A New Solution to Nicotine Addiction? Maybe, Maybe Not
Last week’s headlines were pretty impressive:
“Smokers quit with cheap Bulgarian remedy. For as little as $6, there may be a smoking-cessation remedy that actually works.” Marthe Fourcade, Bloomberg, 9/29/11
“Soviet-era pill from Bulgaria helps smokers quit.” Maria Cheng, Associated Press, 9/29/11
“Smokers get chance to beat the habit with 12 pence tablets.” Denis Campbell, The Guardian, 9/28/11
This publicity was generated by a paper in The New England Journal of Medicine entitled “Placebo-Controlled Trial of Cytisine for Smoking Cessation” (N. Engl. J. Med. 2011; 365: 1193-1200). In this double-blind study, 740 smokers were equally divided into two groups: one taking a cytisine preparation sold in Bulgaria as Tabex, the other given placebo. After 4 weeks of dosing, treatment was stopped and the patients were monitored for a year, after which time 8.4% (31 participants) on cytisine and 2.4% (9 participants) on placebo had quit smoking. How does this compare with other smoking cessation regimens? A similar type of smoking cessation study published in the Journal of the American Medical Association (JAMA, 2006; 296: 56 – 63) showed that Chantix (varenicline) provided 23% continuous abstinence, buproprion 14.6% and placebo 10.3%.
The cytisine study is noteworthy in that, while its anti-smoking effects have been known for over 40 years, this is the first reported clinical trial done in a double-blind placebo controlled manner as required by regulatory agencies like the FDA. But the real driver and interest in this work is the fact that the Tabex brand of cytisine is cheap and available on-line. The leader of the NEJM study, Professor Robert West, predicted that “the publicity surrounding his findings would trigger a surge in people turning to websites to obtain it.” Costs of smoking cessation products vary from country to country, but generally the cost of a course of cytisine therapy is about 10 – 20% that of Chantix. That difference could mean big savings to agencies like Britain’s National Health Service and Medicare in the US.
But let’s not rush to get this drug just yet.
There are still few issues that need to be addressed. First of all, how effective is cytisine compared to the currently marketed agents? Unfortunately, the NEJM study does not include a “positive comparator,” either Chantix or buproprion, so that one can get a sense of how the efficacy of a current treatment compares directly with cytisine in the same study. Looking at the data, it doesn’t seem that cytisine is as effective as the other compounds. If cytisine is only half as effective in causing people to quit smoking, that will cause payers, physicians and patients to think twice about going to cytisine.
However, there is a much bigger issue facing cytisine use – safety. While Tabex had been available in all former socialist countries since the early 1960s, it was withdrawn by many of these countries when they joined the European Union. Safety concerns could have been the reason. The Tabex preparation originates from the plant “Cytisus laborinum L.” Interestingly, there are reports of people getting poisoned with the seeds of this plant. J.F. Etter, in the review article “Cytisine for smoking cessation” (Arch. Intern. Med. 2006; 166, 1553 – 1559), states that “Poisoning in children who eat laborinum seeds is frequent” and that “in an average summer over 3,000 children are admitted to hospitals in England and Wales because of laborinum poisoning.” The symptoms, which include nausea, abdominal pain, respiratory stimulation, and muscle weakness, are consistent with poisoning symptoms with nicotine, which is related chemically as cytisine. Clearly, eating these seeds results in a large overdose of cytisine and the Tabex dose levels of cytisine are much lower. But this points out the need for extensive safety studies for cytisine. The side-effects of Chantix and bupropion are well-known. But these adverse effects were found as a result of the extensive data safety monitoring that has been accumulated by the manufactures over the years these drugs have been on the market. To my knowledge, such an adverse event monitoring system has not been in place for Tabex.
Peter Hajek, director of the Tobacco Dependence Unit at Queen Marry University Hospital in London, said the following to the Associated Press: “It is possible that extensive bureaucracy and over cautious regulations will prevent its (cytisine’s) use in the U.S. and Europe.” One would think that a person in his position would want to be assured of the safety of a drug before it was extensively prescribed.
There is no doubt that cytisine, in the form of Tabex, is a cheap way to help one stop smoking. But is it more effective and safer than existing medicines? That can’t be answered with the current data and more studies are needed. Furthermore, by the time these types of clinical trials are carried out, the generic form of Chantix, varenicline, will be available (2018), making the cost arguments moot.