Cytisine (Tabex)

The molecule Cytisine has been used as an anti-smoking treatment in Eastern Europe for several decades. Studies on its effects have been published since 1967, but none of the early trials conformed to modern scientific standards. Today, everything has changed with the appearance of the first big study showing that Cytisine is effective for smoking cessation. Let's take a closer look at this medicine.

A molecule used in smoking cessation for 40 years

Cytisine is an alkaloid present in all parts of the Cytisus Laburnum plant, especially its seeds. It works in a similar way to nicotine, and the leaves of of Cytisus Laburnum were used as a tobacco substitute during the Second World War. Russian soldiers referred to the plant as "fake tobacco". In 1978, the tobacco industry defined cytisine as the substance whose pharmacological action most closely resembled that of nicotine. An agonist of the nicotine receptors alpha4beta2, cytisine has been used in Eastern Europe as a nicotine substitute for 40 years. The molecule has been commercially packaged by a Bulgarian company under the trade name Tabex. So what are its advantages? Firstly, cytisine tablets can be produced very cheaply, which is why a 25-day Tabex treatment in Russia, Poland or Bulgaria is between 5 and 15 times cheaper than using nicotine patches or gum for the same length of time. In addition, the treatment is short, lasting only 25 days. Each Tabex tablet contains 1.5 mg of cytisine. Quitters should take 6 tablets a day for the first three days after they quit smoking, and then reduce this to 2 tablets a day until day 25, the last day of treatment. Physicians advise that people who suffer from high blood pressure or advanced atherosclerosis should not take Tabex. Despite many years of use in Eastern Europe, cytisine has not yet received authorisation for market sale in Western Europe or the United States because of the lack of scientifically rigorous studies until recently.

Cytisine studies

Studies on the effectiveness of cytisine as an anti-smoking aid were conducted in East and West Germany, Poland and Russia from the 1960s onwards. Three placebo-controlled trials were carried out in East and West Germany in the 1960s and 70s. These studies suggested that cytisine might help smoking cessation and that the product was generally well tolerated by patients, notwithstanding some side effects including weight gain, headaches and heartburn. Sickness, dizziness, diarrhoea and digestive problems were also reported in some studies, but always either without placebo control or without a noticeable difference compared to the placebo. Still other studies recorded that cytisine affected blood pressure, but the figures varied greatly between studies. It should be noted that the side effects suggested by the various studies are not the same as those indicated by the Tabex manufacturer, namely: changes in taste or appetite, dry mouth, headaches, irritability, sickness, constipation, increased heart rate and slightly raised blood pressure. As a partial agonist of nicotine, cytisine produces the same side effects as Nicotine Replacement Therapy (NRT) and varenicline.

On the other hand, none of these studies was carried out in accordance with present-day rules governing the quality of clinic trials. Pre-clinical studies on optimal dosage, which usually precede such trials, were never conducted. Studies of greater weight and scientific rigor were therefore required to ensure that the medicine could satisfy regulations concerning therapeutic goods in Europe and the USA. The first big study was conducted recently and its results were published in The New England Journal of Medicine in September 2011.

A new study demonstrates cytisine's effectiveness

British researchers at University College London carried out a randomised, double-blind study on monocentric cytisine using 740 participants who smoked more than 10 cigarettes a day. Participants received either cytisine (6 1.5 mg tablets for 3 days, then 5 tablets for 9 days, 4 tablets for 4 days, 3 tablets for 4 days, and 2 tablets for the last 5 days) or a placebo, for 25 days in total. Twelve months after the treatment, the cessation success rate was 8.4% in the group who had taken cytisine, compared to 2.4% in the placebo group. The relative difference between the two groups (relative rate = 3.4) is higher than that obtained with NRT (1.6) or varenicline (2.3) in placebo-controlled studies. As for side effects: gastro-intestinal problems (stomach ache, sickness), dizziness and problems sleeping were more frequently reported by the "cytisine" group than the "placebo" group.

The authors of this study concluded that cytisine really is effective for smoking cessation. It remains to be seen if a longer treatment will improve the figures- treatment is 8 weeks for NRT and 12 weeks for varenicline - and whether an approach combining cytisine with professional psychological support will also improve the success rate of the drug. Other studies including more participants should also be undertaken to assess rare side effects linked to cytisine, even if reports from countries where cytisine is available on the market are encouraging. Negative neuropsychiatric effects have been reported by people taking verenicline, however, and as cytisine is a similar medicine, we can expect it to produce similar effects.

These first results are nevertheless promising and they give cause for hope that cytisine may be an effective, low-cost anti-smoking treatment which would be particularly attractive to countries or people with relatively modest budgets.

Manufacturer's website

References

Auteur: Anne-Sophie Glover-Bondeau / novembre 2011

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