Pharmacogenetic testing in children: What to test and how to use it

Because patients and families also have difficulty understanding the reports, we created patient education sheets,³⁶ written at an eighth grade level with feedback from parents and modeled on those provided by St. Jude Children’s Research Hospital.³⁷ St. Jude Children’s Research Hospital also has pharmacogenetic competencies that pharmacists and nurses must pass.^38,39 The following is a sample explanation that one of our nurses uses to educate parents on what is being tested and what effect the results will have on the treatment plan.

“During your child’s stay we will be completing a genetic test to help us understand how he/she processes the types of medications that we may be likely to start during their hospitalization. This does not tell us which medication will be best—unfortunately within the field of psychiatry there is still some unavoidable trial and error; rather, what it will do is tell us how to make sure that the dosing is at a level that would be safe for the way your child’s body breaks down the medicine, so that he/she can get the intended benefit of the medicine’s effects, while decreasing the risk of uncomfortable side effects, where possible.”

Other challenges in pharmacogenetic testing are the cost, disease risk, and concern about how genetic information will be used. Because these tests are often not covered by health insurance, some commercial pharmacogenetic testing companies offer an out-of-pocket maximum in the $250 to $350 range to reduce the cost to the patient. Some pharmacogenetic testing companies also test for genes associated with disease, so if a clinician orders the test, he or she may be responsible for sharing that information with the patient. For most pharmacogenetic testing companies, the turn-around time is 2 to 10 days. Genetic information is protected by federal laws, including Genetic Information Nondiscrimination Act (GINA) and Health Insurance Portability and Accountability Act (HIPAA).

The choice of psychotropic medication is complex, and although we would like pharmacogenetics to be the only answer to why every patient does or does not respond to a medication, it is not. Response to medication is influenced by age, comorbidities, illness severity, illness duration, compliance, gender, concomitant medications, and potentially more.⁴⁰ Pharmacogenetics is another tool at the clinician’s disposal to help in choosing a medication and dose. There is a clear association between CYP2D6 and CYP2C19 and exposure to many antidepressants and antipsychotics (reviewed by Stingl et al³); however, the link between exposure and response is much weaker. It may be strengthened by the inclusion of pharmacodynamic information (the level of expression of the drug target), which can be influenced by genetic variants.⁴¹ At the present time, the most evidence exists for testing CYP2D6 and CYP2C19, and the CPIC^4,5,15 and DWPG⁶ guidelines provide evidence-based recommendations for how to adjust medication dosages based on the results.

There is clearly much more research that needs to be done in the field of neuropsychi­atric pharmacogenetics, especially in pediatric populations. As we see increased utilization of pharmacogenetic tests in psychiatry, there is also a need for pharmaco­genetic education of patients, families, nurses, pharmacists, and psychiatrists. Several good pharmacogenetic resources that contain up-to-date summaries of the available evidence linking pharmacogenetic variants to medication response, implementation resources, and educational resources are available. These include CPIC (www.cpicpgx.org), PharmGKB (www.pharmgkb.org), and the IGNITE Spark Toolbox (https://ignite-genomics.org/spark-toolbox/clinicians/).

Acknowledgements

The author thanks Jen Milau, APRN, for the case study and sample explanation, and Jeffrey Strawn, MD, FAACP, Ethan Poweleit, and Stacey Aldrich, MS, for help with preparing this manuscript.