Characterisation of selected molecular mechanisms influencing pharmacokinetics and pharmacodynamics of antidepressants

Over 350 millions of people suffer from depression worldwide, and an increase in the incidence of the disease is expected in the coming years. Therefore, there is a strong need of knowing the mechanisms of development this disease and its effective treatment. Pharmacological therapy is an essential element of antidepressant therapy and its failure is a serious problem in clinical psychiatry. In spite of large number of available medicines, only 50% of patients achieved remission after single-drug treatment. Genetic factors which predispose to depression development and predict an outcome of its pharmacotherapy, probably play a substantial role in these phenomena. In spite of this, they are still not characterized enough and applied in practice. Therefore, the aim of this study is to present the current knowledge of the impact of selected genes on pharmacokinetics and pharmacodynamics of antidepressants by changing function and/or structure of encoded proteins. In the review the best known polymorphisms of selected genes encoding isoenzymes of cytochrome P-450, responsible for metabolism of popular antidepressant drugs, namely CYP2C19, CYP2D6, CYP1A2, and CYP3A4/5 are described. Further, 4 polymorphisms of ABCB1 gene (rs 1045642, rs 2032582, rs 1128503 and rs 2032583) encoding glycoprotein P, which play a key role in transportation of large number of drugs used in treatment of depression. For benefit of treatment of patients with depression, it is worthy to estimate and to take on the board all so far known mechanisms of planning therapy.