Pharmacogenetic testing in children: What to test and how to use it
Pediatric-specific evidence is limited, but testing can inform treatment, improve outcomes
Limited evidence from studies of commercially available tests
Several pharmacogenetic tests are commercially available, including some that focus on providing information that can be used specifically when prescribing psychiatric medications, such as the GeneSight Psychotropic test, CNSdose, Genomind, and Neuropharmagen.
In an industry-sponsored, nonrandomized clinical trial that included patients for whom prescribing decisions were made based on the GeneSight test, outcomes in adults were improved compared with treatment as usual,27 inpatient stays were shorter,28 and pharmacy costs were reduced.29 In one of these studies, the authors noted that the traditional, single-gene analysis was not associated with improved outcomes, whereas the multiple gene combination (pharmacokinetic and pharmacodynamic genes) was associated with improved outcomes among patients with depression.27 However, when GeneSightwas compared with treatment as usual in a small randomized trial, there was not a significant association between use of the test and improved outcomes among patients with treatment-resistant depression.30 The results of a much larger randomized trial (N = 1,167) are available31 and expected to be published, but patients younger than age 18 were excluded from this study.32 A retrospective study conducted in adult psychiatric patients found that patients whose treatment followed recommendations of a pharmacogenetic test including 20 genes were almost 4 times more likely to improve than patients whose treatment did not follow the recommendations.33
Pharmacogenetic testing at our pediatric inpatient unit
The Cincinnati Children’s Division of Child and Adolescent Psychiatry is the largest psychiatric inpatient service in a U.S. pediatric hospital. Starting in 2004, we adopted pharmacogenetically-guided dosing of psychiatric medications.34 CYP2D6 and CYP2C19 were chosen for testing because the enzymes encoded by these genes metabolize many of the antidepressants and antipsychotics that patients admitted to our unit will receive, and the clinicians wanted all available tools to help improve the care of these patients. To date, the Genetic Pharmacology Service (GPS) has performed >25,000 tests for variants in CYP2D6 and CYP2C19 as part of inpatient care. Patients provide a specimen (blood or buccal swab) at the time of admission to inpatient psychiatry, genotyping is performed onsite by the Molecular Genetics Laboratory (certified by the College of American Pathologists [CAP]/Clinical Laboratory Improvement Amendments [CLIA]) and the results are posted to the medical record within 2 business days. The report contains the patient’s alleles for CYP2D6 and CYP2C19, the genotype-predicted metabolizer phenotype, and dosing recommendations for 19 drugs (provided as a percentage of the standard dose). Insurance is billed for the test, and reimbursement is usually received when the test is performed as part of an inpatient stay.
The GPS team performed a retrospective chart review after the first panel was implemented in 2005.23 The study included 279 patients who were receiving a medication metabolized by one of the 2 genes tested. The poor metabolizers had the highest efficacy and highest number of adverse drug reactions, while ultra-rapid metabolizers had the lowest efficacy and lowest number of adverse reactions during their initial inpatient stay. In patients not treated with medications metabolized by CYP2D6 or CYP2C19, there was no association between metabolizer status and efficacy or adverse drug reactions. In this retrospective study, there was no association between metabolizer status and length of stay.
Overcoming the challenges
One challenge with many of the pharmacogenetic tests is interpretation of the results. The reports can span more than 20 pages, and clinicians may not have time to thoroughly read and understand how best to use all of this information. Sometimes the reports can make it seem like the first-line medication for the patient’s condition is not the best choice, but it could work well when dosed appropriately based on the patient’s genotype. Each commercially available test has a different way of presenting results,13 so when choosing a pharmacogenetic test, one should be sure to see a sample report. Vo et al35 recently reviewed factors to consider when choosing a pharmacogenetic test.
Continue to: Because patients and families also have difficulty understanding the reports...
