Pharmacogenomics Effective for Major Depressive Disorder Patients

John F. Greden, MD

The response rate of antidepressant medications can be low when pharmacogenomics are not taking into account for patients suffering from major depressive disorder (MDD).

A team, led by John F. Greden, MD, University of Michigan Department of Psychiatry and Comprehensive Depression Center, examined the success of guided-care compared to common treatment for major depressive disorder in a 24-week, randomized, controlled trial.

Current guidelines for major depressive disorder have delivered limited treatment success. These treatment options generally rely primarily on antidepressant medications combined with psychotherapy based on the clinician’s choice, preference, and experience.

However, studies show only half of patients with moderate-to-severe major depressive disorder respond adequately to their first medication.

While pharmacogenomics could improve outcomes by identifying genetically inappropriate medications, studies in the past have not adequately explored the full potential of this option.

The Genomics Used to Improve DEpression Decisions (GUIDED) trial included 1167 outpatient diagnosed with major depressive disorder and with a patient or clinician reported inadequate response to at least 1 antidepressant.

In the study, patients were randomized to either a treatment as usual group or a pharmacogenomics-guided intervention group where clinicians had access to a pharmacogenomic test report to inform medication selections.

The investigators were unguided by pharmacogenomic data in the active treatment for patients in the treatment as usual group. For patients in the guided care group, clinicians had access to pharmacogenomic test reports prior to the baseline visit.

This information was used to guide their medication selections.

The investigators considered medications that were congruent or incongruent with the test results. The patients were unblinded after week 8.

The team sought primary outcomes of symptom improvement at week 8, defined by the change in the 17-item Hamilton Depression Rating Scale (HAM-D17).

The secondary outcomes included response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8.

While the investigators required at least 1 failed medication for the trial, the mean number of failed medications was 3.51. General anxiety disorder was also the most common psychiatric comorbidity of the study’s population.

Ultimately, they found symptom improvement for guided-care was not significantly different than the treatment as usual group at week 8 (27.2% vs. 24.4%, P = 0.107). However, there were improvements in response (26.0% vs. 19.9%, P = 0.013) and remission (15.3% vs. 10.1%, P = 0.007) that were statistically significant.

One factor that led to improvements is taking incongruent medications prior to baseline but switching to congruent medications by week 8.

This patient population experienced greater symptom improvement (33.5% vs. 21.1%, P = 0.002), response (28.5% vs. 16.7%, P = 0.036), and remission (21.5% vs. 8.5%, P = 0.007) compared to the segment of patients who remained incongruent. This group also experienced fewer side effects (6.5% vs. 16.5%, P = 0.045].

“Pharmacogenomic testing did not significantly improve mean symptoms but did significantly improve response and remission rates for difficult-to-treat depression patients over standard of care,” the authors wrote.

The study, “Impact of pharmacogenomics on clinical outcomes in major depressive disorder in the GUIDED trial: A large, patient- and rater-blinded, randomized, controlled study,” was published online in the Journal of Psychiatric Research.