Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Aug;65(8):521-530.
doi: 10.1177/0706743720904820. Epub 2020 Feb 17.

Pharmacogenetic Testing Options Relevant to Psychiatry in Canada: Options de tests pharmacogénétiques pertinents en psychiatrie au Canada

Abdullah Al Maruf  1   2 , Mikayla Fan  3 , Paul D Arnold  1   2   4 , Daniel J Müller  5   6 , Katherine J Aitchison  7   8 , Chad A Bousman  1   2   4   9   10
Affiliations
Review

Pharmacogenetic Testing Options Relevant to Psychiatry in Canada: Options de tests pharmacogénétiques pertinents en psychiatrie au Canada

Abdullah Al Maruf et al. Can J Psychiatry. 2020 Aug.

Abstract
in English, French

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.

Objectif:: Identifier et évaluer les options de tests pharmacogénétiques pertinents en psychiatrie au Canada.

Méthode:: Des recherches dans la littérature publiée, les sites Web, et le répertoire des laboratoires du Conseil canadien des normes ont été menées pour repérer les tests pharmacogénétiques offerts au Canada. Les tests identifiés ont été évalués selon 8 questions clés liées à la validité analytique, l’accessibilité, la commande des tests, la livraison des résultats des tests, le délai de traitement, le coût, les données probantes de l’essai clinique, et le contenu des gènes/allèles.

Résultats:: Au total, 13 tests pharmacogénétiques pertinents en psychiatrie au Canada ont été identifiés. Tous les tests étaient facilement accessibles et la plupart ont été menés dans des laboratoires agréés. Tant les tests s’adressant directement aux consommateurs que ceux administrés par un clinicien ont été identifiés, avec des délais de traitement et des coûts oscillant entre 2 à 40 jours et 199 $ à 2 310 $ CAD, respectivement. Deux tests étaient soutenus par des essais randomisés contrôlés. Tous les tests satisfaisaient aux recommandations d’un groupe d’experts relativement au minimum de gènes et d’allèles pour la psychiatrie, mais les groupes d’experts n’étaient jamais identiques. Aucun test n’était sans équivoque supérieur aux autres tests.

Conclusions:: Les tests pharmacogénétiques sont facilement accessibles au Canada mais sont extrêmement variables en ce qui concerne les procédures de commande, la livraison de résultats, les délais de traitement, le coût et le contenu de gènes/allèles. Ainsi, il importe aux psychiatres et aux autres prestataires de soins de santé de comprendre les différences entre les tests offerts pour s’assurer d’une sélection appropriée et de la mise en œuvre dans le cadre de leur pratique.

Keywords: Canada; antidepressant testing tools; implementation; pharmacogenetic testing; psychiatry.

PubMed Disclaimer

Conflict of interest statement

Declaration of Conflicting Interests: 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, Bristol-Myers Squibb and Otsuka Pharmaceuticals Ltd, Otsuka Canada Pharmaceuticals Inc., Lundbeck, and HLS Therapeutics. She has also received research support from companies including Bristol-Myers Squibb and Otsuka Pharmaceuticals, Johnson and Johnson Research and Development, Jannsen Inc. Canada, and Roche Molecular Systems. DJM is coinvestigator in 2 pharmacogenetic studies where genetic test kits were provided as in-kind contribution by Assurex Health (Myriad Neuroscience) to evaluate feasibility of pharmacogenetic testing in clinical practice and potential benefits of pharmacogenetic testing compared to treatment as usual. DJM have not received any payments or received any equity, stocks, or options from this company or any other pharmacogenetic companies. DJM is coinvestigator in 2 filed genetic patents assessing risk for antipsychotic-induced weight gain. CB has received material support from Assurex Health (Myriad Neuroscience), CNSDose, Genomind, and AB-Biotics for research purposes and has ongoing research collaborations with MyDNA but does not have equity, stocks, or options in these companies or any other pharmacogenetic companies. CB, DJM and KA are members of the Genetic Testing Committee of the International Society of Psychiatric Genetics.

Figures

Figure 1.
Figure 1.
Genes included on pharmacogenetic testing panels in Canada. Gray = no actionable guidelines or drug labels for the gene. Black = presence of an actionable guideline or drug label for the gene in relation to a psychiatric medication only. White = presence of an actionable guideline or drug label for the gene in relation to a nonpsychiatric medication only. Striped = presence of an actionable guideline or drug label for the gene in relation to both psychiatric and nonpsychiatric medications. ABCB1 = ATP-binding cassette, subfamily B, member 1; ABCC1 = ATP-binding cassette, subfamily C, member 1; ABCG2 = ATP-binding cassette, superfamily G, member 2; ADD1 = aryloxyalkanoate dioxygenase 1; ADRA2A = adrenoceptor alpha 2A; ADRB1 = adrenoceptor Beta 1; ADRB2 = adrenoceptor Beta 2; AKT1 = v-akt murine thymoma viral oncogene homolog 1; ALI157359 = long intervening non-coding RNA region AL157359; ANK3 = ankyrin 3; ANKK1 = ankyrin repeat and kinase domain containing 1; APOE = apolipoprotein E; BDNF = brain-derived neurotrophic factor; CACNA1C = calcium channel, voltage-dependent, L type, alpha 1C subunit; CACNA1C = calcium voltage-gated channel subunit alpha 1; CESI = carboxylesterase 1; CHRNB2 = cholinergic receptor nicotinic beta 2 subunit; CNR1 = cannabinoid receptor 1; COMT = catechol-O-methyltransferase; COQ2 = coenzyme Q2; COX1 = cytochrome c oxidase I; CSMD1 = CUB and sushi multiple domains 1; CYP1A2 = cytochrome P450, family 1, subfamily A, polypeptide 2; CYP1A6 = cytochrome P450, family 1, subfamily A, polypeptide 6; CYP2B6 = cytochrome P450, family 2, subfamily B, polypeptide 6; CYP2C8 = cytochrome P450, family 2, subfamily C, polypeptide 8; CYP2C9 = cytochrome P450, family 2, subfamily C, polypeptide 9; CYP2C19 = cytochrome P450, family 2, subfamily C, polypeptide 19; CYP2D6 = cytochrome P450, family 2, subfamily D, polypeptide 6; CYP3A4 = cytochrome P450, family 3, subfamily A, polypeptide 4; CYP3A5 = cytochrome P450, family 3, subfamily A, polypeptide 5; CYP4F2 = cytochrome P450, family 4, subfamily F, member 2; DDIT4 = DNA-damage-inducible transcript 4; DPYD = dihydropyrimidine dehydrogenase; DRD2 = dopamine receptor D2; DRD3 = dopamine receptor D3; DRD4 = dopamine receptor D4; EPHX1 = epoxide hydrolase 1; F2 = coagulation factor II; F5 = coagulation factor V; FAAH = fatty acid amide hydrolase; FCHSD1 = FCH and double SH3 domains 1; GNB3 = Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3; GRIA1 = glutamate ionotropic receptor, AMPA type, subunit 1; GRIK1 = glutamate ionotropic receptor, kainate type, subunit 1; GRIK2 = glutamate ionotropic receptor, kainate type, subunit 2; GRIK4 = glutamate ionotropic receptor, kainate type, subunit 2; HLA-A = major histocompatibility complex, class I, A; HLA-B = major histocompatibility complex, class I, B; HSPG2 = heparan sulfate proteoglycan 2; HTR1A = 5-hydroxytryptamine receptor 1A; HTR1B = 5-hydroxytryptamine receptor 1B; HTR2A = serotonin receptor 2A; HTR2C = serotonin receptor 2C; IFNL3 = interferon, lambda 3; KCNIP4 = potassium voltage-gated channel interacting protein 4; LPHN3 = latrophilin 3; MC4R = melanocortin-4-receptor gene; MTHFR = methylenetetrahydrofolate reductase; MT-RNR1 = mitochondrially encoded 12S ribosomal RNA; NEFM = neurofilament medium; NEDD4L = NEDD4 like E3 ubiquitin protein ligase; NUDT15 = nudix hydrolase 15; OPRD1 = opioid receptor, delta 1; OPRM1 = opioid receptor, mu 1; PRKCA = protein kinase C alpha; POLG = DNA polymerase gamma; POR = cytochrome P450 oxidoreductase; RGS4 = regulator of G Protein signaling 4; RPTOR = regulatory associated protein of MTOR, complex 1; SACM1L = SAC1 like phosphatidylinositide phosphatase; SCN1A = sodium voltage-gated channel, alpha subunit 1; SCN2A = sodium voltage-gated channel alpha subunit 2; SLC6A2 = solute carrier family 6, member 2 (serotonin transporter); SLC6A4, solute carrier family 6, member 4 (serotonin transporter); SLCO1B1 = solute carrier organic anion transporter family, member 1B1; TCF7L2 = transcription factor 7 like 2; TNF = tumor necrosis factor; TH = tyrosine hydroxylase; TPH1 = tryptophan hydroxylase 1; TPH2 = tryptophan hydroxylase 2; TPMT = thiopurine S-methyltransferase; UGT1A1 = UDP glucuronosyltransferase 1 family, polypeptide A1; UGT1A4 = UDP glucuronosyltransferase 1 family, polypeptide A4; UGT2B15 = UDP glucuronosyltransferase 2 family, polypeptide B15; VKORC1 = vitamin K epoxide reductase complex, subunit 1; YEATS4 = YEATS domain containing 4; ZNF804A = zinc finger protein 804A.
Figure 2.
Figure 2.
Summary of (A) minimum psychiatry panel, (B) CYP2C19, (C) CYP2C9, and (D) CYP2D6 allelic coverage among the tests evaluated. Total number of tests included was 11. Tests offered by CEN4GEN and PurePharm were excluded because the alleles tested were not made available upon request. Dup = duplication.
See this image and copyright information in PMC

Comment in

  • Re: Pharmacogenetic Testing Options Relevant to Psychiatry in Canada.
    Dawes M, Katzov-Eckert H, Paterson A, Dawes D. Dawes M, et al. Can J Psychiatry. 2020 Aug;65(8):584-585. doi: 10.1177/0706743720925735. Epub 2020 May 13. Can J Psychiatry. 2020. PMID: 32400175 Free PMC article. No abstract available.
  • Reply to Dawes et al.
    Maruf AA, Fan M, Arnold PD, Müller DJ, Aitchison K, Bousman CA. Maruf AA, et al. Can J Psychiatry. 2020 Aug;65(8):586-587. doi: 10.1177/0706743720925736. Epub 2020 May 19. Can J Psychiatry. 2020. PMID: 32425056 Free PMC article. No abstract available.

References

    1. Dunnenberger HM, Crews KR, Hoffman JM, et al. Preemptive clinical pharmacogenetics implementation: current programs in five US medical centers. Annu Rev Pharmacol Toxicol. 2015;55(1):89–106. - PMC - PubMed
    1. Volpi S, Bult CJ, Chisholm RL, et al. Research directions in the clinical implementation of pharmacogenomics: an overview of US programs and projects. Clin Pharmacol Ther. 2018;103(5):778–786. - PMC - PubMed
    1. Bousman CA, Forbes M, Jayaram M, et al. Antidepressant prescribing in the precision medicine era: a prescriber’s primer on pharmacogenetic tools. BMC Psychiatry. 2017;17(1):60. - PMC - PubMed
    1. Haga SB, Kantor A. Horizon scan of clinical laboratories offering pharmacogenetic testing. Health Aff. 2018;37(5):717–723. - PMC - PubMed
    1. Müller DJ, Kekin I, Kao ACC, Brandl EJ. Towards the implementation of CYP2D6 and CYP2C19 genotypes in clinical practice: update and report from a pharmacogenetic service clinic. Int Rev Psychiatry. 2013;25(5):554–571. - PubMed

Substances