UMMS Affiliation

Department of Psychiatry

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Mental and Social Health | Mental Disorders | Pharmacology, Toxicology and Environmental Health | Psychiatry


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.


CPIC guidelines, Clinical validity, Combinatorial pharmacogenomics, Depression, GeneSight, Medication blood levels, Pharmacokinetics

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© 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. (

DOI of Published Version



Rothschild AJ, Parikh SV, Hain D, Law R, Thase ME, Dunlop BW, DeBattista C, Conway CR, Forester BP, Shelton RC, Macaluso M, Brown K, Lewis D, Gutin A, Jablonski MR, Greden JF. Clinical validation of combinatorial pharmacogenomic testing and single-gene guidelines in predicting psychotropic medication blood levels and clinical outcomes in patients with depression. Psychiatry Res. 2020 Dec 15;296:113649. doi: 10.1016/j.psychres.2020.113649. Epub ahead of print. PMID: 33360967. Link to article on publisher's site

Journal/Book/Conference Title

Psychiatry research


Full author list omitted for brevity. For the full list of authors, see article.

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Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.