Pharmacogenetic of response efficacy to antipsychotics in schizophrenia: pharmacodynamic aspects. Review and implications for clinical research

Pharmacogenetics constitutes a new and growing therapeutic approach in the identification of the predictive factors of the response to antipsychotic treatment. This review aims to summarize recent finding into pharmacodynamic approach of pharmacogenetics of antipsychotics and particularly second generation. Studies were identified in the MEDLINE database from 1993 to July 2008 by combining the following Medical Subject Heading search terms: genetic, polymorphism, single nucleotide polymorphism, pharmacogenetics, antipsychotics, and response to treatment as well as individual antipsychotics names. Only pharmacodynamics studies were analyzed and we focused on efficacy studies. We also reviewed the references of ll identified articles. Most studies follow a polymorphism-by-polymorphism approach, and concern polymorphisms of genes coding for dopamine and serotonin receptors. Haplotypic approach has been considered in some studies. Few have studied the combinations of polymorphisms of several genes as a predictive factor of the response to antipsychotics. We present this gene-by-gene approach while detailing the features of the polymorphisms being studied (functionality, linkage disequilibrium) and the features of the studies (studied treatment(s), prospective/retrospective study, pharmacological dosage). We discuss the heterogeneity of the results and their potential clinical implications and extract methodological suggestions for the future concerning phenotype characterization, genotypes variants studied and methodological and statistical approach.