Evidence map›Paper›PMID 24489693›Full record

SynthesisPloS one2014

Impact of ABCB1 and CYP2B6 genetic polymorphisms on methadone metabolism, dose and treatment response in patients with opioid addiction: a systematic review and meta-analysis.

Brittany B Dennis, Monica Bawor, Lehana Thabane, Zahra Sohani, Zainab Samaan

Open access · goldAbstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 2 pooled it
11.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 81 citations in OpenAlex.

  1. Pooled it
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  10. Personalized Medicine in Cancer Pain Management.Journal of personalized medicine · 2023
    Review
  11. Influence ofLife (Basel, Switzerland) · 2023
    Article
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  13. Review
  14. Article
  15. Novel associations betweenPharmacogenomics · 2021
    Observational
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Brittany B DennisDepartment of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada ; Biostatistics Unit, Father Sean O'Sullivan Research Centre, St Joseph's Healthcare, Hamilton, Ontario, Canada ; Population Genomics Program, McMaster University, Hamilton, Ontario, Canada.
Monica BaworPopulation Genomics Program, McMaster University, Hamilton, Ontario, Canada ; McMaster Integrative Neuroscience Discovery & Study (MiNDS) Program, McMaster University, Hamilton, Ontario, Canada.
Lehana ThabaneDepartment of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada ; Biostatistics Unit, Father Sean O'Sullivan Research Centre, St Joseph's Healthcare, Hamilton, Ontario, Canada ; Population Genomics Program, McMaster University, Hamilton, Ontario, Canada ; Departments of Pediatrics and Anesthesia, McMaster University, Hamilton, Ontario, Canada ; Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada.
Zahra SohaniDepartment of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada ; Population Genomics Program, McMaster University, Hamilton, Ontario, Canada ; Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada.
Zainab SamaanDepartment of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada ; Population Genomics Program, McMaster University, Hamilton, Ontario, Canada ; McMaster Integrative Neuroscience Discovery & Study (MiNDS) Program, McMaster University, Hamilton, Ontario, Canada ; Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada ; Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Population Health Research Institute · CAHamilton Health Sciences · CASt. Joseph’s Healthcare Hamilton · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

backgroundGenetic variability may influence methadone metabolism, dose requirements, and risk of relapse.

objectivesTo determine whether the CYP2B6*6 or ABCB1 (rs1045642) polymorphisms are associated with variation in methadone response (plasma concentration, dose, or response to treatment).

methodsTwo independent reviewers searched Medline, EMBASE, CINAHL, PsycINFO, and Web of Science databases. We included studies that reported methadone plasma concentration, methadone response, or methadone dose in relation to the CYP2B6*6 or ABCB1 polymorphisms.

resultsWe screened 182 articles and extracted 7 articles for inclusion in the meta-analysis. Considerable agreement was observed between the two independent raters on the title (kappa, 0.82), abstract (kappa, 0.43), and full text screening (kappa, 0.43). Trough (R) methadone plasma concentration was significantly higher in CYP2B6*6 homozygous carriers when compared to non-carriers (standardized mean difference [SMD] = 0.53, 95% confidence interval [CI], 0.05-1.00, p = 0.03) with minimal heterogeneity (I(2) = 0%). Similarly, trough (S) methadone plasma concentration was higher in homozygous carriers of the *6 haplotype when compared to non-carriers, (SMD = 1.44, 95% CI 0.27-2.61, p = 0.02) however significant heterogeneity was observed (I(2) = 69%). Carriers of the CYP2B6*6 haplotype were not found to be significantly different from non-carriers with respect to dose or response to treatment. We found no significant association between the ABCB1 polymorphism and the trough (R), (S) plasma concentrations, methadone dose, or methadone response.

conclusionAlthough the number of studies included and sample size were modest, this is the first meta analysis to show participants homozygous for the CYP2B6*6 genotype have higher trough (R) and (S) methadone plasma concentrations, suggesting that methadone metabolism is significantly slower in *6 homozygous carriers.

Indexed as

Polymorphism, GeneticAnalgesics, OpioidAryl Hydrocarbon HydroxylasesATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1BiotransformationCytochrome P-450 CYP2B6Databases, BibliographicDrug Administration ScheduleDrug MonitoringHaplotypesHomozygoteHumansMethadoneOpioid-Related DisordersABCB1 protein, humanAnalgesics, OpioidAryl Hydrocarbon HydroxylasesATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1CYP2B6 protein, humanCytochrome P-450 CYP2B6Methadone

Identifiers

PMID24489693
PMCPMC3906028
OpenAlexW1993146774

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.