Less May Be Enough With Varenicline | Journal Scan

Study Questions:

What is the impact on treatment efficacy of increasing varenicline dose in smokers who do not show a response to the standard dosage?


This was a double-blind, randomized, placebo-controlled trial based in a smoking cessation clinic in England. A total of 503 smokers attended the clinic and began varenicline 21 days before their target quit date (TQD). On day 12 of use, nonresponders (no significant nausea, no clear reduction in smoking enjoyment, and <50% reduction in baseline smoking) were randomized to additional varenicline or placebo. The dose of varenicline was increased to a maximum of 5 mg/day. The main outcomes were smoking enjoyment during the prequit period, withdrawal symptoms assessed weekly for the first 4 weeks after the TQD, and abstinence rates (assessed at 1, 4, and 12 weeks after the TQD).


Increase in varenicline dosage, compared to placebo, modestly reduced smoking enjoyment during the prequit period, with mean (standard deviation) ratings of 1.7 (0.8) for varenicline and 2.1 (0.7) for placebo (p = 0.001). Increased dose of varenicline, compared to placebo, did not have a significant impact on severity of withdrawal symptoms or abstinence rates. Compared to the placebo group, the varenicline group had significantly more nausea and vomiting.


Among smokers without a significant response to varenicline in the prequit period, increasing varenicline dose had little effect on tobacco withdrawal symptoms or abstinence rates.


This is a valuable study that casts doubt on a strategy of increasing varenicline dosage in nonresponders to a standard dosage. Less may be enough with varenicline. However, increased dosage did reduce smoking enjoyment in the prequit period. As the authors opine, it will be important to test the impact of varenicline on smoking cessation if the preloading period were longer. Indeed, others have shown that reduced smoking enjoyment (as was seen with a higher dose of varenicline) during the prequit period is associated with abstinence from smoking.

Clinical Topics: Prevention, Smoking

Keywords: Smoking, Smoking Cessation, Tobacco Use Cessation Products, Tobacco Use Disorder, Double-Blind Method, Nausea, Nicotine, Vomiting, Substance Withdrawal Syndrome, Treatment Outcome

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