Pharmacogenomics For Selecting Psychiatric Medications: From Research To Patient Response

Abstract

Pharmacogenomic guidance has been pursued to increase psychiatric treatment response, reduce adverse events, and decrease healthcare utilizations and costs. These clinical properties could mitigate the considerable health care burdens and disabilities for patients with depression, anxiety, psychosis, and other indications.Dr. Altar will describe GeneSight® Psychotropic CPGx™ technology, a proprietary approach which combines and weights the importance of multiple nucleotide variations in genes responsible for the metabolism and response to psychiatric medications. The GeneSight test creates a weighted composite phenotype from allelic variations in twelve genes: six that encode cytochrome P450 (CYP) phase I metabolism enzymes, two that encode UGT phase II metabolism enzymes, two that encode serotonergic drug mechanism of action, and two that encode off-target HLA proteins linked to drug-induced adverse dermatologic responses. The test stratifies 55 antidepressant, anxiolytic, mood stabilizer and antipsychotic medications into one of three categories, based on how an individual’s genetic variation among these 12 genes are likely to affect the metabolism and action of each medication. This information is integrated and provided to clinical caregivers in a personalized report, indicating medication status and dose adjustments for each patient. Five published clinical studies show the benefits of utilizing the GeneSight Psychotropic test for menthal health treatment decisions.The Clinical validity of the GeneSight Psychotropic test was demonstrated in patients with mental illness by its ability to predict symptom improvement, healthcare utilization, disability and employee absenteeism. Across three studies, depressed subjects who at baseline were prescribed genetically discordant “red” medications showed significantly (p = 0.003) less improvement in their depressive symptoms (12%) compared to subjects prescribed genetically concordant “yellow” or “green” category medications (33% and 29%, respectively). In a fourth study, patients with depression and/or anxiety who were prescribed a genetically discordant “red” medication over one year had 69% more healthcare visits, 3X the number of medical absence days from work, and 4x the number of disability claims compared to subjects on genetically concordant medications. Only the weighted multi-genic composite GeneSight results were predictive of outcomes, whereas the gene components individually had little or no predictive value for these same outcomes.Clinical utility was shown in three studies where patients prescribed medications using the GeneSight test had a 2.3-fold greater odds of clinical response (p = 0.004) and a 53% greater improvement in depressive symptoms (p = 0.0002), compared to unguided patients.Economic utility was demonstrated in two studies where psychiatric patients who received GeneSight testing saved on average $1,035 in total medication costs (p = 0.007) and $1,556 in non-pharmacy related healthcare costs annually.The clinical and economic validity and utility of our proprietary CPGx™ approach in mental health pharmacotherapy is contributing to its broadening adoption. The combinatorial approach may be of benefit because it lessens the variability of the empirical approach that has traditionally been used to prescribe medications for psychiatric indications.