Pharmacogenetics Research Clinic

Antidepressant and Placebo response

Major depressive disorder (MDD) is a debilitating psychiatric disorder which affects up to 350 million people worldwide. Although antidepressant medication is a first-line treatment for MDD, there is considerable inter-individual variation in therapeutic response rates. Moreover, placebo-controlled, clinical trials evaluating antidepressant efficacy often show no difference between drug and placebo response, creating a significant challenge toward improving pharmacotherapy for MDD. The primary goal of our research on antidepressant and placebo response is to identify gene variants and gene systems that may be mediating pharmacotherapy outcomes in MDD.

Our research has revealed significant associations between IL-6 variants and both duloxetine and placebo response, see full text in PubMed. Genome-wide association studies have further reported an association between response to placebo and a Chromosome 3 locus that is otherwise implicated in neuronal signal transduction in nociceptive neurons (Müller et al., 2015b), see WCPG book of Abstracts. Machine learning models are also being used to predict therapeutic outcomes to duloxetine in MDD by incorporating gene-variants derived from a GWAS data set implicated in response. Our data provide new insights into genetic pathways implicated in response to antidepressant and placebo medication, and will help identify new drug targets and optimize clinical drug trials.

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