What if we advised people to wear seatbelts only on certain days or when driving on specific highways? Clearly, this would result in real and avoidable harm. Unfortunately, something similar has happened to millions of patients who underwent pharmacogenomics (PGx) testing to aid in selecting drugs and doses for treating depression or anxiety, tailored to their unique genetics, without considering the broader implications. In mental health treatment, patients often endure multiple therapies before finding one that works, making tools to reduce trial-and-error prescribing especially crucial. However, PGx testing focused solely on mental health medications overlooks clinically significant information that can sometimes mean the difference between life and death.
CYP2C19 (pronounced “sip 2 C 19”) and CYP2D6 (pronounced “sip 2 D 6”) are the two genes with actionable, high-evidence mental health drug-gene interactions supported by drug or dose adjustment guidance from the Clinical Pharmacogenetics Implementation Consortium (CPIC), the NIH-funded guidelines body, or the FDA. These two genes impact the metabolism of over one-third of commonly prescribed medications and also have actionable, high-evidence drug-gene interactions for medications used in:
- cardiology
- gastroenterology
- infectious disease
- neurology
- pain management
- reproductive and sexual health
- oncology and hematology
- urology
In a study involving over 30,000 patients referred for PGx testing, nearly 60% were taking medications with high-evidence drug-gene interactions across two or more clinical areas. And that was just at the time of testing; the information would continue to be useful in treating many diseases for future prescriptions, but only if both patients and providers were made aware of the broader impact. A study of almost half a million patients in the UK Biobank confirmed that over 99% of patients have PGx variations that indicate the need for a drug or dose change for 1 in 11 prescriptions.
Consider a patient who underwent PGx testing focused on mental health after experiencing intolerable side effects from escitalopram (Lexapro), prescribed for depression. The testing revealed she was a poor metabolizer for CYP2C19, prompting a recommendation for an alternative to escitalopram in the mental health-focused test report, stored as a PDF in her provider’s electronic health record (EHR). Two years later, she suffered a stroke and was prescribed clopidogrel (Plavix) to prevent recurrence, which offers no benefit to CYP2C19 poor metabolizers. This dangerous prescription, increasing her risk of another stroke threefold, could have been avoided if her test results had included information about concerning medications across all clinical areas. Ideally, such results would be discreetly stored in the EHR to enable clinical decision support tools to consider not only drug-drug interactions but also drug-gene interactions for future prescriptions. After all, the FDA has stated for decades that “drug-gene interactions should be considered to be similar in scope to drug-drug interactions” in drug development guidance.
The impact of PGx testing in mental health should not be understated. One study showed that patients with certain CYP2C19 PGx variations were 9% more likely to be suicide victims when taking citalopram (Celexa) or escitalopram (Lexapro), a 34% increase in the suicide rate. PGx testing in mental health has been demonstrated to shorten the time to remission, reduce pharmacy costs, and decrease psychiatric hospital stays. Recent publications validate that comprehensive PGx testing and applying findings across all clinical areas yields even greater benefits. This includes a study of 7,000 patients in multiple care settings in several European countries that yielded a 30% reduction in clinically significant adverse drug events in just 12 weeks. Additionally, studies have shown dramatic reductions in emergency department visits, hospitalizations, readmissions, and healthcare costs with comprehensive pharmacogenomic testing.
In 2016 alone, $528 billion was spent on suboptimal medications in the United States, with an estimated 275,000 American lives lost annually. If the impact seen in Europe is replicated here, that represents the ability to save $158 billion and over 82,000 lives with the use of comprehensive PGx testing and improved clinical decision support. Medicare has covered PGx panel testing since 2020 and thanks to biomarker legislation efforts, Medicaid and commercial insurance are aligning with Medicare coverage in a growing number of states. However, most policies cover a PGx panel only once per patient’s lifetime, highlighting the urgent need for a more comprehensive approach.
The healthcare industry is investing in the seatbelt; now it must realize the benefits of this patient safety measure by advocating for comprehensive panels that apply results across all clinical areas, provide discreet storage of results in the EHR, and support equal prioritization of drug-gene interactions alongside drug-drug interactions. Supporting the Congressional Right Drug Dose Now Act of 2024 can advance these goals on a national level. Now is the time for organizations to select lab partners offering comprehensive testing and to prioritize investments in PGx clinical decision support tools to safeguard patients, healthcare organizations, and financial outcomes.
About Kristine Ashcraft
Kristine Ashcraft has worked in pharmacogenomics since 2000 and was named one of the 25 leading global voices in precision medicine. She is the founder and president of YouScript (an Aranscia Company), an award-winning clinical decision support tool that has integrated PGx-guided personalized prescribing into the clinical workflow for over a decade. Kristine has 25+ years of experience in various C-level, board, customer success and business development roles. She has authored multiple publications on the clinical and economic benefits of pharmacogenomic testing. She serves on numerous PGx advisory groups including the STRIPE Steering Committee, the FDA collaborative community for pharmacogenomics, CPIC, and the American Cancer Society Cancer Action Network PGx task force.