20 A series of studies have reported a better response to clozapine in patients who had the thymine allele of rs6313. The thymine allele of rs6313 has also been associated with a lower risk for the development of extrapyramidal side effects when taking antipsychotic medications.21-23 The serotonin receptor 2C gene (HTR2C) HTR2C is a very large gene that is located on the X chromosome and consists of 326 074 nucleotides. However, it codes for a protein things product that is composed of only 458 amino acids. Variations in the HTR2C gene have been Inhibitors,research,lifescience,medical associated with a better
clinical response to clozapine. Specifically, patients with schizophrenia who have a copy of the cytosine allele of rs6318 have achieved better control of their psychotic symptoms than patients with Inhibitors,research,lifescience,medical the guanine allele.24,25 However, this same variant has been associated with a higher risk for the development of extrapyramidal side effects in patients who are taking typical antipsychotic medications.26 An increased risk for the development
of weight gain has been linked to a different HTR2C variant. Specifically, Inhibitors,research,lifescience,medical the cytosine allele of rs518147 is associated with increased weight gain, while the thymine allele is conceptualized as providing protection against weight gain.27-29 The clinical utility of pharmacogenomic testing in psychiatric practice Assessing the clinical utility of pharmacogenomic testing is an ongoing process, given that the accuracy of genotyping is continually improving, and new research is identifying additional Inhibitors,research,lifescience,medical genetic variants that influence medication responses. Reports of adverse responses to 2D6 substrate medications in patients with decreased 2D6 metabolic capacity support the use of testing at this most basic level. Specifically, poor 2D6 metabolizers have had quite dramatic side effects to 2D6 substrate medications3 and some toxic reactions have been inhibitor U0126 lethal.30,31 However, there have been no large randomized clinical trials to demonstrate the clinical utility of pharmacogenomic
testing. Such trials Inhibitors,research,lifescience,medical would reinforce the use of testing. However, it is unlikely that these trials will ever be conducted because, by definition, they are not designed to concentrate on those patients who are the most likely to benefit from Entinostat pharmacogenomic testing. Trials that screen vulnerable populations and identify patients at risk for suboptimal responses to medications are a more efficient method to address the clinical usefulness of testing patients with decreased metabolic capacity. These screened patients could then be enrolled in protocols designed to provide optimal response for their specific genotypes and predicted pharmacogenomic phenotypes. Ethical considerations for pharmacogenomic testing in psychiatric practice The provision of pharmacogenomic testing involves relatively few risks, but ethical safeguards are still important to consider.