Clinical utility of pharmacogenetics-guided treatment of depression and anxiety

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.