Genetic Testing May Help Identify Best Antidepressant

Fran Lowry

June 06, 2019

SCOTTSDALE, Arizona — Pharmacogenomic testing may help clinicians choose the most effective antidepressant for their patients with major depressive disorder (MDD) with greater precision.

A study that examined the utility of such testing found that remission, response, and relief from depressive symptoms were greater among patients whose care was guided by such testing, compared to patients who received treatment as usual (TAU), which did not include genetic guidance.

Dr John Greden

"Pharmacogenomic testing won't tell us beforehand which antidepressant may be most effective for a patient, at least not at the present time. But such tests help us know which medicines may be incongruent or not the best choice or incorrect for a given patient," study investigator John F. Greden, MD, executive director, University of Michigan Comprehensive Depression Center, and Rachel Upjohn Professor of Psychiatry, Ann Arbor, told Medscape Medical News.

The findings were presented here at the American Society of Clinical Psychopharmacology (ASCP) 2019 annual meeting.

Clinician Skepticism

Pharmacogenomic testing has not yet been routinely adopted by clinicians as a way to improve outcomes for patients with MDD.

"There's a lot of skepticism about such tests. There is confusion, people are puzzled about them, but there are reasons for this. For one thing, early studies and publications about pharmacogenomics studied small numbers of genes and variants and had small sample sizes and short duration of follow-up. But such testing has come a long way since the early days," Greden said.

"If clinicians know how to use pharmacogenomics data, it will help them make choices that will bring about response and remission," he added.

The World Health Organization reports that clinical depression is the most disabling illness in the world. After heart disease, it is the costliest illness in the United States.

"We should be looking for ways to save money and bring about more response and remission, because better, but not well, in depression is not good enough," said Greden.

In the current study, the investigators sought to determine whether results would be better when choice of treatment was guided by genetic test results, compared with TAU.

For the study, the investigators used the GeneSight psychotropic test (Assurex Health Inc, Myriad Genetics).

The study, a blinded 24-week trial, included 1167 patients with MDD who had previously demonstrated inadequate response to antidepressants.

At week 8, the difference in improvement between guided and nonguided care was not significantly different (27.2% vs 24.4%; P = .107).

However, there was a significant improvement in remission and response rates with guided care compared to nonguided care. Improvement in response was observed in 26% for the guided-care group, vs 20% for the nonguided-care group (P = .013).

Remission occurred in 15% of guided-care patients, vs 10% of nonguided-care patients (P = .007).

The researchers also analyzed outcomes in 213 patients who were found to be taking incongruent medications, that is, medicines that were incompatible, owing to genetic variance in the patients. These patients were switched to congruent medications.

Rates of remission, response, and symptom improvement all increased when these participants were switched to more congruent regimens.

By week 8, these patients experienced greater symptom improvement (33.5% vs 21.1%; P = .002), greater response (28.5% vs 16.7%; P = .036), and greater remission (21.5% vs 8.5%; P = .007), compared to those patients who continued taking incongruent medication.

End of Hit-or-Miss Approach?

Commenting on the findings for Medscape Medical News, Angelos Halaris, MD, professor of psychiatry, Loyola University Medical Center, Chicago, Illinois, said the study provides some badly needed clinical guidance.

Dr Angelos Halaris

"I think psychiatrists in general know about the problem of thirds. Of all the patients we treat for depression, about a third will have remission in ideally 6 to 12 weeks; another third show some response, but not remission, and that response can be good, medium, but certainly not full; and then a final third show absolutely no response," said Halaris.

If patients are unresponsive to a given agent after 3 months, the cycle of trial and error must begin again, and the second agent may or may not work, he said.

"If it fails again, you have two failed adequate trials, both in dose and length of treatment, and that fulfills the criteria for treatment resistance. It's hit or miss," Halaris told Medscape Medical News.

"We've had nothing to guide us until now. That's where pharmacogenomics testing comes into play. We now have sufficient evidence to give us confidence that this is a legitimate, useful, productive approach to take," said Halaris.

He noted that more studies are needed but that the current research by Greden and colleagues has shown "we can increase response and remission rates and reduce unnecessary medication costs.

"So, can we make a little dent into treatment resistance? Avoid the hit or miss, the trial and error, the prolonged exposure to failed outcomes that are costly not only in terms of money but, even more importantly, in terms of personal pain and suffering? I think pharmacogenomics testing will help here. And if we can do something to at least diminish this trial and error, we are moving in the right direction," he said.

The study was funded by Assurex Health Inc. Greden and Halaris report no relevant financial relationships.

American Society of Clinical Psychopharmacology (ASCP) 2019: Abstract 3001655. Presented May 28, 2019.

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