NEW YORK – Customers of Myriad Genetics' GeneSight Psychotropic test will see a new layout for its reports on how patients are likely to metabolize mental health medications, now divvied up by smoking status.
But while the report update could help bring attention to how lifestyle and environmental factors such as smoking influence drug therapy, some pharmacogenomic experts aren't convinced there's reason to include it as part of PGx-informed prescribing.
"It is certainly important to know someone's smoking status when prescribing," said Daniel Streetman, an associate director of clinical content at Wolters Kluwer Health who focuses on PGx and drug interactions. "Dozens of medications have potentially significant interactions with smoking. Whether this belongs on a pharmacogenomic report is the question."
The update, which Myriad rolled out this summer, adds information to the reports it returns to customers of its PGx test for mental health medications. Reports now include how smoking may influence a patient's response to certain medications on account of a specific mutation in CYP1A2, a gene that encodes enzymes involved in drug metabolism.
The variant is the -163C>A polymorphism, also known as the CYP1A2*1F allele, which has been linked with metabolism of various antidepressants and antipsychotics.
"This really helps ensure the test provides an even more complete picture of a patient's potential outcomes," said Holly Johnson, a director of medical affairs at Myriad. Based on an analysis of internal data from Myriad, she said about 91 percent of 2.1 million tested patients had the CYP1A2*1F allele.
Salt Lake City-based Myriad offers genetic tests for cancer risk, reproductive health, and mental health. The GeneSight Psychotropic test, in particular, assesses how patients will likely respond to 64 depression, anxiety, attention deficit hyperactivity disorder, and other psychiatric medications based on their genetics.
CYP1A2 plays a role in response to about two dozen of the drugs on that report, including several antidepressants, anxiolytics, hypnotics, and antipsychotics. The gene's link to smoking is especially important to consider when treating these patients, Johnson said, since people with mental health conditions are more likely to smoke than the general population. In fact, nearly one-quarter of Americans with a mental illness reported smoking cigarettes in 2020, compared to 14.5 percent of those without a mental illness, according to data from the US Centers for Disease Control and Prevention.
The report update, according to Johnson, is based on a body of research that's found smoking can change how the CYP1A2 gene is expressed in patients with the CYP1A2*1F allele and increases the activity of the enzymes the gene encodes. That can result in smokers needing higher doses of certain drugs since they may metabolize them more quickly.
With the update, Myriad now provides separate pages of results for antidepressants, anxiolytics, hypnotics, and antipsychotics for smokers and nonsmokers in all reports for patients with the CYP1A2*1F allele, which clinicians can consult when making prescribing decisions. For other drug classes, such as mood stabilizers and stimulants, it specifies that the same results apply to smokers and nonsmokers.
Myriad doesn't collect the information on patient smoking status. Since smoking status can rapidly change, the firm decided clinicians should have access to results for both groups. "We wanted to make sure we were providing all of the information to clinicians," Johnson said. "Then, they can have that discussion with the patient."
Myriad defines smoking as daily inhalation of cigarettes or marijuana; however, it does not include vaping products. That's because smoking induces enzyme activity in the CYP1A2 gene due to inhalation of hydrocarbons from the burning of plant material, according to Johnson, which means it isn't thought to apply to tobacco products such as e-cigarettes.
Changes to smoking status must be a key consideration for prescribers, Wolters Kluwer Health's Streetman wrote in an email. If prescribed drugs are sensitive to smoking, patients should be asked to report any attempts to quit smoking or switch to other tobacco products, and need to be aware of the risk that their current dosage may be too high.
"It is important for providers to realize that smoking cessation, while clearly a tremendously beneficial lifestyle change, can require a decrease in the dose of some medications to prevent adverse effects," Streetman said. He added that this is the first example he's seen of a PGx report that presents distinct recommendations for smokers and nonsmokers.
Michael Schuh, a pharmacist and medication therapy management coordinator at Mayo Clinic, agreed that it's uncommon for PGx tests to return results categorized by smoking status.
"It makes Myriad or other companies who may offer it unique," he wrote in an email.
However, Streetman and Schuh remained unconvinced whether the report update would be helpful for prescribing decisions. PharmGKB, an online PGx resource funded by the US National Institutes of Health, characterizes the PGx effects of CYP1A2 variation at an "early stage" compared to other CYP enzymes. There are no prescribing recommendations in its database for CYP1A2*1F.
In terms of its connection to smoking, there's much that remains unknown, such as the effect of exposure to secondhand smoke, Streetman said. Smoked cannabis remains less studied than cigarettes.
Adding information on smoking status could help to raise awareness among clinicians to think about dose adjustment of certain medications for patients who stop or start smoking during drug therapy, Schuh said, and provides another variable to consider if an adverse drug reaction occurs with a patient.
But, while a novel offering, Schuh added that the test may be of only limited utility for a few reasons. Most drugs metabolized by CYP1A2 are also metabolized by other CYP enzymes, so the effect may not be as strong as one might think, he said. On top of that, there are other common lifestyle and environmental factors that could have an effect on drug metabolism.
"It may be difficult, if not impossible, to determine dosage of the agent inhaled/smoked due to frequency of inhalation [or] dose of smoke delivered by whatever product was used," Schuh wrote. "Some foods may also induce CYP1A2 (grilled meat, cruciferous vegetables), too, further muddying the water."