O-2-2 - CYP2D6 drug interaction potential of four SSRI's using in vivo dextromethorphan

Abstract

Treatment non-response and adverse reactions are common in patients receiving antidepressants. Personalizing psychiatric treatment based on pharmacogenetic testing has been proposed to help clinicians guide antidepressant selection and dosing. This systematic literature review assesses the two most robustly studied drug-metabolizing enzymes, CYP2D6 and CYP2C19, and examines whether obtaining CYP2D6 and CYP2C19 testing can be used to predict antidepressant response or adverse drug reactions in order to improve clinical outcomes. In general, literature reviews published prior to 2013 indicated that results have been inconsistent linking CYP2D6 and CYP2C19 to antidepressant treatment outcomes, suggesting that more evidence is required to support the clinical implementation of genotyping to predict outcomes. We thus performed an extensive and systematic literature review, focusing on studies published from 2013 through 2018. Sixteen studies were found to be relevant. The results yielded inconsistent findings, suggesting that CYP2D6 and CYP2C19 testing may predict response in certain individuals, but it remains unclear if this will translate to improved clinical outcomes. Further research is required to determine when pharmacogenetic testing should be utilized and in which populations it is indicated. Randomized, controlled, prospective trials with adequate sample sizes would best clarify whether genotype-guided antidepressant selection will ultimately improve clinical outcomes.