J Pharm Pharmacogn Res 2(Suppl. 1): S114, 2014

Special supplement with the abstract book of LATINFARMA 2013

Plenary Lecture


Llerena A.

Clinical Research Centre, Extremadura University Hospital and Medical School, Badajoz, Spain.

Hispanic populations are diverse according to their genetic composition resulting from the inter-ethnic crosses between Amerindians, Europeans and Africans. The frequency of CYP2D6 PMs and UMs in Spain is 7-10% and 4.9%, respectively (Llerena et al., 2009). The CEIBA-RIBEF Network Consortium aimed to evaluate the most relevant CYPs genetic polymorphism in different Ibero-American populations (from Spain, South-, Central-Caribe and North-America in a population of almost 6500 Healthy Volunteers included in the CEIBA consortium. Differences have been found, the frequency of CYP2D6 PMs ranged from 6%-3.9% in Nicaraguans-Cuban-Mestizos. The genetic polymorphism of the most studied cytochrome P450, CYP2D6, is among the major determinants of the interindividual and interethnic variability of pharmacokinetics and drug response. Two CYP2D6 phenotypes have been described: “poor metabolizers” (PM), and “extensive metabolizers” (EM) including a group of Ultra-rapid Metabolizers (UMs). CYP2D6, antidepressants discontinuation and suicide. A higher frequency of UMs has been found among individuals who committed suicide (Zackrisson et al, 2010). One explanation for this relationship could be treatment failure with antidepressant drugs metabolized by CYP2D6 (Llerena et al., 2004) widely used to prevent suicide or to treat mood disorders. A complementary explanation could be via the implication of the polymorphic CYP2D6 in the endogenous metabolism. CYP2D6 has been associated with behavioral and clinical risk factors such as personality and vulnerability to psychopathology (Llerena et al., 1993; 2007; Gonzalez et al., 2008; Peñas-Lledó et al., 2009, 2010). Consistently, we found a relationship between UMs and severity of suicide and lifetime history of suicidal behavior among Eating Disordered patients (Peñas-LLedó et al., 2010, 2011, 2012a). Moreover it seems also been related to antidepressant discontinuation as recently shown in Mexican depressive patients (Peñas-LLedó et al 2012b). The pharmacogenetics of CYP2D6 may be a useful tool to predict unexpected side-effects, interactions, or therapeutic failures of many relevant drugs and may explain the interethnic differences observed not only in the response to psychotropic drugs, but also in the vulnerability to psychopathology including suicide.