05 Jul 2006

Smoking drug making waves

The drug Chantix (varenicline) quadruples a smoker's odds of kicking the habit, and is twice as effective as another smoking-cessation drug, Zyban (bupropion), according to three studies published in the July 5 Journal of the American Medical Association.

Chantix, which won US Food and Drug Administration approval on May 11, also greatly decreases smokers' likelihood of relapse in the first six months after quitting, one of the studies found.

The research - much of which was presented in November at an American Heart Association meeting and all of which was funded by the drug maker, Pfizer Inc. - is encouraging, experts said, because smokers have little that's pharmacologically useful in helping them to quit.

Hype may be unwarranted
But an editorial that accompanies the three JAMA studies warns that much of the hype around the new drug may be unwarranted, because Chantix remains a far-from-perfect means of quitting smoking.

Whenever a new smoking-cessation aid gets FDA approval, "there is often unbridled enthusiasm regarding the potential to solve the problems associated with smoking," wrote Robert Klesges and colleagues at the University of Tennessee Health Science Centre, in Memphis.

That enthusiasm may not be merited, they added. While Chantix does appear to perform better than either a placebo or Zyban, high rates of both side effects and treatment failure mean the drug "definitely is not a panacea for smoking cessation," the Tennessee experts concluded.

Stimulates release of dopamine
Chantix works in a way that's distinct from either nicotine-replacement methods - such as the popular patches or gums - or Zyban, which helps inhibit the reuptake by neurons of addiction-linked brain chemicals such as dopamanine and norepinephrine. Instead, the pill works by stimulating the release of dopamine, to reduce cravings, while simultaneously blocking brain cell receptors that help sustain addiction.

In one of the two studies, researchers led by David Gonzales at the Oregon Health & Science University, in Portland, compared the effectiveness of Chantix, Zyban and a placebo in helping 1 025 adult smokers quit over the course of one year.

At the 12-week point, 44 percent of those taking Chantix had remained smoke-free for at least the prior month, the researchers reported, compared to 29.5 percent of those taking Zyban and just under 18 percent of those on a placebo.

Long-term quit rates less impressive
Long-term quit rates were lower. According to the study, the rate of "continuous abstinence" from weeks nine to 52 was lower for people using all three interventions: just under 22 percent for Chantix, about 16 percent for Zyban, and 8.4 percent for those on a placebo.

A second, similar trial of 1 027 smokers, this one led by Douglas Jorenby of the University of Wisconsin, found almost identical results.

Finally, a third trial of more than 1 900 smokers living in seven countries looked specifically at the issue of relapse.

All of the smokers first underwent 12 weeks of Chantix therapy. About two-thirds of that group (1 236) were deemed to have kicked the habit by the end of the three-month period.

The researchers then gave these new "quitters" either Chantix or a placebo daily for the next 12 weeks.

Drug reduces relapse
By the end of the full 24-week study period, 70.5 percent of people who continued on Chantix remained non-smokers, the researchers reported, compared to just under half (49.6 percent) of those who stopped using the drug at week 12.

"An additional 12 weeks of treatment was more beneficial than placebo, both to the end of treatment and to one year," study lead researcher Dr Serena Tonstad, an attending physician in the department of preventive cardiology at Ulleval University Hospital in Oslo, Norway, told HealthDay at the AHA meeting.

The authors of the JAMA editorial - which is subtitled Definite Promise, But No Panacea - were reserved in their praise for the new drug.

High level of side effects
"Several issues temper some of the enthusiasm for this agent," they wrote. One is the relatively high level of side effects noted in the trials, with almost 30 percent of participants reporting nausea, and many others experiencing "abnormal dreams" while on Chantix.

Dropout rates were also high (35 percent in the Wisconsin trial), although this rate is similar to that usually seen in smoking-cessation trials. However, the editorialists pointed out that in the Norwegian trial, only those smokers who had quit by 12 weeks were allowed to enter the second, relapse-focused phase of the trial.

Because about one-third of the original participants did not succeed in quitting within three months, "the authors have eliminated [from their analysis] approximately one third of individuals for whom this drug does not appear to be effective," the Tennessee experts noted.

Finally, they said, all of these Pfizer-funded trials took place under the very best conditions, at academic research centres where smokers were closely monitored and instructed on proper use of the drugs.

That's a far cry from a "real world" situation where the average smoker is left more or less on his own after receiving a prescription from a doctor, they added.

No magic bullet
So, while the results of these trials are promising, the editorialists pointed out that nicotine addiction remains an impossibly tough challenge for most smokers - in fact, "the majority of participants in these three studies did not quit smoking, even with varenicline," they wrote.

The resilience of the smoking habit against all interventions suggests that "patients currently cannot and probably never will simply be able to 'take a pill' that will make them stop smoking," the editorialists concluded. – (HealthDayNews)