Clinical validation of combinatorial pharmacogenomic testing and single-gene guidelines in predicting psychotropic medication blood levels and clinical outcomes in patients with depression. (February 2021)

• Record Type: Journal Article
• Authors: Rothschild, Anthony J.; Parikh, Sagar V.; Hain, Daniel; Law, Rebecca; Thase, Michael E.; Dunlop, Boadie W.; DeBattista, Charles; Conway, Charles R.; Forester, Brent P.; Shelton, Richard C.; Macaluso, Matthew; Brown, Krystal; Lewis, David; Gutin, Alexander; Jablonski, Michael R.; Greden, John F.
• Is Part Of: Psychiatry research. Volume 296(2021)
• Publication Date: 2021-02
• Subjects: GeneSight -- Combinatorial pharmacogenomics -- Pharmacokinetics -- CPIC guidelines -- Clinical validity -- Medication blood levels -- Depression; Psychiatry -- Periodicals; Psychiatry -- periodicals; Psychiatrie -- Périodiques; 616.89
• DOI: 10.1016/j.psychres.2020.113649
• Languages: English
• ISSNs: 0165-1781

Abstract

Highlights: Pharmacogenomics (PGx) can be used to identify gene-drug interactions (GDI) PGx tests or single-gene guidelines are often used to guide prescribing based on GDI Only the PGx test predicted variation in outcomes for patients with depression Both single-gene guidelines and the PGx test predicted medication blood levels The combinatorial PGx test was a better predictor than the single-gene guidelines Abstract: We evaluated the clinical validity of a combinatorial pharmacogenomic test and single-gene Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines against patient outcomes and medication blood levels to assess their ability to inform prescribing in major depressive disorder (MDD). This is a secondary analysis of the Genomics Used to Improve DEpression Decisions (GUIDED) randomized-controlled trial, which included patients with a diagnosis of MDD, and ≥1 prior medication failure. The ability to predict increased/decreased medication metabolism was validated against blood levels at screening (adjusted for age, sex, smoking status). The ability of predicted gene-drug interactions (pharmacogenomic test) or therapeutic recommendations (single-gene guidelines) to predict patient outcomes was validated against week 8 outcomes (17-item Hamilton Depression Rating Scale; symptom improvement, response, remission). Analyses were performed for patients taking any eligible medication (outcomes N=1, 022, blood levels N=1, 034) and the subset taking medications with single-gene guidelines (outcomes N=584, blood levels N=372). The combinatorial pharmacogenomic test was the only significant predictor of patient outcomes. Both the combinatorial pharmacogenomic test and single-gene guidelines were significant predictors of blood levels for all medications when evaluated separately; however, only the combinatorial pharmacogenomic test remained significant when both were included in the multivariate model. There were no substantial differences when all medications were evaluated or for the subset with single-gene guidelines. Overall, this evaluation of clinical validity demonstrates that the combinatorial pharmacogenomic test was a superior predictor of patient outcomes and medication blood levels when compared with guidelines based on individual genes.