The Cochrane Tobacco Addiction Group celebrated its 20th birthday in 2016 and continues to produce new and updated reviews that help people making decisions about ways to quit smoking. In May 2016, the Group updated its review of the effects of nicotine receptor partial agonists and we asked the group’s Managing Editor and one of the authors of the review, Nicola Lindson-Hawley from the University of Oxford in England, to tell us what they found.
John: Hello, I'm John Hilton, editor of the Cochrane Editorial unit. The Cochrane Tobacco Addiction Group celebrated its 20th birthday in 2016 and continues to produce new and updated reviews that help people making decisions about ways to quit smoking. In May 2016, the Group updated its review of the effects of nicotine receptor partial agonists and we asked the group’s Managing Editor and one of the authors of the review, Nicola Lindson-Hawley from the University of Oxford in England, to tell us what they found.
Nicola: When people stop smoking they experience cravings to smoke and unpleasant mood changes. The drugs we assessed in this review, called nicotine receptor partial agonists, aim to reduce these withdrawal symptoms and make smoking less satisfying by activating receptors in the brain which would usually be activated by nicotine. One of the most well-known and widely used of these drugs is varenicline, which is licensed as a first-line treatment for smoking cessation, and marketed as Champix or Chantix. Other types are cytisine, which is not licensed widely, and dianicline, which has been withdrawn from further development.
Our updated Cochrane Review now contains 27 trials of approximately twelve and a half thousand smokers who had been randomized to take varenicline or a placebo as part of their efforts to quit smoking. Combining the results in a meta-analysis of long-term quit rates shows that varenicline increases the chances of quitting by between two- and three-fold, when compared with placebo. This is based on high quality evidence, as judged according to the GRADE standard, which makes us very confident that the true effect is close to this estimate.
We also found two studies which compared quit rates with cytisine versus those with placebo. These demonstrated a benefit for cytisine, but the quit rates were low in both groups and we rated the quality of this evidence as low because it’s based on only two studies, with a small number of events. We’d like to see more research to investigate this drug further, not least because a large trial of cytisine versus nicotine replacement therapy, which was published in 2014, found higher quit rates overall, and a benefit of cytisine over NRT.
We found information on two trials of dianicline, but the results of only one of these were accessible for our review. That trial found no statistically significant difference between the quit rates in the dianicline and placebo groups.
Turning to side effects, the main reported adverse effect of varenicline was nausea, but this was mostly at mild or moderate levels, usually subsided over time and was associated with low discontinuation rates. New for this update, we’ve included analyses of the incidence of depression and suicidal ideation. The event rates for both of these outcomes were higher in the placebo groups than in the varenicline groups, although neither difference was statistically significant.
Overall, our meta-analysis of serious adverse event data from 29 trials suggests there may be a 25% increased risk of such events among smokers allocated varenicline compared with those allocated placebo, and the high quality of this evidence gives us high confidence in this estimate. However, whilst this finding reaches statistical significance, it must be noted that it is based on simple counts across the trials of participants reporting one or more such events, and does not distinguish between events attributed to treatment and those unrelated to treatment.
In summary, our updated review shows that varenicline’s proven benefits in helping people to quit smoking substantially outweigh its possible side effects; and early reports of possible links to suicidal ideation and behaviour have not been confirmed by current research.”
John: To read more about this accumulating evidence on varenicline and the smaller amounts of data for the other drugs, you can find the full review at Cochrane Library dot com with a search for ‘nicotine receptor partial agonists’.