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

Abstract

Danute Balkeliene d,e Algirdas Utkus d,e and Edgaras Dlugauskas a,e 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. MethodsWe assessed the CYP2C19 genotypepredicted metabolic phenotypes (normal, intermediate or ultrarapid, there were no poor metabolisers) in patients with moderate or severe depression. We used the selfrated 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. ResultsSeventy-six patients participated in the present study. At baseline, impaired CYP2C19 metabolisers, compared to normal metabolisers, had higher BDI-II (P = 0.046; η p 2 = 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; η p 2 = 0.131 and P = 0.030; η p 2 = 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 polymorphismpredicted activity was associated with more severe depression after an empirical treatment trial. The lack of association between the prescription of CYP2C19metabolised drugs and treatment response calls for a further look into the role of endogenous substrates of CYP2C19.

CYP2C19-rs4986893 confers risk to major depressive disorder and bipolar disorder in the Han Chinese population whereas ABCB1-rs1045642 acts as a protective factor

“…Recent studies have suggested that impaired CYP2C19 metabolizers had higher self-rated Beck Depression Inventory-II scores than normal metabolizers. Damaged CYP2C19 enzyme activity was associated with more severe MDD, despite CYP2C19-metabolized medication treatment and treatment discrepancy status [ 7 ]. CYP2C19 polymorphism has been demonstrated to affect the conversion and degradation of endogenous compounds, including psychoactive steroid hormones (e.g.…”

“…Based on previous studies on risk variants contributing to psychiatry disorders, 13 genes containing 20 SNPs were selected for further analysis. CYP2C19 (rs12248560, rs4986893, rs4244285) was obtained from the findings of a 4-week prospective study by Strumila et al [ 7 ]. CYP2C9 (rs1057910) was chosen from a case-control study in a European population [ 14 – 16 ].…”