Pharmacogenetic aspects of the efficacy and safety of trazodone therapy

Objective: The effectiveness and safety of antidepressant therapy is a major problem. Only 25 % of patients with major depressive disorder (MDD) received adequate treatment, whereas only 20–30 % of patients whose symptoms were fully controlled by treatment relapsed. Trazodone is a triazolopyridine derivative can be used as monotherapy and as part of a combination strategy for addressing patients with treatment-resistant depression. Purpose: Systematization of data about the role of pharmacogenomics factors ontrazodone effectiveness and adverse trazodone reactions. Method: A literature search was conducted from Google Scholar, PubMed, Oxford academic, Scopus, PubChem, MedLine, Web of Science, e-LIBRARY and Pharm GKB databases from 1976 to 2018 using the combination of terms Trazodone AND Personalized Medicine OR SNP OR Pharmacogenetics. Results: 8 single-nucleotide polymorphisms (SNPs) cytochrome P450 (CYP2D6, CYP3A4, CYP1A2 and CYP3A5) and P-glycoprotein (ABCB1) genes were analyzed. Conclusions: The most promising markers of safety and efficacy of trazodone are SNP serotonin receptors genes, cytochrome P450 genes (CYP3A4 and CYP1A2) and ABCB1 gene. However, unambiguous results were obtained only for rs1045642 polymorphismsABCB1 gene and CYP3A5*3 СYP3A5 gene. Other genotype dSNPs not having any strong association with the therapeutic response. Future studies, including larger sample sizes, are needed.

trazodone, pharmacogenetics, major depressive disorder, SNP, personalized medicine

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