Antipsychotic drugs and QTc prolongation: the potential role of CYP2D6 genetic polymorphism.
Although the most common, and usually serious, side effects of first-generation (or typical) antipsychotic drugs, such as Parkinsonism, dystonias and tardive dyskinesia, were known from early times, their cardiovascular safety was not properly in the focus of treatment management. The growing evidence of these drug-related cardiac changes and the appearance of potentially fatal dysrhythmias have increased the interest on their safety profile. Thus, the introduction of the new second-generation (atypical) antipsychotic drugs put emphasis on the preregistration evaluation of the potential cardiac side effects and electrocardiogram predictors (QT interval lengthening). In spite of this, these drugs do not appear to be exempt from these potential risks. The present review summarizes up-to-date knowledge about the cardiac safety of antipsychotic drugs, and analyses the role of drug metabolic processes (CYP2D6 genetic polymorphism) in the complex pathophysiology of the phenomenon. In addition, some recommendations are formulated.
Dorado
Pedro
P
University of Extremadura, Department of Pharmacology and Psychiatry, Centro de Investigación Clínica CICAB, Servicio Extremeño de Salud, Hospital Universitario Infanta Cristina, Badajoz, Spain.
Berecz
Roland
R
Peñas-Lledó
Eva M
EM
Llerena
Adrián
A
D014150:Antipsychotic Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D004562:Electrocardiography; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology; D011110:Polymorphism, Genetic
D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6