Randomized, controlled, participant‐ and rater‐blind trial of pharmacogenomic test‐guided treatment versus treatment as usual for major depressive disorder

Abstract

Background Cohort and cost‐effectiveness studies suggest that measuring variation in genes that influence metabolism of common drugs could improve antidepressant treatment outcomes. Prior randomized trials have yielded inconsistent results. Method Multicenter randomized double‐blind (subject and rater), controlled trial of pharmacogenomic testing among outpatients with nonpsychotic major depressive disorder. Study participants (n = 304) were randomized 1:1 to assay‐guided treatment (AGT; N = 151) or treatment‐as‐usual (TAU; N = 153). Participants and raters were blinded to study arm; unblinded clinicians received results of a pharmacogenomic test and adjusted treatment in light of the test report. Primary outcome was change over 8 weeks in Hamilton Depression Rating Scale (SIGH‐D‐17). Results For the primary comparison of interest, change in SIGH‐D‐17, no significant difference was detected between AGT and TAU at Week 8 (p = .53). Rates of study completion also did not differ between the arms (AGT 92.7%, TAU 92.2% (χ2 = 0.03, df = 1, p = .86). Exploratory analyses suggested significantly fewer individuals experienced worsening of depressive symptoms following AGT, and that treatment concordant with assay results was associated with greater likelihood of remission. Conclusion Pharmacogenomic testing using a panel of pharmacokinetic and pharmacodynamic variants was not associated with significant improvement in the primary efficacy outcome when providers were unconstrained by the assay results. Further investigation is needed to understand the discordance with cost‐effectiveness results and among randomized trials.

Pharmacogenomics guided versus standard antidepressant treatment in a community pharmacy setting: A randomized controlled trial

“…Thus, biases (e.g., expectancy bias and performance bias) may have influenced results. Blinding of participants, outcome assessors, as well as prescribers 19 would buoy these results in future replications. Notably, the current investigation did not find expected differences in treatment satisfaction across groups.…”

“…Mixed effect models have been applied in recent investigations of pharmacogenomics guided treatment. 19 This analysis approach handles missing values using maximum likelihood estimation, which is able to use all available information in all recruited participants, and is associated with the least bias in a comparison of methods for dealing with missing data. 38 We followed the intention‐to‐treat principle and analyzed all randomized participants.…”

“…Findings from these investigations are equivocal with respect to whether pharmacogenomic testing improves depression response, remission, and symptom severity. 15 , 16 , 17 Several, recent RCTs have failed to find a positive effect of pharmacogenetic treatment on their primary outcomes of symptom improvement 18 , 19 or patient‐reported sustained response. 20 On the other hand, recent meta‐analyses have concluded that acute treatment for depression guided by pharmacogenetic testing improved response and remission relative to treatment as usual (TAU), 17 with testing associated with 1.71 greater likelihood of symptom remission following acute treatment.…”

Review and Consensus on Pharmacogenomic Testing in Psychiatry

“…Two meta-analytic evaluations of the clinical efficacy of commercial PGx testing in psychiatry have been conducted for prospective and retrospective clinical trials and showed that testing improves the likelihood of achieving symptom remission compared to treatment as usual [85,86]. However, recent inconclusive or negative trial findings have been reported [87,88], leading some to conclude that commercial PGx testing is not ready for widespread use in psychiatry This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.…”

“…Two meta-analytic evaluations of the clinical efficacy of commercial PGx testing in psychiatry have been conducted for prospective and retrospective clinical trials and showed that testing improves the likelihood of achieving symptom remission compared to treatment as usual [85,86]. However, recent inconclusive or negative trial findings have been reported [87,88], leading some to conclude that commercial PGx testing is not ready for widespread use in psychiatry [89]. Furthermore, evidence of clinical efficacy has primarily been constrained to adults of European-ancestry with major depressive disorder who had a history of antidepressant non-response or adverse drug reactions, suggesting evaluations of clinical efficacy in other clinical populations (e. g., non-Europeans, treatment-naïve, children, schizophrenia) are required.…”