Weighted and combined multi-gene pharmacogenomic testing significantly increased clinical response and remission rates for patients with major depressive disorder (MDD) receiving active pharmacogenomic-guided care compared with those undergoing unguided active treatment (TAU), according to a study published in the Journal of Psychiatric Research.
In this study, researchers sought to evaluate outcomes when pharmacogenomic testing was used to guide medication selection vs unguided active treatment. They noted that the Genomics Used to Improve DEpression Decisions (GUIDED, ClinicalTrials.gov Identifier: NCT02109939) study is the largest randomized, long-term, blinded, controlled trial using pharmacogenomics testing to guide MDD therapy to date.
For inclusion in the study, patients had to be ≥18 years, diagnosed with MDD (≥11 on the 16-item Quick Inventory of Depression Symptomology [QIDS-C16] and self-rated QIDS-SR16 at screening and baseline), and had experienced a lack of clinical improvement or intolerable side-effects to at least one documented psychotropic treatment included on the pharmacogenomics test report within the current depressive episode.
Of the 2,004 patients, who were screened for inclusion, a total of 1541 patients completed the baseline visit and were included in the final intent-to-treat cohort. For the per-protocol cohort, an additional 143 patients were excluded. All eligible patients were blindly randomized 1:1 to the guided care arm and to TAU. However, clinicians were not blinded to their respective study arms as test results had to be consulted to select medication for patients under guided care.
Pharmacogenomic testing was performed for all patients between screening and baseline visits, and symptom improvement, response, and remission were monitored over 24 weeks with the primary endpoint at week 8. The GeneSight® Psychotropic test from Assurex Health, Inc. (Mason, OH) was used for pharmacogenomics testing on all patients to weigh the combined influence of each individual genotype on patient response to each medication.
The primary outcome was symptom improvement at week 8 in the per-protocol cohort, which was measured by the percent change in Hamilton Rating Scale for Depression-17 Item (HAM-D17) from baseline. Secondary outcomes included response and remission at week 8. Response was defined as greater than or equal to 50% decrease at week 8 in the assessment of interest (HAM-D17, QIDS-C16 or 9-item Patient Health Questionnaire [PHQ-9]) from baseline. Remission was defined as having a score of less than or equal 7 for HAM-D17, less than or equal to 5 for QIDS-C16 and less than 5 for PHG-9.
At week 8, there was no significant difference in the primary outcome (27.2% decrease in HAM-D17 scores in the guided care arm; 24.4% decrease in TAU; P =.107). However, the response rate in the guided care arm was 26.0% (146/150) at week 8, which was significantly higher than in TAU [19.9% (121/607), P =.013].
Over the 24-week study period, patients in the guided arm sustained a decrease on the HAM-D17 rating scale, decreasing 42.5% at week 24 relative to baseline. In addition, the response and remission rates increased by 70% and 100% respectively from week 8 to week 24.
In this trial, patients in both arms received active treatment, setting the GUIDED trial apart from traditional drug studies.
The study authors concluded that “pharmacogenomic testing is effective in improving response 18 and remission rates among those with prior treatment resistance, particularly for patients who are treated with medications that are incongruent with their genetic profile.”
Researchers reported several limitations to the study, and further noted that the “conclusions from this trial cannot be generalized to the entire array of pharmacogenomics tests”.
Disclosures: Multiple authors declare affiliations with the pharmaceutical industry. Please refer to original reference for full list of author disclosures.
Greden JF, Parikh S, Rothschild A, 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 2, 2019]. J Psych Res.