Estimating the Potential Impact of CYP2C19 and CYP2D6 Genetic Testing on Protocol-Based Care for Depression in Canada and the United States

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) algorithm is the most recognized protocol-based care approach for moderate to severe depression. However, its implementation results in one-third of individuals receiving modest to no symptom remission. One possible explanation is the inter-individual differences in antidepressant metabolism due to CYP2C19 and CYP2D6genetic variation. Here, we aimed to determine the potential benefit of pairing CYP2C19 and CYP2D6testing with the five-step STAR*D algorithm. To estimate the proportion of individuals that could benefit from CYP2C19 and CYP2D6 testing, we simulated the STAR*D algorithm using ethnicity-specific phenotype (e.g., metabolizer status) frequencies published by the Clinical Pharmacogenetics Implementation Consortium and census data from the Canada and the US. We found that up to one-third of the US and Canadian populations being treated for depression could benefit from the addition of CYP2C19and CYP2D6 genetic testing. The potential benefit varied for each step of the algorithm and for each province, territory, and state. CYP2C19 genotyping had the greatest potential impact within the first two steps of the algorithm, while CYP2D6 genotyping had the most notable impact in Steps 3, 4, and 5. Our findings suggest the implementation of CYP2C19and CYP2D6 genetic testing alongside the STAR*D treatment algorithm may improve depression treatment outcomes in Canada and the US.