Pharmacogenetics of quetiapine

Abstract

(1) Introduction: Quetiapine (QTP) is a dibenzothiazepine derivative, a second generation antipsychotic (AP), which is structurally similar to clozapine. The main indications for use are schizophrenia and depressive disorder. Under manic episodes in bipolar disorder can be used alone or in combination with lithium. The frequency of prescribing QTP is on average 11,987 per 100,000 population, with a positive trend in dynamics: a growth rate of more than 800% within the period 2002 to 2017.(2) Purpose: The review of studies of pharmacogenetic pharmacokinetic and pharmacogenetic pharmacodynamic markers of QTP efficacy and safety.(3) Materials and Methods: A search was carried out for publications of the Science Index, PubMed, Web of Science, Springer databases by keywords and their combinations over the last 10 years. In addition, the review includes earlier publications of historical interest. Despite extensive searches of these commonly used databases and search terms, it cannot be ruled out that some publications may have been missed.(4) Results: The review considers the following pharmacokinetic markers of QTP efficacy and safety: genes are coding isoforms of cytochrome P450 (CYP2D6, CYP2C19, CYP3A4, CYP3A5), P-glycoprotein (ABCB1); pharmacogenetic pharmacodynamic markers of the efficacy and safety of QTP : genes of dopamine receptor isoform (DRD3), dopamine transporter (SCL1A1) and catecholO-methyltransferase (COMT), serotonin receptor isoforms (HTR2C), melanocortin receptor (MC4R), NOTCH protein (NOTCH4), phosphodiesterase 4D (PDE4D), SPoPL protein (SPoPL), multiple EGFlike domain (MEGF10), protocadherin-7 (PCDH7), contactin-associated protein 5 (CNTNAP5) , TRAF2 and NCK-interacting protein kinase (TNIK), spermatogenesis-associated protein 6 (SPATA6L), neurobihin (NBEA), synaptic vesicle protein-2C (SVC2) .(5) Conclusion: Disclosure of pharmacogenetic markers of pharmacokinetics and pharmacodynamics of QTP efficacy and safety in the treatment of patients with schizophrenia and other psychiatric disorders, may provide a key to developing a strategy for its personalized prevention of adverse grug reactions (ADRs) and therapy strategy in real clinical practice.