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The study by Aubin et al1 published in this issue is significant in that it is the first head-to-head comparison of the two smoking cessation pharmacotherapies: varenicline and nicotine replacement therapy (NRT). The results suggest that varenicline yielded higher rates of smoking abstinence than NRT. However, an important flaw in the design hampers the interpretation of the results. An imbalance resulted from the fact that the varenicline group began treatment 1 week before the target quit date whereas the NRT group began treatment on the quit date. Although the authors justified this decision based on current manufacturer’s instructions for using NRT, the asymmetrical design is problematic.
The problem with the imbalanced design stems from the finding that initiating NRT before the quit date approximately doubles the efficacy of NRT compared with beginning treatment on the quit date.2 It is plausible that a similar enhancement of efficacy results from initiating varenicline before the quit date. Therefore, beginning varenicline but not NRT before the quit date may have created an unfair advantage for varenicline. Although most studies of pre-cessation NRT have used pretreatment for 2 weeks as opposed to 1 week, it is conceivable that even pre-cessation exposure to treatment for 1 week augments success rates.
A likely mechanism for the enhancement in efficacy with pre-cessation treatment is behavioural extinction.3 Extinction results from a reduction in the rewarding effects of cigarettes when they are smoked concurrently with NRT or with a nicotinic antagonist such as mecamylamine,4 or with the nicotinic receptor partial agonist varenicline.5 This decrement in smoking reward may, in turn, reduce dependence levels and facilitate quitting smoking.
Pre-cessation NRT is not approved by the Food and Drugs Administration, but this recommendation may change as more studies replicate the positive results with pre-cessation NRT.6 Moreover, the main concern expressed regarding smoking concurrently with NRT—nicotine overdose—can be obviated by switching patients to denicotinised cigarettes during pre-cessation treatment with NRT.4
A comparison of NRT and varenicline using equal pre-cessation treatment regimens will ultimately prove informative in evaluating these two treatments.
Competing interests: The author is a named inventor on several nicotine replacement patents.
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