COMMENTARY

Cytisine and Cigarettes

Jacqueline A. Hart, MD

Disclosures

October 03, 2006

Cytisine for Smoking Cessation: A Literature Review and a Meta-analysis

Etter JF
Arch Intern Med. 2006;166:1553-1559

To evaluate the effectiveness of an alkaloid derivative of the plant Cytisus laburnum L., or golden rain tree, known as cytisine (not to be confused with cytosine or cysteine), a review of the literature and a meta-analysis were conducted. Ten studies reporting the effects of cytisine on smoking cessation, published between the years 1967 and 2005, were identified, including 3 placebo-controlled trials. The studies, all from Bulgaria, Germany, Poland, and Russia, involved a total of 4404 smokers treated with cytisine and 3518 controls.

Quit/abstinence rates, based on survey (not biochemical) assessment, ranged from 13.8% to 70% anywhere from 15 days to 14 months following treatment with cytisine. Meta-analysis of the 3 placebo-controlled trials revealed an odds ratio (OR) of 1.93 (95% confidence interval [CI], 1.21-3.06) for short-term outcome of 4 weeks. A separate meta-analysis of the 2 placebo-controlled trials that had long-term follow-up found a pooled OR of 1.83 (95% CI, 1.12-2.99) for continued abstinence after 3-6 months. One placebo-controlled study reported abstinence rates 2 years post cytisine treatment with an OR of 1.77 (95% CI, 1.29-2.43).

The most common form of cytisine is a tablet containing 1.5 mg of the active ingredient. Recommended dose is 6 tablets per day (total of 9 mg of cytisine) for the first 3 days with a gradual taper to 2 tablets per day by day 25 at which point the treatment is stopped. Another mode of delivery is a film placed between the gum and lip containing either 1.5 mg of cytisine or 0.75 mg of cytisine and 0.75 mg of anabasine. Patients are instructed to use 4-6 films per day for 5 days, gradually decreasing until day 15. The films take 1.5 hours to dissolve in the person's mouth.

Manufacturers of cytisine list hypertension and advanced atherosclerosis as contraindications. Potential side effects include:

  • Weight gain;

  • Change in taste and appetite;

  • Dryness in the mouth;

  • Headache;

  • Irritability;

  • Nausea;

  • Heartburn;

  • Vertigo;

  • Digestive problems, including either constipation or diarrhea; and

  • Tachycardia.

Despite use of C laburnum leaves as a tobacco substitute dating back to World War II and use of cytisine (marketed by a Bulgarian company as Tabex) for smoking cessation in Germany and Eastern Europe for decades, the English scientific literature pays virtually no attention to the potentials of this plant-based treatment for quitting nicotine. In fact, recent reviews of options for smoking cessation[1] make no mention of either cytisine or varenicline, a drug derived from this plant alkaloid approved by the United States Food and Drug Administration in May 2006.[2] Not only does this reflect a concerning bias or prejudice against studies published in non-English languages, but it also may limit the options available to patients.

To play devil's advocate, however, the quality of the studies conducted regarding cytisine may not have been up to "current" standards of smoking cessation trials and this might explain their exclusion from English journals. For example, only 1 of the cytisine studies reviewed in this article used biochemical (rather than survey) verification of smoking status — a practice considered standard today. Also, of the 3 placebo-controlled studies evaluating cytisine, only 1 described a clear randomization process. Similarly, some of the early, poor-quality trials reported unrealistically high quit rates of 60% to 70%. The quit rates from the 3 placebo-controlled studies included in this review and meta-analysis, however, were comparable to short-term outcomes and quit rates found in reviews of other smoking cessation drugs such as bupropion.[1]

Given this comparability, the investigator of this review suggests that, at the very least, the English literature should pay credence to the possibility that cytisine may be an option for smoking cessation and that further studies assessing this possibility should be conducted, particularly in the areas of toxicity and with use of adjunctive behavioral interventions. I agree with him.

Abstract

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