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Mar 30 11 12:30 PM
The below new Chantix/Champix study review proclaims that the difference in success rates between the NRT and Chantix/Champix at six months is "not statistically significant." If true, with so much concern about serious varenicline adverse events, why isn't this rather important decision making info being widely shared with smokers? I submit that it's the exact same reason that pharm industry financial influence worked so hard in 1999/2000 to get cold turkey (abrupt nicotine cessation) declared non-science-based and black-listed as a government approved quitting method: money/profits. There is nothing wrong with making money. What's wrong is leading smokers to believe that these products are vastly more effective than they really are. What's wrong is marketing that suggests that few succeed at quitting cold turkey, when each year it generates more successful long-term quitters than all other quitting methods combined, or that these products prevailed over cold turkey quitters when no such trials have ever been conducted, when the industry is afraid to do so, when it knows that doing so would expose and kill its golden "placebo" goose. Although an extremely limited view that only shows us quitting rates at week 4, the best on-going real-world varenicline data we have to look at comes from the UK NHS Stop Smoking Services, possibly the best/most intense government quitting programs of any nation (except for heavy reliance upon approved quitting products). When reflecting upon the below figures, keep in mind the following factors: (1) that these are 4 week figures, not 6 month rates as discussed in the below study review; and (2) that at 4 weeks, non-medication quitters have already ended dopamine pathway stimulation, re-sensitized receptors and down-regulated the number of receptors to levels seen in non-smokers, while those using "medication" still have 4 to 8 weeks of "treatment" before attempting to adjust to and get comfortable with natural stimulation. So why does UK NHS limit the data it presents to 4 weeks? We don't know. What we know is that these products were evaluated and approved using 8 to 12 week treatment plans. We also know that the pharmaceutical industry's ties to UK government health officials is likely as great or greater than here in the U.S. Anyway, Stop Smoking Services 4 week quitting method quit rates between 2007 and 2010 were as follows:UK NHS Week 4 Quitting Rates
2007-08 - Non-medication quitters 55% | NRT 49% | Varenicline 63% (Source: 1st XLS doc - .74MB - see Table 4.5)2008-09 - Non-medication quitters 48% | NRT 48% | Varenicline 61% (Source: 1st XLS doc - 1.06MB - see Table 4.5)2009-10 - Non-medication quitters 49% | NRT 47% | Varenicline 60% (Source: 1st XLS doc - 1.16MB - see Table 4.4)
Link to entire NHS Stop Smoking Services data collection So what do long-term (6 months to 1 year) UK NHS Stop Smoking Services quitting rates look like? Well, so far there has only been one study which looked at long-term rates (1 year), the sampling was rather small, and was conducted prior to Chantix / Champix coming on the market. Still, it's the only long-term UK data we have. I prepared the chart to the right from it (link to full text copy of the study - see bottom of Table 6) . Now, in your mind try to guess where varenicline will fall at 1 year, once users attempt to adjust to its absence and natural stimulation of brain dopamine pathways. Putting it all together, I suspect that varenicline would fall slightly higher than NRT but substantially lower than no medication. I've shared this info to try and help those just starting out feel a tad more comfortable about your quitting method decision, to help you understand that those claiming that these products double your chances are not being truthful. Yes, inside randomized clinical trials they consistently defeat placebo but placebo isn't a real quitting method. So why do they work inside clinical trials and yet fall flat on their face in real-world use? The quick answer is that clinical trials were not blind as claimed, that you cannot hide full blown withdrawal from an experienced quitter who is an expert at knowing exactly how it feels. Participants joined the trial seeking 8 to 12 weeks worth of free quitting products that they hoped with diminish withdrawal's intensity. They grew frustrated upon realizing that they had been given an inert placebo instead. We know from the few blinding integrity assessments that have been published that 3 to 4 times as many placebo group members correctly identify their assignment to placebo as guess wrong. If you'd made the same realization, would you have stuck around and allowed researchers to toy with you for weeks or months? Many of them didn't either.So, if just starting out and worrying that maybe you've taken the less successful road, rest assured that you've made an excellent selection! In fact, cold turkey provides 100% odds of success so long as all nicotine remains on the outside. Yes, there was always only one rule ... no nicotine today!Breathe deep, hug hard, live long,John (Gold x11)
Varenicline Increases Smoking Abstinence at 6 Months to a Year Compared With Placebo or Bupropion; Nausea Is the Most Commonly Reported Adverse Effect
Cigarette smoking is the leading cause of preventable premature death in the world, with an estimated 5 million smoking-related deaths worldwide. Quitting substantially reduces the health risk associated with smoking. Treatments available for smoking cessation include nicotine replacement therapies (NRTs), bupropion and the most recently marketed, varenicline. Varenicline, an analogue of cytisine, is a partial agonist for the α4β2 subtype of nicotinic cholinergic receptors, which are associated with the addictive effects of nicotine. Varenicline may help smokers quit smoking by reducing the rewarding effects of nicotine as well as attenuating the withdrawal symptoms.1 This meta-analysis evaluated the efficacy and safety of partial nicotine agonists, varenicline or cytisine, compared with placebo or other treatments in clinical trials conducted worldwide.
Cahill and colleagues conducted a Cochrane review evaluating the efficacy of partial nicotine agonists, varenicline or cytisine, for smoking cessation. Randomised controlled trials comparing active drug with placebo were included in the analyses. The review also included studies comparing the efficacy of varenicline with bupropion or NRT. Studies were excluded if they did not have a minimum of 6-month follow-up data from the beginning of treatment. Literature searches were conducted using the Cochrane trial register and other databases including MEDLINE, up to September 2010. The main outcome was the smoking abstinence rate at 6 months or more. Biochemical measures of smoking abstinence were the preferred outcome. One author extracted the data, and another author checked them. The authors used a meta-analysis to produce a RR, using the Mantel–Haenszel fixed-effect model. The heterogeneity of the studies and publication bias were also assessed.
A total of 16 studies were included in the analyses, 15 for varenicline and 1 for cytisine. Twenty-one studies were excluded. The main finding of the review was that the usual recommended dose of varenicline, 1 mg twice daily, was more effective than placebo for continuous abstinence at 6 months or longer (RR 2.31, 95% CI 2.01 to 2.66). Lower or variable doses of varenicline were also more effective than placebo (RR 2.09, 95% CI 1.56 to 2.78). Results also indicated that varenicline was more effective than bupropion at 1 year after the initiation of treatment (RR 1.52, 95% CI 1.22 to 1.88). Similarly, varenicline was more effective than NRT at 24 weeks, although this effect was not statistically significant (RR 1.13, 95% CI 0.94 to 1.35). Overall, varenicline was well tolerated even beyond the 12-week recommended treatment period. Nausea was the most common side effect, with a dose-dependent effect. The results did not show the behavioural adverse events reported in the postmarketing stage including depressed mood, agitation and suicidal behaviour or ideation. The single trial of cytisine was inconclusive.
The results demonstrate the efficacy of varenicline, relative to placebo, as a pharmacological treatment for smoking cessation in the usual recommended dose as well as at lower or flexible-dosing schedules. The results also suggest that varenicline may be more effective than bupropion. However, this comparison of efficacy was based on only a few studies. Future studies specifically designed to compare the efficacy of NRTs, bupropion and varenicline are needed.
What remains to be determined is whether varenicline will have similar efficacy in samples representative of all smokers. The clinical trials included in the meta-analyses excluded smokers with medical or psychiatric comorbidity or with other addictions. It has been estimated that at least one-third of smokers in the USA have a psychiatric disorder or another addiction.2 Thus, it will be important to conduct studies including these subject populations as well. Indeed, the authors identified numerous ongoing trials in these areas. In addition, clinical trials generally provide more psychosocial treatment than those provided in clinical settings. It will also be important to show the efficacy of varenicline in real-world settings.
This meta-analysis supports the safety of varenicline up to 1-year duration. These findings do not support the postmarketing reports of depressed mood, agitation and suicidal behaviour or ideation associated with varenicline treatment. However, due to the selection biases of the included studies, the absence of these putative severe adverse events in this review is by no means dispositive. The causal relationship of these side effects to varenicline treatment or smoking cessation effect remains to be determined.
Competing interests MEM has received unrestricted research grants, including salary support, from Pfizer. MS and DD have no conflicting interests.
Grant BF, Hasin DS, Chou SP, et al. Nicotine dependence and psychiatric disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry 2004; Volume 61, Pages 1107- 1115.
Source Link: http://ebm.bmj.com/content/early/2011/03/09/ebm1200.extract
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