Are higher doses of nicotine replacement more effective for smoking cessation?

Hughes, John R.; Lesmes, George R.; Hatsukami, Dorothy K.; Richmond, Robyn; Lichtenstein, Edward; Jorenby, Douglas E.; Broughton, Joseph O.; Fortmann, Stephen P.; Leischow, Scott J.; McKenna, James; Rennard, Stephen I.; Wadland, William C.; Heatley, Scott A.

doi:10.1080/14622299050011281

Cited by 135 publications

(71 citation statements)

References 35 publications

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“…Further, as another indication that the 42 -mg dose of transdermal nicotine was well-tolerated, there was no difference in the rate of participant withdrawal from the study and no difference in the rate of participant adherence with patch use recommendations across the treatment arms. These results converge with the general literature on the use of higher doses of transdermal nicotine (see Dale et al, 1995 ;Fredrickson et al, 1995 ;Hatsukami et al, 2007 ;Hughes et al, 1999 ).…”

Section: Nicotine and Tobacco Researchsupporting

confidence: 89%

High Dose Transdermal Nicotine for Fast Metabolizers of Nicotine: A Proof of Concept Placebo-Controlled Trial

Schnoll

Wileyto

Leone

et al. 2012

Nicotine & Tobacco Research

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Previous clinical trials have examined doses of transdermal nicotine substantially higher than the standard 21 -mg dose. Although these trials have demonstrated that higher doses of transdermal nicotine are safe, compared with the standard dose of transdermal nicotine (21 mg), higher doses (42 mg) do not generally result in higher smoking cessation rates ( Fiore et al., 2008 ;Stead et al., 2008 ). However, no clinical trial of high dose transdermal nicotine has targeted smokers who are fast metabolizers of nicotine. As a next step toward improving response rates to transdermal nicotine by considering smoker ' s interindividual variability in nicotine metabolism, we conducted this proof of concept study to evaluate the differential effi cacy of Abstract Introduction: Smokers with a faster rate of nicotine metabolism, estimated using the ratio of 3 Ј -hydroxycotinine (3-HC) to cotinine, have lower plasma nicotine levels and are more likely to relapse with 21 mg nicotine patch therapy, than smokers with slower rates of nicotine metabolism. Thus, faster metabolizers of nicotine may require a higher nicotine patch dose to achieve cessation.Methods: This proof of concept randomized placebocontrolled trial evaluated the effi cacy and safety of 8 weeks of 42 mg transdermal nicotine versus 21 mg, among 87 fast metabolizers of nicotine (3-HC/cotinine ≥ 0.18).Results: After 1 week of treatment, an intent-to-treat (ITT) analysis showed that participants treated with 42 mg nicotine had signifi cantly higher expired-air carbon monoxide (CO)-confi rmed 24-hr abstinence (75% vs. 58.1%; OR = 3.21; 95% CI : 1.12 -9.24, p = .03) but not 7-day abstinence (50% vs. 34.9%; OR = 2.02; 95% CI : 0.82 -4.94, p = .13). After 8 weeks of treatment, ITT analysis showed that participants treated with 42 mg nicotine had marginally higher rates of CO-confi rmed 24-hr abstinence (45.5% vs. 30.2%; OR = 2.32; 95% CI : 0.92 -5.92, p = .08) but not 7-day abstinence (29.6% vs. 23.3%; OR = 1.52, 95% CI : 0.57 -4.07, p = .41). Percent nicotine and cotinine replacement were signifi cantly greater for 42 mg nicotine versus 21 mg ( p < .005). There were no signifi cant differences between treatment arms in the frequency of severe side effects and serious adverse events or blood pressure during treatment ( p > .10). Conclusions:Further examination of the effi cacy of 42 mg nicotine patch therapy for fast metabolizers of nicotine is warranted.

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Section: Nicotine and Tobacco Researchsupporting

confidence: 89%

High Dose Transdermal Nicotine for Fast Metabolizers of Nicotine: A Proof of Concept Placebo-Controlled Trial

Schnoll

Wileyto

Leone

et al. 2012

Nicotine & Tobacco Research

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“…Although the point estimate favoured nicotine inhalers over placebo (odds ratio 2.17), these results were not conclusive because the 95% credible interval included unity (95% CrI 0. 59 15/44 9/43 Fiore et al 57 13/56 9/56 Glavas et al 58 10/57 4/55 Fiore et al 57 17/60 5/60 Paoletti et al 56 16/78 2/80 Westman et al 55 22/100 12/99 Abelin et al 53,54 21/103 15/104 Killen et al 52 15/109 11/108 Killen et al 52 28/113 10/107 Sachs et al 51 19/150 10/75 Kornitzer et al 50 33/120 17/120 Hurt et al 49 16/119 6/160 Hughes et al 46 16/154 3/144 Tonnesen et al 48 29/154 14/153 Richmond et al 47 4/160 6/160 Hughes et al 46 12/160 6/160 Hughes et al 46 27/184 16/185 Daughton et al 45 24/244 9/160 Jorenby et al 13 analysis, we found that all 7 pharmacotherapies were more efficacious than placebo ( Figure 6). …”

Section: Efficacy Of Smoking Cessation Pharmacotherapiesmentioning

confidence: 99%

Pharmacotherapies for smoking cessation: a meta-analysis of randomized controlled trials

Eisenberg¹,

Filion²,

Yavin³

et al. 2008

Canadian Medical Association Journal

271

181

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Health Canada recently approved the use of varenicline as a pharmacotherapy for smoking cessation. Varenicline works by stimulating dopamine, which results in reduced cravings and withdrawal symptoms. The drug also blocks nicotine receptors, which prevents the dopamine release associated with nicotine consumption. 1The drug has been examined in a few small randomized controlled trials.2-5 Despite limited evidence concerning its use, varenicline is viewed by many clinicians and researchers as the most effective smoking cessation aid. Consequently, there is a need for a systematic assessment of the effectiveness of varenicline relative to placebo. Furthermore, there is a need to compare the efficacy of varenicline with that of existing pharmacotherapies, including sustained-release bupropion and approved nicotine replacement therapies.We undertook a meta-analysis of placebo-controlled randomized controlled trials of the efficacy of 7 pharmacotherapies approved for smoking cessation. We had 3 objectives: to summarize the efficacy of each pharmacotherapy; to undertake a direct comparison of varenicline and bupropion by analyzing trials that contained both varenicline and bupropion treatment arms; and to undertake an indirect comparison of all 7 pharmacotherapies using the results of the individual trials.

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“…The relapse rate in the first month of unaided abstinence is about 80 percent, and only 3-5 percent of untreated patients remain abstinent after 6 months (Polosa et al 2011;Gualano et al 2014). Furthermore, only about 20-25 percent of smokers will achieve abstinence with six months or more of goldstandard treatment (Hurt et al 1997;Hughes et al 1999;Jorenby et al 1999;Killen et al 1999;Holmes et al 2004Holmes et al , 2004. These observations suggest that smoking leads to persistent modifications in the brain that contribute to high relapse rates (DeBry & Tiffany 2008), an area of research which remains largely unexplored.…”

Section: Introductionmentioning

confidence: 90%

Cigarette smoking leads to persistent and dose-dependent alterations of brain activity and connectivity in anterior insula and anterior cingulate

et al. 2015

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Although many smokers try to quit smoking, only about 20-25 percent will achieve abstinence despite 6 months or more of gold-standard treatment. This low success rate suggests long-term changes in the brain related to smoking, which remain poorly understood. We compared ex-smokers to both active smokers and non-smokers using functional magnetic resonance imaging (fMRI) to explore persistent modifications in brain activity and network organization. This prospective and consecutive study includes 18 non-smokers (29.5 ± 6.7 years of age, 11 women), 14 smokers (≥10 cigarettes a day >2 years of smoking, 29.3 ± 6.0 years of age, 10 women) and 14 ex-smokers (>1 year of quitting 30.5 ± 5.7 years of age, 10 women). Participants underwent a block-design fMRI study contrasting smoking cue with control (neutral cue) videos. Data analyses included task-related general linear model, seed-based functional connectivity, voxel-based morphometry (VBM) of gray matter and tract-based spatial statistics (TBSS) of white matter. Smoking cue videos versus control videos activated the right anterior insula in ex-smokers compared with smokers, an effect correlating with cumulative nicotine intake (pack-years). Moreover, ex-smokers had a persistent decrease in functional connectivity between right anterior insula and anterior cingulate cortex (ACC) compared with control participants, but similar to active smokers. Potentially confounding alterations in gray or white matter were excluded in VBM and TBSS analyses. In summary, ex-smokers with long-term nicotine abstinence have persistent and dosedependent brain network changes notably in the right anterior insula and its connection to the ACC.

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Are higher doses of nicotine replacement more effective for smoking cessation?

Cited by 135 publications

References 35 publications

High Dose Transdermal Nicotine for Fast Metabolizers of Nicotine: A Proof of Concept Placebo-Controlled Trial

High Dose Transdermal Nicotine for Fast Metabolizers of Nicotine: A Proof of Concept Placebo-Controlled Trial

Pharmacotherapies for smoking cessation: a meta-analysis of randomized controlled trials

Cigarette smoking leads to persistent and dose-dependent alterations of brain activity and connectivity in anterior insula and anterior cingulate

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