There was a non-significant trend for higher cessation rates at EOT and 6-months for transdermal nicotine versus lozenge. At EOT, smokers who expressed a preference for transdermal nicotine or reported low levels of reactivity to smoking cues or smoking to alleviate emotional distress or enhance cognitive function had higher quit rates with transdermal nicotine. At 6-months, smokers who expressed a preference for transdermal nicotine had higher quit rates with transdermal nicotine, whereas participants who exhibited high self-medication showed a significantly lower quit rate on nicotine lozenge. This first direct comparison of nicotine patch to nicotine lozenge suggests that transdermal nicotine yields a modest yet meaningful increase in quit rates in a real-world setting, especially for certain sub-groups of smokers.
A survey of tobacco control scientists indicated that patient preference for treatment modality should be considered in personalizing nicotine dependence treatment (Bader et al., 2009
). However, little empirical data exist to support this recommendation. The ability to select a preferred NRT may reduce smoking rates vs. assigning NRT randomly (Leischow et al., 1997
). Yet, allocation to one's preferred NRT was not found to influence response to NRT vs. random selection (West et al., 2001
). From the present results, NRT preference may influence NRT response in the context of real-world use but only for transdermal nicotine, rather than to NRTs in general. Notably, more than two-thirds of the sample indicated a preference for transdermal nicotine, an imbalance that may have influenced the present outcome. Nevertheless, the relationship between a preference for transdermal nicotine and quit rate on transdermal nicotine was maintained at the 6-month outcome, indicating some sustainability for this relationship.
Previous research suggests that acute dosing NRTs (e.g., gum, lozenge), which can be dose titrated, may significantly reduce post-cessation craving among smokers who are responsive to smoking cues (Shiffman et al., 2003
). Thus, we expected that smokers who were highly reactive to smoking cues would show higher quit rates on nicotine lozenge. We found, however, that smokers who reported low cue reactivity showed significantly higher quit rates on transdermal nicotine; level of cue reactivity did not affect response to nicotine lozenge. The inability for nicotine lozenge to increase quit rates among smokers reactive to cues may have been attributable to low compliance with this NRT; indeed, mean lozenge use in this study resembled the rate of participants considered “low-lozenge users” in a large placebo-controlled trial of lozenges, who showed significantly lower quit rates versus “high-lozenge users” (Shiffman, 2007
). The increased effectiveness of nicotine patch among those low in cue reactivity may be explained by the congruence between this sub-group's more consistent smoking habits and the steady dosing of transdermal nicotine. This effect was only evident at EOT, suggesting that the influence of cue reactivity on response to transdermal nicotine may be confined to the treatment phase. Overall, these findings extend the literature on cue reactivity and response to NRT, including previous lab-based studies (e.g., Waters et al., 2004
Finally, self-medicating with nicotine to alleviate affective distress or stimulate cognitive function is considered central to the effective treatment of nicotine dependence (Evans and Drobes, 2009
; Gehricke et al., 2007
). Since the dose of nicotine from lozenges can be titrated upwards during acute situations that challenge a smoker's affective state or cognitive abilities, we expected that those who reported high smoking self-medication would show higher quit rates on nicotine lozenge. However, smokers who were low on self-medication showed significantly higher EOT quit rates on transdermal nicotine; there was no significant difference at EOT between high and low self-medication for those treated with nicotine lozenge. The interaction effect for self-medication and treatment arm was significant at 6-months. Quit rate was significantly lower among those high in self-medication treated with lozenge vs. patch. The nicotine lozenge, therefore, may not be effective for smokers who report higher levels of smoking self-medication. Again, the lack of effect for the nicotine lozenge may be attributable to low compliance with this medication, whereas the effect for transdermal nicotine among those low in self-medication may be attributable to congruence between the steady dosing of transdermal nicotine and the consistent self-administration of tobacco among smoker's who do not smoke to enhance cognitive function or alleviate emotional distress.
These results should be viewed in the context of study limitations. First, this was an effectiveness trial, so the study methodology was devised to approximate “real-world” experience. Effectiveness trials emphasize study external validity vs. efficacy trials, which focus on internal validity. The eligibility criteria were minimized, the behavioral counseling was limited, and the treatments were unblinded. The present results should be compared to NRT effectiveness trials and studies of OTC NRT. The quit rates found in this trial converge with OTC NRT trials, which are far lower than efficacy trials (i.e., 1-11%; Hughes et al., 2003b
). Second, no placebo was included in this trial, so it is not possible to determine the effectiveness of the NRTs relative to no treatment. The efficacy of these NRTs, relative to placebo, is already established, and this design was selected in accordance with an effectiveness design. Third, the overall reduced effectiveness of the lozenge and the lack of enhanced effectiveness of the lozenge in hypothesized sub-groups may have been due to low compliance among lozenge users. Only about one-quarter of the participants randomized to nicotine lozenge used the approximate recommended dose. We used the original COMMIT lozenge, which has since been enhanced with flavorings to enhance taste and palatability. The present results may be different if the new generation of nicotine lozenges were used. Notably, however, lozenge compliance was similar across participants who preferred the patch vs. the lozenge, across participants low vs. high in cue reactivity, and across participants low vs. high in self-medication (data not shown). Fourth, the nicotine patch and nicotine lozenge have different step-down procedures, which may have also contributed to variation in response to these NRTs. Finally, as is common in effectiveness trials, a substantial proportion of participants were lost to follow-up. However, an ITT approach was used to account for missing outcome data and the rate of missing outcome data compare to recent nicotine dependence clinical trials (Gonzales et al., 2006
; Jorenby et al., 2006
) and previous effectiveness studies with NRT (Hasford et al., 2003
; Shiffman et al., 2002b
This study provides, for the first time, data on the relative effectiveness in the real-world of nicotine patch and nicotine lozenge for treating nicotine dependence and information that can help smokers and clinicians select an appropriate NRT. Smokers with a preference for transdermal nicotine and smokers who are less reactive to smoking cues or less driven to smoke to augment cognitive function or alleviate distress may be good candidates for transdermal nicotine. Nicotine lozenges, in contrast, were less effective for all smokers and for sub-groups of smokers studied in this trial. Initially, we thought that differences in effectiveness between these NRTs could be attributable to the disparity in the pharmacokinetics between transdermal nicotine and nicotine lozenges, which allows for dose titration with the lozenge. However, expectations of smokers regarding the utility of these NRTs, the situational effectiveness of the lozenge, and compliance barriers with the nicotine lozenge may serve as alternative theoretical explanations for the differences in effectiveness for these NRTs. Additional research is needed to verify these results, including studies that prospectively select treatments based on individual smoker characteristics found in this trial to be related to NRT effectiveness. Such studies may yield methods to personalize treatment selection for nicotine dependence in order to enhance NRT effectiveness.