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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Am J Health Behav. Author manuscript; available in PMC 2010 September 29.
Published in final edited form as:
PMCID: PMC2947084

Predictors of Smokeless Tobacco Abstinence

Jon O. Ebbert, MD, MSc, Elbert Glover, PhD, FASHA, FAAHB, FRIPH, Eri Shinozaki, MD, Darrell R. Schroeder, MS, and Lowell C. Dale, MD



To investigate predictors of tobacco abstinence among smokeless tobacco (ST) users.


Logistic regression analyses assessed characteristics associated with tobacco abstinence among ST users receiving bupropion SR.


Older age was associated with increased tobacco abstinence in both placebo and bupropion SR groups at end of treatment and one year. Abstinence was lower at one year for subjects with a history of major depression. At end of treatment, a 2-way interaction was detected suggesting bupropion SR may be efficacious for subjects with other household tobacco users.


Younger ST users and those with a history of depression are less likely to quit ST use.

Keywords: tobacco, smokeless, tobacco use cessation, bupropion SR


Approximately 7.7 million individuals in the United States report current (past month) use of smokeless tobacco (ST). Among all racial/ethnic groups, current ST use is highest among Native Americans and Alaska Natives aged 18 years or older.1 ST use has been associated with oral mucosal lesions,2 periodontal disease,3,4 precancerous oral lesions5 and oral cancer.6 Long-term use has been associated with death from cardiovascular disease, cerebrovascular disease, and cancer.7

Behavioral interventions, but not pharmacotherapies [ie, nicotine replacement therapy and bupropion SR (sustained-release)], have been shown to be effective for increasing long-term (> 6 months) tobacco abstinence rates among ST users.8,9 Previous pharmacotherapy studies have observed high end-of-treatment point prevalence tobacco abstinence rates in the control groups (42.6% to 51%),1012 suggesting that many ST users may be able to quit without pharmacologic interventions. Tailoring both pharmacologic and nonpharmacologic intervention efforts for ST users requires an understanding of characteristics that predict ST abstinence.

Previous studies have observed that ST users were more likely to be abstinent if they were older,12,13 smoked cigarettes,14 used chewing tobacco rather than snuff,15 used less ST per week or per day13,15,16 or for a shorter duration of time per week,15 and had higher levels of motivation15 or confidence in quitting.13,17 Previous studies have also shown that ST users are more likely to relapse if they are younger or have higher nicotine dependence scores.18 No information is currently available on whether bupropion SR is associated with tobacco abstinence among specific subsets of ST users.

We conducted this study to investigate the predictors of abstinence among ST users enrolled in a clinical trial investigating the efficacy of bupropion SR for ST cessation.



This analysis is based upon subject data collected for a multicenter, randomized, double-blind, placebo-controlled, clinical trial conducted assessing the efficacy and safety of bupropion SR for tobacco abstinence among ST users.10 The study was conducted at the Mayo Clinic in Rochester, Minnesota, and the West Virginia University School of Medicine in Morgantown, West Virginia. The institutional review board at each study site approved the study protocol prior to recruitment and enrollment.

Subjects recruited from the local community were eligible for enrollment if they were ≥ 18 years, identified ST as their primary tobacco product, had used ST for the past year, were willing to quit, and were in good general health.10 The primary tobacco product was assessed by a potential subject’s self-report.

A total of 225 study subjects (113 bupropion SR, 112 placebo) were recruited.10 All subjects were male. The mean age was 38.1 years (range 19 to 72 years), and the mean duration of regular ST use was 19.0 years (range 2 to 60 years). Exclusive use of snuff was reported by 91%, 7% exclusively used chewing tobacco, and 2% used both snuff and chewing tobacco. Subjects used an average of 4 cans/pouches per week in the previous 6 months. The average time of dipping in mouth was 104 minutes in the bupropion SR group and 70 minutes in the placebo group. Among recruited subjects, 21% never attempted to quit, 39% attempted 1–2 times, 22% attempted 3–4 times, and 17% tried 5 or more times. Ninety-eight percent of subjects were white. Level of highest education was categorized into less than high school graduate, high school graduate, some college, and college graduate; the proportions were 2%, 26%, 45%, and 27%, respectively. In addition to ST use, 91 subjects (40%) reported “ever” cigarette smoking (> 100 cigarettes in lifetime) with a median duration of cigarette abstinence of 8 years, and 3 subjects reported current cigarette smoking at baseline (2 bupropion SR, 1 placebo). The 2 subjects in the bupropion SR group smoked 1 and 4 cigarettes per day (cpd), and the placebo subject smoked 10 cpd.


Following an initial telephone screening, eligible ST users reported to the research center; informed consent was obtained, and baseline questionnaires were completed. A tobacco use history was obtained and tobacco dependence measures including the Fagerström Tolerance Questionnaire-Smokeless Tobacco.19 A blood sample was obtained for the serum tobacco alkaloids nicotine and cotinine.20 Subjects were randomly assigned in a double-blind fashion to oral bupropion SR 150 mg twice per day or identical-appearing placebo for 12 weeks. The target quit date was the eighth day after the start the medication. Serum tobacco alkaloids were collected at baseline.

Both groups received an oral exam and a behavioral intervention. For the behavioral intervention, we used a manual designed specifically for ST users used in a previous pilot study.21 At each visit, a study assistant discussed a different topic from the manual for 5 to 10 minutes with the subject. Sixteen counseling sessions were provided during the 52-week study, 2 of which were conducted by phone at weeks 16 and 20.

The primary end point was the biochemically confirmed point-prevalence tobacco abstinence rate at end of treatment (12 weeks). The primary end point was defined as self-reported abstinence from all tobacco in that last 7 days confirmed by a urine cotinine of < 50 ng/mL.

Statistical Analyses

Logistic regression analyses were performed to assess characteristics potentially associated with tobacco abstinence. Because the primary end point for assessing treatment efficacy was end-of-treatment (12 weeks), one set of analyses focused on predictors of abstinence at this time point. Initial univariate analyses were performed separately for each treatment group. Subsequent exploratory analyses were performed using data from all subjects with treatment group (bupropion SR versus placebo) and the treatment-by-characteristic interaction effect included as additional explanatory variables. Characteristics found to have some evidence of an association with tobacco abstinence from these analyses were included in a final multivariable model assessing predictors of abstinence at the end of treatment. A second set of exploratory logistic regression analyses was performed to assess characteristics potentially associated with biochemically confirmed 7-day point-prevalence tobacco abstinence at 12 months. In all cases, 2-tailed P-values ≤ 0.05 were considered statistically significant.


Of the 225 subjects included in this trial, 112 (49.8%) met criteria for biochemically confirmed 7-day point-prevalence tobacco abstinence at the end of treatment, and 81 (36.0%) met criteria for biochemically confirmed 7-day point-prevalence tobacco abstinence at one year. End-of-treatment and one-year abstinence rates were not found to differ significantly between bupropion SR and placebo [53.1% vs 46.4% at end of medication, 35.4% vs 36.6% at one year).

Older age was the only significant predictor for tobacco abstinence observed at end of treatment both in the placebo and bupropion SR groups (P<0.001 and P=0.015, respectively) [Table 1]. No additional variables were found to be significantly associated with abstinence in the bupropion SR group. In the placebo group, longer years of regular smokeless tobacco use and absence of other tobacco users in household were also observed to be univariately associated with abstinence at end of treatment. However, the association between longer years of regular tobacco use and abstinence was not significant after adjusting for age.

Table 1
Univariate Analysis of ST User Characteristics Associated With Tobacco Abstinence at End of Treatment

In the exploratory multiple logistic regression model, we observed that the likelihood of abstinence at end of treatment was found to increase significantly with age (OR= 2.21 per 10-year increase, 95% C.I. 1.57 to 3.12) [Table 2]. In addition, a statistically significant (P=0.023) 2-way interaction was detected between treatment assignment and other tobacco users in the household. Our finding suggests that for subjects without other tobacco users in the household, no evidence of bupropion SR efficacy exists (OR=1.01, 95% C.I. 0.55 to 1.86). However, among subjects with other tobacco users in the household, bupropion SR was associated with an increased likelihood of abstinence (OR=6.70, 95% C.I. 1.48 to 30.26).

Table 2
Multiple Logistic Regression Analyses

From the analysis of the one-year end point, we again found that the likelihood of abstinence increased significantly with age (OR = 1.74 per 10-year increase, 95% C.I. 1.28 to 2.38) [Table 2]. There was also evidence suggesting that abstinence was lower for subjects with a history of major depression compared to those without this history (OR = 0.24, 95% C.I. 0.07 to 0.86). Abstinence at one year was not found to be associated with treatment group (OR=0.95 for bupropion SR relative to placebo, 95% C.I. 0.54 to 1.69), and no significant treatment-by-characteristic interactions were identified.


We observed that older age is a significant predictor of ST abstinence at end of treatment and one year. For ST users with other tobacco users in the household, bupropion SR was associated with an increased likelihood of tobacco abstinence at end of treatment. A history of major depression was associated with tobacco use at one year.

Our findings contribute to the current literature on the treatment of ST users for which no data exist suggesting that pharmacotherapy convincingly increases tobacco abstinence rates among ST users.9 Our data would suggest that for patients who may have increased difficulty quitting due to external factors (ie, other tobacco users in the household), bupropion SR might be clinically indicated for facilitating abstinence. Previous studies have suggested that tobacco craving and withdrawal are distinct clinical entities controlled by separate processes.22 Craving has been attributed to dopaminergic pathways, and the mechanisms of action of bupropion are mediated by blockage of the reuptake of dopamine and norepinephrine in the “reward centers” of the brain.23 We hypothesize that bupropion may facilitate abstinence by modifying the craving for tobacco.

We observed that a history of major depression was associated with a decreased likelihood of tobacco abstinence at one year. Among cigarette smokers, a lifetime history of major depression is not an independent risk factor for failure to achieve tobacco abstinence.24 However, little information is available about the relationship between mood disorders and ST use.

Our study has several strengths. First, the data are derived from a large multicenter, double-blinded, randomized controlled clinical trial. Second, our sample was representative of ST users seeking treatment with regard to the demographic characteristics of race as well as type and amount of ST use.1012, 25 Third, our data are consistent with other studies in which age has been shown to be a strong predictor of ST abstinence.12, 13

In conclusion, age is a strong predictor of tobacco abstinence with older ST users more likely to achieve tobacco abstinence at 3 and 12 months. For subjects with users of any other type of tobacco in the household, bupropion SR may be indicated to assist in the quit attempt. ST users with a history of major depression may be less likely to achieve tobacco abstinence.


This project and manuscript was supported by National Cancer Institute R01 9088.

Contributor Information

Jon O. Ebbert, Assistant Professor of Medicine, Mayo Clinic College of Medicine; Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55905; ude.oyam@noj.trebbe; Telephone: (507) 266-1944; Fax: (507) 266-7900.

Elbert Glover, Professor & Chair Department of Public & Community Health (PCH) Director, Center for Health Behavior Research (CHBR); University of Maryland School of Public Health, 2387 HHP Building, College Park, MD 20742; ude.dmu@1revolge; Telephone: (301) 405-2029; Fax: (301) 314-9167(PCH)

Eri Shinozaki, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55905; ude.oyam@ire.ikazonihs; Telephone: (507) 266-1944; Fax: (507) 266-7900.

Darrell R. Schroeder, Professor of Biostatistics; Mayo Clinic College of Medicine; Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55905; ude.oyam@ddeorhcs; Telephone: (507) 284-3437; Fax: (507) 266-7900.

Lowell C. Dale, Associate Professor of Medicine, Mayo Clinic College of Medicine; Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55905; ude.oyam@llewol.elad; Telephone: (507) 266-1948; Fax: (507) 266-7900.


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