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Strumila R, Lengvenyte A, Ambrozaityte L, et al. CYP2C19 polymorphisms are associated with severity of depression at initial evaluation and after the treatment independently of the prescribed medications: 4 weeks prospective study. Psychiatr Genet. 2021;31(5):177-185doi: 10.1097/YPG.0000000000000287.
Strumila, R., Lengvenyte, A., Ambrozaityte, L., Balkeliene, D., Utkus, A., & Dlugauskas, E. (2021). CYP2C19 polymorphisms are associated with severity of depression at initial evaluation and after the treatment independently of the prescribed medications: 4 weeks prospective study. Psychiatric genetics, 31(5), 177-185. https://doi.org/10.1097/YPG.0000000000000287
Strumila, Robertas, et al. "CYP2C19 polymorphisms are associated with severity of depression at initial evaluation and after the treatment independently of the prescribed medications: 4 weeks prospective study." Psychiatric genetics vol. 31,5 (2021): 177-185. doi: https://doi.org/10.1097/YPG.0000000000000287
Strumila R, Lengvenyte A, Ambrozaityte L, Balkeliene D, Utkus A, Dlugauskas E. CYP2C19 polymorphisms are associated with severity of depression at initial evaluation and after the treatment independently of the prescribed medications: 4 weeks prospective study. Psychiatr Genet. 2021 Oct 01;31(5):177-185. doi: 10.1097/YPG.0000000000000287. PMID: 34133409.
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Psychiatr Genet. 2021 Oct 01;31(5):177-185. doi: 10.1097/YPG.0000000000000287.

CYP2C19 polymorphisms are associated with severity of depression at initial evaluation and after the treatment independently of the prescribed medications: 4 weeks prospective study.

Psychiatric genetics

Robertas Strumila, Aiste Lengvenyte, Laima Ambrozaityte, Danute Balkeliene, Algirdas Utkus, Edgaras Dlugauskas

Affiliations

  1. Psychiatric Clinic, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
  2. Department of Emergency Psychiatry and Acute Care, CHRU Montpellier.
  3. IGF, University of Montpellier, CNRS, INSERM, CHU de Montpellier, Montpellier, France.
  4. Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University.
  5. Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania.

PMID: 34133409 DOI: 10.1097/YPG.0000000000000287

Abstract

BACKGROUND: The cytochrome P-450 2C19 (CYP2C19) enzyme is involved in the metabolism of numerous antidepressants. It also metabolises some endogenous substrates, which could also confer to vulnerability. We aimed to establish whether the severity of depression and treatment response are associated with the genetically predicted CYP2C19 phenotype.

METHODS: We assessed the CYP2C19 genotype-predicted metabolic phenotypes (normal, intermediate or ultrarapid, there were no poor metabolisers) in patients with moderate or severe depression. We used the self-rated Beck Depression Inventory-II (BDI-II) scale and the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, after 2 and 4 weeks of an empirical treatment trial. Patients and clinicians were blind to the genetic testing results.

RESULTS: Seventy-six patients participated in the present study. At baseline, impaired CYP2C19 metabolisers, compared to normal metabolisers, had higher BDI-II (P = 0.046; ηp2 = 0.08) but not MADRS score. Intermediate metabolisers more often had a diagnosis of severe depression than normal metabolisers (P = 0.003). After 4 weeks of empirical treatment, intermediate metabolisers had significantly higher MADRS and BDI-II scores than normal metabolisers (P = 0.006; ηp2  = 0.131 and P = 0.030; ηp2 = 0.091). These differences were independent of the use of CYP2C19-metabolised medications in the treatment trial, as well as the treatment discrepancy status.

CONCLUSIONS: Intermediate CYP2C19 polymorphism-predicted activity was associated with more severe depression after an empirical treatment trial. The lack of association between the prescription of CYP2C19-metabolised drugs and treatment response calls for a further look into the role of endogenous substrates of CYP2C19.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

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