Genetic Testing Improves Short- and Long-Term Remission, Response Rates in MDD

John Greden, MD

In comparison with the usual approach for medication selection, GeneSight pharmacogenomic testing has been shown to improve short- and long-term response and remission rates in adults with depression.

Ultimately, patients that had their medication selection guided by the testing were 50% more likely to achieve remission and 30% more likely to achieve treatment response.

The results could have tremendous implications for patients with the condition, as many of them struggle with medications. Led by John Greden, MD, the founder and executive director of the University of Michigan’s Comprehensive Depression Center, the data were presented at the American Psychiatric Association’s annual meeting in New York City.

“The people who treat clinical depression struggle because they have never had any guided type of treatment to tell them what really works best,” Greden told MD Magazine. “This study, the largest, longest, randomized, controlled of its kind, was designed to figure out if we could come up with a test that would aid clinicians in helping to know which medicines are not going to interact in a bad way with the person's genetics, and the results were fairly remarkable.”

The study randomized 1398 patients with major depressive disorder (MDD) to either treatment as usual (TAU; n = 717) or pharmacogenomic testing (PGx; n = 681) for an 8-week double-blinded period, followed by a 4-week unblinded period and a 12-week open label phase. All told, the PGx group lost 157 patients and the TAU group lost 158 patients to follow-up by the 8-week mark.

Patients were assessed for remission, measured by the Hamilton Depression scale (HAM-D17), and defined as achieving a HAM-D17 score <7; response, defined as a 50% decrease in HAM-D17 from baseline; and symptom improvement, defined as percent change in HAM-D17 score baseline.

At week 8, the PGx arm showed a 27.2% improvement in symptoms compared to 24.4% in the TAU arm, although the difference between groups was not statistically significant (P = .11). However, the differences between the groups in terms of response (PGx = 26.0%; TAU = 19.9%; P = .01) and remission (PGx = 15.3%; TAU = 10.1%; P = .007) rates did achieve significance. These rates continued to improve through week 24.

“Doctors treating depression, regardless of who they are—psychiatrists, obstetricians, primary care doctors&mdash;are forced now to choose the medications that they use, which are pretty essential for anybody with moderate or severe depressions, on the basis of a favorite or their clinical experience or guesswork,” Greden said. “Meanwhile, the patient and the family suffer. The reason that that guesswork as a problem is that some of the medicines are incongruent&mdash;they don't work with the person's genes.”

Due to this, Greden and colleagues measured the patient outcomes for those in the study that were taking incongruent medications at baseline. They found that by week 8, for those who switched to congruent medication after 8 weeks, all outcomes were improved significantly—symptom improvement (33.5% vs. 21.1%; P = .002), response rates (28.5% vs. 16.7%; P = .04), and remission rates (21.5% vs. 8.5%; P = .007)—compared to those remaining on incongruent medications.

“The test is simple. It [takes] cheek swabs, results come back quickly, and they give a guided approach to those that are safe [and] not having the difficulties of interacting in a bad way like incongruent ones do,” Greden said. “What was unique about this is [that] it assesses 56 different antidepressants using 12 genes, so it's also pretty thorough.”

The study, “Combinatorial Pharmacogenomics Significantly Improves Response and Remission for Major Depressive Disorder: A Double-Blind, Randomized Controlled Trial,” was presented at the APA’s annual meeting.

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