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Cytisine: Another Option for Smoking Cessation

By: Andrew Leong, Staff Writer

Quitting smoking greatly reduces the risk of many diseases such as lung cancer, coronary heart disease, and stroke, all of which increase morbidity and mortality in patients. Currently in North America, there are three main pharmacological therapies used in the management of smoking cessation. The most recognizable one, nicotine replacement therapy (NRT), can come as a patch, gum, or lozenge. Antidepressants, such as bupropion and nortriptyline, also have some use as smoking cessation therapies. Finally, varenicline is a nicotinic receptor partial agonist and works by binding to the receptor more weakly than nicotine, therefore reducing cravings and withdrawal symptoms.1

Cytisine is another nicotinic receptor partial agonist that has been used since the 1960s in Eastern Europe. Four systematic reviews were conducted and they all found that cytisine was superior to placebo for short-term and long-term abstinence. Cytisine was also shown to have no significant increase in adverse effects when compared to placebo although gastrointestinal symptoms were more common.2

In a recent parallel-group, open label, randomized, controlled, noninferiority trial, it was hypothesized that 25 days of cytisine (the manufacturer’s recommendation3) plus low-intensity behavioral support would be at least as effective as 8 weeks of NRT plus low-intensity behavioral support for smoking cessation.4 Conducted in New Zealand, it is the first study that has compared these two treatment modalities.

Participants were at least 18 years of age, daily smokers, and motivated to quit. Exclusion criteria were chosen on the basis of varenicline-related concerns such as self-reported pheochromocytoma, a blood pressure above 150/100 mmHg, or pregnancy. Participants were also excluded if they were already taking cessation medication or if they were already in another cessation program or study. The primary endpoint of the study was self-reported continuous abstinence from smoking for one month after quit date. After all criteria were met, 655 participants were chosen for each study arm.4

The study found that cytisine was non-inferior to nicotine-replacement therapy: 1 month continuous abstinence rates were significantly higher in the cytisine group than in the NRT group (40% vs. 31%, p<0.001). Additionally, at each of the point-prevalence abstinence times (1 week, 1 month, 2 month, and 6 month), cytisine was statistically significantly superior to NRT. At 1 week, 41% of the cytisine participants had abstained versus the 30% of the NRT participants (p< 0.001). At 1 month, 42% had abstained versus 33% (p<0.001). At 2 months, 38% had abstained versus 32% (p=0.020). At 6 months however, results were not statistically significant (31% vs. 30%, p=0.549).4

Approximately 53% of participants were adherent to the guidelines for cytisine treatment (they had taken at least 80 tablets), whereas 67% in the NRT group were adherent with treatment guidelines (they had used NRT at both 1 week and 1 month). While this could mean any number of things, the most probable reason is the adverse event profile. As expected of a varenicline analogue, 31% of participants in the cytisine group had experienced some type of adverse effect compared to 20% in the NRT group. The most common of these adverse effects were nausea and vomiting (5% vs. < 1%) and sleep disorders (4% vs. < 1%).4

Because the study was not completely blinded, there is potential bias. The study authors concluded that “… researchers were aware of treatment allocation, [and] there may have been a reporting bias in favor of cytisine.” Another possible bias was the fact that participants in the cytisine group received a 25-day course of tablets by courier while participants in the NRT group received vouchers from Quitline that were redeemable from community pharmacies for various NRTs. Couriers could have been given to both groups to eliminate any skew in results. In addition, according to the Word Health Organization (WHO), “an ex-smoker is considered a subject who has been abstinent for a period of at least 1 year.”4 This is in contrast to the 1-month abstinence primary endpoint of the trial. Thus, the trial may not be reflective of real-world patient populations.

With this trial, there may be increased interest in bringing cytisine to market beyond Eastern Europe. Practically speaking, cytisine is a lower cost cessation option compared to current therapies; a full regimen costs $20-$35, compared to $70 for NRT (although prices can often be higher depending on severity of addiction), $116 for bupropion, and $277 for varenicline.1,6,7 Due to the seemingly significant cost differences, the study authors conclude that a head-to-head, non-inferiority trial between cytisine and varenicline is justified. Cytisine seems to be another viable, first-line therapy for smoking cessation, and may be a better alternative to current smoking cessation therapies.


  1. Lexicomp. Varenicline (Lexi-Drugs). Lexicomp website. Available at http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/512661. Accessed March 29, 2015.
  2. Hajek P, McRobbie H, Myers K. Efficacy of cytisine in helping smokers quit: systematic review and meta-analysis. Thorax. 2013;68:1037-1042.
  3. Biogenic Stimulants. Tabex. Tabex Web site. https://www.tabex.net. Accessed March 8, 2015.
  4. Walker N, Howe C, Glover M, et al. Cytisine versus nicotine for smoking cessation. N Engl J Med. 2014;371(25):2353-62.
  5. WHO; World Health Organization Classification of Diseases ICD 10, 2015; Chapter: Mental and behavioural disorders due to psychoactive substance use (F10-F19).
  6. Lexicomp. Nicotine (Lexi-Drugs). Lexicomp website. Available at http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7365. Accessed March 29, 2015.
  7. Lexicomp. Bupropion (Lexi-Drugs). Lexicomp website. Available at http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6485. Accessed March 29, 2015.


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