Combinatorial Pharmacogenomic Algorithm is Predictive of Citalopram and Escitalopram Metabolism in Patients with Major Depressive Disorder

PSYCHIATRY RESEARCH

卷:290

Article

Shelton, Richard C.^1,2  Parikh, Sagar V.^3,4,5  Law, Rebecca A.⁶  Rothschild, Anthony J.^7,8  Thase, Michael E.^9,10  Dunlop, Boadie W.¹¹  DeBattista, Charles¹²  Conway, Charles R.^13,14  Forester, Brent P.^15,16  Macaluso, Matthew¹⁷  Hain, Daniel T.⁶  Aguilar, Aime Lopez⁶  Brown, Krystal¹⁸  Lewis, David J.⁶  Jablonski, Michael R.⁶  Greden, John F.^3,4,5 

[1] Univ Alabama Birmingham, Dept Psychiat, 1720 2nd Ave S, Birmingham, AL 35294 USA

[2] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA

[3] Univ Michigan, Comprehens Depress Ctr, Ann Arbor, MI 48109 USA

[4] Dept Psychiat, Ann Arbor, MI USA

[5] Natl Network Depress Ctr, Ann Arbor, MI USA

[6] Myriad Neurosci, Mason, OH USA

[7] Univ Massachusetts, Med Sch, Worcester, MA 01605 USA

[8] UMass Mem Healthcare, Worcester, MA USA

[9] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[10] Corporal Michael Crescenz VAMC, Philadelphia, PA USA

[11] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA

[12] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA

[13] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[14] John Cochran Vet Adm Hosp, St Louis, MO USA

[15] McLean Hosp, Div Geriatr Psychiat, 115 Mill St, Belmont, MA 02178 USA

[16] Harvard Med Sch, Boston, MA 02115 USA

[17] Univ Kansas, Sch Med Wichita, Dept Psychiat & Behav Sci, Wichita, KS USA

[18] Myriad Genet Inc, Salt Lake City, UT USA

关键词: GeneSight;    Pharmacokinetics;    Medication Blood Levels;    Depression;    Citalopram;    Escitalopram;   

DOI  :  10.1016/j.psychres.2020.113017

来源: Elsevier

【 摘 要 】

Pharmacogenomic tests used to guide clinical treatment for major depressive disorder (MDD) must be thoroughly validated. One important assessment of validity is the ability to predict medication blood levels, which reflect altered metabolism. Historically, the metabolic impact of individual genes has been evaluated; however, we now know that multiple genes are often involved in medication metabolism. Here, we evaluated the ability of individual pharmacokinetic genes (CYP2C19, CYP2D6, CYP3A4) and a combinatorial pharmacogenomic test (GeneSight Psychotropic (R); weighted assessment of all three genes) to predict citalopram/escitalopram blood levels in patients with MDD. Patients from the Genomics Used to Improve DEpression Decisions (GUIDED) trial who were taking citalopram/escitalopram at screening and had available blood level data were included (N=191). In multivariate analysis of the individual genes and combinatorial pharmacogenomic test separately (adjusted for age, smoking status), the F statistic for the combinatorial pharmacogenomic test was 1.7 to 2.9-times higher than the individual genes, showing that it explained more variance in citalopram/escitalopram blood levels. In multivariate analysis of the individual genes and combinatorial pharmacogenomic test together, only the combinatorial pharmacogenomic test remained significant. Overall, this demonstrates that the combinatorial pharmacogenomic test was a superior predictor of citalopram/escitalopram blood levels compared to individual genes.

【 授权许可】

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