Evidence map›Paper›PMID 22048466›Full record

Trial reportNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2012

Smoking cessation pharmacogenetics: analysis of varenicline and bupropion in placebo-controlled clinical trials.

David P King, Sara Paciga, Eve Pickering, Neal L Benowitz, Laura J Bierut, David V Conti, Jaakko Kaprio, Caryn Lerman, Peter W Park

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 7 pooled it
–field-weighted citation impact
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

69 citing papers in PubMed, 7 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Antidepressants for smoking cessation.The Cochrane database of systematic reviews · 2020
    Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Antidepressants for smoking cessation.The Cochrane database of systematic reviews · 2014
    Pooled it
  8. Can We Predict Who Will Experience Adverse Events While Using Smoking Cessation Pharmacotherapy? A Secondary Analysis of the EAGLES Clinical Trial.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2025
    Trial
  9. Trial
  10. Trial
  11. Trial
  12. Organic cation transporter variation and response to smoking cessation therapies.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2014
    Trial
  13. Trial
  14. Trial
  15. Treatment for tobacco dependence: effect on brain nicotinic acetylcholine receptor density.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2013
    Trial
  16. Pharmacogenetic smoking cessation intervention in a health care setting: a pilot feasibility study.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2013
    Trial
  17. Trial
  18. Trial
  19. Review
  20. Article

9 more citing papers are in PubMed but not listed here.

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

9 authors.

David P KingPfizer Global Research and Development, Groton, CT 06340, USA. davidpendletonking@gmail.com
Sara Paciga
Eve Pickering
Neal L Benowitz
Laura J Bierut
David V Conti
Jaakko Kaprio
Caryn Lerman
Peter W Park

Funding

Human Genetics of Addiction: A Study of Common and Specific FactorsK02DA021237 · NIDA · WASHINGTON UNIVERSITY · PI BIERUT, LAURA J. · 2007 to 2011
$567k
NIDA NIH HHS K02 DA021237NIDA NIH HHS K02DA021237
6 · The paper itself

Abstract

Despite effective therapies for smoking cessation, most smokers find quitting difficult and most successful quitters relapse. Considerable evidence supports a genetic risk for nicotine dependence; however, less is known about the pharmacogenetics of smoking cessation. In the first pharmacogenetic investigation of the efficacy of varenicline and bupropion, we examined whether genes important in the pharmacodynamics and pharmacokinetics of these drugs and nicotine predict medication efficacy and adverse events. Subjects participated in randomized, double-blind, placebo-controlled smoking cessation clinical trials, comparing varenicline, a nicotinic acetylcholine receptor (nAChR) partial agonist, with bupropion, a norepinephrine/dopamine reuptake inhibitor, and placebo. Primary analysis included 1175 smokers of European ancestry, and 785 single nucleotide polymorphisms from 24 genes, representing 254 linkage disequilibrium (LD) bins (genes included nAChR subunits, additional varenicline-specific genes, and genes involved in nicotine or bupropion metabolism). For varenicline, continuous abstinence (weeks 9-12) was associated with multiple nAChR subunit genes (including CHRNB2, CHRNA5, and CHRNA4) (OR=1.76; 95% CI: 1.23-2.52) (p<0.005); for bupropion, abstinence was associated with CYP2B6 (OR=1.78; 95% CI: 1.27-2.50) (p<0.001). Incidence of nausea was associated with several nAChR subunit genes (OR=0.50; 95% CI: 0.36-0.70) (p<0.0001) and time to relapse after quitting was associated with HTR3B (HR=1.97; 95% CI: 1.45-2.68) (p<0.0001). These data provide evidence for multiple genetic loci contributing to smoking cessation and therapeutic response. Different loci are associated with varenicline vs bupropion response, suggesting that additional research may identify clinically useful markers to guide treatment decisions.

Indexed as

AdultAgedBenzazepinesBupropionDopamine Uptake InhibitorsDouble-Blind MethodFemaleHumansMaleMiddle AgedNicotinic AgonistsPharmacogeneticsQuinoxalinesResearch DesignSmoking CessationTobacco Use DisorderBenzazepinesBupropionDopamine Uptake InhibitorsNicotinic AgonistsQuinoxalinesVarenicline

Identifiers

PMID22048466
PMCPMC3260990

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.