These genetic tests are being used to guide depression treatment. 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 you’re prescribed another medication, and you roll the serotonin-steeped dice all over again, hoping that this time relief will come.

It’s unfortunate, to say the very least, that two out of every three people with depression aren’t helped by the first antidepressant they’re prescribed — and up to a third don’t respond at all to those medications.

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

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

I quickly learned that my instinct was correct — this product is too good to be true. The U.S. Food and Drug Administration formally warned patients and doctors in 2018 against using pharmacogenomic tests to guide the treatment of depression.

“The FDA is aware of genetic tests that claim results can be used by physicians to identify which antidepressant medication would have increased effectiveness or side effects compared to other antidepressant medications,” the agency said in a statement.

“However, the relationship between DNA variations and the effectiveness of antidepressant medications has never been established. Moreover, the FDA is aware that healthcare providers have made changes to patients’ medication based on genetic test results that claim to provide information on the personalized dosage or treatment regimens for some antidepressant medications, which could potentially lead to patient harm.”

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

The iffy science behind genetic tests for antidepressants

Doctors increasingly use information about genes to determine patients’ risk for some diseases, such as BRCA genes linked to breast cancer. Gene testing can also determine the best drug treatment for diseases such as acute leukemia and AIDS.

“The hope is, you could do the same thing for depression,” Cohen said. “Is there a gene, or a few genes, that can guide you to a particular medication? It’s not an unreasonable medical question.”

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

For example, several companies now claim that their products can guide depression treatment 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 metabolizers of medications. Their liver just chews it up and spits it out, and they may require a higher dose,” Rothschild said. “Other people are slow metabolizers, and they 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 undergoes one of these tests, they’ll receive a report with “green, yellow, and red light medications.” If a drug is listed under the green light, it’s unlikely — hypothetically — that their metabolism will interfere with how their body processes it, Rothschild said.

A major issue here, though, is that very few people have the kind of super slow or super fast metabolisms that would interfere with the efficacy of antidepressants, Cohen said. And factors such as your age, your diet and other medicines you’re taking are believed to have a much greater influence on metabolism than genetics.

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

To date, at least a dozen clinical trials have studied these gene test 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 in spite of the fact that most studies were completely unblinded (meaning that doctors and patients knew they’d been administered 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 tests in depression treatment.

Doctors also have less costly ways of gathering information about how you metabolize drugs and what antidepressant might work best for you, experts said — such as asking questions about your general sensitivity to medications and whether you tend to take high or low doses, what psychiatric medicines have worked for people in your family, and what side effects you’ve experienced while taking any other antidepressants.

Genetic tests for depression treatment, in practice

Yet these tests are being 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 taken its GeneSight test. The company’s revenue from the test grew 36% in 2022 when compared to the previous year. (I contacted Myriad multiple times to ask about the efficacy of GeneSight and did not hear back.)

Mayo Clinic, which employs thousands of doctors across the U.S., has endorsed the use of pharmacogenomic tests for depression treatment in its clinics (I reached out to Mayo Clinic to ask about this, but the organization declined to comment). And certain health insurance plans reimburse for the tests, including Medicare and United Healthcare, the nation’s largest private health insurer.

“I’ve noticed these tests are a lot more popular among my non-psychiatric colleagues, like primary care doctors,” Rothschild said. “You can imagine the appeal of doing a genetic test, for patients and physicians alike. Everyone is a little desperate for relief and everyone is rushed for time.”

But at the end of the day, these tests are expensive, especially for a product that seemingly doesn’t deliver on their promise. A GeneSight test will run you around $330 if you have insurance, according to Myriad, and a lot more if you don’t.

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

There’s still so much we do not know about the brain, body or mental health conditions, and it seems we will need to first learn a lot more about those things before these tests can be effective.

For now, Cohen recommends steering clear of them. Maybe there will be a future in which these kinds of tests can deliver on their promises, but it appears we aren’t there yet.

Until next week,

Laura

If what you learned today from these experts spoke to you or you’d like to tell us about your own experiences, please email us and let us know if it is OK to share your thoughts with the larger Group Therapy community. The email GroupTherapy@latimes.com gets right to our team. As always, find us on Instagram at @latimesforyourmind, where we’ll 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 might be getting left behind, according to this 2018 piece by STAT News. STAT looked at one company in particular, Color, which touts applications for not only depression but also bipolar disorder, ADHD and PTSD.

DNA tests for psychiatric drugs are controversial, but some insurers are covering them. Companies that make these genetic tests say they can save patients and doctors from prolonged searching for the right medication and save insurance companies from paying for ineffective drugs. But many researchers say the tests don’t have enough evidence to back them up.

Other interesting stuff

The pandemic has worsened the stress of college applications because distance learning-induced isolation — as well as concerns over fitting back in at school or bringing home COVID-19 — have taken a toll on teen mental health, writes my High School Insider colleague Delilah Brumer. Now, teens are asking for a kinder college admissions process and more support from school faculty and teachers.

A new study is being used to argue that the COVID-19 lockdown had little effect on mental health — but the truth is more complicated, writes Devi Sridhar, chair of global public health at the University of Edinburgh. “What’s needed here is nuance,” she said. “Only that can capture what has undoubtedly been a traumatic few years — in which millions of people have felt loss, anger and frustration. And this is where general studies on ‘everyone’s mental health’ are misleading.”