Editorial: Beyond Red Light, Green Light: Examining the Role of Pharmacogenomics in Evidence-Based Care in Child and...

The role of pharmacogenetics in guiding psychopharmacologic treatment for children and adolescents remains elusive for many clinicians. In the absence of a solid and comprehensive evidence base, sufficient training, education, and consensus guidelines, commercial promotion of pharmacogenetic testing panels has the potential to become the main source of information for providers. Commonly, these tests include multigene panels and group medications into color-coded bins. These panels include both pharmacokinetic (PK) and pharmacodynamic (PD) genes and, using combinatorial algorithms, direct clinicians to use medications "as directed" or caution that "moderate gene-drug interaction(s)" or "significant gene-drug interaction(s)" may exist. Many industry-sponsored studies in adults have concluded that that when clinicians select medications based on pharmacogenomic guidance, patients have better outcomes,¹ although some caution against this approach.² To provide evidence on the clinical impact and potential of pharmacogenetic testing panels in clinical practice in child and adolescent psychiatry, in this issue of the Journal, Vande Voort³ and colleagues report the results of a prospective trial of pharmacogenetically guided treatment versus treatment as usual in depressed adolescents. The authors randomized adolescents aged 13 to 18 years with moderate to severe major depressive disorder (N = 176) to treatment guided by combinatorial pharmacogenetic testing that was either available at the baseline visit (GENE arm, n = 84) or at the 8-week visit (treatment-as-usual arm, n = 92). Patients and raters were blinded, but the treating psychiatrist was not blinded and could prescribe any medication deemed clinically indicated for the patient. Improvement, side effects, and satisfaction were assessed throughout the study and at a 6-month follow-up visit. There was no significant difference in terms of symptom improvement, side effect burden, or satisfaction at 8 weeks or 6 months between patients in the GENE and treatment-as-usual arms, respectively. However, significantly more patients in the treatment-as-usual arm received selective serotonin reuptake inhibitors (SSRIs) compared with patients in the GENE arm (81.5% vs 66.7%). Therefore, there was no significant clinical impact when clinicians used combinatorial pharmacogenomic testing to guide treatment for depressed adolescents. If anything, this guidance influenced providers to more frequently prescribe medications that are not considered first-line for the treatment of depression in youths (serotonin-norepinephrine reuptake inhibitors [SNRIs], atypical antidepressants) and for which double-blind placebo-controlled trials have failed to demonstrate efficacy in depressed youths.^4,5.