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Guest lectures
GL.02 The future of pharmacogenetics in neurology and psychiatry
  1. David Mrazek

    Dr Mrazek joined Mayo Clinic in September of 2000 as Chair of the Department of Psychiatry and Psychology. His specialty is in the area of Child and Adolescent Psychiatry, however his research interests and publications cover a broad range of psychiatric illnesses that occur in patients of all ages. Most recently Dr Mrazek has begun several new research initiatives in genomics. He has collaborated with other investigators in studying various links between genomic variability and psychiatric illnesses such as depression, bipolar illness, and attention deficit hyperactivity disorder.

Abstract

While pharmacogenomics has been evolving over the past 30 years, there has been a rapid acceleration of the translation of research findings over the past decade. While genomically informed strategies to provide a more rationale approach to medication management has influenced every medical subspecialty, pharmacogenomic testing has the potential to have the greatest impact on psychiatry as a consequence of the large variety of available psychotropic medications and the central role that psychopharmacology plays in current psychiatric practice.

While individual laboratories initiated psychiatric pharmacogenomic testing prior to 2004, the approval of the Amplichip by the Federal Department of Administration (FDA) in the USA provided high profile recognition of the importance of identifying psychiatric patients who had atypical metabolic capacity. While the initial two genes included in this initial product were the cytochrome P450 2D6 gene (CYP2D6) and the cytochrome P450 2C19 gene (CYP2C19), several other cytochrome P450 genes have subsequently been added to laboratory profiles providing greater sophistication in identifying patients with a problematic metabolic capacity.

The second major class of pharmacogenomically relevant genes has been broadly described as “target genes.” These include the neurotransmitter transporter receptor genes. With the ability to create a more comprehensive pharmacogenomic profile for a given patient, there has been increased precision in establishing both the probability of side effects and the likelihood of a clinical response.

Gene variations providing information about a specific medication have also been identified. A good example is the *1502 variant of the HLA-B gene. After an FDA warning about the risk of Asian patients developing Stevens Johnson Syndrome, it quickly became standard practice to screen patients of Asian ancestry for the *1502 allele prior to prescribing carbamazepine.

We are currently in the early adoption state of pharmacogenomic testing in the USA. A number of academic medical centres, including the Mayo Clinic and the Cincinnati Children's Hospital, have been genotyping drug metabolising enzyme genes and selected target genes for almost a decade. However, the adoption of pharmacogenomic testing has been less rapid in community practice because of problems with the reimbursement for testing. However, with increasing appreciation of the benefits of testing, it is widely anticipated that psychiatric pharmacogenomic testing will become the standard of clinical practice in the US within the next 5 years. Possible barriers to adoption will be reviewed and discussed, as well as the imperative need for the translation of new research findings.

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