Cochrane Summaries

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Can nicotine receptor partial agonists, including cytisine, dianicline and varenicline, help people to stop smoking?

Cahill K, Stead LF, Lancaster T
Published Online: 
6 June 2013

When people stop smoking they experience cravings to smoke and unpleasant mood changes. Nicotine receptor partial agonists aim to reduce withdrawal symptoms and smoking satisfaction. Two recent trials of cytisine (937 people) confirm that it can be an effective and affordable treatment for smoking cessation. Quit rates were low, however, at around 9% in the treatment groups. The rate might be boosted in future studies by longer treatment and more intensive or extended counselling.
A single trial of dianicline did not detect any benefit over placebo in helping smokers to quit. This drug is no longer being developed.
We found 15 randomized controlled trials of varenicline compared with placebo. Three of these trials also included a direct comparison with bupropion. We also found one trial comparing varenicline plus counselling with counselling alone. One other trial tested varenicline against placebo, as maintenance therapy for those who had recently quit with varenicline. Two further trials compared varenicline with nicotine patches. One trial gave varenicline to all participants, but varied the delivery of behavioural support. This trial is not included in the analyses, but contributes to the data on safety and tolerability.
From these data (14 trials, 6166 people), varenicline at standard dose increased the chances of quitting more than two-fold compared with placebo. Low-dose varenicline (four trials, 1272 people) roughly doubled the chances of quitting, and reduced the number and severity of side effects. The number of people stopping smoking with varenicline was higher than with bupropion (three trials, 1622 people). The two trials with nicotine patches (778 people) did not show a clear benefit of varenicline over the patches. The main side effect of varenicline was nausea, but this was mostly at mild or moderate levels and usually subsided over time. There may be a one-third increase in the chance of severe side effects among people using varenicline, but this finding needs to be tested further. After the licensing phase, there were concerns that varenicline may be linked with an increase in depressed mood, agitation, or suicidal thinking and behaviour in some smokers. There are also concerns that it may slightly increase heart and circulatory problems in people already at increased risk of these illnesses. Surveillance studies and further analyses of the trial data have not found strong support for either of these associations so far, but we cannot rule out the possibility of such links.

This record should be cited as: 
Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD006103. DOI: 10.1002/14651858.CD006103.pub6
Assessed as up to date: 
14 March 2012