These genetic tests are being used to guide the treatment of depression. Do they work?

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It’s a painfully common scenario: Your doctor prescribes an antidepressant, and after a few months, nothing has changed. Then another medication is prescribed and you roll the serotonin-loaded dice again, hoping this time for relief.

It is unfortunate, to say the least, that two out of three people with depression are not helped by the first antidepressant they are prescribed, and up to a third does not respond at all to those medications.

But what if you could know in advance which drugs are most likely to work? Some companies claim to have developed products that do just that, and a Group Therapy reader asked us about them: “Are the DNA tests used to determine the most effective psychiatric medication based on evidence of effectiveness or unproven?”

When I first read this question, I was surprised that such a test could exist, given the complexities of depression and the medications that treat it.

I quickly learned that my instincts were correct: this product is too good to be true. The US Food and Drug Administration formally warned patients and clinicians in 2018 against the use of pharmacogenomic testing to guide treatment of depression.

“The FDA is aware of genetic testing that states that clinicians can use the results to identify which antidepressant medication would have greater efficacy or side effects compared to other antidepressant medications,” the agency said. in a sentence.

“However, the relationship between DNA variations and the efficacy of antidepressant medications has never been established. In addition, the FDA is aware that health care providers have made changes to patients’ medications based on the results of genetic tests that claim to provide information about personalized dosing or treatment regimens for some antidepressant medications, thereby that could cause harm to the patient.

To learn more about these tests, I spoke with Bruce Cohen, director of the Neuropsychiatric Research Program at McLean Hospital, a Massachusetts psychiatric treatment and research center affiliated with Harvard Medical School; and Anthony Rothschild, the Brudnick chair in psychiatry at UMass Chan School of Medicine and co-author of industry-funded studies examining the efficacy of these products.

The Dubious Science Behind Genetic Testing For Antidepressants

Information about genes is increasingly being used by doctors to determine patients’ risk for certain diseases, such as BRCA genes related to breast cancer. Genetic testing can also determine the best drug treatment for diseases such as acute leukemia and AIDS.

“The hope is that you can do the same thing with depression,” Cohen said. “Is there a gene, or genes, that might guide you toward a particular drug? It’s not an unreasonable medical question.”

genes determine some our risk of depression and some of our responses to treatment. But no single gene, or even a collection of several genes, has been found that can help doctors determine our potential response to antidepressants, Cohen told me. Even in the case of mental health conditions that are thought to be heavily influenced by genetics, such as schizophrenia, there may be “thousands of genes that determine disease,” Cohen said.

For example, several companies now claim that their products can guide the treatment of depression by testing the genetics of certain liver enzymes, which are responsible for metabolizing antidepressants and all other medications.

“There are some people who are rapid drug metabolizers. Their liver just chews it up and spits it out, and they may need a higher dose,” Rothschild said. “Other people are slow metabolizers and will require a lower dose. These tests are trying to measure who is a slow metabolizer of Drug A, who is a fast metabolizer of Drug C, etc.”

When someone takes one of these tests, they will receive a report with “green, yellow, and red light drugs.” If a drug is on the green light list, it’s unlikely, hypothetically, that your metabolism would interfere with the way your body processes it, Rothschild said.

A major problem here, however, is that very few people have the kind of super-slow or super-fast metabolism that could interfere with the effectiveness of antidepressants, Cohen said. And factors like your age, diet, and other medications you’re taking are thought to have a much greater influence on metabolism than genetics.

“These tests are scientifically premature,” Cohen said. “We simply don’t yet know the genes that determine drug response.”

To date, at least a dozen clinical trials have studied these genetic testing panels that are designed to support the treatment of depression, and none of them have shown evidence of real effectiveness. “They don’t work at all,” Cohen said. This is despite the fact that most of the studies were not blinded (meaning that clinicians and patients knew they had been given some sort of test) and in these cases a placebo effect is much more likely. Impartial experts have repeatedly advised against the use of genetic testing in the treatment of depression.

Doctors also have less expensive ways to gather information about how you metabolize medications and which antidepressant might work best for you, experts said, such as asking questions about your general drug sensitivity and whether you tend to take high or low doses, which medications psychiatric medications have worked for people in your family and what side effects you have experienced while taking other antidepressants.

Genetic testing for the treatment of depression, in practice

Yet these tests are aggressively marketed to physicians, experts told me. Myriad Genetics, one of the most prominent companies in this space, says on its website that more than 2 million people have had the GeneSight test. of the company test revenue grew 36% in 2022 compared to the previous year. (I have contacted Myriad several times to inquire about the efficacy of GeneSight and received no response.)

Mayo Clinic, which employs thousands of doctors across the US, has endorsed the use of pharmacogenomic testing for the treatment of depression in their clinics (I contacted the Mayo Clinic to inquire about this, but the organization declined to comment). And certain health insurance plans reimburse for tests, even state health insurance and united Health, the largest private health insurer in the country.

“I have noticed that these tests are much more popular with my non-psychiatric colleagues, such as primary care physicians,” Rothschild said. “You can imagine the appeal of doing a genetic test, both for patients and doctors. Everyone is a bit desperate for relief and everyone is in a rush for time.”

But at the end of the day, these tests are expensive, especially for a product that apparently doesn’t deliver on its promise. A GeneSight test will cost you about $330 if you have insurance, according to Myriad, and much more if you don’t.

What I find most problematic about these tests is that they give people hope, sometimes FAKE I hope that a relief from the heaviness of depression is just around the corner, so much so that these tests may create a kind of placebo effect, Rothschild told me. He has seen firsthand how excited people get at the prospect of taking a test that could change everything for them. “It gives this scientific aura to the process, the belief that this work,” he said. “But the problem is that a placebo response doesn’t usually last.”

There’s still a lot we don’t know about the brain, the body, or mental health conditions, and it looks like we’ll have to learn a lot more about those things first before these tests can be effective.

For now, Cohen recommends staying away from them. Perhaps there will be a future in which these types of tests can fulfill their promises, but it seems that we are not there yet.

Until next week,

laura

If you’re convinced by what you learned from these experts today, or if you’d like to tell us about your own experiences, drop us an email and let us know if it’s okay to share your thoughts with the broader group therapy community. The email GroupTherapy@WhatsNewDay.com comes directly to our team. As always, find us on Instagram at @latimesforyourmindwhere we will continue this conversation.

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More perspectives on today’s topic and other resources

In the race to use genetic tests to predict whether antidepressants will work, science could be left behindaccording to this 2018 STAT News article. STAT looked at one company in particular, Color, which promotes apps not only for depression, but also for bipolar disorder, ADHD, and PTSD.

DNA testing for psychiatric drugs is controversial, but some insurers cover it. Companies that do these genetic tests say they can save patients and doctors from searching long for the right drug and save insurance companies from paying for ineffective drugs. But many researchers say the evidence they don’t have enough evidence to back them up.

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