Introduction Expert groups have created dosing guidelines to facilitate the implementation of pharmacogenetic knowledge into clinical practice and commercial pharmacogenetic tests are becoming increasingly accessible. However, the extent to which these commercial tests facilitate the implementation of dosing guidelines is not clear. Methods Gene-drug pairs included on 22 commercial pharmacogenetic test panels were extracted and cross-referenced with the 74 gene-drug pairs with dosing guidelines in the Pharmacogenetics Knowledgebase, with particular attention given to the 28 gene-drug pairs relevant to psychiatry. Results On average, 70% of the 28 gene-drug pairs most relevant to psychiatry were covered by the examined tests. Six gene-drug pairs (CYP2D6-venlafaxine, CYP2D6-paroxetine, CYP2D6-amitriptyline, CYP2C19-sertraline, CYP2C19-citalopram, CYP2C19-amitriptyline) were included by all tests. Gene-drug pairs included on less than half of the test panels included HLA-B-phenytoin (14%), HLA-A-carbamazepine (24%), HLA-B-carbamazepine (29%), and CYP2D6-zuclopenthixol (43%). Discussion Most commercial pharmacogenetic tests we examined are well-equipped to facilitate implementation of the majority of dosing guidelines relevant to psychiatry but are limited in their ability to facilitate implementation of the full spectrum of dosing guidelines currently available.

Objective: To identify and assess pharmacogenetic testing options relevant to psychiatry in Canada. Method: Searches of published literature, websites, and Standard Council of Canada’s Laboratory Directory were conducted to identify pharmacogenetic tests available in Canada. Identified tests were assessed on 8 key questions related to analytical validity, accessibility, test ordering, delivery of test results, turnaround time, cost, clinical trial evidence, and gene/allele content. Results: A total of 13 pharmacogenetic tests relevant to psychiatry in Canada were identified. All tests were highly accessible, and most were conducted in accredited laboratories. Both direct-to-consumer and clinician-gated testing were identified, with turnaround times and cost ranging from 2 to 40 days and CAD$199 to CAD$2310, respectively. Two tests were supported by randomized controlled trials. All tests met minimum gene and allele panel recommendations for psychiatry, but no 2 panels were identical. No test was unequivocally superior to all other tests. Conclusions: Pharmacogenetic testing in Canada is readily available but highly variable in terms of ordering procedures, delivery of results, turnaround times, cost, and gene/allele content. As such, it is important for psychiatrists and other health-care providers to understand the differences between the available tests to ensure appropriate selection and implementation within their practice.

Objectives To facilitate decision-making and priority-setting related to Alberta’s Pharmacogenomics (PGx) testing implementation strategy by identifying gene–drug pairs with the highest potential impact on prescribing practices in Alberta. Patients and methods Annual drug dispensing data for Alberta from 2012 to 2016 for 57 medications with PGx-based prescribing guidelines were obtained, along with population estimates and demographics (age and ethnicity). Frequencies of actionable PGx genotypes by ethnicity were obtained from the Pharmacogenomics Knowledgebase (PharmGKB). Annual dispensing activity for each of the 57 medications was calculated for the full population (all ages) and children/youth (0–19 years). Alberta ethnicity data were cross-referenced with genetic frequency data for each of the main ethnic groups from PharmGKB to estimate the proportion of individuals with actionable genotypes. Actionable genotype proportions and drug dispensing frequencies were collectively used to identify high impact gene–drug pairs. Results We found (a) half of the drugs with PGx-based prescribing guidelines, namely, analgesics, proton pump inhibitors, psychotropics, and cardiovascular drugs, were dispensed at high frequencies (>1% of the entire population), (b) the dispensing rate for about one-third of these drugs increased over the 5-year study period, (c) between 1.1 and 45% of recipients of these drugs carried actionable genotypes, and (d) the gene–drug pairs with greatest impact in Alberta predominatly included CYP2C19 or CYP2D6. Conclusions We uncovered specific patterns in drug dispensing and identified important gene–drug pairs that will inform the planning and development of an evidenced-based PGx testing service in Alberta, Canada. Adaptation of our approach may facilitate the process of evidence-based PGx testing implementation in other jurisdictions.

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<i> CYP2C19</i> and <i>CYP2D6</i>genetic variation. Here, we aimed to determine the potential benefit of pairing <i>CYP2C19</i> and <i>CYP2D6</i>testing with the five-step STAR*D algorithm. To estimate the proportion of individuals that could benefit from <i>CYP2C19</i> and <i>CYP2D6</i> 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 <i>CYP2C19</i>and <i>CYP2D6</i> genetic testing. The potential benefit varied for each step of the algorithm and for each province, territory, and state. <i>CYP2C19</i> genotyping had the greatest potential impact within the first two steps of the algorithm, while <i>CYP2D6</i> genotyping had the most notable impact in Steps 3, 4, and 5. Our findings suggest the implementation of <i>CYP2C19</i>and <i>CYP2D6</i> genetic testing alongside the STAR*D treatment algorithm may improve depression treatment outcomes in Canada and the US.

We thank Dawes and colleagues 1 for their clarification on the features of their algorithm that we regretfully failed to mention in our recent review of pharmacogenetic testing options available in Canada. 2 We also would like to take this opportunity to acknowledge that several of the testing options we included in our review employed decision algorithms that may contain or have the capability to incorporate similar features (e.g., age, weight, current medications, renal, and liver functioning) that were highlighted by Dawes et al. but were not disclosed in the materials we used in our review. This is an inherent limitation to any review of commercially available pharmacogenetic testing options, resulting in part from the proprietary nature of several of the test manufacturer's algorithms. These algorithms, often referred to as "black box" algorithms, deliberately conceal the features used and/or the process by which these features are translated into clinical recommendations. 3 Although the testing option highlighted by Dawes et al. is not an example of a black box algorithm, it is important to note that head-to-head trials comparing open and black box pharmacogenetic testing algorithms have yet to be published, and all randomized clinical trials of pharmacogenetic testing in psychiatry have utilized black box algorithms with unique features. 4 As such, there is currently not enough evidence to suggest any test or algorithm is superior to another. However, common sense would suggest that pharmacogenetic testing options that include clinical features commonly used to make medication selection and dosing decisions would better facilitate safer and more efficacious therapy for those with a psychiatric disorder. Declaration of Conflicting Interests The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AAM, DJM, and CB are members of the Clinical Pharmacogenomics Implementation Consortium. CB is supported by the Cumming School of Medicine at the University of Calgary and the Alberta Children's Hospital Research Institute. MF declares no conflicts. PDA holds the Alberta Innovates Translational Health Chair in Child and Youth Mental Health. KA has acted in a consulting capacity for companies including Roche Diagnostics,