Pharmacogenomics-guided policy in opioid use disorder (OUD) management: An ethnically-diverse case-based approach

Ettienne, Earl; Chapman, Edwin; Maneno, Mary; Ofoegbu, Adaku; Wilson, Bradford; Settles-Reaves, Beverlyn; Clarke, Melissa; Dunston, Georgia; Rosenblatt, Kevin P.

doi:10.1016/j.abrep.2017.05.001

Cited by 15 publications

(16 citation statements)

References 9 publications

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“…Similarly, ultrarapid metabolizers may have lower plasma levels, which may induce opioid cravings and/or withdrawal symptoms. This particular scenario was observed in a case report involving an African American male undergoing OUD management with buprenorphine/naloxone [ 65 ] . During every medical appointment, a urine screening was performed to assess adherence and detect the use of unauthorized or illicit substances.…”

Section: Pharmacogenes: Metabolismmentioning

confidence: 96%

“…Phenotypic classifications have been developed to categorize functional variants of CYP3A4 , as poor (PM), intermediate (IM), extensive (EM), or ultrarapid (UM) metabolizers [ 65 ] . Without dose adjustments, poor metabolizers may have higher than normal plasma levels of buprenorphine, potentially increasing the risk for adverse events.…”

Section: Pharmacogenes: Metabolismmentioning

confidence: 99%

“…Findings from Ettienne et al . [ 65 , 67 ] suggest that dosing patients by CYP3A4 phenotype can improve treatment outcomes. Patients with an increased metabolic rate (i.e., EM and UM) may need higher doses to prevent withdrawal symptoms and maintain opioid abstinence.…”

Section: Pharmacogenes: Metabolismmentioning

confidence: 99%

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A review of the pharmacogenomics of buprenorphine for the treatment of opioid use disorder

Seguí¹,

Melin²,

Santiago³

et al. 2020

jtgg

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As the opioid epidemic continues to grow across the United States, the number of patients requiring treatment for opioid use disorder continues to climb. Although medication-assisted treatment presents a highly effective tool that can help address this epidemic, its use has been limited. Nonetheless, with easier dosing protocols (compared to the more complex dosing required of methadone due to its long and variable half-life) and fewer prescribing limitations (may be prescribed outside the setting of federally approved clinics), the increase in buprenorphine use in the United States has been dramatic in recent years. Despite buprenorphine’s demonstrated efficacy, patient-specific factors can alter the response to the medications, which may lead to treatment failure in some patients. Clinical characteristics (sex, concurrent medications, and mental health comorbidities) as well as social determinants of health (housing status, involvement with the criminal justice system, and socioeconomic status) may impact treatment outcomes. Furthermore, a growing body of data suggests that genetic variations can alter pharmacological effects and influence therapeutic response. This review will cover the available pharmacogenomic data for the use of buprenorphine in the management of opioid use disorders. Pharmacogenomic determinants that affect opioid receptors, the dopaminergic system, metabolism of buprenorphine, and adverse events are discussed. Although much of the existing data comes from observational studies, clinical research is ongoing. Nevertheless, the development of pharmacogenomic-guided strategies has the potential to reduce opioid misuse, improve clinical outcomes, and save healthcare resources.

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Section: Pharmacogenes: Metabolismmentioning

confidence: 96%

Section: Pharmacogenes: Metabolismmentioning

confidence: 99%

See 1 more Smart Citation

A review of the pharmacogenomics of buprenorphine for the treatment of opioid use disorder

Seguí¹,

Melin²,

Santiago³

et al. 2020

jtgg

View full text Add to dashboard Cite

show abstract

“…Based on evidence from, Ettienne et al 123 , 124 utilization of pharmacogenetic testing has paved the way for “precision” dosing of buprenorphine to a highly substance dependent African-American population in Washington DC. Buprenorphine, a partial μ agonist, is considered by many as a safe and effective Opiate Substitution Therapy (OST) for opioid dependence.…”

Section: Overcoming “Genomic Disparity” With Precision Medicinementioning

confidence: 99%

“…This will at least determine more personalized or precision pharmacologically based buprenorphine dosing that will reduce relapse by increasing drug efficacy, thereby reducing diversion and poly-pharmacy adverse effects. Finally, the Ettienne et al 123 data suggest that higher doses of buprenorphine will be needed in some subpopulations to decrease treatment failures; and (1) are unlikely due to widespread patient diversion of medication; (2) should not be limited by the cost of medication; and (3) should be guided by the patients’ genetic/epigenetic variations and needs regarding metabolism of drugs.…”

Section: Overcoming “Genomic Disparity” With Precision Medicinementioning

confidence: 99%

A Review of DNA Risk Alleles to Determine Epigenetic Repair of mRNA Expression to Prove Therapeutic Effectiveness in Reward Deficiency Syndrome (RDS): Embracing “Precision Behavioral Management”

Blum¹,

Steinberg²,

Gondré–Lewis³

et al. 2021

PRBM

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This is a review of research on “Precision Behavioral Management” of substance use disorder (SUD). America is experiencing a high prevalence of substance use disorder, primarily involving legal and illegal opioid use. A 3000% increase in treatment for substance abuse has occurred between 2000 and 2016. Unfortunately, present day treatment of opioid abuse involves providing replacement therapy with powerful opioids to, at best, induce harm reduction, not prophylaxis. These interventions do not enhance gene expression and restore the balance of the brain reward system’s neurotransmitters. We are proposing a generalized approach called “Precision Behavioral Management”. This approach includes 1) using the Genetic Addiction Risk Severity (GARS, a 10 candidate polymorphic gene panel shown to predict ASI-alcohol and drug severity) to assess early pre-disposition to substance use disorder; 2) using a validated reward deficiency syndrome (RDS) questionnaire; 3) utilization of the Comprehensive Analysis of Reported Drugs (CARD™) to assess treatment compliance and abstinence from illicit drugs during treatment, and, importantly; 4) utilization of a “Pro-dopamine regulator (KB220)” (via IV or oral [KB220Z] delivery systems) to optimize gene expression, restore the balance of the Brain Reward Cascade’s neurotransmitter systems and prevent relapse by induction of dopamine homeostasis, and; 5) utilization of targeted DNA polymorphic reward genes to direct mRNA genetic expression profiling during the treatment process. Incorporation of these events can be applied to not only the under-considered African-American RDS community, but all victims of RDS, as a demonstration of a paradigm shift that uniquely provides a novel putative “standard of care” based on DNA guided precision nutrition therapy to induce “dopamine homeostasis” and rebalance neurotransmitters in the Brain Reward Cascade. We are also developing a Reward Deficiency Syndrome Diagnostic Criteria (RDSDC) to assist in potential tertiary treatment.

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Genetic Variants Associated With Opioid Use Disorder

Freiermuth

Kisor

Lambert

et al. 2023

Clin Pharma and Therapeutics

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Genetics are presumed to contribute 30-40% to opioid use disorder (OUD), allowing for the possibility that genetic markers could be used to identify personal risk for developing OUD. We aimed to test the potential association among 180 candidate single nucleotide polymorphisms (SNPs), 120 of which were related to the dopamine reward pathway and 60 related to pharmacokinetics. Participants were randomly recruited in 2020-2021 in a crosssectional genetic association study. Self-reported health history including Diagnostic and Statistical Manual of Mental Disorders (DSM-5) OUD criteria and buccal swabs were collected. A total of 1,301 participants were included in the analyses for this study. Of included participants, 250 met the DSM-5 criteria for ever having OUD. Logistic regression, adjusting for age and biologic sex, was used to characterize the association between each SNP and DSM-5 criteria consistent with OUD. Six SNPs found in four genes were associated with OUD: increased odds with CYP3A5 (rs15524 and rs776746) and DRD3 (rs324029 and rs2654754), and decreased odds with CYP3A4 (rs2740574) and CYP1A2 (rs2069514). Homozygotic CYP3A5 (rs15524 and rs776746) had the highest adjusted odds ratio of 2.812 (95% confidence interval (CI) 1.737, 4.798) and 2.495 (95% CI 1.670, 3.835), respectively. Variants within the dopamine reward and opioid metabolism pathways have significant positive (DRD3 and CYP3A5) and negative (CYP3A4 and CYP1A2) associations with OUD. Identification of these variants provides promising possibilities for genetic prognostic and therapeutic targets for future investigation.

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Pharmacogenomics-guided policy in opioid use disorder (OUD) management: An ethnically-diverse case-based approach

Cited by 15 publications

References 9 publications

A review of the pharmacogenomics of buprenorphine for the treatment of opioid use disorder

A review of the pharmacogenomics of buprenorphine for the treatment of opioid use disorder

A Review of DNA Risk Alleles to Determine Epigenetic Repair of mRNA Expression to Prove Therapeutic Effectiveness in Reward Deficiency Syndrome (RDS): Embracing “Precision Behavioral Management”

Genetic Variants Associated With Opioid Use Disorder

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