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Take heed: Turn to the experts to interpret pharmacogenetic tests

In the burgeoning field of pharmacogenetics, adhering to expert-developed guidelines is increasingly important, a Stanford Medicine physician emphasizes.

Pharmacogenetic tests -- which examine how genes affect your ability to process medications -- are on the rise. Dozens of companies are entering the field and expanding their offerings as more genes that alter drug metabolism are discovered. And at the same time, care providers who don't specialize in pharmacogenetics are turning to the tests for answers.

This makes it increasingly important that providers and companies are on the same page and adhere to guidelines set by the Clinical Pharmacogenetics Implementation Consortium, an international group of pharmacogenetics experts, says Latha Palaniappan, MD, a Stanford Medicine internist and clinical researcher.

When companies and providers use different standards to interpret the tests, patients like Susan Born, a 65-year old Bay Area resident, can receive conflicting or confusing advice.

The case of one anxiety patient

Born had been grappling with anxiety for months when her care provider suggested trying a drug-based therapeutic option. Born was hesitant, in part because she has quite a few allergies. How would her body accept a new medication?

The worry prompted her care provider to order a special test for Born, one that could help predict whether she would have an abnormal reaction to certain drugs.

Born agreed to the test, recalling that her results surprised both her and her care provider. "We were floored," she said.

It turned out that Born had a variant in a gene called CYP2D6, which altered the way her body metabolized certain medications.

Born's care provider wasn't trained to interpret the finer details of the results and just passed along the interpretation of the company that conducted the test.

The company made a sweeping recommendation, telling Born that she should avoid common drugs such as codeine, morphine and selective serotonin reuptake inhibitors (SSRIs), which are typically used to treat depression and anxiety disorders.

Born heeded the advice. Still, she had questions -- should she stay away from all these drugs? Or just some? Would it be dangerous to take the drug? Or would it just not work?

She asked her care provider and even called the company that issued the test. Her hunt for answers was met with one overarching -- and frustrating -- response: We don't know.

Seeking a second opinion

In search of answers, Born sought out pharmacogenetic experts at Stanford Medicine, where she met Palaniappan.

"It was really fantastic to see that Susan had chosen to preemptively find out what her pharmacogenetic profile was, even before considering a drug," said Palaniappan.

Palaniappan wanted to start from square one, ordering the test again from a different company. When the results came back, it indeed showed that Born had the same variant in CYP2D6 that the previous test had flagged -- but Palaniappan's recommendation was different.

Palanipappan and others published this case study in the Journal of Personalized Medicine last fall.

Just like lanes on a highway

When it comes to this gene, you can be a poor metabolizer, an intermediate metabolizer, or a normal metabolizer, she explained.

A poor metabolizer means you cannot process drugs that CYP2D6 plays a role in processing and you should not take them. Intermediate metabolizers basically function on the next level up -- they may be able to process the drug, but to a lesser extent. Normal metabolizers can handle the drug just fine.

"When I describe it to my patients, I explain it like open lanes and traffic on a highway," said Palaniappan. "Normal metabolizers have access to both lanes on the highway. If you're an intermediate metabolizer, you can only access one lane on the highway. Poor metabolizers have no lanes."

Reindeer blocking part of the road
Pharmacogenetic tests are like lanes on a highways, says physician Latha Palaniappan. Results can show two lanes open (capable of processing a medication), one lane blocked or both lanes blocked.

Born's care provider had essentially told her she was a poor metabolizer with no lanes.

But Palaniappan turned to guidance from the Clinical Pharmacogenetics Implementation Consortium. She was able to tell Born that the variant in CYP2D6 actually meant that she had decreased ability to process certain drugs, but not a complete inability. In other words, Born had one open lane.

That means that in the future, SSRIs could be an option for Born.

Guiding precision prescriptions

Without widespread adherence to the CPIC guidelines, confusing situations, like that of Born's, are bound to happen. Furthermore, new studies show that almost everyone has an atypical response to at least one drug, making universal standards of interpretation even more crucial, Palaniappan said.

"As with all new innovations there's an adjustment period where everyone, from regulators to users -- or in this case, companies, clinicians and patients -- need to learn how to implement and properly utilize that tool," said Palaniappan. "We're at the beginning of that stage with pharmacogenetics, but I'm hopeful that the CPIC standards will become universally accepted so that we can help patients feel comfortable and confident as we help them determine what therapeutics are most appropriate for them."

Photos by Sharon McCutcheon/ Roberto Hanas

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