A Randomized Controlled Trial of Combinatorial Pharmacogenetics Testing in Adolescent Depression

Jennifer L. Vande Voort, Scott S. Orth, Julia Shekunov, Magdalena Romanowicz, Jennifer R. Geske, Jessica A. Ward, Nicole I. Leibman, Mark A. Frye, Paul E. Croarkin

Research output: Contribution to journalArticlepeer-review


Objective: Numerous commercial pharmacogenetics panels are now widely available for clinical use in psychiatric practice. However, there is a paucity of literature evaluating the use of combinatorial pharmacogenetics panels to enhance outcomes in the treatment of adolescents with depression. This study sought to prospectively evaluate the clinical impact of combinatorial pharmacogenetics testing in a double-blind, randomized, controlled effectiveness study for the pharmacologic treatment of adolescents with depression. Method: Adolescents aged 13 to 18 years (N = 176) with moderate to severe major depressive disorder (MDD) were randomized to treatment arm guided by testing in which pharmacogenetic testing results were available at the baseline visit (GENE arm, n = 84) or a treatment-as-usual arm (TAU arm, n = 92) in which testing results were not available until an 8-week visit. Raters, participants, and families were blinded to group allocation. Symptom improvement, side effects, and satisfaction were assessed throughout the study at 4 weeks, 8 weeks, and 6 months. Results: There were no differences between the GENE and TAU arms at 8 weeks or 6 months for symptom improvement, side effect burden, or satisfaction. Selective serotonin reuptake inhibitors were prescribed at higher rates in the TAU arm compared to the GENE arm (p = .024). Conclusion: Combinatorial pharmacogenetics−guided treatment did not demonstrate improved outcomes compared to TAU in adolescents with MDD. Future research should examine how specific medication−gene pairs may affect clinical outcomes in the treatment of adolescents with depression and how best to integrate pharmacogenetics into clinical practice. Clinical trial registration information: A PK/PD Genetic Variation Treatment Algorithm Versus Treatment As Usual for Adolescent Management Of Depression; https://www.clinicaltrials.gov; NCT02286440.

Original languageEnglish (US)
Pages (from-to)46-55
Number of pages10
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Issue number1
StatePublished - Jan 2022


  • depression
  • double-blind
  • pharmacogenetics testing
  • randomized

ASJC Scopus subject areas

  • Developmental and Educational Psychology
  • Psychiatry and Mental health


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