Pharmacogenomic Profiling of Pediatric Patients on Psychotropic Medications in an Emergency Department

Background:

The Centers for Disease Control and Prevention estimate that 13-20% of children living in the United States experience a mental disorder in a given year and an estimated $247 billion is spent each year on childhood mental disorders. In the last 5 years, emergency departments (ED) have been facing dramatic increases in the volume of pediatric patients presenting for evaluation and treatment of mental and behavioral disorders, to the point where it has been termed a national pediatric mental health crisis. Coincident with this increase has been the exponential increase in the number of children, both children as young as 2 years of age and adolescents, being prescribed 1 or more psychotropic medications-antidepressants (AD), antipsychotics (AP), and medications for Attention Deficit Hyperactivity Disorder (ADHD)-- for various mental and behavioral disorders in the last 10 years. More intentional overdoses, therapeutic errors, and/or adverse drug reactions (ADR) to these classes of medications are being evaluated in our pediatric emergency department (PED), potentially attributable to the increased number of children taking these medications. National Poison Data System (NPDS) -reported exposures to these medication classes continue to increase in both children and adolescents.

Numbers and rates of adverse drug event (ADE) emergency department visits involving psychiatric medications among US adults are significant, although the numbers in children are less well defined. The development of adverse medical conditions related to antipsychotic and other psychotropic medication use in children and adolescents has been found to be significantly associated with higher total costs of health care and to higher utilization of outpatient, emergency, and inpatient services over time.

Interindividual differences of people's clinical responses to psychotropic drugs and adverse drug reactions despite identical disease severity or etiology may be better explained by genetic variation among patients than other various factors. We will determine if genetic polymorphisms for genes coding for CYP450 drug metabolizing enzymes are associated with therapeutic failures and/or toxicity using the GeneSight® buccal swab test. Multiple published adult clinical studies have demonstrated that this combinatorial, multi-gene test better predicts antidepressant treatment outcomes for patients with depression and their use of health care resources, than any of the individual genes that comprise the test. One study demonstrated 70% greater improvement in depressive symptoms when GeneSight® guided physicians' treatment compared to unguided treatment, while another demonstrated a 67% increase in total healthcare visits when medication plans did not match their genetic profiles, contributing to significant increase in healthcare costs.19,20 Recent recommendations from the Clinical Pharmacogenetics Implementation Consortium of the National Institutes of Health Pharmacogenomics Research Network suggest that current data indicate that genotypes for CYP2D6 and CYP2C19 can lead to specific treatment recommendations.

To the investigators knowledge, this study is one of the first to propose the use of pharmacogenomic tests to study toxicity or treatment failure in pediatric patients using psychotropic medications and assess its clinical utility in patients presenting in crises to an ED. The results of this study are very likely to change clinical practice leading to increased pharmacogenomic testing of children and adolescents at their point of care in outpatient clinics, inpatient services, or PEDs. If successful, this project will lay the groundwork for future prospective analyses of genotypic "match" versus "mismatch" and either symptomatic or toxic adverse outcomes in this cohort presenting to a PED compared to a control population in an outpatient setting.