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

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

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

But what if you knew 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 it: “Are DNA tests used to determine the most effective psychiatric medications based on evidence of effectiveness or are they unproven?”

When I first read this question I was surprised that such a test could exist given the complexity of depression and the drugs 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 physicians in 2018 opposed the use of pharmacogenomic testing as a guideline for treating depression.

“The FDA is aware of genetic testing that claims the results can be used by physicians to determine which antidepressants have greater effectiveness or side effects compared to other antidepressants,” the agency said. in a statement.

“However, the relationship between DNA variations and the effectiveness of antidepressants has never been established. In addition, the FDA is aware that health care providers have made changes to patients’ medications based on genetic test results that purport to provide information about the personalized dosage or treatment regimens for some antidepressants, potentially leading to patient harm.

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, Brudnick Chair in Psychiatry at UMass Chan Medical School and the co-author of industry-funded studies on the efficacy of these products.

The dubious science behind genetic testing for antidepressants

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

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

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

“Some people are fast metabolizers of drugs. 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 need a lower dose. These tests try 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 receive a report with “medications for green, yellow, and red light.” If a drug is under the green light, it’s — hypothetically — unlikely that their metabolism will interfere with the way their bodies process it, Rothschild said.

A key issue here, though, is that very few people have the kind of super-slow or super-fast metabolisms that would interfere with the effectiveness of antidepressants, Cohen said. And factors such as your age, your diet, and other medications you take would have a much greater impact on metabolism than genetics.

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

To date, at least a dozen clinical trials have examined these gene test panels designed to aid in the treatment of depression, and none of them have shown evidence of true effectiveness. “They don’t work at all,” Cohen said. This is despite the fact that most of the studies were completely unblinded (meaning doctors and patients knew they had been given some kind of test) and in these cases a placebo effect is much more likely. Having impartial experts repeatedly advised in return for the use of genetic testing in the treatment of depression.

Doctors also have cheaper ways to collect information about how you metabolize drugs 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. , what psychiatric drugs have worked for people in your family, and what side effects you’ve 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 leading companies in this field, says on its website that more than 2 million people have taken its GeneSight test. The companies sales from the test grew by 36% in 2022 compared to the previous year. (I have contacted Myriad several times to ask about GeneSight’s efficacy and have heard nothing.)

Mayo Clinic, which employs thousands of physicians in the US, has endorsed using pharmacogenomic testing to treat depression in its clinics (I contacted Mayo Clinic to ask about this, but the organization declined to comment). And certain health insurance policies will reimburse the tests, including Medicare And united healthcare, the largest private health insurer in the country.

“I’ve noticed that these tests are much more popular among my non-psychiatric colleagues, such as general practitioners,” Rothschild said. “You can imagine how attractive it is to do a genetic test, both for patients and doctors. Everyone is a bit desperate for relief and everyone is in a rush for time.”

But in the end, these tests are expensive, especially for a product that seemingly fails to deliver on their promise. A GeneSight test will cost you about $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 sometimes give people hope false I hope a reprieve from the severity of depression is just around the corner — so much so that these tests can create a kind of placebo effect, Rothschild told me. He’s 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, a belief that this will happen work,” he said. “But the problem is that a placebo response doesn’t often last.”

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

For now, Cohen recommends keeping them away. Perhaps there will be a future where these kinds of tests can deliver on their promises, but it seems we’re not there yet.

Until next week,

Laura

If what you learned today from these experts resonated with you or if you would like to tell us about your own experience, please email us and let us know if you’d like to share your thoughts with the wider group therapy community. The e-mail [email protected] joins our team. Find us as always 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 testing to predict whether antidepressants will work, science may lag behind, according to this 2018 piece from 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 cover them. Companies that conduct these genetic tests say they can save patients and doctors from a lengthy search for the right medication and that insurance companies can save on paying for ineffective drugs. But many researchers say the tests don’t have enough evidence to support them.

Other interesting things

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

A new study is used to claim 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 – during which millions of people have felt loss, anger and frustration. And this is where general studies on ‘everyone’s mental health’ are misleading.”