Use of Varenicline for 4 Weeks Before Quitting Smoking: Decrease in Ad Lib Smoking and Increase in Smoking Cessation Rates

Study Questions:

The use of varenicline alleviates post-quit withdrawal discomfort, and reduces the “reward” associated with smoking. The current treatment schedule, which commences 1 week before quitting, relies primarily on the first mechanism. Does increasing the pre-quit medication period render cigarettes less satisfying and facilitate quitting?


A total of 101 smokers attending a stop smoking clinic in London, United Kingdom, were randomly allocated to receive varenicline for 4 weeks before the target quit date (TQD) or to receive placebo for 3 weeks before the TQD, followed by varenicline for 1 week before the TQD. In both groups, standard varenicline treatment was given for 3 months after the TQD. Measures included smoking satisfaction and smoke intake before quitting, urges to smoke and withdrawal discomfort after quitting, and sustained abstinence from the TQD to 3 months.


There was no difference between groups for mean age of 45 years, mean cigarettes per day (15.5 vs. 18.2), previous quit attempts (2.7), partner smoking, or body mass index. Varenicline preloading reduced pre-quit enjoyment of smoking (p = 0.004) and smoke intake (p < 0.001), with 36.7% of participants reducing their cotinine concentrations by more than 50% (reducers). Varenicline preloading did not affect post-TQD withdrawal symptoms, but it increased 12-week abstinence rates (47.2% in the varenicline arm vs. 20.8% in the placebo arm, p = 0.005). The effect was particularly strong among the reducers in the varenicline arm (66.7% in reducers vs. 22.6% in nonreducers, p = 0.002). Varenicline preloading was well tolerated.


Although several issues remain to be clarified, varenicline preloading can generate a substantial reduction in ad lib smoking and enhance 12-week quit rates. Current treatment schedules may lead to suboptimal treatment results.


The results are more robust than expected. In the large trials, the standard protocol with just 1 week of pretreatment with varenicline, the 12-week post-quit date abstinence rate is over 40% compared to the 20% in this study. This proof of principle designed protocol needs to be expanded to include long-term follow-up, a much larger cohort, and other options including longer duration of treatment. Cigarette smoking is the most preventable cause of illness, death, and excess health care costs in the United States, accounting for more than 440,000 deaths annually and $157 billion in health-related economic losses.

Keywords: Great Britain, Follow-Up Studies, London, Substance Withdrawal Syndrome, Quinoxalines, Tobacco Use Disorder, Smoking Cessation, Benzazepines, United States

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