Pharmacogenomic Testing Improves Outcomes in Major Depressive Disorder

Patients with major depressive disorder who were switched from incongruent medications that is drugs with a potentially adverse gene-drug interactions benefitted from pharmacogenomics testing and switching to congruent medications.

Pharmacogenomic testing improved response rates and remission rates for patients with major depressive disorder, according to a study published in the Journal of Psychiatric Research.

Researchers of the Genomics Used to Improve Depression Decisions (GUIDED, NCT02109939) trial evaluated the impact pharmacogenomic testing had on treatment choices and the subsequent changes in symptoms, response rates, and remission rates over 24 weeks. Patients were randomly assigned to treatment as the usual arm or the guided-care arm. Both arms received active treatments, but for patients in the guided-care arm, clinicians used pharmacogenomic data to help make medication selections. Data collection occurred at baseline and weeks 4, 8, 12, and 24. The patient and raters were blinded through week 8. The 17-item Hamilton Depression Rating Scale, the 16-item Quick Inventory of Depression Symptomology, and the 9-item Patient Health Questionnaire were used to evaluate depression and symptoms. Additional data collected included all prescribed medications and side effects.

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Of the total 1398 patients included in this study, the mean age was 47.5 years old, 70.6% were women, 80.6% were white, and 36.7% were diagnosed with very severe depression, according to the Hamilton Depression rating scale. The treatment as usual arm included 717 patients and the guided-care arm included 681 patients. From baseline to week 8, there was not a significant difference in the mean Hamilton Depression rating scale score between the treatment as usual arm and the guided-care arm, but there were significant differences in response and remission rates. The response rate in the treatment as usual arm was 19.9% and the response rate in the guided-care arm was 26% (P =.013). The remission rate in the treatment as usual arm was 10.1% and the remission rate in the guided-care arm was 15.3% (P =.007). In the guided-care arm, 213 patients were taking incongruent medications at baseline, and after switching to a congruent medication based on the pharmacogenomic testing results, there was a 33.5% decrease in the mean Hamilton Depression rating scale score.

When this subset of the guided-care arm is compared with the patients who were on congruent medications at baseline, the patients who switched had significant improvements in depression symptoms (P =.002), response rates (P =.036), and remission rates (P =.007). The patients who switched to congruent medications experienced fewer side effects from baseline to week 8 (P =.002) compared with those who did not switch. Fewer patients who switched experienced side effects when compared with those patients who did not (P =.045).

The limitations of this study include the treating clinician not being blinded, the lack of diversity in the study population, and the study not including patients with mild depression.

The researchers concluded that their findings “indicate that pharmacogenomic testing is effective in improving response and remission rates among those with prior treatment resistance, particularly for patients who are treated with medications that are incongruent with their genetic profile.”

This study was sponsored by Assurex Health Inc., and several authors report multiple associations with pharmaceutical companies. Please see the original reference for a full list of authors’ disclosures.


Greden JF, Parikh SV, Rothschild AJ, et al. Impact of pharmacogenomics on clinical outcomes in major depressive disorder in the GUIDED trial: a large, patient- and rater-blinded, randomized, controlled study [published online January 4, 2019]. J Psychiatr Res. doi: 10.1016/j.jpsychires.2019.01.003