A Genetic Test Could Help Predict the Right Antidepressant For You

Depression is a complicated condition, and so are the people it affects. It’s often difficult — and can take months or even years — to find the right drugs to treat the heterogeneous mood disorder.

But for decades, doctors have been treating depression essentially by prescribing a drug and hoping for the best. They rely on asking people about their family history of mental illness and fold in as much information as they can about symptoms. Since 2010, however, there has been a genetic test that can help doctors learn how a person’s genetic makeup can also affect their response to various antidepressants.

In a new study presented at the American Psychiatric Association annual meeting, researchers say that people using the test, called GeneSight, are 50% more likely to achieve remission after eight weeks, and 30% more likely to the respond to the drugs the test recommended, compared to people treated without the test. (The study has not been published in a peer-reviewed journal.)

While there are more than a dozen antidepressant drugs — from the newer serotonin– and norepinephrine-based medications that adjust levels of the brain’s mood chemicals, to the older tricyclic and MAOI drugs — there is little to guide doctors in matching the patients to the right drugs for them. Much of the treatment for depression relies on trial and error, with anywhere from a third to 40% of people failing to respond to their first drug treatment.

GeneSight, from Myriad Genetics, looks at 12 genes involved in how people break down 56 different antidepressant drugs. These genes code for things such as enzymes that break down the key chemicals in the medications, as well as receptors that respond to brain chemicals that are targeted by the antidepressants, like serotonin. In many cases, the way people break down drugs can affect whether they respond to these drugs or not.

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That’s why GeneSight combines the information on the activity of the 12 genes and categorizes antidepressants into green, yellow and red groups. The categories don’t necessarily reflect how effective the drugs are, but instead indicate whether there are any issues between the person’s genetic makeup and the drug that would prevent the drugs from working. Green drugs, for example, are medications that show no potential interactions between the person’s genes and the drug; these medications likely will cause few or no side effects. Yellow drugs may be used, but could contain some potential gene-drug interactions that would lead to side effects. Red-labeled drugs are the most useful category, since they indicate the drugs that the person should not be prescribed; these medications are thought to only lead to adverse reactions and little effective treatment.

“Red medications should be avoided, since they simply are not right for the patient,” says Dr. John Greden, the study’s lead investigator and founder and executive director of the University of Michigan’s Comprehensive Depression Center. “It’s as important to know what not to do as it is to know what to do,” he says about prescribing antidepressants.

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But the tests are not completely accurate, and some psychiatrists warn that most studies of such gene-based testing for antidepressant prescribing to date have involved only a small group of people who have been followed for a short period of time. Greden notes that the current study included nearly 1,200 people with moderate to severe depression, and the results from the large number of patients supports the utility of incorporating the test for treating depression.

The test is not necessarily designed to guide doctors to the ‘right’ drugs for treating an individual person’s depression; it’s more useful in helping them navigate away from the drugs that might cause people to experience bad side effects. Greden and other depression experts see GeneSight as one additional tool that can help them to better match the right drugs to the right person.

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Ronni Shapiro says she’s been helped by the test. Going through a difficult divorce in the fall of 2010, Shapiro was diagnosed with situational depression and suicidality. “I just wanted to disappear,” she says. “I truly thought I would be doing everyone a favor if I just committed suicide and I was no longer there. I truly believed my sons would have a better life, and the world would be free of this crying, unhappy person.”

Shapiro embarked on a nearly year-long journey cycling through treatments, many of which only made her experience worse. One psychiatrist ended up prescribing eight different drugs over four months. Some of the drugs did nothing to relieve her depressive symptoms and thoughts of suicide, while others made her sleepy, lethargic and unable to function; one caused her to vomit. Finally, she and her psychiatrist hit upon a two-drug combination that seemed to help — Xanax and Lexapro.

A nurse practitioner also suggested she get the GeneSight test to determine if additional drugs might help. “What was so incredible to me was that all of the drugs I had taken were in the ‘do not work’ column,” says Shapiro. “Except for Xanax and Lexapro.”

Based on the test results, her new psychiatrist suggested she add Wellbutrin to her two-drug treatment regimen; Wellbutrin is designed to enhance the effectiveness of the other two medications.

“Within seven days, I was back to my old self,” says Shapiro. “It was such a remarkable transformation. I was laughing, going out with friends. There are times when I do slip back into that dark hole — but the hole is not so deep, and there is a ladder, and I can see hands on the top waiting to help me up.”

Shapiro says she wants more people to learn about and use the test, so fewer of the millions who struggle with depression will experience the pain she did. She shared her story with Myriad and offered to tell others about her experience without compensation. “I feel really strongly about this test. I know people have taken it, and it hasn’t worked for everybody. But my point still is, there is nothing to lose,” says Shapiro.

Some depression experts agree, especially since the genetic information can help doctors to diagnose and treat depression earlier, when it’s easier to manage. “Data show that the longer you’re in a state of depression, the more damage occurs,” says Greden. “Why do you want the guesswork when you can have some clues? We don’t have all the answers yet, but we have some powerful information to help guide treatment.”