Antipsychotic drugs and QTc prolongation: the potential role of CYP2D6 genetic polymorphism

Abstract

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.

Keywords::

• antipsychotic drugs
• cardiac side effects
• CYP2D6
• drug metabolism
• QT interval lengthening
• torsades de pointes-type arrhythmia

Acknowledgments and conflicts of interests

Thanks are due to our collaborators A de la Rubia, M Cáceres and I González for assistance in collecting data and providing fruitful comments. The study was supported by Junta de Extremadura, Consejería de Sanidad y Consumo (SCSS.05.75), and by the Spanish Ministry of Health, Instituto de Salud Carlos III, Red de Enfermedades Mentales (REM-TAP Network), and coordinated in the Iberoamerican Network of Pharmacogenetics (CYTED206RT0290). P Dorado is supported by a grant (REI05A003) from Junta de Extremadura, Consejería de Infraestructura y Desarrollo, and European Union, Fondo Social Europeo.