1. In a population of smokers who failed to respond to standard varenicline dosage, an increased dosing regimen of varenicline had no effect on the frequency of urges to smoke, the strength of urges, or the severity of withdrawal symptoms, as compared to placebo.
2. There was a reduction in smoking enjoyment, as well as significantly more adverse events of nausea and vomiting in the varenicline arm as compared to placebo.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Varenicline tartrate, a partial agonist at α4β2 nicotinic receptors, has been proposed to alleviate withdrawal symptoms and reduce the rewarding effects of cigarettes. Previous studies have shown that varenicline could be effective at reducing cigarette enjoyment and smoke intake. However, some patients had no response, and those nonresponders had significantly lower quit rates than patients who responded. The standard varenicline dosing was formulated to avoid adverse events in patients, which have largely included nausea and vomiting. This study examined whether a higher dosing regimen in patients who had no response to standard dosage could safely improve treatment efficacy.
The increased dosing regimen of varenicline had no effect on the frequency of urges to smoke, the strength of urges, or the severity of withdrawal symptoms. However, there was a reduction in smoking enjoyment. There were no significant differences on rates of smoking cessation at 1, 4, or 12 weeks. Strengths of the study include the study design, which was double-blinded, randomized, and placebo-controlled. Limitations include the subjective nature in which response was measured, which was provided by survey. Moreover, although most baseline characteristics were similar between the two study arms, there were more women in the varenicline group as compared to the placebo group.
In-Depth [randomized controlled trial]: This study examined smokers 18 years of age or older. Patients were excluded if they were breastfeeding or pregnant, had psychiatric illness, unstable heart disease, or end-stage renal disease. Patients started varenicline 21 days prior to their target quit date (TQD) at standard dosing that was titrated up to 2 mg/day. On day 10 of their regimen, patients were assessed by phone to assess for response to treatment. Nonresponders were those without strong nausea, no clear reduction in smoking enjoyment, and less than 50% reduction in baseline smoking. Nonresponders were randomized to receive varenicline 0.5 mg or placebo for up to twice-daily use. The dosage used at their TQD was maintained for 21 additional days, with 4 weekly support sessions. Participants were invited to attend a session at 12 weeks after the TQD to establish smoking status.
A total of 200 varenicline nonresponders were randomized. The Fagerstrom Test for Nicotine Dependence was administered at the first session, and the Mood and Physical Symptoms Scale, measuring withdrawal symptoms and smoking urges, was completed at subsequent contacts. For participants abstinent in the first week after the TQD, there was no significant difference in the frequency of urges to smoke (2.5 vs 2.4, P=0.72), ratings for withdrawal symptoms or composite withdrawal score (1.6 vs 1.6, P=0.67). Including all participants did not change results. There were no differences in the abstinence rates at 1, 4, or 12 weeks (P=0.14, 0.32, 0.61, respectively). There was a reduction in smoking enjoyment in the prequit period, as well as increased nausea and vomiting in the varenicline group.
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