Pharmacogenetics and antipsychotics in the light of personalized pharmacotherapy.
The concept of personalized drug therapy on the basis of genetic investigations has become a major issue in psychopharmacology. Pharmacogenetic studies have focused on polymorphisms in liver cytochrome P450 isoenzymes that metabolize many antidepressant and antipsychotic medications. The most significant results are the association between drug metabolic polymorphisms of cytochrome P450 with variations in drug metabolic rates and side effects. Additionally, polymorphisms in dopamine and serotonin receptor genes are repeatedly found associated with response phenotypes, probably reflecting the strong affinities that most antipsychotics display for these receptors. The contribution of kinetic factors to the clinical outcome of antipsychotic treatment has a strong evidence base. Genetic tests for the pretreatment prediction of antipsychotic response have obvious implications for the selection of most appropriate drug and dose and contribute for the optimization of antipsychotic treatment. The pretreatment determination of individual's drug metabolic rates by CYP genotyping is the leading field. This review summarizes the present knowledge of associations between cytochrome P450 isoenzymes and the efficacy and side effects of antipsychotics.
Mihaljević-Peles
Alma
A
Department of Psychiatry, University Hospital Centre Zagreb, 10000 Zagreb, Croatia. apeles@mef.hr
Sagud
Marina
M
Bozina
Nada
N
Zivković
Maja
M
Jovanović
Nikolina
N
D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D004347:Drug Interactions; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008657:Metabolic Clearance Rate / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics; D057285:Precision Medicine / Q000379:methods*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*
D014150:Antipsychotic Agents; D007527:Isoenzymes; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6