Antidepressant Prescribing in the Precision Medicine Era: a Prescriber's Primer on Pharmacogenetic Tools

Abstract

About half of people who take antidepressants do not respond and many experience adverse effects. These detrimental outcomes are in part a result of the impact of an individual's genetic profile on pharmacokinetics and pharmcodynamics. If known and made available to clinicians, this could improve decision-making and antidepressant therapy outcomes. This has spurred the development of numerous pharmacogenetic-based decision support tools. In this article, we provide an overview of pharmacogenetic decision support tools, with particular focus on tools relevant to antidepressants. We briefly describe the evolution and current state of antidepressant pharmacogenetic decision support tools in clinical practice, followed by the evidence-base for their use. Finally, we present a series of considerations for clinicians contemplating use of these tools and discuss the future of antidepressant pharmacogenetic decision support tools.

A Pharmacogenomic-based Antidepressant Treatment for Patients with Major Depressive Disorder: Results from an 8-week, Randomized, Single-blinded Clinical Trial

“…Recently a number of commercially available and valid pharmacogenomic decision support kits exist in market as a part of precision medicine to minimize 'trial and error' and to have easy access to 'right drug for right time'. [26][27][28][29][30] However, the complexity of antidepressants' action mechanism and genetic etiology of MDD clearly limit the single gene phenotype testing. Hence the combinatorial PGATx involving such as PK-PK, PK-PD, and PD-PD gene interactions has been suggested to provide more advanced and improved pharmacogenomic testing.…”

Current challenges and possible future developments in personalized psychiatry with an emphasis on psychotic disorders

“…Described in the next sections are only several examples of such biomarkers of psychotic and other psychiatric disorders, including genetic biomarkers, and therefore a brief overview of the existing body of knowledge. This brief list is not meant to name only fully studied and reliable biomarkers that are ready to be introduced into clinic, because at this point such biomarkers, with exception of few pharmacogenetic biomarkers [45,85,86,87,88], have not been discovered.…”

Deuterium‐substituted 2‐(2′‐((dimethylamino)methyl)‐4′‐[18F](fluoropropoxy)phenylthio)benzenamine as a serotonin transporter imaging agent

“…Then the reaction mixture was cooled in ice water, and 10-mL water was added. The resulting mixture was loaded on a 3-cm 3 Oasis HLB cartridge (preconditioned with 10-mL ethanol and 10-mL water). The cartridge was flushed with 15-mL water.…”

“…The crude product was eluted from the cartridge with 1-mL acetonitrile, diluted with 1-mL water, and purified by pre-HPLC (Gemini 250 × 4.6 mm, ACN/water 60/40, 4 mL/min); fraction at 21 minutes was collected. The solution was diluted with 30-mL water, pushed through 3-cm 3 Oasis HLB cartridge (preconditioned with 10-mL ethanol and 10-mL water), and washed with 3-mL water, and the dose was eluted with 1-mL EtOH (0.38 GBq) and analyzed by injecting into an HPLC system. The HPLC for radiochemical reaction studies was equipped with a gamma ray radiodetector and a UV/Vis detector (Agilent 1200 series system; Ascentis C18, 150 × 4.6 mm, 5 μm; mobile phase: ACN/10mM AFB 50/50, 1 mL/min; [ 18 F]1 = 4.323 min).…”

“…Consequently, SSRIs are useful in the treatment of depression as well as many other psychiatric conditions by regulating the serotonin concentration in the synapse. 3 Positron emission tomography (PET) imaging for SERT binding sites in the brain with [ 11 C]DASB (T 1/2 = 20 min) ( Figure 2) has been reported, and its clinical application is well reported in the literature. [4][5][6][7] A suitably 18 F-labeled SERT imaging agent with its longer physical half-life (T 1/2 = 110 min) is more convenient to manufacture and distribute for probing pathophysiological and therapeutic mechanisms in various psychological diseases.…”