Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate

Crist, Richard C.; Li, James; Doyle, Glenn A.; Gilbert, A. Ph. W.; Dechairo, Bryan; Berrettini, Wade H.

doi:10.1080/00952990.2017.1420795

Cited by 27 publications

(31 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Genetic variation impacting pharmacokinetics and pharmacodynamics for buprenorphine will likely be important for treatment outcomes, although there is no published research identifying polymorphisms associated with buprenorphine dose or serum concentration [36]. There have been some studies of the pharmacogenetics of buprenorphine efficacy, implicating OPRD1, SLC6A3, SLC6A4, and COMT; however, far more research must be done in larger sample sizes for further discovery [23,24,37,38]. There is also the unexplored area of the pharmacogenomics of adverse reactions to buprenorphine [36].…”

Section: Improving Successful Opioid Substitution Therapymentioning

confidence: 99%

The importance of buprenorphine research in the opioid crisis

Pendergrass

Crist

Jones³

et al. 2019

Mol Psychiatry

Self Cite

View full text Add to dashboard Cite

With the urgency to treat patients more effectively for opioid use disorder in the midst of the opioid epidemic, a key area for precision medicine is to improve individualized medication-assisted treatment for opioid use disorder. The expansion of medication-assisted treatment is a key to reducing illicit opioid use, preventing opioid overdose deaths, and reducing the comorbidities and societal impacts of opioid use disorder. The most common medication for opioid use disorder will soon be buprenorphine. Research to date shows the successful impact of buprenorphine treatment, including the pharmacogenomics of buprenorphine response and treatment efficacy. Buprenorphine is also a promising treatment for depression and anxiety, and neonatal opioid withdrawal syndrome (NOWS). However, the rates of success with medication-assisted treatment for opioid use disorder, particularly at the beginning of treatment, still show many individuals relapsing to illicit opioid use. With the scope of the opioid crisis, there is an urgent need for expansion of buprenorphine treatment research to provide critical information for improving outcomes of opioid use disorder. Implementing the best strategies for opioid use disorder treatment is of dire urgency and will save lives.

show abstract

Section: Improving Successful Opioid Substitution Therapymentioning

confidence: 99%

The importance of buprenorphine research in the opioid crisis

Pendergrass

Crist

Jones³

et al. 2019

Mol Psychiatry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Data from the randomized clinical trial Starting Treatment With Agonist Replacement Therapies (START), has been used to perform several pharmacogenomic analyses of OUD treatment outcomes [ 44 ] . Genotypic information was available for 60% ( n = 764/1,267) of the patient population, which was primarily composed of European Americans ( n = 599), with few African Americans ( n = 79) and other ethnicities ( n = 96) [ 29 ] . Over a 24-week period, participants treated with methadone ( n = 364, 66% male) or buprenorphine/naloxone ( n = 410, 71% males) were submitted to weekly urine drug screens.…”

Section: Pharmacogenes: Opioid Receptorsmentioning

confidence: 99%

“…Social determinants of health such as housing status, involvement with the criminal justice system, and socioeconomic status may also impact treatment outcomes [ 4 , 27 , 28 ] . Lastly, genetic variations can alter pharmacological effects and influence therapeutic response [ 29 – 31 ] . Pharmacogenomic studies evaluate genotypic-phenotypic associations and their potential impact on pharmacokinetic (e.g., metabolic function, dosing requirements) and pharmacodynamic (e.g., receptor activity, treatment efficacy) parameters.…”

Section: Introductionmentioning

confidence: 99%

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

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.

show abstract

“…Various in vitro and in vivo studies have shown the involvement of different cytochrome P450 (CYP) enzymes, particularly CYP2B6, in methadone metabolism, associated with the CYP2B6‐G516T genetic polymorphism and, to a lesser extent, CYP2D6, CYP3A4, and the gene encoding ATP Binding Cassette Subfamily B Member 1 ( ABCB1 , the permeability glycoprotein [P‐gp] transporter) . The influence of genetic polymorphisms on pharmacodynamic properties and treatment response has been less explored, and is not supported by much evidence . Moreover, the impact of genetic variations could be compounded by interactions between many environmental and individual factors …”

Section: Introductionmentioning

confidence: 99%

“…The results of pharmacogenomics studies in the field of methadone maintenance treatment (MMT) have been described in terms of dose magnitude, plasma or dose‐adjusted plasma concentrations, responders vs nonresponders, and adverse effects. In these previous studies, the response to treatment was defined by the dose requirement, continued opioid use or composite criteria, including the nonconsumption of heroin and cocaine, the absence of complaints of withdrawal symptoms, the steady and regular attendance at the therapy programme, dropout rate and mean dose …”

Section: Introductionmentioning

confidence: 99%

Relevance of CYP2B6 and CYP2D6 genotypes to methadone pharmacokinetics and response in the OPAL study

Victorri-Vigneau

Verstuyft

Bouquié

et al. 2019

Brit J Clinical Pharma

View full text Add to dashboard Cite

Aims: Our study aimed to evaluate the impacts of the cytochrome P450 (CYP) 2B6-G516T and CYP2D6 genetic polymorphisms on pharmacokinetic and clinical parameters in patients receiving methadone maintenance treatment. Methods: Opioid PhArmacoLogy (OPAL) was a clinical survey of the sociodemographic characteristics, history and consequences of pathology associated with methadone maintenance treatment response and current addictive comorbidities. A subgroup of 72 methadone patients was genotyped. Results: When comparing the three CYP2B6 genotype groups, the methadone (R)and (S)-methadone enantiomer concentrations/doses (concentrations relative to doses) were different (P = .029, P = .0019). The CYP2D6 phenotypes did not seem to be relevant with regard to methadone levels. On multivariate analysis, neither the CYP2B6 genotype nor the CYP2D6 phenotype explained the (R)-methadone concentration/dose values (P = .92; P = .86); the (S)-methadone concentration/dose values (P = .052; P = .95 [although there was a difference between the TT group and GT and GG groups {P = .019}]); or opiate cessation (P = .12; P = .90).Conclusion: The genotyping of CYP2B6 G516T could be an interesting tool to explore methadone intervariability.

show abstract

Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate

Cited by 27 publications

References 45 publications

The importance of buprenorphine research in the opioid crisis

The importance of buprenorphine research in the opioid crisis

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

Relevance of CYP2B6 and CYP2D6 genotypes to methadone pharmacokinetics and response in the OPAL study

Contact Info

Product

Resources

About