Though more payers are covering laboratory-developed genetic tests for conditions such as depression, the tests remain uncleared by the FDA

Clinical pathologists interested in pharmacogenetics tests for depression and other psychiatric disorders may be interested to learn that UnitedHealthcare (NYSE:UNH) announced in its Network Bulletin a change to its Molecular Pathology Policy and is now covering certain molecular diagnostics. That’s despite the federal Food and Drug Administration (FDA) warning “against the use of many genetic tests with unapproved claims to predict patient response to specific medications.”

In its Safety Communication, the FDA stated healthcare providers and clinical laboratories that “are using, or considering using, a genetic test to predict a patient’s response to specific medications, be aware that for most medications, the relationship between DNA variations and the medication’s effects has not been established.”

In its coverage of the FDA’s warning, The Dark Report, sister publication to Dark Daily, wrote, “Serious concerns are associated with some pharmacogenetic tests and whether physicians have the training and knowledge needed to use this genetic test data appropriately in patient care.”

Should the FDA Even Be Regulating Clinical Laboratory Tests?

Experts note that it is notoriously difficult in some cases for providers to identify which drug or group of drugs is most likely to help a patient with a psychiatric disorder such as depression. Pharmaceuticals that work well for one individual may actually worsen things for someone else.

Nevertheless, the idea that a genetic test could reveal how a psychiatric patient is likely to react to a particular drug is extremely appealing. It could save years of trial and error, which is often terribly disruptive for the patient.

Thus, several molecular diagnostics companies have come up with laboratory-developed tests (LDTs) for pharmacogenomics that they claim can do exactly that. Genomind and Myriad Genetics, as well as others are all marketing LDTs for pharmacogenomics, including Inova Genomics Laboratory, of Falls Church, Va. However, after receiving its own warning letter from the FDA, Inova discontinued sales of its MediMap genetic tests.

Currently, there’s quite a debate about whether these tests should be available, who should take them, and whether they offer any kind of guidance for providers. There’s even a faction that maintains the FDA should not be regulating clinical laboratory tests at all.

In its coverage of the FDA’s warning, NPR reported that Victoria Pratt, PhD (above), a medical and clinical molecular geneticist who at the time was President of the Association for Molecular Pathology (AMP), said, “Tests conducted in a lab are a medical service, not a medical device that’s shipped like a product. As a medical service, clinical laboratories are already regulated by the Centers for Medicare and Medicaid Services. It would be redundant to have dual regulation by both the FDA and CMS.” (Photo copyright: AMP.)

Does Evidence of Pharmacogenomics Effectiveness Exist?

Studies regarding the effectiveness of genetic tests for psychiatric disorders have had, at best, mixed results. “Genes determine some of our risk for depression and some of our response to treatment,” wrote Bruce Cohen, MD, PhD, and George Zubenko, MD, PhD, in a Harvard Health Blog post, titled, “Gene Testing to Guide Antidepressant Treatment: Has Its Time Arrived?” The authors go on to say that although the genes that are tested in the panels can have an effect on the levels of the drugs in the patient’s blood, they “generally don’t predict clinical response.”

The authors then discussed the results of a dozen studies that looked into the genetic panels. “Most studies were completely unblinded,” they wrote. “Even with that bias, the use of gene results showed no evidence of effectiveness.”

Advocacy Groups, Payors, and Clinicians Support Pharmacogenomics

Nevertheless, even with the FDA’s warning—and tepid study results— pharmacogenetic testing has its supporters. In large part, that is because identifying the most appropriate medication for any given patient can be incredibly difficult.

“Right now, one of our greatest frustrations is that when [patients] comes in with depression, we have very little idea of what the right treatment for them is,” said Amit Etkin, MD, PhD, Founder and CEO of Alto Neuroscience. Etkin is a professor in the Department of Psychiatry and Behavioral Sciences at Stanford and a member of the Wu Tsai Neuroscience Institute. He authored a study published in Nature that investigated measuring patients’ brainwaves to identify the most appropriate treatment. “Essentially, the medications are chosen by trial and error.”

“You use the science that you currently have,” Reyna Taylor, Vice President of Public Policy and Advocacy, National Council for Behavioral Health, told NPR. She says that doctors should be able to use the tests to inform their choice of medication.

Daniel Mueller, MD, PhD, a psychiatrist and clinical scientist, agrees. Mueller is a professor at the University of Toronto and head of the Pharmacogenetic Research Clinic at the Center for Addiction and Mental Health (CAMH) in Toronto. He told NPR that the pharmacogenomic clinical laboratory tests “are not an alternative intervention. It’s additional information.” He suggests that anyone who can afford the test should take it, because it could help them avoid “the cost of depression and weeks of suffering.”

The decision by UnitedHealthcare to cover genetic tests for depression and other psychiatric disorders could be important. “We expect this to be a tipping point,” Shawn Patrick O’Brien, CEO of Genomind, told NPR, adding that he expects other insurance companies to begin covering the cost of the tests, as well, “because they don’t want to be uncompetitive in the marketplace.”

Historically, there have been few clinical laboratory tests for patients with psychiatric disorders, and while these tests may open a new market in the future, for now, caution is warranted. In addition to the warning from the FDA, there will likely be challenges regarding physician education and curbing fraud.

—Dava Stewart

Related Information:

The FDA Warns Against the Use of Many Genetic Tests with Unapproved Claims to Predict Patient Response to Specific Medications: FDA Safety Communication

DNA Tests for Psychiatric Drugs Are Controversial but Some Insurers Are Covering Them

Gene Testing to Guide Antidepressant Treatment: Has Its Time Arrived? 

An Electroencephalographic Signature Predicts Antidepressant Response in Major Depression

Concerns Raised of Pharmaceutical Tests