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

• Published in: Depression and anxiety Vol. 37; no. 9; pp. 834 - 841
• Main Authors: Perlis, Roy H., Dowd, Daniel, Fava, Maurizio, Lencz, Todd, Krause, David S.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.09.2020
• Subjects: antidepressants; Antidepressive Agents - therapeutic use; Clinical trials; depression; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - genetics; Discordance; Double-Blind Method; Double-blind studies; Drug metabolism; Genetics; Humans; Mental depression; Pharmacodynamics; Pharmacogenetics; Pharmacogenomic Testing; Pharmacogenomics; Pharmacokinetics; pharmacotherapy; Precision medicine; Psychotropic drugs; Remission; Treatment Outcome; antidepressants; clinical trials; genetics; depression; pharmacotherapy
• ISSN: 1091-4269; 1520-6394; 1520-6394
• DOI: 10.1002/da.23029

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.