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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Arch Intern Med. Author manuscript; available in PMC 2010 November 9.
Published in final edited form as:
PMCID: PMC2826277

The impact of repeated cycles of pharmacotherapy on smoking cessation: A longitudinal cohort study

A. Paula Cupertino, Ph.D.,1 Jo A. Wick, Ph.D.,2 Kimber P. Richter, PhD, MPH,1 Laura M. Mussulman, MPH,1 Niaman Nazir, MBBS, MPH,1 and Edward F. Ellerbeck, MD, MPH1



To examine the uptake and effectiveness of repeated offers of pharmacotherapy to promote smoking cessation


Longitudinal cohort


50 rural primary care clinics


726 adult smokers


Offers of either bupropion or transdermal nicotine at 6 month intervals to continuing smokers over a two-year period

Main outcome measure

Self-reported, seven-day, point prevalence abstinence from cigarettes


During the first cycle of treatment, 464 (63.9%) took smoking cessation pharmacotherapy. Among continuing smokers, 52.7% of 383, 45.8% of 177 and 64.7% of 68 took 2nd, 3rd and 4th consecutive cycles of pharmacotherapy, respectively. The odds ratios for quitting among pharmacotherapy users versus non-users was 2.56, 1.83, 1.85, and 3.08 after the 1st, 2nd, 3rd, and 4th cycles of treatment. Successful smoking cessation was not related to the number of previous pharmacotherapy-assisted quit attempts.


A large portion of continuing smokers are willing to engage in repeated pharmacotherapy-assisted quit attempts. The effect of pharmacotherapy does not appear to diminish even after multiple prior quit attempts.


Smoking cessation pharmacotherapy can double quit rates,6 but smokers often fail after a single quit attempt, and quitting smoking often involves multiple quit attempts over the course of months or years. 25 Few studies have tested the impact of providing repeated courses of pharmacotherapy to help smokers recover from relapses and engage in new cessation attempts. As part of a study of chronic disease management for smoking cessation, we followed a cohort of smokers that was offered up to four courses of pharmacotherapy over two years. We examined their continued interest in using pharmacotherapy and the effect of that treatment.


Setting and participants

We recruited smokers, regardless of their interest in quitting, from 50 rural primary care clinics throughout the state of Kansas.16 Smokers were excluded if they were < 18 years of age, smoked < 10 cigarettes/day, smoked fewer than 25 of the past 30 days, did not speak English, did not have a working telephone, and did not consider one of the participating physicians to be their primary care doctor. Smokers were also excluded if they were pregnant or planning to become pregnant within the next 2 years, were planning to move out of the study area, had dementia or severe mental illness, or lived with a smoker already enrolled in the study. For the present analysis, we also excluded smokers who died or were incarcerated during the two-year follow-up period. We also excluded participants who took varenicline, a drug not offered as part of the study, resulting in a final cohort of 726 smokers. This study was approved by the ethics committee of the University of Kansas Medical Center.


At six month intervals (months 0, 6, 12 and 18), participants were asked if they wanted to receive a 6-week course of 21mg/day nicotine patch or a 7-week course of bupropion SR 150 mg twice daily. Participants requested pharmacotherapy by either returning a stamped postcard or calling research staff at a toll-free number.17 All participants were followed for 2 years. Smokers were randomly assigned to receive one of three different levels of chronic disease management to support smoking cessation. Rates of utilization of pharmacotherapy were similar across the treatment arms, and the primary outcomes of this study have been reported previously.16

Measurements and Follow up

Smoking cessation was defined as self-reported seven-day point prevalence abstinence from cigarettes and was assessed at the end of each 6-month cycle via a brief telephone survey. Follow-up calls were completed on 91%, 87%, 83% and 85% of participants respectively following cycles 1, 2, 3 and 4.

Statistical Analyses

To reduce self-selection bias and isolate the effects of repeated courses of medication on cessation, we created a generalized linear mixed model using the SAS GLIMMIX procedure which allowed us to assess the effect of participant characteristics on whether or not they requested pharmacotherapy over multiple time periods. Variables significant at the 0.05 level were incorporated into a second generalized linear mixed model which examined the effect of pharmacotherapy on smoking cessation over multiple time periods.

In our longitudinal analyses, subjects were censored at the end of any treatment cycle in which they failed to request medication – this permitted us to compare the 6-month quit rates among participants who had used/not used pharmacotherapy during that cycle. Because we wanted to examine the impact of repeated cycles of pharmacotherapy on smokers who had failed to quit during a prior medication-assisted attempt, we also censored subjects who requested medication but also reported that they had stopped smoking. The flow of continuing smokers across four consecutive cycles of pharmacotherapy-assisted quit attempts and those censored is described in the Figure. SAS version 9.1 was used for all analyses.

Association between Multiple Consecutive Cycles of Pharmacotherapy and Cessation Rates


The figure describes medication utilization across the four consecutive cycles of pharmacotherapy-assisted quit attempts. Of the 726 participants, 464 (63.9%) took medication in the first cycle of treatment. Among continuing smokers, 52.7% of 383, 45.8% of 177 and 64.7% of 68 opted for 2nd, 3rd and 4th consecutive cycles of pharmacotherapy, respectively. In the generalized linear mixed model, a positive relationship existed between the probability of requesting medication and baseline stage of change, baseline motivation, and previous nicotine replacement therapy.

Cessation rates were consistently higher for pharmacotherapy users compared to non-users. Smokers that opted to use pharmacotherapy had six-month quit rates of 17.4% (n=464), 12.4% (n=202), 16.0% (n=81) and 15.9% (n=44) after the 1st, 2nd, 3rd, and 4th consecutive rounds of pharmacotherapy. (Figure) The odds ratio for quitting among pharmacotherapy users versus non-users was 2.56 (1.529, 4.284), 1.83 (0.904, 3.686), 1.85 (0.746, 4.578), and 2.08 (0.397, 10.920) after the 1st, 2nd, 3rd, and 4th cycles of treatment, respectively.

In a generalized linear mixed model that controlled for baseline characteristics related to pharmacotherapy use, pharmacotherapy use was found to be significantly associated with the probability of quitting (OR = 1.99, p = 0.002). The probability of quitting was not related to the number of previous pharmacotherapy-assisted quit attempts (OR = 1.004, p = 0.81).


The study has several limitations. Smokers who chose to use pharmacotherapy were self-selected. However, we did adjust for baseline factors related to who would select medication. Moreover, the success associated with use of pharmacotherapy is similar to that seen in randomized controlled trials6 and is much higher than seen in general populations of smokers that are not receiving offers for free treatment. Success in smoking cessation was based on self-report and follow-up was restricted to 6 months due to the timing of the repeat interventions. Studies with longer follow-up and biochemical validation would help to confirm these findings.

Nevertheless, this study showed that one in two smokers was willing to make a second pharmacotherapy quit attempt within 6 months of a treatment failure; this rate of willingness to reengage in treatment did not diminish over time. Pharmacotherapy appeared to remain effective even in the presence of multiple prior treatment failures. These results support a model of care in which smokers who initially fail treatment are quickly reengaged in a new, pharmacotherapy-assisted quit attempt. Insurance programs that currently limit the number of courses of treatment that smokers receive should reexamine those policies.


Trial Registration: identifier: NCT00440115


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