BHIPP Bulletin

Volume 10, Issue 2

August 2024

This month's BHIPP Bulletin is a contribution from the BHIPP team and Yen Dang, PharmD, Associate Professor of Pharmacy Practice and Administration at the University of Maryland Eastern Shore.

Pharmacogenomic (PGx) testing has emerged as a tool in psychiatry to enhance medication selection and dosing. Traditional methods often involve a trial-and-error approach, which can result in prolonged periods of inadequate symptom management and adverse drug reactions. In theory, PGx testing offers a strategy to predict medication responses based on genetic variations, aiming to individualize treatment and improve outcomes. However, PGx testing in child and adolescent psychiatry currently has limited clinical benefit. While it may offer some insights, the evidence supporting its utility in guiding treatment decisions remains insufficient. Clinicians should rely primarily on comprehensive clinical evaluations and evidence-based practices.

Mechanisms of Pharmacogenomics:

PGx testing focuses on genetic variants that affect drug metabolism, particularly those involving cytochrome P450 enzymes (CYP2D6, CYP2C19). These enzymes play a critical role in the metabolism of many psychotropic medications, including antidepressants and antipsychotics. By identifying genetic variants that influence enzyme activity, PGx testing can help guide the selection and dosing of medications to minimize adverse effects and potentially enhance therapeutic efficacy.

Types of Pharmacogenomic Tests:

Single-gene tests analyze specific genes that are known to influence the metabolism of psychiatric medications such as CYP2D6, CYP2C19, CYP2C9, and HLA alleles. Multi-gene panels are more common and test for multiple genes simultaneously, providing a comprehensive overview of genetic factors that may impact the pharmacokinetics and pharmacodynamics of various psychiatric drugs. Pharmacokinetic panels focus on genes involved in the metabolism of drugs (e.g. CYP450 enzymes) and in theory can help predict how a patient metabolizes specific medications. Pharmacodynamic panels analyze genes that affect drug targets, such as neurotransmitter receptors and transporters.

Evidence and Guidelines:

The majority of PGx studies have been done on adults with results extrapolated to adolescents/children, so there will be more variability in results. Studies using PGx as a blanket tool for all patients initially to aid in medication selection and side effects are ongoing. For now, 20% of PGx tests likely with clinical utility have an associated cost-utility data. Most studies use PGx information after a patient has failed therapy (incomplete responses) or if they are experiencing side effects.

The American Academy of Child and Adolescent Psychiatry recommends that: 1) clinicians avoid using PGx testing to select psychotropic medication in children and adolescents, and 2) future high quality prospective studies to assess the clinical significance of PGx testing in children and adolescents are needed.¹ Of note, a recent study randomizing adolescents (ages 13-18) with Major Depressive Disorder to treatment guided by PGx testing versus treatment as usual found no difference between arms in symptom improvement, side effects, or satisfaction.² However, a post-hoc analysis found that patients taking medications associated with high likelihood of gene-drug interactions were more likely to report side effects compared to those taking medications with low or medium risk of gene-drug interactions. The study authors suggested that PGx testing may have utility in guiding medication decisions to minimize side effect burden.³

Applications in Clinical Practice:

In theory, PGx testing can impact clinical practice by reducing the trial-and-error period associated with psychotropic medications. For example, patients with specific CYP2D6 or CYP2C19 variants may require dose adjustments or alternative medications to avoid adverse effects and achieve optimal therapeutic responses. The interpretations are as follows:

CYP2D6 or CYP2C19 Testing

• Poor Metabolizers (PM): Patients with little or no CYP2D6 or CYP2C19 activity. These patients have higher blood levels of the drug and are at increased risk of side effects. Dose reductions or alternative medications are recommended.
• Intermediate Metabolizers (IM): Patients with reduced CYP2D6 or CYP2C19 activity. These patients may need dose adjustments to avoid side effects.
• Normal Metabolizers (NM): Patients with typical CYP2D6 or CYP2C19 activity. Standard dosing is usually appropriate.
• Ultrarapid Metabolizers (UM): Patients with increased CYP2D6 or CYP2C19 activity. These patients may require higher doses to achieve therapeutic effects due to faster metabolism.

HLA Testing

• Positive HLA-B*15:02 Result: Positive status is associated with a high risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Alternative medications should be considered for patients of Asian descent, where this allele is more common.
• Positive HLA-A*31:01 Result: Increased risk of hypersensitivity reactions, including SJS/TEN and DRESS.
• Negative Results: The patient does not carry the high-risk alleles for severe adverse reactions to the tested medications so standard prescribing practices can be followed.

PGx results will explain pharmacokinetic information, which is the effect of the body on the drug (e.g., CYP450). However, it does not cover pharmacodynamic data, which is the effect of the drug on the body (e.g., serotonin reuptake transporter proteins). There are other parts of the treatment puzzle including but not limited to patient comorbidities, age, organ function, current medications, and diet that are not included in the test results which should be considered in the treatment selection process.

Barriers:

The implementation of PGx testing in psychiatry faces several challenges. These include variability in test interpretation, limited access to testing, and the need for clinician education on PGx applications. The costs of the PGx tests range from $300 - $1500 but vary based on test panels and insurance coverage (some testing is not covered by insurance).

Conclusion:

PGx testing can be part of the treatment puzzle and can be used as a decision support tool; it does not replace clinical judgement and evidence-based guidelines. If you have PGx results, first think of medication options based on clinical guidelines and patient-specific factors and rank the order of the medications (e.g., first-line, second-line). Then, look at the PGx results to see if there are any medications on the list that you ranked in the first-line category that can be used for medication treatment. These results can be a probability shifter and narrow the scope of medication selection. Please call BHIPP if you have PGx results that need interpretation as what has been mentioned above is not inclusive of all situations that could come up.

Resources for Providers When Interpreting Tests:

1. Clinical Pharmacogenetics Implementation Consortium (CPIC): https://cpicpgx.org/

2. Pharmacogenomics Knowledgebase (PharmGKB): https://www.pharmgkb.org/

3. FDA Table of Pharmacogenomic Biomarkers in Drug Labeling: https://www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling

As always, if you have questions about the behavioral health needs of your patients, we encourage you to call the BHIPP consultation line at 

855-MD-BHIPP (632-4477), open 9am-5pm Monday-Friday, for resource/referral networking or consultation support.

We will keep you informed about all our services and training events through our website (www.mdbhipp.org) and monthly e-newsletters. Additionally, BHIPP is on LinkedIn, X, and Facebook. We invite you to follow us there to stay up-to-date on upcoming training events, pediatric mental health research, and resources for providers, families and children.

BHIPP Announcements

Register for the next BHIPP Webinar!

Register for an upcoming BHIPP Webinar on September 12th at 12:00pm! BHIPP Webinars are a series of interactive, web-based learning sessions that are a virtual space for pediatric primary care, emergency medicine, and behavioral health providers to connect, learn and share about strategies, practices and resources to promote mental health and resilience among children and families as well as providers. Free CME and CEU credit is available for participation.

Join BHIPP and NAPNAP MD: Chesapeake for an In-Person Training Event!

Maryland Behavioral Health Integration in Pediatric Primary Care (BHIPP) is pleased to partner with the National Association of Pediatric Nurse Practitioners (NAPNAP), Maryland Chesapeake Chapter to offer an in-person training event in Ocean City, MD. 

This conference will feature a presentation about BHIPP and the services we offer to primary care providers in Maryland, a presentation by Paige Seegan, PhD on Non-pharmacological Approaches to Managing Disruptive Behavior in Young Children, and a presentation by Erika Chiappini, PhD on Surveillance and Screening in the Primary Care Setting.

Date: Saturday, September 14th, 2024

Time: 8:30am-12:30pm

Location: Holiday Inn Ocean City, 6600 Coastal Highway, Ocean City, MD 21842

Free CME/CEU credits will be available for participation.

For more information, visit https://community.napnap.org/newmarylandchapter/maryland-bhipp/maryland-bhipp

Register for the upcoming BHIPP & MACS training!

Register for a BHIPP and Maryland Addiction Consultation Service (MACS) training on September 19th from 12:00-1:00pm focusing on Approaches to Treatment of Opioid Use Disorder (OUD) in the Pediatric Population. This training will be presented by MACS consultant, Marc Fishman, MD. Free CME and CEU credit is available for participation.

Announcing the next BHIPP Webinar!

Register for an upcoming BHIPP Webinar on October 29th at 12:00pm! BHIPP Webinars are a series of interactive, web-based learning sessions that are a virtual space for pediatric primary care, emergency medicine, and behavioral health providers to connect, learn and share about strategies, practices and resources to promote mental health and resilience among children and families as well as providers. Free CME and CEU credit is available for participation.

Complete this survey on Tourette Syndrome to receive a

$50 e-gift card!

The Tourette Syndrome Center of Excellence at Johns Hopkins Medicine and Kennedy Krieger Institute in collaboration with Maryland Behavioral Health Integration in Pediatric Primary Care (BHIPP) is conducting a brief survey to better understand pediatric primary care providers (PCPs) knowledge about Tourette Syndrome and related tic disorders (collectively TS) and to identify current practices of PCPs when encountering children and adolescents with TS. We will use this information to inform development of clinical tools to assist PCPs when encountering youth with TS in their everyday practice. PCPs will receive a $50 e-gift card upon completion of this 20-minute survey.