Paxil or Prozac, Zoloft or Lexapro? When treating a patient suffering from depression, Brent Forester considers which anti-depressant to prescribe—ideally, one that will ease psychic pain without side effects. It can be a tough call. Deciding “becomes somewhat of an art—and a lot of it is educated guesswork,” says Dr Forester, chief of geriatric psychiatry at McLean Hospital in Belmont, Mass., an affiliate of Harvard Medical School. He worries that sometimes psychiatrists “may think we are better than we are” at making these choices. That may change as Dr Forester, and others enlist genomics, a form of precision medicine and an intriguing new frontier for the elusive science of the human psyche.
Other branches of medicine, such as oncology, have embraced gene-based testing to help determine which cancer patients need chemotherapy or surgery. But psychiatrists typically haven’t let genomics guide treatment decisions, Dr Forester says. One test, called GeneSight, uses a genetic analysis of DNA samples from a cheek swab to help doctors figure out which drugs are likely to combat a patient’s depression. The test examines a dozen genes to determine how well the patient will metabolise certain drugs and how his or her brain will respond to them. The test predicts the effects of more than 50 anti-depressants and anti-psychotics. Based on a patient’s results, drugs are categorised as ones to be avoided, ones that have some drawbacks and ones that can be used “as directed.”
Barbara Dellovade, a retired real estate broker in Acton, Mass., became depressed last year. Ms Dellovade, who is 78 years old, was taking an anti-depressant, but “I wasn’t reacting well to it, and it wasn’t helping me at all.” She consulted Ipsit Vahia, a geriatric psychiatrist at McLean Hospital and assistant professor at Harvard Medical School. Dr Vahia told Ms Dellovade about the genomics test, which retails for $1,500 and is covered by Medicare and some health plans. After receiving an analysis of Ms Dellovade’s results, he switched her to a different anti-depressant, and she began to respond in about six weeks, he says. Ms Dellovade has been feeling better, she says, though “I am still not there.” Dr Vahia has been using the gene test more with his older depressed patients but says clinical judgment remains paramount in prescribing. “The brain…is the most complex organ in the body,” he says. “This is a small step, but it is an important step. We are adding a degree of precision” to treating depression.
McLean Hospital is one of 60 sites across the country that took part in a randomised trial of GeneSight. The results, which will be unveiled this week at the American Psychiatric Association meeting, showed that patients fared better when physicians chose a medication with the help of the test, rather than relying solely on their judgment. Among the 1,167 patients in the trial, half took the GeneSight test and half were prescribed drugs based purely on their doctors’ clinical assessments. Genetics helps you “marry” a patient with the appropriate medication, says Bryan Dechairo, executive vice president for clinical development at Myriad Genetics , which funded the trial. Assurex Health, a subsidiary of Myriad Genetics, developed the GeneSight test. The results were striking, according to doctors at several medical centres who participated in the trial. Patients were more likely to respond to anti-depressants when the gene test was used to determine which drug they should be on; researchers found a 30% greater response to the medicine when the test was applied. Every patient in the trial had been on at least one anti-depressant that failed to work, and some had been on several that failed.
The study shows that genetic tests can lead to better prescribing decisions, says John Greden, the principal investigator in the trial. Dr Greden, a psychiatrist and executive director of the University of Michigan’s Comprehensive Depression Center, says that until now, many doctors took the following approach: “My favourite anti-depressant is this one, so I will try it. Oh, that didn’t work so that I will try this one.” Unfortunately, he says, under that hit-or-miss method—albeit informed by training and experience—“fewer than 40% of patients achieve remission.” Every year, 16 million Americans suffer an episode of depression, he says, making pinpointed diagnoses essential.
Some doctors took a while to come around to the GeneSight test. Charles DeBattista, a professor of psychiatry and behavioural sciences at the Stanford University School of Medicine, says initially he was “somewhat sceptical.” “Before the study, I used it very rarely,” says Dr DeBattista, who specialises in patients with treatment-resistant depression. He has been using the test more on patients who “have had problems tolerating medicine in the past,” he says. “There is nothing magical about it; it is not a substitute for clinical judgment.” But it does inform him what drug to try on a patient with serious depression. His Stanford colleague Alan Schatzberg isn’t persuaded. The test “has some value,” says Dr Schatzberg, a psychiatrist and a former president of the American Psychiatric Association. “It has some use but what it doesn’t do is tell you which specific drug to use.” He adds, “What the field wants is a test that tells me which specific drug I should put my patient on.” That is precisely what Charles Conway, a professor of psychiatry at Washington University School of Medicine in St. Louis, likes about it. The test “provides recommendations,” Dr Conway says. “It doesn’t say: ‘Give this drug only.’ It says: ‘You have a range of choices, which you will [make] based on your clinical judgment.’ ”
Credit: Lucette Lagnado for The Wall Street Journal, 6 May 2018.