The Kick It at Swope III study (KIS-III) is the first randomized, double-blind placebo-controlled clinical trial to test the efficacy of bupropion SR for smoking cessation treatment among African American light smokers. The abstinence rates at week 26 indicated no statistically significant long-term treatment effect of the standard 7-week treatment with bupropion SR compared with placebo. However, participants who received bupropion SR were more likely to achieve initial abstinence early in the treatment period and to be abstinent at the end of the medication phase of treatment compared with participants who received placebo.
To date, KIS-III is among the first studies to evaluate pharmacotherapy for light smokers (9
). It is the second randomized placebo-controlled study of smoking cessation treatment for African American light smokers (9
). Consistent with our previous KIS trials of African American smokers (8
), study participants were largely low income and predominantly menthol smokers who were highly interested in stopping smoking.
In contrast to the current negative findings of long-term treatment effects, previous placebo-controlled clinical trials of bupropion have demonstrated efficacy in producing long-term abstinence in moderate to heavy smokers (≥10 CPD), with smokers using active bupropion being more than twice as likely to be abstinent at 6 months following treatment compared with those using placebo (11
). The majority of previous bupropion trials had predominantly white participants. Like these other studies, our KIS-I placebo-controlled trial of bupropion SR for African American moderate to heavy smokers (≥10 CPD) found a statistically significant treatment effect of bupropion SR at the end of the medication phase of treatment (36.0% and 19.0% verified abstinence in bupropion SR and placebo groups, respectively) in addition to sustained abstinence at week 26 follow-up (21.0% and 13.7% in bupropion SR and placebo groups, respectively) (8
). A critical question is why these long-term treatment effects seen in heavier African American smokers were not observed in this study of African American light smokers.
It is noteworthy that the current findings demonstrate initial benefit of bupropion SR for light smokers during the medication phase of the study as indicated by the higher abstinence rates in the bupropion SR group at weeks 3 and 7. African American light smokers who were given bupropion SR were almost three times as likely to quit smoking at week 7 compared with those who were given placebo (OR = 2.92, 95% CI = 1.78 to 4.77). This benefit of bupropion SR was seen early on in treatment, as evidenced by differences in abstinence rates between the study groups at week 3. The difference in abstinence rates between bupropion SR and placebo groups during the treatment phase was not related to retention or completion of counseling as no differences in these variables were seen between groups. Furthermore, although some studies have identified an impact of bupropion on reducing withdrawal and symptoms of depression (19
), no such treatment effects were evident in this study. This finding is of particular interest given almost a third of our sample reported elevated symptoms of depression. While abstinence rates within the placebo group remained stable between the end of treatment at week 7 and follow-up at week 26, abstinence rates within the bupropion SR group decreased from 23.7% at week 7 to 13.3% at week 26. Notably, within the bupropion SR group, individuals who achieved long-term abstinence demonstrated higher medication adherence early in treatment, reflected in the evaluation of total bupropion levels in the blood at week 3 compared with those still smoking at week 26, suggesting a clinical benefit of bupropion use in facilitating abstinence for some light smokers. Indeed, attention to medication adherence in enhancing pharmacotherapy efficacy merits further consideration.
Limited study of smoking cessation treatment among light smokers has produced mixed findings regarding the benefit of pharmacotherapy for light smokers (9
). Within the KIS-II placebo-controlled study of nicotine gum for African American light smokers (1–10 CPD), Ahluwalia et al. (9
) found no statistically significant treatment effect at month 6, with cotinine-verified abstinence of 14.2% and 11.1% for nicotine and placebo groups, respectively. Lack of medication effect may have been related, in part, to challenges in underdosing or underadherence (9
). In contrast, within a largely white sample of smokers who used 1–15 CPD and were randomized to placebo or nicotine lozenge, Shiffman (39
) found that nicotine lozenge statistically significantly increased carbon monoxide–verified abstinence rates relative to placebo 6 weeks into treatment (45.7% vs 31.1%) and at 12-month follow-up (19.2% vs 10.0%). Gariti et al. (10
) compared nicotine patch with bupropion within a racially mixed sample of light smokers (6–15 CPD; 68% African Americans) and found that within the nicotine patch group, quit rates appeared relatively stable over time, with verified abstinence rates of 26.8%, 26.0%, and 23.0% at weeks 12, 26, and 52, respectively. In contrast, bupropion produced abstinence rates of 27.1%, 18.0%, and 15.9% at weeks 12, 26, and 52, respectively, demonstrating higher early abstinence but subsequent decrease in abstinence with time (10
). Across treatment groups, African Americans were less likely than whites to be abstinent at the end of the study (10
). Benefit of pharmacotherapy and identification of mechanism of action for light smokers warrant additional study, with attention to enhancing initial treatment efficacy and increasing long-term abstinence for African American light smokers.
In this study, although motivation to stop smoking was high within the sample of light smokers, abstinence rates were modest. Indeed, nine of 10 light smokers who received placebo were smoking within the first 3 weeks of treatment, demonstrating that even motivated light smokers had difficulty with initial quit attempts or struggled with early relapse. These findings further support the need to identify effective treatment approaches for light smokers (11
). Although this cohort of African American light smokers reported use of approximately 8.0 CPD, findings show notably high levels of cotinine, similar to those seen in our previous study of African American light smokers (9
). The majority of these light smokers reported smoking soon after wakening, suggesting physical nicotine dependence (40
). Given notable nicotine intake, nicotine dependence, and the early impact of bupropion SR on facilitating abstinence during the medication phase of treatment, these findings support the idea that some light smokers benefit from pharmacotherapy to aid initial cessation. Future studies with African American light smokers could examine extended use of bupropion as a means of building on the initial medication effect to support sustained abstinence over time. Although extended use of bupropion has not been established as a method of relapse prevention (41
), a number of studies suggest that long-term use of bupropion (eg, up to 1 year) may promote sustained abstinence (42
Successful recruitment and retention within this study support the feasibility of enrolling African American light smokers into a clinical treatment trial involving biological data collection (7
). The present findings further support the importance of biochemical verification of smoking status, previously identified in KIS clinical trials (8
), consistent with guidelines on biochemical verification (34
This study has a few limitations. Generalizability of the findings to other smokers may be limited based on study inclusion criteria that address smoking cessation in African American light smokers motivated to stop smoking and based on study exclusion criteria that largely focus on medical eligibility to use bupropion (20
). Although this study design included assessment points standard for smoking cessation treatment studies, that is, end of treatment and 6-month follow-up, the lack of assessment between these points limited the ability to characterize the process of relapse among smokers in the bupropion SR group who experienced initial abstinence. For example, it is not clear if these light smokers more commonly experienced rapid or gradual relapse following the medication phase. Interest in more comprehensive evaluation of smoking behavior change in future study will need to be weighed against considerations of participant burden and study retention.
In summary, KIS-III contributes to the limited literature on treatment of African American light smokers. Standard bupropion SR treatment did not produce long-term abstinence, despite facilitating initial abstinence during medication use. Further investigation is needed to build upon these findings to identify 1) mechanisms of action of bupropion in early use, 2) methods to enhance sustained abstinence, and 3) individuals for whom this treatment approach is most effective. The ultimate goal of this research is to advance treatment, increase long-term abstinence, and reduce tobacco-related health disparities.