Smoking cessation - varenicline
More than half of all smokers will die as a result of their addiction. Although most of the illnesses are caused by chemicals other than nicotine, such as carbon monoxide and tar, the nicotine is the major psychoactive chemical, and is largely responsible for smoking's addictive effects.
More than half of all smokers will die as a result of their addiction. Although most of the illnesses are caused by chemicals other than nicotine, such as carbon monoxide and tar, the nicotine is the major psychoactive chemical, and is largely responsible for smoking's addictive effects.
These result from nicotine's agonist activity at neuronal nicotinic acetylcholine receptors, or nAChRs. It modulates these receptors' desensitisation and upregulation, and induces tolerance and physiological dependence.
The a4ß2 nAChR subtype is believed to be responsible for the dependence effects, and while nicotine replacement therapies suppress cravings by supplying a controlled release of nicotine, they do not prevent nAChR activation. As a result, Pfizer has developed varenicline, which acts as a partial agonist at the nAChR receptor.1
Several clinical trials have been carried out. In one randomised double blind placebo-controlled trial, 638 healthy cigarette smokers aged between 18 and 65 were given 0.3 or 1mg varenicline once a day or 1mg twice a day for six weeks plus placebo for one week, or seven weeks of 150mg sustained release bupripion twice a day, or placebo.2 Those given all bar the lowest dose of varenicline had a significant increase in quit rate compared to placebo or bupropion. In a second trial, 647 subjects were randomly given 0.5 or 1mg varenicline twice a day or placebo.3 Again, quit rates were much better - around 50% compared to 12% - for those given the new drug.
A further pair of Phase II trials were carried out in 2,000 smokers, who were given 1mg varenicline twice a day, 150mg bupropion in sustained release form twice a day, or placebo for 12 weeks. They were followed up for a further 40 weeks without treatment. In both of these studies, 44% of the varenicline treated patients had quit after the 12 weeks, compared to 30% of the bupripion group and 18% of the placebo group. After a year, those who had received varenicline were significantly more likely to remain smoke-free.
In an additional study, smokers who had managed to quit after 12 weeks of treatment with varenicline were given a further 12 weeks of either varenicline or placebo. Follow-up 28 weeks after treatment finished shows that 71% of those who had received the additional course of active were still not smoking, and 50% of those who had had placebo for the second 12 week period.4
Varenicline has recently been approved for use in both the US (under the brand name Chantix) and the EU (as Champix).