Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medications for anxiety and depression in children and adolescents—but finding the right drug and dose often involves weeks or months of trial and error.
Pharmacogenomic testing, which uses a patient’s genetic information to better understand how they metabolize certain medications, has been proposed as a way to help inform behavioral health prescribing decisions. While formal guidelines exist for adults, there is limited evidence describing how those recommendations may apply to pediatric patients.
Now, researchers in the Center for Personalized Medicine at Children’s Hospital Los Angeles are collaborating on a multi‑site observational study to examine how pharmacogenomic test results are used when prescribing SSRIs for children and adolescents, and to better understand how pediatric patients respond over time and their side effect profile.
The study is in collaboration with the Sanford Children’s Genomic Medicine Consortium, a national group of pediatric academic medical centers, including CHLA, that are working to advance the implementation of genomic and pharmacogenomic practices across pediatrics.
Jenny Nguyen, PharmD, and Matthew Deardorff, MD, PhD, spearhead CHLA’s study site.
While the group’s current efforts will focus on gathering data to better understand how pediatric patients respond to medications based on their genetics—and how providers use the information—the ultimate goal will be to establish stronger recommendations for pediatric patients.
The idea is that those recommendations could better support medication selection and dosing for pediatric patients, with the aim of minimizing trial and error. “We want to optimize the experience as much as we can for pediatric patients,” says Dr. Nguyen.
In the body, medications are broken down by a variety of drug-metabolizing enzymes in the liver; SSRIs are metabolized by the CYP450 enzyme family.
Each individual’s drug metabolism is hard-wired: Genetic information within their DNA can inform how effectively CYP450 enzymes break down medications and affect drug concentrations in the body.
Pharmacogenomic testing can be used to understand people's metabolizer types based on the genetic variants in their DNA. These tests look at a set of well validated pharmacogenomic-related genes, rather than sequencing the whole genome.
For example, a person whose enzyme is not functional is considered a “slow metabolizer” for medications broken down by that enzyme. This causes higher drug levels in their blood, often leading to greater risk for side effects
People with a “slow metabolizer” enzyme may need a much lower dose than the recommended starting dose to benefit from that medication, or to switch to a medication that’s broken down by a different enzyme.
“Behavioral health providers and families have long expressed their frustration around the trial-and-error method of prescribing,” Dr. Nguyen explains. Unlike medications many other medications, SSRIs can take several weeks to reach full effectiveness, which adds to the time providers need to assess the patient’s response to the new medication.
To better understand how pharmacogenomic results are used in this context, researchers are enrolling patients aged 8 to 17 with anxiety and/or depression who anticipate starting an SSRI.
Study participants provide a saliva sample for pharmacogenomic analysis. Once results are ready, the team shares its recommendations based on the current adult clinical guidelines to the treating provider.
For six months, patients complete regular surveys to measure their depression and anxiety symptoms, as well as side effects.
“We’re hoping to measure a couple of factors,” Dr. Nguyen explains. “We want to see if the providers accept the recommendations, as well as how the patient tolerates their medication afterward and whether their symptoms improve with time.”
Ultimately, the team plans to add alerts directly into the electronic health record (EHR) to help guide clinical decision-making around SSRI dosage and medication type based on a patient’s pharmacogenomic results. “We all know providers are busy,” Dr. Nguyen says. “That's why we're building alerts to advise providers of patient information to empower them to make the best decision in an efficient way at the time of prescribing.”
The team has already implemented these alerts for a specific clinical decision-making scenario in Oncology—to glowing reviews.
“Since we’ve been doing more whole genome sequencing for kids with neurodevelopmental disorders and other indications, we’ve sometimes been able to pull pharmacogenomic information from that existing data for this additional use.”
Dr. Matthew Deardorff, MD, PhD
“The goal will be that behavioral health providers don’t have to wait for the results of another genomic test to make a prescribing decision for their patient, which is a major advance,” Dr. Deardorff explains.
One potential barrier, however, is the cost of the test. Pharmacogenomic testing typically costs a few hundred dollars and insurance coverage is variable.
Dr. Deardorff notes that this study is one example of CHLA’s commitment to implementing genomics in pediatric care.
“Support from hospital leadership has empowered us to be on the leading edge of pediatric pharmacogenomics,” he says. “Our goal is to leverage opportunities where existing genomic data could be applied across other areas of care for personalized treatment to create additional value both for patients and for CHLA.”
(Newswise/HG)
