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Although we’ve established that 60% or more of the new cases of lung cancer in the US each year are now in never-smokers or former smokers, active smoking is still a big problem. Ongoing smoking can worsen survival in patients receiving active treatment for lung cancer, and the risk of developing lung cancer in people who don’t have it already can be decreased significantly by quitting smoking as early as possible (see prior post).
There are several approaches to consider, and several of these are highlighted in a prior post. But one that has emerged as among the more effective is chantix (varenicline), which is a drug that was developed by modifying the structure of a naturally occurring plant derivative called cytisine. The modified version gets into the brain much better than cytisine itself. Once in the central nervous system, chantix works by attaching to and partially stimulating the nicotine receptor (actually the nicotinic subtype of the acetylcholine receptor) in the reward centers of the brain (the same ones that mediate the pleasurable feeling of eating when hungry, drinking when thirsty, sex (gasp!), as well as reward of drugs like cocaine), but in partially activating the receptor, it blocks the receptor from being stimulated by nicotine, which provides the full reward effect.
(click to enlarge)
I don’t need to tell smokers that nicotine is truly addictive and leads to unpleasant withdrawal symptoms when those receptors are unoccupied for too long – this is exactly why it’s so hard to quit smoking. So chantix blocks the withdrawal symptoms by providing just enough stimulation of the nicotine receptor, at the same time blocking the more powerful reward effects of tobacco-delivered nicotine itself.
There have been several clinical trials that have shown that chantix is better than a placebo in helping people to quit smoking. Some of these studies compare chantix to zyban (long-acting buproprion), another medication to help patients with smoking cessation, including two that each compared chantix at 1 mg by moth twice daily to wellbutrin XR at 150 mg by mouth twice daily, or placebo. Together, they enrolled over 2000 patients, comparing the rates of being off of cigarettes after 12 weeks, finding that the abstinence rates were significantly lower in the chantix recipients than those on either zyban or a placebo (50% vs. 36% vs. 21%, respectively). As you might expect, many people who managed to abstain (defined as 7 days without a cigarette) slipped with later follow-up, but it was still higher a year after the start of the trial (and 9 months after stopping the medications) with chantix (29% vs. 23% vs. 15%).
Another study looked at the duration of treatment, enrolling people who had already completed 12 weeks of chantix and then randomizing them to receive 12 more weeks or switch to a placebo. They then evaluated the rates of successful quitting at a year and found a statistically significant 34% improvement from 24 weeks compared with 12 weeks on chantix. Patients on these studies noted that chantix decreased cravings, withdrawal symptoms, and the satisfaction of smoking – definitely a help and consistent with its mechanism of action described above.
Finally, there have been a couple of open-label studies (also known as non-blinded, where, everyone knows what they’re receiving) that directly compared chantix to nicotine-replacement approaches (gum, patches, etc.). One study that randomized patients to either chantix vs. the nicotine patch found that rates of not smoking over the preceding four weeks was significantly higher with chantix (56% vs 43%); another trial out of the UK that studied 412 smokers showed that the quitting rate was higher with chantix than nicotine replacement (70% improvement).
We’ll cover the side effects and current guidelines for chantix soon.
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