Impact of Pharmacogenomics on Pediatric Psychotropic Medication Prescribing in an Ambulatory Care Setting.

Objective: Evidence for pharmacogenomic (PGx) guided treatment in child and adolescent psychiatry is growing. This study evaluated the impact of PGx testing on psychotropic medication prescribing in an ambulatory child and adolescent psychiatry and a developmental pediatrics clinic. Methods: This was a single-center, retrospective, descriptive analysis of patients who underwent PGx testing between January 2015 and October 2022 at a child and adolescent psychiatry clinic or developmental pediatrics clinic. The primary outcome was the proportion of patients with at least one psychotropic medication modification made 6-month posttesting that could be attributed to CYP2C19, CYP2D6, HLA-B*15:02, or HLA-A*31:01. Secondary outcomes included reason for testing, types of therapeutic modifications made, and whether the therapeutic modifications concorded with PGx guidelines. Results: A total of 193 patients were analyzed. The average age was 10 ± 4 years old, 60% were male, 78% were Caucasian. Sixty-eight percent had a primary diagnosis of a neurodevelopmental disorder, namely autism spectrum disorder (51%), and attention-deficit/hyperactivity disorder (14%). The reasons for PGx testing included medication inefficacy (34%), medication intolerance (20%), and family request (19%). At the time of PGx testing, 37% of patients were taking ≥1 psychotropic medication with PGx annotation. Overall, 35 PGx-related therapeutic modifications were made in 32 (17%) patients. These included continuing current PGx medication (6.2%) and starting PGx medication (5.2%). These modifications mainly involved antidepressants. Out of these 35 PGx-related therapeutic modifications, 94% were concordant with PGx guidelines. Among 29 patients who were prescribed at least one CYP2D6 inhibitor, 25 (86%) underwent CYP2D6 phenoconversion. Conclusions: It is critical to apply pediatric age-specific considerations when utilizing PGx testing in child and adolescent psychiatry. PGx testing stewardship could provide a framework to guide the clinical utility of PGx in a pediatric population with mental health conditions, including neurodevelopmental disorders.

Long-term use of antidepressants, mood stabilizers, and antipsychotics in pediatric patients with a focus on appropriate deprescribing.

It is estimated that 8% to 12% of youth are prescribed psychotropic medications. Those in foster care, juvenile justice systems, residential treatment facilities, and with developmental or intellectual disabilities are more likely to be prescribed high-risk regimens. The use of psychotropic medications in this age group is often off-label and can be associated with significant risk, warranting critical evaluation of their role. Landmark trials, pediatric-specific guidelines, and state-driven initiatives play critical roles in supporting evidence-based use of psychotropic medications in children. Overall, there is a lack of literature describing the long-term use of psychotropic medications in youth-particularly with regard to neurobiological, physical, and social changes that occur throughout development. Deprescribing is an important practice in child and adolescent psychiatry, given concerns for over-prescribing, inappropriate polytherapy, and the importance of reevaluating the role of psychotropic medications as children develop.

The Utility of Pharmacogenetic-Guided Psychotropic Medication Selection for Pediatric Patients: A Retrospective Study.

BACKGROUND: To describe trends and clinical experiences in applying commercial pharmacogenetic testing among pediatric patients with neuropsychiatric disorders. METHODS: Demographic and clinical data of patients receiving GeneSight® testing from January 2015 to November 2016 at an urban pediatric hospital were retrospectively extracted from medical charts. Outcome data included pharmacogenetic test results and medication prescriptions before and after the test. RESULTS: A total of 450 patients (12.1 ± 4.3 years) diagnosed with anxiety disorder, attention deficit hyperactivity disorder, developmental disorders including autism, and/or a mood disorder received testing, and 435 of them were prescribed medications. Comparing data before and after testing, the total number of psychotropic prescriptions were reduced by 27.2% and the number of prescribed medications with severe gene-drug interactions decreased from 165 to 95 (11.4% to 8.9% of total medications prescribed). Approximately 40% of actionable genetic annotation were related to CYP2CD6 and CYP2C19. Patients of Asian descent had significantly higher likelihood than other races of being classified as poor to intermediate metabolizers of antidepressants, mood stabilizers, and antipsychotics (p = 0.008, 0.007, and 0.001, respectively). Diagnoses, including autism spectrum disorder, were not associated with increased risks of severe gene-drug interactions. CONCLUSIONS: Pharmacogenetic testing in child and adolescent psychiatry is currently based on few clinically actionable genes validated by CPIC and/or FDA. Although this approach can be moderately utilized to guide psychotropic medication prescribing for pediatric patients with psychiatric disorders, clinicians should cautiously interpret test results while still relying on clinical experience and judgment to direct the final selection of medication.

Providers' perspectives on the clinical utility of pharmacogenomic testing in pediatric patients.

Aim: To assess providers' knowledge, attitudes, perceptions, and experiences related to pharmacogenomic (PGx) testing in pediatric patients. Materials & methods: An electronic survey was sent to multidisciplinary healthcare providers at a pediatric hospital. Results: Of 261 respondents, 71.3% were slightly or not at all familiar with PGx, despite 50.2% reporting prior PGx education or training. Most providers, apart from psychiatry, perceived PGx to be at least moderately useful to inform clinical decisions. However, only 26.4% of providers had recent PGx testing experience. Unfamiliarity with PGx and uncertainty about the clinical value of testing were common perceived challenges. Conclusion: Low PGx familiarity among pediatric providers suggests additional education and electronic resources are needed for PGx examples in which data support testing in children.

L-methylfolate Augmentation to Antidepressants for Adolescents with Treatment-Resistant Depression: A Case Series.

Despite antidepressant treatment, some patients continue to experience significant symptoms of depression. Literature has demonstrated modest benefit of folate supplementation in treatment-resistant depression among adults, though evidence is lacking in the pediatric population. This case series describes 10 adolescents (mean age 14.4 ± 2.8 years) with treatment-resistant depression prescribed adjunctive l-methylfolate (LM). The patient population was predominantly female (80%), Caucasian (90%), with an average of three comorbid psychiatric diagnoses, and failures of three psychotropic medications before starting LM. The majority of patients (80%) had a single mutation among the two methylene tetrahydrofolate reductase (MTHFR) gene variants evaluated (50% A1298 AC; 30% C677 CT), indicating reduced MTHFR activity. Eighty percent of patients demonstrated improvement in depression, anxiety, and irritability. Overall, LM was well tolerated. These cases suggest that LM as an adjunct to antidepressant treatment may be a safe and effective strategy for managing treatment-resistant depression in pediatric patients.