Farmacogenética em psiquiatria: influência dos polimorfismos CYP1A2*1F e CYP2C19*17 na refratariedade ao tratamento à clozapina e ao escitalopram
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2015-08-26
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Universidade Federal de Goiás
Resumo
The aim of pharmacogenetics is to understand the hereditary basis of
therapeutic response and side effects of pharmacological agents for each individual.
Antipsychotics and antidepressants are effective drugs for schizophrenia and major
depressive disorder (MDD) treatment, respectively. Although a number of patients
respond satisfactorily to antipsychotics and antidepressants, 20-40% of them present
inadequate response, and the treatment with ineffective medication may take weeks
of unremitted illness, potential adverse drug reactions and nonadherence to
treatment. This study aims to identify polymorphisms in genes that potentially
influence the treatment response to clozapine in schizophrenic patients and the
treatment with escitalopram in MDD patients. This approach involved the study of
CYP1A2 and CYP2C19 genes related to the metabolism of these drugs and which
may to affect the efficacy of treatment. It was studied 54 schizophrenic patients
taking clozapine and 31 patients with MDD treated with escitalopram, both for long
term. The investigated polymorphisms, CYP1A2*1F in schizophrenic patients and
CYP2C19*2 and CYP2C19*17 in depressive patients, were analyzed by polymerase
chain reaction (PCR), followed by sequencing (CYP1A2*1F) or by restriction
fragment length polymorphism (RFLP) (CYP2C19*2 and *17) techniques. The results
pointed for the association between CYP1A2*1F polymorphism and super-refractory
clozapine treatment and for the association between CYP2C19*17 polymorphism
and the decreased response to escitalopram treatment. No association was
observed between CYP2C19*2 and the response to escitalopram treatment. These
findings suggest that these genetic variants have an important influence on the
treatment effectiveness of antipsychotics and antidepressants in psychiatric
disorders, as schizophrenia and MDD. The pharmacogenetics may be useful to the
psychiatrists helping in the choice of drugs and doses more efficient for each patient,
reducing suffering and costs and contributing to improve the quality of life for patients
and families.
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BRITO, R. B. Farmacogenética em psiquiatria: influência dos polimorfismos CYP1A2*1F e CYP2C19*17 na refratariedade ao tratamento à clozapina e ao escitalopram. 2015. 70 f. Tese (Doutorado em Biologia) - Universidade Federal de Goiás, Goiânia, 2015.