Issues In Pharmacogenetic Testing.

ONTARIO; TORONTO (Ont.)

In pharmacogenomics the amount of information from DNA studies of cohorts and clinical trials is growing rapidly. This large amount of data creates challenges in terms of how to wrangle the genomic and phenotypic (response) variables and perform the most appropriate analyses. The main phenotypic target is the inter-individual differences in response and side effects to antidepressant and antipsychotic medications. Our psychiatric pharmacogenetics study based in Toronto and across the province of Ontario (www.IM-PACT.ca; n=9,000 patients tested) has shown that the vast majority of physicians found our user-friendly genetic report to be easy to understand. We have surveyed over 200 psychiatrists and 100 family practitioners and over 90% believe that pharmacogenetics testing will become standard of care for medication treatment in psychiatry in the future. A practical question from regulatory authorities is: Are physicians able to efficiently translate complex genetic information into clinical decision-making? Our survey and results show that primary care and psychiatry physicians report no significant difficulty in ordering and interpreting the pharmacogenetic test. A particular challenge in psychiatry is that current medications are largely selected by trial and error. For example, the physician is forced to choose between risk for weight gain and diabetes with the newer generation drugs versus the risk of tardive dyskinesia and other motor side effects with first generation antipsychotics. We have developed a model of seven genes (melanocortin-4 receptor, serotonin 2C, neuropeptide Y, CNR1, GCG, HCRTR) that predicts 67% of the variance in risk for this weight gain (Tiwari et al, 2015). Regarding the imperfect success of antidepressant treatment, there are now several replicated studies showing significant benefit of genetic panel guidance of medication selection over treatment as usual (Altar et al, 2015). Genes tested include CYP2D6, CYP2C19, CYP1A2, CYP3A4, 5HT2A, and 5HTTLPR. Our Toronto study has shown a significant reduction (30%, p < 0.002) in BDI depression scores during 8 weeks of follow-up, in patients who are on a genetically appropriate medication as opposed to those who are not. In addition to significant clinical improvement and increased tolerability, there is also reduction in health care costs when genetic guidance is used in antidepressant treatment. While these findings are encouraging for the wider clinical application of pharmacogenetic testing, much more work needs to be done, including surveying the patients to determine if they have concerns regarding the collection, reporting, and storage of their genetic information. [ABSTRACT FROM AUTHOR]

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