In the field of pharmacogenomics, strong positive results have been produced by studying medications that require clinicians to tailor carefully the dose to each individual patient’s needs.69 An initial GWAS of warfarin dose in 181 patients detected a genome-wide significant association signal upstream of the gene (VKORC1) encoding the drug’s target.72 The case of warfarin is instructive for the study of methadone, providing an example of efforts to clinically implement genotype-guided dosing.73 Warfarin differs from methadone, however, in that the International Normalized Ratio (INR) test can provide precise biochemical feedback to guide warfarin dosing, making it difficult for genotype-based algorithms to improve on treatment as usual.74, 75 In contrast, there are currently no biological assays to help clinicians decide which patients will require more aggressive methadone dosing, suggesting that genetics could play a role in improving clinical outcomes. Prospective studies, including randomized controlled trials of genotype guided dosing, are needed to define better the magnitude of the genetic contribution to dose requirements, and to assess the clinical utility of this information.
