Randomized trial: Pillcheck-guided pharmacist care improved depression and anxiety

Ruslan Dorfman, PhD, MBA4 Nov 2026

A randomized controlled trial in three Canadian community pharmacies found that people with depression and anxiety improved more when pharmacists used Pillcheck pharmacogenetic testing (also called pharmacogenomic or PGx testing) to guide their antidepressant treatment. Over 6 months, depression, anxiety and disability improved about twice as much as with standard care. The results were published in the peer-reviewed journal Clinical and Translational Science on February 28, 2021.

Why is it hard to find the right antidepressant?

Antidepressants are a first-line treatment for depression and generalized anxiety, but the first medication often does not work well enough or causes side effects. In the large STAR*D study, only about 37% of people with depression reached remission with their first antidepressant. Finding the right medication and dose can take several attempts, and each attempt can take weeks.

Genes help explain why. Genes such as CYP2D6 and CYP2C19 affect how quickly your body breaks down many antidepressants. Poor metabolizers may build up high levels and get more side effects, while ultrarapid metabolizers may clear the medication before it can work. Expert guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) use these genes to guide the choice and dose of antidepressants.

How was the study done?

Who took part: 213 adults aged 18 to 77 with major depression and/or generalized anxiety disorder. All were taking an antidepressant that had been started or changed recently and were not satisfied with it, because of side effects or because it was not working well enough.
Where: three large community pharmacies in Toronto and Oakville, Ontario, between 2018 and 2019.
Design: participants were randomly assigned to pharmacogenetics-guided care (105 people) or standard care (108 people). Everyone gave a cheek swab, but only the pharmacogenetics-guided group's Pillcheck results were used during the study. Participants did not know which group they were in.
Care in both groups: pharmacists reviewed each person's medications and sent recommendations to the prescriber, who could accept or decline them. In the pharmacogenetics-guided group, pharmacists also used the Pillcheck report.
What was measured: depression, anxiety, disability and treatment satisfaction, using standard questionnaires at the start and after 1, 3 and 6 months.

What did the study find?

Symptoms improved in both groups, but they improved more in the pharmacogenetics-guided group. Over 6 months:

Depression improved by 36% with pharmacogenetics-guided care, compared with 18% with standard care.
Anxiety improved by 41%, compared with 23%.
Disability, meaning how much symptoms interfered with work, social and family life, improved by 44%, compared with 18%.
Treatment satisfaction improved by a similar amount in both groups.

Prescribers were also more likely to act on the pharmacist's advice when it was based on genetic results: they accepted 75% of recommendations in the pharmacogenetics-guided group, compared with 53% in the standard care group. Most accepted changes were dose adjustments or switches to a different medication. The results held up when the researchers accounted for age, sex, pharmacy, type of prescriber and how medications were paid for.

How does this study fit with other research?

This trial contributed to the critical evidence that people who receive DNA-guided antidepressant therapy recover sooner. It was included in two meta-analyses, studies that pool the results of many randomized trials:

A 2023 meta-analysis of 12 randomized trials of tests that include CYP2D6 and CYP2C19 found that, compared with standard treatment, pharmacogenetics-guided treatment raised the odds of improvement by 63%, of response by 46% and of remission by 85%.
A 2024 meta-analysis of 15 randomized trials found a 37% higher remission rate and an 18% higher response rate after 8 weeks of pharmacogenetics-guided treatment.

Other meta-analyses point the same way. Across 13 trials with 4,767 patients, people who received DNA-guided antidepressant therapy were 41% more likely to reach remission. An analysis of 11 studies with 5,347 patients found higher response and remission rates at 8 and 12 weeks and concluded that patients may reach these goals more quickly.

The effect of pharmacogenetics-guided therapy also depends on when the test results reach the prescriber. Results help most when they are available before a medication is chosen, ideally at the time of diagnosis, rather than after several medications have failed. In the PRIME Care trial at 22 US Veterans Affairs medical centres, 1,944 people with depression were tested as they started or switched an antidepressant. When clinicians received the results, 59% of patients were prescribed an antidepressant with no predicted drug-gene interaction, compared with 26% with usual care, and remission rates over 24 weeks were higher, with the difference seen mainly in the first weeks of treatment. In the large European PREPARE study, testing before the first prescription reduced clinically important side effects by about 30%. Pharmacogenetic insights help avoid treatment failures.

Was the study independent?

Yes. The study was designed and run by pharmacists and researchers from Shoppers Drug Mart, the Centre for Addiction and Mental Health, the University of Toronto, Green Shield Canada and Radboud University in the Netherlands. The tests were purchased from GeneYouIn, the company that developed Pillcheck, which analyzed the samples but, as the paper states, had no other involvement in the study. The trial was registered in advance at ClinicalTrials.gov (NCT03591224).

What are the study's limitations?

No single study is the final word. Prescribers and the people collecting results knew which group each participant was in, which can introduce bias. The results were based on questionnaires that participants filled in themselves, and all three pharmacies were in urban areas. Regular check-ins over 6 months may also have helped participants in both groups. Larger studies with full blinding would strengthen the findings. Read about another clinical trial of pharmacogenetic testing for depression led by the Centre for Addiction and Mental Health.

What does this mean for you?

If you are living with depression or anxiety and your medication causes side effects or is not working well enough, a pharmacogenetic test can help your pharmacist and prescriber choose a medication and dose that suits your genes. Do not stop or change your medication on your own. Share your results with your prescriber and pharmacist and make changes together. Read more about how personalized medicine improves mental health treatment and how DNA testing can help find the best anxiety and depression medication.

How can a Pillcheck test help?

The Pillcheck report has grown since the study. The version used in the trial covered 19 genes and more than 200 medications. Today, a Pillcheck pharmacist reviews your results together with all your medications and prepares recommendations for antidepressants, anxiety medications, pain relievers and many other medications, to share with your prescriber.

Pillcheck testing is performed in CAP- and COLA-accredited clinical genetic laboratories located in Canada. 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. The Pillcheck test panel ensures high accuracy for people of non-European and admixed ancestries. Your results last a lifetime, and report updates are free of charge.

Summary

A randomized controlled trial in three Canadian community pharmacies tested Pillcheck-guided antidepressant care in 213 adults with depression and/or anxiety.
Over 6 months, depression improved by 36% versus 18%, anxiety by 41% versus 23% and disability by 44% versus 18% compared with standard care.
Prescribers accepted 75% of pharmacist recommendations based on genetic results, compared with 53% without them.
The trial was included in meta-analyses showing that DNA-guided antidepressant therapy makes response and remission more likely.
The study was run by independent researchers; Pillcheck's developer only supplied and analyzed the tests.
Prescribers were not blinded, so larger, fully blinded studies would strengthen the findings.

Frequently asked questions

Was this study funded or run by Pillcheck?

No. The study was designed and run by independent pharmacists and researchers. The tests were purchased from GeneYouIn, Pillcheck's developer, which analyzed the samples and had no other involvement.

How much did depression improve?

Over 6 months, depression scores improved by 36% in the pharmacogenetics-guided group, compared with 18% with standard care.

Should I change my antidepressant based on my results?

Not on your own. Your results help your prescriber and pharmacist choose a medication and dose. Any change should be made together with them.

Is today's Pillcheck report the same as the one in the study?

It has grown. The study used a report covering 19 genes and more than 200 medications. Today's report covers 24 genes and 355 medications, and it is updated as guidelines change.