By Masih Khalatbari and Patrick Pearson
Jim Halliday was sweating and convulsing. The soles of his feet started itching.
“I had to rip my shoes off. It was uncontrollable,” he recalls.
Halliday, a former managing director at the Bank of Montreal, wondered if the intense symptoms were related to his first dose of a new medication he started taking the night before.
His doctor had prescribed a common antidepressant off-label to treat dizziness.
The doctor initially dismissed the idea that the drug could be to blame. After a few days, as symptoms intensified, he eventually told Halliday to stop taking it.
But Halliday’s symptoms continued to worsen and new ones set in. He started waking up with his limbs stiffly sticking straight up in the air.
For nearly three years, he searched for an explanation until a new doctor told him to take a pharmacogenetic test. It revealed all of Halliday’s suffering might have been avoided.
Pharmacogenomic testing uses DNA to examine how a patient’s genes affect the way their body responds to specific drugs. Tests typically cost around $500. No Canadian provincial health insurance currently covers the tests except in special circumstances.
Widespread genetic tests would save lives, doctors say
If widely implemented, pharmacogenomic testing would save lives, avoid tragic side effects from drug interactions gone wrong and help doctors treat conditions more effectively, say many medical genetics experts. The tests could help reduce trial and error as prescribing doctors try to find the drug likeliest to help a patient.
The U.K.’s public health-care system is already taking steps toward it. But in Canada, governments question whether the cost to the public health-care system would be worth the benefits.
For now, the tests are primarily available to Canadians who have the time and money to seek them out, though some researchers are calling for them to be more widely available.
“It could save money in the health system if properly applied,” says Dr. Bruce Carleton, a professor of pediatrics at the University of British Columbia. “Get to successful treatment faster.”
Five years since his ordeal began, Halliday continues to suffer from frozen limbs, chronic pain, tinnitus, and damage to his brain, skin, and muscles. His condition has numbed his libido and has made him unable to cry.
“It handicapped me,” says Halliday, who would regularly go on runs, golf and tend to a farm as a hobby before taking Paxil.
“This is torture.”
Dr. Lawrence Schmidt and his patient Jim Halliday. Halliday recalls the look of a light bulb going off in the physician’s eyes as he described his symptoms on their first visit. Photo credit: Tannis Toohey for the Toronto Star
Now, he is on a mission to make more widely available a simple test that could have prevented the harm that came to him and possibly thousands of others who experience drug-related side effects.
“This is right there, there’s an answer to hell,” he says.
Ontario review questioned tests’ ‘cost-effectiveness’
The U.K.’s National Health Service is piloting pharmacogenomic testing to inform clinicians when prescribing drugs.
The program is part of a broader national strategy to widen genetic testing in routine care, which includes training health-care professionals about the testing and making it easy to access and interpret pharmacogenomic test results.
The NHS began the pilot program last year, allowing a handful of general practitioners to use genetic testing prior to prescribing some drugs, with plans for it to be expanded nationwide if it is successful.
The testing “has the potential to transform patient’s lives by … matching people to the most effective medications and interventions, reducing the likelihood of an adverse drug reaction,” according to the NHS.
In 2021, Ontario Health, the agency that oversees the administration of the province’s health-care system, recommended against funding pharmacogenomic testing for individuals with major depression on the basis that the tests have limited “clinical utility and cost-effectiveness.”
“The level of uncertainty about cost-effectiveness for testing was high,” says the recommendation, noting that funding the tests would cost an estimated $52 million over five years.
The agency did not respond to specific questions sent by the IJB.
Experts say that, at the time, there was no evidence to suggest the benefits of widespread testing would economically outweigh its cost.
That picture is changing.
A 2023 European study spanning seven nations found a 30-per-cent reduction in adverse reactions to common clinically prescribed drugs through pharmacogenomic testing.
Pharmacogenomic testing could save health-care system money, study finds
Tens of thousands of Canadians experience a suspected adverse drug reaction — or ADR — every year. ADRs happen when a drug has negative side effects that can range from drowsiness to hospitalization, permanent conditions, disability, and even death.
Scientists only understand genetic interactions for around 500 of the most commonly prescribed drugs but proponents of wider testing say that broader application would improve the understanding of genetic-drug interactions and thus prevent a growing number of ADRs.
A study last year published in the Canadian Medical Association Journal projected publicly funded pharmacogenomic testing for patients with major depression disorder could save the health-care system nearly a billion dollars over 20 years in British Columbia alone by decreasing hospitalizations and deaths and improving the quality of life, productivity, and overall health of patients.
There is also little action to study and prevent ADRs, says UBC’s Carleton, who’s also the founder of the Canadian Pharmacogenomics Network for Drug Safety (CPNDS).
The CPNDS has an active surveillance network that studies genetic causes of common ADRs to prevent them from happening as frequently. He says pharmacogenomic testing can help prevent ADRs.
“We’re learning how to make better choices based upon what the patient is likely to benefit from or not be harmed by,” says Carleton. “If we understand the mechanism of why a reaction occurs, the underlying biological pathway, then we can exploit that knowledge by designing better drugs.”
Tens of thousands of Canadians suffer suspected drug side effects
In 2019, roughly 96,000 suspected ADRs were reported to Health Canada, 70 per cent of which were serious in nature. Nearly 6,120 ADRs “mentioned a suspected link between a death that had occurred and the use of a drug or natural health product,” according to a 2020 Health Canada report.
But tracking the number of ADRs won’t do much to prevent them, says Carleton.
“Solution finding is what regulators should be doing, not just recording reactions,” he says. “It’s better that we solve five adverse drug reactions a year than we report 90 per cent of reactions.”
For now, pharmacogenomic testing in Ontario, as well as B.C., is only used in special circumstances, like in cancer cases where potent chemotherapy drugs are used.
For most of the population, pharmacogenomic testing won’t reveal any red flags because their bodies metabolize drugs normally, says Kristen Watt, a community pharmacist and pharmacy owner in Southampton, Ont., who handled Halliday’s test.
Due to the relatively high cost, “physicians aren’t going to recommend it if overall the benefit for you is very low,” Watt said.
However, Carleton says that even if no genetic variants are found, pharmacogenomic testing is still helpful. “Knowing that I’m normal for codeine metabolism, for example, would reassure me that in the case of severe pain, I can effectively use that medication.”
The results are most revelatory for the small number of patients who are “really fast metabolizers or the people who are really slow metabolizers,” says Dr. Jehannine Austin, professor of psychiatry and medical genetics at UBC and co-author of the CMAJ study on the cost-effectiveness of the test for treating major depression.
While slow metabolizers are at risk of having ADRs, those who metabolize drugs too quickly might not see any benefits — prolonging the condition they’re suffering from and its consequences.
‘They’ve all missed the boat somehow’
Halliday found one doctor, then another, as he searched for relief. He saw nearly a dozen medical specialists before finding Dr. Lawrence Schmidt, a general practitioner based in Sauble Beach, Ont.
He recalls the look of a light bulb going off in the physician’s eyes as he described his symptoms on their first visit.
Dr. Lawrence Schmidt, who practices out of the Sauble Beach Family Heath Team. He says the reluctance to adopt pharmacogenomic testing here is rooted in Canada’s public health philosophy, says Schmidt. “It’s not a health care system, it’s a sick care system.” Photo credit: Tannis Toohey for the Toronto Star
To Schmidt, it was obvious what was going on.
“He had the classic triad of serotonin syndrome,” said Schmidt. “Mental confusion, akathisia, which is muscle stiffness, and an autonomic dysfunction too, which was his temperature went up and then it plummeted.”
“When I heard his story, I thought something is missing here. They’ve all missed the boat somehow.”
For a long suffering patient, ‘it felt good to be listened to’
Halliday mailed a swab of his saliva to a lab in the U.S. He got his results back within a week. The test revealed Halliday lacks the enzyme CYP2D6, an absence which prevents his body from properly metabolizing SSRIs (commonly prescribed antidepressants) such as Paxil.
“When we got the report, it was pretty obvious that was the start point of his troubles,” said Schmidt.
“It felt good to be listened to,” said Halliday once a doctor finally confirmed the drug may be causing his symptoms. “It felt like redemption.”
The reluctance to adopt the testing here is rooted in Canada’s public health philosophy, says Schmidt.
“It’s not a health-care system, it’s a sick-care system,” he says. “We react to problems. We don’t prevent them and that’s the problem. There has to be a major shift in the way governments think.”
“The tool the government gives us to look after patients is a prescription pad, basically.”
It would make a “huge difference” if pharmacogenomic testing was easily accessible for all Canadians, Schmidt says. “There would be lives saved from drug interactions.”
The Investigative Journalism Bureau is a non-profit newsroom based at the Dalla Lana School of Public Health.
The story is also available on the Toronto Star website.