Pharmacogenomic Testing in Pain Management and Behavioral Health: A Pharmacist Perspective

Pain, in its many forms (e.g., nociceptive, neuropathic, inflammatory, etc.), affects upwards of 100 million people in the United States resulting in costs reaching $600 billion per year.1 Treatment of pain symptoms through the inappropriate prescribing and use of opioids has fueled an opioid abuse crisis in the United States that continues to be a major public health issue. Over 2 million people across the nation may be suffering from opioid abuse/addiction resulting in annual medical costs of more than $29 billion.2 The opioid epidemic requires urgent action. Successfully addressing the crisis will require multiple approaches. One such promising intervention is the use of pharmacogenomics (PGx) to guide the pharmacotherapy of pain.

Overview of Pharmacogenomics

PGx testing is a diagnostic tool that can be useful in predicting a patient’s response to a particular drug. PGx analyzes specific genes that impact drug response via pharmacodynamic and/or pharmacokinetic pathways. Pharmacodynamic pathways are the mechanisms by which the drug acts on the body to produce physiological responses. Pharmacokinetic pathways are the mechanisms by which the body acts on the drug – absorption, distribution, metabolism, and excretion.

In PGx testing, a patient’s genotype (i.e., genetic/hereditary information) is analyzed for variations in genes which affect drug response. Variations in particular genes are referred to as alleles. PGx testing identifies a patient’s genotype information in regards to specific alleles, and results in a PGx report describes the patient’s phenotype (i.e., the observable expression of their genes). For example, CYP2D6 is one of the enzymes that metabolizes many drugs including opioids used in pain management such as codeine, tramadol, hydrocodone, and oxymorphone. The gene that codes for CYP2D6 can vary between individuals. The various genotypes of the gene, CYP2D6, a are comprised of combinations of two alleles where each allele may have increased enzyme function, normal enzyme function, or reduced enzyme function. The genotypes, in turn, produce phenotypes described as ultrarapid metabolizers (UM), extensive metabolizers (EM), intermediate metabolizers (IM), or poor metabolizers (PM). The patient’s phenotype can then be used to guide pharmacotherapy decisions (Table 1 – Examples of CYP2D6 Genotypes with Corresponding Codeine Metabolizing Phenotypes and Potential Pharmacotherapy Implications (adapted from 3). # The asterisk followed by a number or number/letter combination refers to a specific allele of the gene. ).3

Role of Pharmacy

Pharmacists hold or maintain various roles and responsibilities in the treatment of patients with chronic pain. With the high abuse potential of opioids, pharmacists are well equipped to advise on alternative approaches to pain management. PGx is increasingly becoming an important tool for tailoring pharmacotherapy to patient needs. Pharmacies that offer PGx testing typically provide related PGx clinical services, such as, data interpretation, pharmacotherapy recommendations, patient monitoring, etc. Two of the major clinical areas in which Allure Specialty Pharmacy uses PGx testing are pain management and behavioral health.

Role of PGx in Pain Management

A major gene of interest in opioid use is the gene that codes for the CYP2D6 enzyme. In pain management, those drugs of interest include tramadol, codeine, hydrocodone, and oxymorphone. CYP2D6 is responsible for metabolizing codeine to morphine, tramadol to O-desmethyltramadol (a metabolite with 200-fold greater potency), oxycodone to oxymorphone, and hydrocodone to hydromorphone.3 As described above and in Table 1, the different genotypes of CYP2D6 produce a range of metabolizing phenotypes: UM, EM, IM, or PM. Codeine and, to some extent, other opioids (e.g., tramadol, hydrocodone, and oxycodone) are not recommended for use in the UM and PM phenotypes, which may account for up to 12% of the population. In the UM phenotype, increased codeine metabolism results in a greater risk of toxicity due to the higher levels of morphine generated. In the PM phenotype, low to no codeine metabolism results in a lack of efficacy.3 Even in the IM phenotype, which accounts for up to 11% of the population, patients may need to use alternative analgesics. This suggests that knowing a patient’s CYP2D6 genotype and corresponding phenotype could be critically important information when considering pharmacotherapy for pain management. A recent paper demonstrated the practical utility of PGx in guiding opioid therapy. Smith, et al, determined that using PGx information to guide pain management resulted in greater improvements in pain control for IM and PM phenotype patients who were originally on codeine or tramadol.4 At Allure Specialty Pharmacy, we offer PGx testing and have used the results to guide opioid dosing.5

Role of PGx in Behavioral Health: Antidepressants

PGx testing can also be helpful in managing patients with depression. In fact, the FDA requires labeling information, primarily with respect to CYP2D6 and CYP2C19, for a number of psychiatric drugs6. The labeling requirements can focus on potential drug interactions or adverse events. For example, CYP2C19 poor metabolizer taking citalopram has an increased risk of QT prolongation.7 The PGx testing offered by Allure Specialty Pharmacy includes analysis of CYP2C19 and other enzymes related to antidepressant metabolism. We have successfully used the data to guide antidepressant pharmacotherapy.

Services Offered – PGx Testing Specialty Services for TRD

At Allure Specialty Pharmacy, we offer PGx testing to aid in pharmacotherapy decisions, particularly for pain management and behavioral health conditions. Allure Specialty Pharmacy has an educational and clinical partnership with Admera Health to provide PGx testing and to offer a pharmacist fellowship program in pharmacogenomics. In comparison to other companies that offer PGx for psychiatric conditions, Admera Health offers an expanded gene-testing panel that covers over 300 drugs used in conditions for psychiatry, pain management, neurology, cardiology, and oncology (Table 2: Comparison of PGx Testing). The pharmacists at Allure Specialty Pharmacy are trained to provide PGx counseling to treat patients holistically.

Allure Specialty Pharmacy has incorporated PGx in treating patients with treatment resistant depression (TRD). Patients with TRD have not responded to two or more antidepressant drugs. Incidence rates for TRD can vary substantially with recent estimates ranging from 13.08 per 100,000 to 120.20 per 100,000.8 TRD places undue economic and quality of life burden on patients. Olfson et al found that Medicaid patients with TRD have significantly higher annual health care costs compared to patients whose depression responds to treatment ($18,982 for TRD patients v $11,642 for non-TRD patients).9 Spravato™ (esketamine, Janssen Pharmaceuticals) is a promising new therapy for TRD that is administered nasally under supervision of a healthcare professional in a certified treatment center.10,11 Allure Specialty Pharmacy is an authorized distributor of Spravato™ and provides clinical consultation to the All Med Medical Group, a certified treatment center in the Bronx, for patients undergoing Spravato™ treatment.

Pharmacists can be valuable partners in the care and treatment of patients with pain or behavioral health conditions. Pharmacists can apply their expertise with current technology (e.g., PGx testing) and/or specialty drugs (e.g., Spravato™) to optimize pharmacotherapy and improve health outcomes in patients.

Allure Specialty Pharmacy is committed to improving the quality of patient lives through innovative customized pharmaceutical treatments and superior customer service. Please visit for more information. Dr. Ronnie Moore, Dr. Vick Youmbi, and Mr. Angelo O’Neill can be reached at

Acknowledgements: The authors thank Thomas J. Cook, PhD, RPh, for medical writing and editing assistance.

Ronnie Moore, PharmD, is Director of Pharmacogenomics Program; Ludovick Youmbi, PharmD, is Pharmacist-in-Charge; and Angelo O’Neill, MSW; is Director of Business Development, at Allure Specialty Pharmacy.

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