delivered less than was expected in randomised clinical trials in the areas of cardiovascular disease, [6] diabetes [7] and depression. [8] Given the importance of improving the selection of medicines for patients, so as to maximise efficacy and to minimise adverse effects, there is thus clearly a need for new technologies to work in tandem with pharmacogenomics to improve the current personalised or precision medicine paradigm. The rest of this article will introduce pharmacometabonomics as one such methodology that can help achieve that.…”

Why do antidepressant therapies have such a poor success rate?

“…As long as these are not available, we have to do the best with currently available drugs and thereby also consider optimizing strategies. Supportive and helpful for many patients and in many situations is monitoring of drug concentrations in blood [22] and to some extent genotyping of cytochrome P450 enzymes involved in the degradation of antidepressant drugs [23,24]. These methods allow identification of compliance problems or pharmacokinetic peculiarities that may hinder response.…”