The Impact of Repeated Cycles of Pharmacotherapy on Smoking Cessation: A Longitudinal Cohort Study FREE

Smoking cessation pharmacotherapy can double quit rates.¹ However, smokers often fail after a single quit attempt, and quitting smoking often involves multiple quit attempts over the course of months or years.^2- 5 Few studies have tested the impact of providing repeated courses of pharmacotherapy to help smokers recover from relapses and engage in new cessation attempts.^6- 11 As part of a study of chronic disease management for smoking cessation, we followed a cohort of smokers that was offered up to 4 courses of pharmacotherapy over 2 years. We examined their continued interest in using pharmacotherapy and the effect of that treatment.

We recruited smokers, regardless of their interest in quitting, from 50 rural primary care clinics throughout the state of Kansas.¹² Smokers were excluded if they were younger than 18 years, smoked fewer than 10 cigarettes per day, smoked fewer than 25 cigarettes in 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 physician. 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 2-year follow-up period. We also excluded participants who took varenicline tartrate, 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, Kansas City.

At 6-month intervals (months 0, 6, 12, and 18), participants were asked if they wanted to receive a 6-week course of 21-mg/d nicotine patch or a 7-week course of bupropion hydrochloride sustained release, 150 mg twice daily. Participants requested pharmacotherapy by either returning a stamped postcard or calling research staff at a toll-free telephone number.¹³ All participants were followed up for 2 years. Smokers were randomly assigned to receive 1 of 3 different levels of chronic disease management to support smoking cessation. Rates of use of pharmacotherapy were similar across the treatment arms, and the primary outcomes of this study have been reported previously.¹² In addition to pharmacotherapy management, the 2 disease management groups received telephone counseling. Counselors used motivational interviewing techniques following a semistructured protocol to promote a smoking cessation attempt or encourage relapse prevention for abstinent smokers.

The baseline questionnaire included an assessment of demographic characteristics and nicotine dependence.^14- 16 Smoking cessation was defined as self-reported 7-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 for 91%, 87%, 83%, and 85% of participants following cycles 1, 2, 3, and 4, respectively.

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 (SAS Institute Inc, Cary, North Carolina), which allowed us to assess the effects of participant characteristics on whether they requested pharmacotherapy over multiple periods. Variables significant at the .05 level were incorporated into a second generalized linear mixed model that examined the effect of pharmacotherapy on smoking cessation over multiple 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 or 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 had stopped smoking at the end of the previous treatment cycle. The flow of continuing smokers across 4 consecutive cycles of pharmacotherapy-assisted quit attempts and those censored is described in the Figure. SAS version 9.1 software was used for all statistical analyses (SAS Institute Inc).

The Figure describes medication use across the 4 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, 202 of 383 (52.7%), 81 of 177 (45.8%), and 44 of 68 (64.7%) opted for second, third, and fourth 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 with nonusers. Smokers who opted to use pharmacotherapy had 6-month quit rates of 17.4% (n = 464), 12.4% (n = 202), 16.0% (n = 81), and 15.9% (n = 44) after the first, second, third, and fourth consecutive rounds of pharmacotherapy, respectively (Figure). The odds ratios (95% confidence intervals) for quitting among pharmacotherapy users vs nonusers were 2.56 (1.53-4.28), 1.83 (0.90-3.69), 1.85 (0.75-4.58), and 2.08 (0.40-10.92) after the first, second, third, and fourth 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 (odds ratio, 1.99; P = .002). The probability of quitting was not related to the number of previous pharmacotherapy-assisted quit attempts (odds ratio, 1.004; P = .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 trials¹ and is much higher than that seen in general populations of smokers who are not receiving offers for free treatment. Success in smoking cessation was based on self-report, and follow-up was restricted to 6 months owing to the timing of the repeated interventions. Studies with longer follow-up and biochemical validation would help to confirm these findings.

Nevertheless, this study showed that 1 in 2 smokers was willing to make a second pharmacotherapy quit attempt within 6 months of a treatment failure. 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 in whom treatment initially fails 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.

Correspondence: Dr Cupertino, Preventive Medicine and Public Health, University of Kansas Medical Center, 3901 Rainbow Blvd, Mail Stop 1008, Kansas City, KS 66106 (acupertino@kumc.edu).

Author Contributions:Study concept and design: Cupertino, Richter, and Ellerbeck. Acquisition of data: Cupertino, Mussulman, and Ellerbeck. Analysis and interpretation of data: Cupertino, Wick, Richter, Nazir, and Ellerbeck. Drafting of the manuscript: Cupertino, Wick, Richter, Nazir, and Ellerbeck. Critical revision of the manuscript for important intellectual content: Cupertino, Wick, Richter, Mussulman, and Ellerbeck. Statistical analysis: Cupertino, Wick, and Nazir. Obtained funding: Cupertino and Ellerbeck. Administrative, technical, and material support: Cupertino and Mussulman. Study supervision: Cupertino and Ellerbeck.

Financial Disclosure: None reported.