Background: Varenicline (Chantix) promotes smoking cessation by reducing discomfort from nicotine withdrawal and reducing smoking-related pleasure. To date, this second mechanism has been demonstrated only during the one-week preloading period before the target quit date. Hajek and colleagues hypothesize that extending the varenicline preloading period before the target quit date could further weaken the association between smoking and reward, and enhance overall smoking cessation rates.

The Study: Overall, 101 heavy smokers (approximately 19 cigarettes per day) were randomized to start varenicline four weeks before the target quit date, or to receive placebo for three weeks followed by varenicline for one week before the target quit date. Both groups received 1 mg per day of varenicline for their first week of use, followed by 2 mg per day beginning in their second week and continuing for 12 weeks after the target quit date. This differs from the standard varenicline instructions to use 0.5 mg per day for three days, followed by 1 mg per day for four days, followed by 2 mg per day for up to six months after the target quit date. Exclusion criteria included psychiatric or other serious illness, and the use of varenicline in the past six months. Smoking status was assessed by self-report, salivary cotinine, and end-expired carbon monoxide concentrations during the study. Outcome measures included smoking satisfaction and smoke intake, withdrawal discomfort after quitting, and abstinence rates at four weeks and at 12 weeks after the target quit date.

Results: Baseline traits between the two groups were similar, as were nausea rates after varenicline was initiated (approximately 30 percent in each group). Dropout rates also were similar (seven in each group). The two groups did not differ significantly in the composite score of urges to smoke or in the level of discomfort associated with smoking withdrawal, although the longer duration varenicline group did report significantly less smoking enjoyment than did the shorter duration varenicline group. The smoking abstinence rates were significantly higher in the longer duration varenicline group at 12 weeks after the target quit date (19 versus 7 percent in the shorter duration group).

Conclusion: Using varenicline for four weeks before the target quit date decreased enjoyment associated with smoking, and enhanced abstinence rates at 12 weeks after the target quit date, with no difference in the overall adverse effect rates. The authors note that the overall nausea rate associated with varenicline in this study appeared to be higher than in other studies of varenicline.