A Drug Better Than Nicotine for Smoking Cessation?

Nicholas Gross, MD, PhD


January 23, 2015

Study Summary

Cytisine Versus Nicotine for Smoking Cessation

Walker N, Howe C, Glover M, et al
N Engl J Med. 2014;371:2353-2362

To counter one of the most potent enemies to the health of humans, we as clinicians are always looking for effective smoking cessation modalities.

Nicotine replacement therapy, which can be undertaken in a variety of methods, is the most widely used method to date. However, short- and long-term smoking cessation is not very widely achieved through the use of nicotine itself.

An agonist of the nicotine acetylcholine receptor, such as varenicline, seems to be more effective than nicotine replacement therapy without unacceptably serious adverse events.

Cytisine (not to be confused with the nucleic acid base cytosine) is a plant alkaloid that is a partial agonist of the nicotinic receptor. It has been used mainly as a smoking cessation modality in Eastern Europe, from which a few clinical trials show efficacy in smoking cessation.

The present trial was conducted in New Zealand. Investigators recruited 1310 long-term smokers who were motivated to quit smoking. They were randomly assigned to receive oral cytisine for 25 days or nicotine replacement (via patches, gum, or lozenges) for 8 weeks. The trial design was "open-label" and "noninferiority." The primary outcome was continuous smoking abstinence at 1 month.

At 1 month, 40% of those in the cytisine group were determined to be continuously smoking-free, versus 31% of the nicotine-replacement group (P < .001).

Although relapses after 1 month were seen in both treatment arms, continuous withdrawal remained more common in the cytisine group through the observation period, which lasted 6 months.

Adverse events were significantly more common in the cytisine group, with a rate ratio of 1.7 to 1.0. Adverse events in both groups included nausea, vomiting, and sleep disturbances. In subgroup analyses, cytisine was more effective than nicotine replacement in women.


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