An effectiveness study of combinatorial pharmacogenetics testing to guide the treatment of depression in adolescents

Washington, DC, January 25 , 2022 – A study in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), published by Elsevier, reports that, combinatorial pharmacogenetics-guided treatment did not demonstrate improved outcomes for adolescents with depression compared to those who received treatment as usual.  Further research however is needed to determine how single medication-gene pairs may affect clinical outcomes for youth struggling with depression.

Pharmacogenetics testing, the testing for gene variations that could influence a patient’s response to a medication, has been increasingly considered in clinical practice. Over the years, many commercially available combinatorial pharmacogenetics testing platforms have come to the market with the promise of bringing a precision medicine approach to the practice of psychiatry.

There has been a lack of literature evaluating the use of these combinatorial panels to enhance outcomes in adolescents with depression, however lead author, Jennifer Vande Voort, MD, Associate Professor at the Mayo Clinic, Rochester, MN, said: “Our study sought to evaluate the clinical impact of combinatorial pharmacogenetics testing in a double-blind, randomized, controlled effectiveness study.”

The findings, based on the Adolescent Management of Depression study, included 176 adolescents aged between 13 to 18 years of age, already diagnosed with moderate to severe major depressive disorders.

Participants were randomized to one of two groups: 84 participants were randomized to the guided treatment (or GENE arm), where the treating psychiatrist had the testing results before the participant started a medication; and 92 were randomized to the treatment as usual (TAU) arm, where the treating psychiatrist did not have the testing results until an 8-week follow-up visit.

The results showed that depressive symptoms improved with treatment in participants throughout the duration of the study regardless of treatment arm assignment. There was no statistical difference in improvement between the GENE or TAU arms on depression rating scales, or side effect scales. Interestingly, there was a statistically significant difference in prescribing practices for the various medication classes between the GENE and TAU arms. This suggests that testing results may influence physician decision-making.

“The results of this study may reflect an actual outcome that pharmacogenetics testing does not impact the treatment of depression, but it is possible that the results in this study were diluted by patients in the treatment as usual arm who were incidentally prescribed a medication in the ‘use as directed’ category, said Paul Croarkin, DO, MS, Professor at the Mayo Clinic.

“It is possible that pharmacogenetics testing may be useful in certain cases where individuals have genes that significantly interact with particular medications.  More research is needed regarding specific medication-gene pairs and how these individual pairs, rather than a combinatorial panel, impacts clinical outcomes,” Dr. Croarkin concluded.

In support of these findings, Dr. Vande Voort added: “Depression is a very complex disorder with potentially many underlying mechanisms for illness and treatment response. Antidepressant response is not only dictated by gene-drug interactions. It is important to talk to families about what this testing may and may not mean beforehand, to have a clear understanding of their testing results, and how it may impact their clinical care.”

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Notes for editors
The article is “A Randomized Controlled Trial of Combinatorial Pharmacogenetics Testing in Adolescent Depression” by Jennifer L. Vande Voort, MD, Scott S. Orth, DO, Julia Shekunov, MD, Magdalena Romanowicz, MD, Jennifer R. Geske, MS, Jessica A. Ward, BA, Nicole I. Leibman, MD, Mark A. Frye, MD, Paul E. Croarkin, DO, MS (https://doi.org/10.1016/j.jaac.2021.03.011). It currently appears in the Journal of the American Academy of Child and Adolescent Psychiatry, volume 61, issue 1 (January 2022), published by Elsevier.

Copies of this paper are available to credentialed journalists upon request; please contact the JAACAP Editorial Office at support@jaacap.org or +1 202 587 9674. Journalists wishing to interview the authors may contact Jennifer L. Vande Voort, MD, e-mail at vandevoort.jennifer@mayo.edu

About JAACAP
Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP) is the official publication of the American Academy of Child and Adolescent Psychiatry. JAACAP is the leading journal focusing exclusively on today’s psychiatric research and treatment of the child and adolescent. Published twelve times per year, each issue is committed to its mission of advancing the science of pediatric mental health and promoting the care of youth and their families.

The Journal‘s purpose is to advance research, clinical practice, and theory in child and adolescent psychiatry. It is interested in manuscripts from diverse viewpoints, including genetic, epidemiological, neurobiological, cognitive, behavioral, psychodynamic, social, cultural, and economic. Studies of diagnostic reliability and validity, psychotherapeutic and psychopharmacological treatment efficacy, and mental health services effectiveness are encouraged. The Journal also seeks to promote the well-being of children and families by publishing scholarly papers on such subjects as health policy, legislation, advocacy, culture and society, and service provision as they pertain to the mental health of children and families.

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