SYMPOSIA

Bulletin of Clinical Psychopharmacology, Vol: 21, Supplement: 2, 2011 - www.psikofarmakoloji.org
Abstracts of the Invited Speakers
substrates of p-glycoprotein there is a significant statistical relationship between polymorphism and remission rate after 4 to 6 weeks.
Clinically, genetic analysis of ABCB1 polymorphisms may be used to predict how likely it is that a patient will respond to therapy with
antidepressants or other centrally acting drugs. This in turn will help to select the right drug and/or dosage (Neuron 2008, 57:203-209).
Further data from a preliminary pilot study suggest that the treatment of depression could be optimized by a routine application of
an ABCB1 gene test. Patients carrying the less favourable ABCB1 genotype with respect to the clinical efficacy of antidepressants may
especially benefit from a dosage increase.
P-glycoprotein in the membrane of vascular cells causes centrally acting drugs such as citalopram, paroxetine, venlafaxine and others to be
transported from the brain back to the vascular lumen. If the protein is missing or if its function is impaired, more drugs pass from the blood into
the brain. Depending on changes (polymorphisms) in the ABCB1 gene, p-glycoprotein allows varying amounts of a drug to pass into the CNS.
Bulletin of Clinical Psychopharmacology 2011;21(Suppl. 2):S44-5
Relationship between pharmacogenetics and personality traits: Relevance for suicide
Adrián Llerena
International Union of Basic and Clinical Pharmacology (IUPHAR), Extremadura University Hospital
E-mail: allerena@unex.es
CYP2D6 genetic polymorphism is related to variability of the enzyme’s hydroxylation capacity. Subjects carrying zero CYP2D6 active
genes are classified as Poor Metabolizers (PMs). The rest are Extensive Metabolizers (EMs) with one or two active genes, including a group
of Ultra-rapid Metabolizers (UMs) with more than two active alleles. UMs have a hydroxylation capacity more than 100 times higher than
PMs. The frequency of PMs and UMs in Spain is 7-10% and 4.9%, respectively (Llerena et al., 2009).
A higher frequency of UMs has been found among individuals who committed suicide vs. those who died from natural causes (Zackrisson
et al, 2010). One explanation for this relationship could be treatment failure with antidepressant drugs metabolized by CYP2D6
(fluoxetine, paroxetine, fluvoxamine, venlafaxine, citalopram, etc.) (Llerena et al., 2004; Llerena et al., 2009) 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. Since we found an association between this drug metabolizing enzyme and psychological functioning, CYP2D6 has been
associated with behavioral and clinical risk factors such as personality and vulnerability to psychopathology (Llerena et al., 1993; Llerena
et al., 2007; Gonzalez et al., 2008; Peñas-Lledó et al., 2009, Peñas-LLedó et al., 2010). These two hypotheses could explain the relationship
found between CYP2D6 and suicide (Peñas-LLedón et al 2011, in press)
The biotransformation of several antidepressants and antipsychotic drugs is mainly determined by genetic factors mediating the
CYP2D6 gene polymorphism. Additionally, the potential interaction between CYP2D6 and endogenous metabolism must be taken into
consideration due to its potential implication for personality traits (LLerena et al 1993; Gonzalez et al 2008) and functioning, such as:
neurocognition (Peñas-Lledó et al 2009) and psychopathology, eating disorders (Peñas-LLedó et al., 2010) and suicide (Peñas-Lledó et al.,
2011). In summary, 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 oberserved in the response to psychotropic drugs, but also
vulnerability to psychopathology including suicide.
Bulletin of Clinical Psychopharmacology 2011;21(Suppl. 2):S45
Genetic causes of hypersensitivity to antipsychotics – the clozapine story
Ingolf Cascorbi
Institute of Experimental and Clinical Pharmacology, University of Kiel, Germany
E-mail: cascorbi@pharmakologie.uni-kiel.de
Clozapine is considered to be the most efficacious drug to treat schizophrenia, but despite these benefits, clozapine prescriptions
comprise only 2-10% of the total antipsychotic market for schizophrenia in the United States. It was introduced on the market in 1971 but
was withdrawn in 1975 after reports of clozapine-induced agranulocytosis (CIA) in Finland. Due to its high efficacy in treatment-resistant
schizophrenia, it was reapproved in 1990 by the FDA and health authorities in most other countries; however, regular hematological
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