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Combination pharmacotherapy for stopping smoking: what advantages does it offer?

ABSTRACT: Globally, tobacco kills almost 5 million people around the world annually. Seven first-line pharmacotherapies are currently available and recommended by the United States Public Health Service (USPHS) clinical practice guideline for treating tobacco dependence, all of which have been proven to be effective for increasing tobacco abstinence rates when used as monotherapy. However, not all smokers are able to quit with single-drug therapy. Some smokers may benefit from combination therapy that includes the simultaneous use of different nicotine replacement therapies (NRTs) or medications with different mechanisms of action (e.g. NRT and bupropion). Combination therapy with different types of NRT may provide a therapeutic advantage by increasing serum nicotine concentrations, and combination therapy with different drugs may capitalize on synergy obtained from two different mechanisms of action. However, controversy exists regarding this approach. Available data suggests that combination therapy may increase abstinence rates compared with monotherapy. However, the cost effectiveness of this approach has not been clearly demonstrated.

SUBMITTER: Ebbert JO

PROVIDER: S-EPMC3164516 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Combination pharmacotherapy for stopping smoking: what advantages does it offer?

Ebbert Jon O JO Hays J Taylor JT Hurt Richard D RD

Drugs 20100401 6

Globally, tobacco kills almost 5 million people around the world annually. Seven first-line pharmacotherapies are currently available and recommended by the United States Public Health Service (USPHS) clinical practice guideline for treating tobacco dependence, all of which have been proven to be effective for increasing tobacco abstinence rates when used as monotherapy. However, not all smokers are able to quit with single-drug therapy. Some smokers may benefit from combination therapy that inc ...[more]

PMID: 20394453

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Project description:BackgroundMultiple studies have made robust associations between differential DNA methylation and exposure to cigarette smoke. But whether a DNA methylation phenotype is established immediately upon exposure, or only after prolonged exposure is less well-established. Here, we assess DNA methylation patterns from peripheral blood samples in current smokers in response to dose and duration of exposure, along with the effects of smoking cessation on DNA methylation in former smokers.MethodsDimensionality reduction was applied to DNA methylation data at 90 previously identified smoking-associated CpG sites for over 4900 individuals in the Generation Scotland cohort. K-means clustering was performed to identify clusters associated with current and never smoker status based on these methylation patterns. Cluster assignments were assessed with respect to duration of exposure in current smokers (years as a smoker), time since smoking cessation in former smokers (years), and dose (cigarettes per day).FindingsTwo clusters were specified, corresponding to never smokers (97·5% of whom were assigned to Cluster 1) and current smokers (81·1% of whom were assigned to Cluster 2). The exposure time point from which >50% of current smokers were assigned to the smoker-enriched cluster varied between 5 and 9 years in heavier smokers and between 15 and 19 years in lighter smokers. Low-dose former smokers were more likely to be assigned to the never smoker-enriched cluster in the first year following cessation. In contrast, a period of at least two years was required before the majority of former high-dose smokers were assigned to the never smoker-enriched cluster.InterpretationOur findings suggest that smoking-associated DNA methylation changes are a result of prolonged exposure to cigarette smoke, and can be reversed following cessation. The length of time in which these signatures are established and recovered is dose dependent. Should DNA methylation-based signatures of smoking status be predictive of smoking-related health outcomes, our findings may provide an additional criterion on which to stratify risk.

Dataset Information

Combination pharmacotherapy for stopping smoking: what advantages does it offer?

Publications

Combination pharmacotherapy for stopping smoking: what advantages does it offer?

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