Pharmacogenetic Testing of Children and Adolescents with Mental Health Conditions: Real-World Experiences

Background/Objectives: Medication discontinuation attributable to adverse drug reactions (ADRs) and/or inefficacy remains a concern of psychotropic medications among children and adolescents. Pharmacogenetic (PGx) testing has been proposed to individualize treatment, although its utility remains uncertain. We retrospectively evaluated whether PGx testing of two key metabolism genes (i.e., CYP2C19 and CYP2D6) explains reported episodes of ADRs and treatment inefficacy experienced by children and adolescents with diverse mental health conditions. Methods: PGx testing of CYP2C19 and CYP2D6 was conducted for 100 participants before, during, or after the use of psychotropic medication(s) that have clinical practice guidelines supporting PGx-guided dosing. The theoretical impact on medication dosing was reviewed in the context of clinical guidelines. We then evaluated whether the PGx-inferred metabolizer phenotype was consistent with reported ADR and/or treatment inefficacy. Results: If PGx testing had been performed before the start of treatment, 43% (35/82) of participants would have been recommended dose adjustments or alternative therapy of at least one medication. PGx test results corroborated 8% (6/76) of ADR events and 3% (2/61) of inefficacies. However, no single participant had all prior reported ADRs or inefficacies explained by the results of CYP2C19 nor CYP2D6 testing. Conclusions: Reactive testing of CYP2C19 and CYP2D6 provided limited insight into isolated incidents of psychotropic medication intolerance in this population. No individual's PGx test results explained all episodes of ADR or suboptimal response. Variation in drug metabolism genes alone does not provide an explanation for multiple episodes of inefficacy or adverse reaction. In the setting of child and adolescent psychiatry, PGx testing is best suited for preemptive use to complement clinical decision making.