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Farmacogenetics as a tool for clinical decision-making on refractory schizophrenia

Grant number: 09/17960-1
Support Opportunities:Regular Research Grants
Duration: March 01, 2010 - February 29, 2012
Field of knowledge:Health Sciences - Medicine - Psychiatry
Principal Investigator:Wagner Farid Gattaz
Grantee:Wagner Farid Gattaz
Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil


Longitudinal studies suggest that 20-30% of schizophrenia patients will develop resistance to pharmacological treatment, condition also known as refractory schizophrenia. Several studies, including meta-analyses, have confirmed the superiority of clozapine in the treatment of refractory schizophrenia, establishing it as first choice drug for this condition. The current knowledge about polymorphisms in some key-genes for drug-metabolizing enzymes and its partial influence in the treatment response is making pharmacogenetic tests an important tool for clinical decision-making, as the determination of the metabolic status can enhance the efficacy of pharmacotherapy in 10-15% and reduce the incidence of side effects in 15-20 % of the patients. The present study aims to 1) examine the hypothesis that there is a higher prevalence of ultra-rapid metabolizers among patients with refractory schizophrenia, 2) to confirm the role of some polymorphisms in neurotransmitter receptors genes as markers of resistance to treatment with neuroleptics other than clozapine. The eventual confirmation of this hypothesis, together with the progressive cost-reduction of pharmacogenetic tests, would justify the inclusion of pharmacogenetic testing as routine for those patients who show resistance to common used dosages of at least two different antipsychotic agents, before introducing clozapine, 3) to verify the possible association between some polymorphisms and better cognitive performance in patients under treatment and its role in their rehabilitation plannig. (AU)

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