Encountering Pharmacogenomic Test Results in Psychiatry

Pharmacogenomic (PGx) testing, also called pharmacogenetics, uses a person's genetic information to help guide medication choice and dosing. In psychiatry, it can help shorten the search for an antidepressant or antipsychotic that works and is tolerated, and it can contribute to better outcomes. More patients now arrive at appointments with PGx results, and some clinicians feel unsure how to judge or use them. A paper in The Canadian Journal of Psychiatry, "Encountering Pharmacogenetic Test Results in the Psychiatric Clinic," offers practical strategies and resources for these situations. Its authors include psychiatrists and pharmacogenomics researchers from the University of Calgary, the Centre for Addiction and Mental Health (CAMH) and the University of Toronto, as well as members of the Pillcheck team.

How can you tell if a pharmacogenomic test is reliable?

PGx tests from different providers are not equivalent or interchangeable. Three features increase confidence in the results:

1. An accredited laboratory. The test should be performed in a laboratory accredited for clinical testing.
2. The right genes and variants. The test should focus on pharmacokinetic genes, such as CYP2C19 and CYP2D6, that have a direct effect on drug levels and tolerability. It should include at least the minimum set of variants (Tier 1) recommended by the Association for Molecular Pathology, and ideally the extended set (Tier 2). For CYP2D6, this includes detecting gene deletions and extra copies, which change metabolizer status. Testing more variants makes results more accurate across populations, including people of European, Asian, African and Indigenous ancestry. Learn more about star alleles and gene copy number.
3. Guideline-based recommendations. Prescribing recommendations should come from evidence-based sources, such as the Clinical Pharmacogenetics Implementation Consortium (CPIC), the Dutch Pharmacogenetics Working Group (DPWG), or Health Canada and FDA drug labels. Recommendations that have not gone through this kind of review may lead to unexpected and harmful outcomes.

Some commercial tests also report "pharmacodynamic" genes, such as SLC6A4 (the serotonin transporter) and HTR2A (a serotonin receptor). In its 2023 antidepressant guideline, CPIC reviewed these genes and made no prescribing recommendations for them, because the evidence was not strong enough.

Are prescribing recommendations medication-specific?

Yes. Recommendations apply to each gene-drug pair, and two medications in the same class can have different recommendations because they are cleared by different enzymes. For example, for a CYP2C19 poor metabolizer, CPIC suggests considering a lower starting dose of escitalopram, citalopram or sertraline, because blood levels can be much higher than usual. The same person may need no change for paroxetine or vortioxetine, which are cleared mainly by CYP2D6. A CYP2C19 ultrarapid metabolizer, on the other hand, may not respond to citalopram or escitalopram at standard doses and may do better with a medication that does not depend on CYP2C19.

What else can change the meaning of a PGx result?

A genetic result describes enzyme activity, but other factors can change it:

• Drug interactions (phenoconversion). Strong enzyme blockers, such as bupropion, fluoxetine and paroxetine for CYP2D6, can make a genetic normal metabolizer behave like a poor metabolizer.
• Smoking speeds up CYP1A2 and lowers levels of clozapine and olanzapine. Stopping smoking can raise them.
• Pregnancy, age, liver and kidney function can also change drug levels.

This is why PGx results should be read together with the patient's full medication list and clinical picture.

How should PGx results be discussed with patients?

PGx testing supports shared decision-making. It helps set realistic expectations: results can guide the choice of medication and dose and lower the risk of some side effects, but they cannot guarantee that a medication will work. Genetic results do not change over a lifetime, so the same report can guide future prescriptions. Physicians should be familiar with the guidelines and drug labels for the medications they prescribe most often and consider PGx results when they are available.

What does Pillcheck include?

Pillcheck combines a PGx test with a medication review by a clinical pharmacist trained in pharmacogenomics. The Pillcheck test is performed at CAP- and COLA-accredited clinical genetic laboratories located in Canada. It reports CYP2D6, including gene deletions and duplications, CYP2C19, CYP2B6, CYP1A2, CYP3A4 and other genes. Pillcheck reports on 24 genes, increasing coverage with new guidelines and drug labels (see the genes tab), and covers 355 medications, which account for over 70% of dispensed prescriptions. In addition to mental health, Pillcheck covers medications for heart conditions, gastrointestinal problems, pain, cancer and other areas in every report. Results from an independent randomized controlled trial using Pillcheck showed improved treatment for people with depression and anxiety.

Pillcheck can be ordered online by patients, or offered through clinics and pharmacies. Learn more for healthcare providers.

Summary

• PGx tests are not interchangeable. Look for an accredited lab, recommended CYP2C19 and CYP2D6 variants (including CYP2D6 copy number) and guideline-based recommendations.
• CPIC makes no recommendations for SLC6A4 or HTR2A, which some tests still report.
• Recommendations apply to each gene-drug pair, so two medications in the same class may be handled differently.
• Drug interactions, smoking and other factors can change how a genetic result plays out.
• PGx testing complements clinical judgment and supports shared decision-making with patients.

Frequently asked questions

Do PGx results tell me which antidepressant will work?

No. PGx results show how a patient is likely to process many medications, which helps guide the choice and dose and avoid some side effects. Clinical judgment remains essential.

What if a patient's result conflicts with their past experience with a medication?

Consider drug interactions, adherence, dose and other factors. A patient's past response is important information to weigh alongside the genetic result.

Are PGx results valid for life?

Yes. Genetic results do not change, although guideline recommendations are updated as evidence grows. Some PGx testing providers require a paid subscription for updated reports, while Pillcheck report updates are free of charge.

Which guidelines should I use?

CPIC and DPWG guidelines, along with Health Canada and FDA drug labels, are the main evidence-based sources for gene-drug recommendations.

References

Bousman CA, Mukerjee G, Men X, Dorfman R, Müller DJ, Thomas RE. Encountering Pharmacogenetic Test Results in the Psychiatric Clinic. Can J Psychiatry. 2022;67(2):95-100.

Bousman CA, Stevenson JM, Ramsey LB, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants. Clin Pharmacol Ther. 2023;114(1):51-68.

Pratt VM, Del Tredici AL, Hachad H, et al. Recommendations for Clinical CYP2C19 Genotyping Allele Selection: A Report of the Association for Molecular Pathology. J Mol Diagn. 2018;20(3):269-276.

Pratt VM, Cavallari LH, Del Tredici AL, et al. Recommendations for Clinical CYP2D6 Genotyping Allele Selection: A Joint Consensus Recommendation of the Association for Molecular Pathology, College of American Pathologists, Dutch Pharmacogenetics Working Group of the Royal Dutch Pharmacists Association, and the European Society for Pharmacogenomics and Personalized Therapy. J Mol Diagn. 2021;23(9):1047-1064.