Clinical Utility of Combinatorial Pharmacogenomics-Guided Antidepressant Therapy: Evidence from Three Clinical Studies

Abstract

DNA of 258 patients with treatment-resistant depression was collected in three 8-10 week, two-arm, prospective clinical trials. Forty-four allelic variations were measured in genes for the cytochrome P450 (CYP) enzymes CYP2D6, CYPC19, and CYP1A2, the serotonin transporter (SLC6A4), and the 5-HT_2A receptor (HTR2A). The combinatorial pharmacogenomic (CPGx™) GeneSight test results were provided to clinicians to support medication changes from baseline (guided arm), or they were provided at the end of each study to clinicians of unguided patients who were treated as usual (TAU). TAU subjects who at baseline were prescribed medications genetically discordant for them showed only a 12% symptom improvement, far less than the 32.5% or 28.5% improvements of the TAU subjects on yellow-category (‘use with caution'; p = 0.002) or green-category medications (‘use as recommended'; p = 0.02), respectively. The odds of a clinical response were increased 2.3-fold among all GeneSight-guided compared to all TAU subjects (p = 0.004), and overall, the guided group had a 53% greater improvement in depressive symptoms (p = 0.0002), a 1.7-fold relative improvement in response (p = 0.01), and a number needed to treat for one clinical response above that seen in the TAU group of 6.07.

Pharmacogenomics Implementation: Considerations for Selecting a Reference Laboratory

“…These comments may be based on analysis of a single gene at a time or in combination. The interpretative report might include comments on a single medication, multiple medications, or a disease‐specific set of medications (e.g., cardiology panel) . Disease‐specific medication set reports may not cover the complete clinical importance of the results if the results applied to medications in multiple clinical areas.…”

Value of Supportive Care Pharmacogenomics in Oncology Practice

“…Multiple studies have recently been published illustrating the clinical value of multigene pharmacogenetic panels when treating patients with depression. At least four rigorous studies have shown significantly better treatment outcomes for major depressive disorder with pharmacogenomic guidance compared with the standard clinical approach .…”

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

“…For example, it is unclear whether these pharmacogeneticguided tools can shorten the time to remission and/or sustain the duration of remission from depression. Furthermore, the utility of these tools for assisting in the decision to switch or augment a patient's current prescription remains uncertain, although preliminary evidence suggests these tools may assist with medication changes [33]. Finally, the cost-effectiveness of pharmacogenetic decision support tools remains unclear [34] and until robust economic studies are conduced, firm clinical guidelines or recommendations cannot be made.…”