Clinical utility of pharmacogenetics-guided treatment of depression and anxiety

Abstract

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are associated with significant morbidity/mortality risk. Prolonged episodes increase impact on quality of life, risk for suicide, and harbor greater societal costs. Current management is inadequate as half of individuals do not respond to first-line therapies. Identification of an optimal treatment may hinge on exploiting interindividual genetic variability, which-in combination with other extraneous factors-is associated with heterogeneous antidepressant response. We evaluated the use of Genecept testing in an open-label trial of 468 patients, focusing on the methylenetetrahydrofolate reductase (MTHFR) and serotonin transporter (SLC6A4) genes and evaluating their plausibility as putative predictors of MDD/GAD treatment outcome. After receiving genotyping, 50.6% of clinicians made assay-congruent changes to treatment. This yielded a selective serotonin reuptake inhibitor (SSRI) discontinuation rate of 19.0% in patients with a risk SLC6A4 genotype, and, an acute folate derivative addition rate of 41.8% in MTHFR risk allele carriers. After 8 weeks of treatment, patients with a risk MTHFR genotype that were treated with assay-guided treatment regimens-as compared to those that were not-demonstrated a greater reduction in Quick Inventory of Depressive Symptoms (QIDS-SR) and Undersøgelser (UKU) scores, and an increased quality of life score (Q-LES-Q-SF). SLC6A4 risk patients who adhered to assay-guided treatment achieved a greater reduction in QIDS-SR and UKU scores and a statistically significant increase in Q-LES-SF scores, versus those that did not. Results support the utility of genotyping in the treatment of MDD/GAD and propose SLC6A4 and MTHFR as biological predictors of treatment outcome.

Individual response to antidepressants for depression in adults-a meta-analysis and simulation study

“…The aim is to match the individual patient to a therapy that best suits their specific characteristics and condition [22]. Personalized medicine includes the search for potential pharmacogenetic markers [23,24], other biomarkers [25,26], and clinical characteristics [27]. Those are hoped to predict the response to antidepressants and to help identify those patients who are most likely to "respond" to antidepressants.…”

Clinical Utilization of Pharmacogenetics in Psychiatry – Perspectives of Pharmacists, Genetic Counselors, Implementation Science, Clinicians, and Industry

“…To date, almost all prospective PGx studies have included patients with MDD who have failed 1 medication trial and inclusion/exclusion criteria are relatively broad, but similar across trials. Finally, most PGx data have been synthesized from retrospective studies and retrospective studies of specific commercial PGx tests have also been performed in order to show clinical validity and economic utility[55][56][57][58][59][60][61][62][63]. It is therefore beneficial for PGx testing to have various trial designs supporting its use in psychiatry.…”

5-HTTLPR and MTHFR 677C>T polymorphisms and response to yoga-based lifestyle intervention in major depressive disorder: A randomized active-controlled trial

“…5-HTTLPR polymorphism is shown to be a therapy response biomarker for SSRI drug therapy in MDD. [ 35 75 ] Several studies have reported poor response with SS/SL genotype. [ 35 36 37 38 76 77 ] A meta-analysis by Porcelli et al .…”