Pharmacogenetics of Antipsychotic Drugs in Schizophrenia Treatment

Piotr      Tybura; Beata      Trzesniowska-Drukala; Jerzy      Samochowiec

Abstract

Marked inter-individual variations in response to psychotropic drugs create a clinical dilemma that can only be resolved through long empirical pharmacogenetic drug trials. The principal objective of this study is to identify and categorise the genetic factors that underlie these differences and to apply these observations in clinical practice. Candidate genes for this type of investigation were extracted after observations in neurotransmission, neuronal plasticity, and transport and neurotransmitters metabolism.

Pharmacokinetic factors are closely connected with treatment response variability.

Functional polymorphism has been verified in the genes coding for CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 enzymes. Variations in the genes coding for receptors and transporters have been suggested in pharmacogenetic studies. Candidate genes implicated in schizophrenia etiophatology and treatment response are as follows: five subtypes of dopamine receptors D1-D5, 5HT1A, 5HT2A, 5HT2C, NMDA, receptor genes polymorphisms and variants of genes coded MAOA, COMT, DAT, 5HTT.

This article reviews recent pharmacogenetic studies regarding treatment response and adverse events in schizophrenia patients. The outcomes of these studies require verification on larger groups. However, future investigations in this direction will probably find more factors influencing antipsychotic treatment.

Keywords: Agranulocytosis, CYP, COMT, DRD2, DRD3, DRD4, DAT1, GRIN2B, 5HT1A, 5HT2A, 5HT2C, MAOA, neuroleptic malignant syndrome, neuroleptics, NMDAR1, pharmacodynamics, pharmacogenetics, pharmacokinetics, psychopharmacotherapy, schizophrenia, side effects, tardive diskinesia, treatment response, weight gain