Earlier Initiation of Smoking Cessation Drug Before Quitting Improves Outcomes

"The use of varenicline tartrate alleviates postquit withdrawal discomfort, but it also seems to reduce the 'reward' associated with smoking," write Peter Hajek, PhD, from United Kingdom Centre for Tobacco Control Studies, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, United Kingdom, and colleagues. "The current treatment schedule, which commences 1 week before quitting, relies primarily on the first mechanism. We set out to determine whether increasing the prequit medication period renders cigarettes less satisfying and facilitates quitting."

Participants consisted of 101 smokers attending a stop-smoking clinic in London, United Kingdom. These were randomly assigned 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. For 3 months after the TQD, both groups also received standard varenicline treatment. Study outcomes 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.

In the group that received varenicline preloading, prequit enjoyment of smoking (P = .004) and smoke intake (P < .001) were less vs the group that did not receive varenicline preloading, and cotinine concentrations decreased by at least 50% in more than one third (36.7%) of participants (reducers).

Varenicline preloading was associated with improved 12-week abstinence rates (47.2% in the varenicline group vs 20.8% in the placebo group; P = .005), although postquit withdrawal symptoms did not differ between the groups.

For reducers in the varenicline group, the 12-week abstinence rate was 66.7% vs 22.6% in nonreducers (P = .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," the study authors write. "Current treatment schedules may lead to suboptimal treatment results. Trials with longer follow-up periods are needed to corroborate these findings."

Limitations of this study include insufficient power for long-term follow-up and lack of data on abstinence rates beyond 3 months. In addition, the study was designed to examine only 1 possible mediating mechanism (the effect of varenicline preloading on withdrawal discomfort), and it did not include measures of cue reactivity, which could also be another possible explanatory factor.

An accompanying Invited Commentary by Joel A. Simon, MD, MPH, from the San Francisco VA Medical Center, University of California School of Medicine, discusses various smoking cessation interventions.

"Additional pharmacotherapies are in the pipeline (eg, the nicotine vaccine), and innovative nonpharmacologic approaches continue to be investigated (eg, Web-based interventions, hypnosis, and text messaging)," Dr. Simon writes. "However, there already exists a sufficient evidence base for counseling and drug interventions that if broadly, wholeheartedly, and effectively implemented would likely result in decreased tobacco-related misery."