Update on Pharmacogenomic Testing and Use in Behavioral Health Treatment for Pediatric Patients

At the 2020 Virtual Conference on Pediatric Health Care, Kimberly Erlich, MSN, RN, MPH, CPNP, PMHS, presented an update on current understandings of pharmacogenomic testing and its use as a tool in the treatment of behavioral health issues in a pediatric population.

Erlich made clear her definition of pharmacogenomics at the beginning of the lecture. She defined the term as a discipline that uses information about individual genetic makeup to choose the medication and dosage that would be most likely to benefit an individual. In turn, pharmacogenomic testing has the goal of minimizing adverse effects and maximizing the efficacy of a medication based on a patient’s DNA.

Erlich explained that in the field of pharmacogenomics, updates are critical due to the ever-changing nature of the field.

“The field of pharmacogenomics, specifically related to behavioral health, is extremely dynamic and constantly changing. So, we really do need to update knowledge on this information frequently,” Erlich said during her lecture. “If we waited until the following year, the information would likely be different.”

Erlich explained that among the pediatric population, 25% of youth aged 9 to 17 years have a diagnosable psychiatric disorder that causes impairment. Of these individuals, a significant number will take psychoactive medication during their lifetime. Antidepressants, stimulants, and antipsychotics are among those most commonly prescribed.

Since medications such as psychoactives have the potential to interact with multiple metabolic pathways, and genetic variants can contribute to medication response, pharmacogenomic testing can support pediatric clinicians’ efforts to find the appropriate treatment for each individual patient. Specifically, pharmacogenomic testing allows for the consideration of the most up-to-date treatment options available.

“Every step involved with drug metabolism, transport, and action is susceptible to genetic variation. It’s estimated that approximately 42% of individual variability in antidepressant response, for example, can be contributed to common genetic differences. That really underscores the importance of understanding the options for pharmacogenomic testing and what that can lend to your prescribing practices,” Erlich explained in her lecture.

Erlich noted that the labels on more than 40 FDA-approved neuropsychiatric medications currently list gene-drug interactions. This information can be difficult to use effectively without the aid of a tool such as pharmacogenomic testing.

Erlich explained that studies of the utility of pharmacogenomic testing have mainly focused on diagnoses such as major depressive disorder and its application in an adult population. However, studies of bipolar disorder, schizophrenia, attention-deficit hyperactivity disorder (ADHD), and anxiety are also being conducted to assess the applicability of pharmacogenomics in the treatment of patients.

Yet, few drug trials have been conducted assessing efficacy in a pediatric population, according to Erlich.

“Testing could potentially be less applicable for a pediatric population because they might have not had as many drug trials as people who are adults,” Erlich said in an interview with Contemporary Clinic.

However, Erlich noted that she uses testing in her own practice with a pediatric population when applicable. In terms of what is available for clinicians when conducting pharmacogenomic tests, most commercially available tests use a combination of pharmacokinetic and pharmacodynamic gene panels.

During the interview, Erlich explained how pharmacokinetics and pharmacodynamics differ.

She said, “Pharmacokinetics refers to what the body does to the drug and pharmacokinetics, therefore, then includes different concepts such as absorption, distribution, metabolism, and excretion of these medications. In contrast, pharmacodynamics is referred to as what the drug itself does to the body—sort of the body's response to the drug.”

Current commercial gene panels also usually group by condition, such as ADHD, schizophrenia, or depression. Additionally, each company’s algorithm for the relative contribution of each gene is proprietary, which means companies may not be willing to disclose details regarding how the algorithm categorizes the contribution of each gene.

For example, selective serotonin reuptake inhibitors, a commonly prescribed class of drugs, are metabolized by cytochrome P450 pathways. Pharmacogenomic testing has the ability to show metabolizer phenotype in order to help prescribers with target dosing for patients. These metabolizer phenotypes include poor, intermediate, normal, rapid, and ultra-rapid types.

“We know that sertraline is primarily metabolized by CYP2C19 and 2B6, whereas fluoxetine is primarily metabolized by 2D6 and 2C19,” Erlich said during her lecture. “In contrast, celexa, citalopram, and escitalopram are most primarily metabolized by 2C19, whereas duloxetine is primarily metabolized by 2D6. All of these are also metabolized by the pharmacodynamic gene SLC684. So, it really does make sense to understand an individual patient’s metabolizer phenotype when thinking about dosing for that patient.”

When considering pharmacogenomic testing, Erlich noted that there are 2 schools of thought. There is a school of thought that considers testing appropriate for patients before prescribing any medication in order to use it as a guide, and there is a second school of thought that considers testing appropriate as a means to help monitor patient response.

“I, myself, use this testing exclusively after prescription of medications after patients have tried at least a couple of different medications,” Erlich said in the interview. “Most typically, I have no hard and fast rules, but I myself don't use this testing pre-prescription. I understand that some people are using it like that, but that's not how I use it. I use it as a tool in my toolbox, my sort of virtual toolbox, as a medications prescription support tool, sort of a decision support tool, to think about how to help patients through sort of an inadequate response or an unexpected response to medications.”

REFERENCE

Erlich K. Update: Pharmacogenomics and Behavioral Health. Paper presented at: 2020 Virtual Conference on Pediatric Health Care; June 4 – June 5, 2020; Virtual. event.vconferenceonline.com/vconference/odplayer_flash.aspx?id=16563. Accessed July 14, 2020.