Thanks to technologic advances in genetic testing, psychiatrists can predict which patients might experience adverse effects from commonly prescribed psychotropic medications, and, to a lesser extent, who might respond well to a particular drug.
Commercially available pharmacogenomic testing "can improve the probability of your selecting a medication that will be helpful to your patient. It can do that most certainly by avoiding adverse effects, but additionally, you can increase the probability of finding a medication that is more likely to be efficacious," Dr. David Mrazek said in an interview.
"When I started teaching doctors about this 10 years ago, it was about what could be. Now we’re teaching them how to use this tool, and I think it’s going to change the way we practice," said Dr. Mrazek, professor of pediatrics and psychiatry at the Mayo Clinic in Rochester, Minn.
Dr. Joel Winner agreed.
"Pharmacogenetic testing is here and will only become more entrenched in psychiatric treatment over the next several years," Dr. Winner, medical director of AssureRx Health Inc., a company that provides a pharmacogenomic test, said in an interview.
"Currently, I recommend testing for the complicated patient," Dr. Winner said. "I treat mostly anxiety and depression. I have found it to be the most helpful in those patients who have failed one or two medications. Anxious and somatic patients often have a difficult time with medications, because they obsess about them."
More precision with prescribing may be necessary with more complex patients. "If you’re dealing with mild or low-priority problems, it’s not as important to get the drug dead-on straight the first time," Dr. Mrazek said. "You have a little more latitude to do the trial and error [prescribing]."
Pharmacogenomic testing is based on assessment of how an individual patient metabolizes a particular drug through the body’s cytochrome P450 system. Results can identify a patient as a poor or ultra-rapid metabolizer. For example, a poor metabolizer of a CYP2D6 medication will not break a particular drug down at a normal rate. As a result, prolonged exposure to high serum levels puts that patient at risk for more adverse events.
"This is first and foremost a safety issue," said Dr. Winner, a psychiatrist in private practice in Boulder, Colo.
For example, Dr. Winner recently consulted on a patient experiencing "fairly severe side effects," including weight gain and sexual side effects, associated with high-dose paroxetine treatment. The patient was on paroxetine for several years and, despite the side effects, was concerned about stopping the medication. Pharmacogenomic testing revealed the patient was a poor metabolizer of CYP2D6. "He was likely not breaking down the paroxetine appropriately and likely had high levels of paroxetine in his system. My recommendation was to transition to another medication that would be more appropriately dosed according to his genotype," Dr. Winner said.
Through a referral, Dr. Mrazek also recently evaluated a poor 2D6 metabolizer. The patient had been treated for years by clinicians unaware of her impaired drug metabolism. "They did figure out that she could only tolerate low doses of psychotropics, but that was through trial and error," Dr. Mrazek said. Prior to the genetic testing revelation, the patient was taken to the emergency department for an episode of acute anxiety. She received haloperidol, a drug primarily cleared through the 2D6 pathway that "also has one of the highest frequencies of extrapyramidal side effects." The patient later was released but experienced a dystonic reaction. "She had a pretty powerful medicine on board at a high dose for a long time and she ended up in the ICU. She remained there for 5 days until she cleared herself of the medication," Dr. Mrazek said. "That’s a very unusual story, but 5 days in the ICU is a very expensive and very scary proposition."
The clearest indication for pharmacogenomic testing is prevention of such adverse effects, Dr. Mrazek said. "We’re much better at knowing which patient is going to have a poor reaction than we are being able to say, with any certainty, whether they will definitely respond or not."
Currently, the biggest barrier to testing is cost, and cost is highly variable, Dr. Mrazek said. "I can’t even keep it straight. It varies from company to company and from month to month." Specific genetic testing can cost between $300 and $700, with full genome testing approaching $10,000, according to a previous report from this news organization.
The cost for full genome sequencing is coming down, Dr. Winner said. "We should expect the $1,000 genome in the next few years." He predicted that more and more patients will come in expecting guidance in this area. "Shrewd clinicians who continue to educate themselves and become comfortable with the genetic information we can offer now are leading the way." Future research will ... continue to help guide decisions at the point of care.