Where There’s Smoke: Cytisine versus Nicotine Replacement Therapy

Published - Written by Rena Xu

Motivation, it’s often said, is half the battle of behavior change.  In the battle against nicotine addiction, however, motivation alone may not be enough.  Mass media campaigns have helped to raise awareness about the dangers of smoking.  But for the majority of smokers who already want to quit, the question remains: how?

In 2006, a drug called varenicycline — more commonly known as Chantix — entered the market.  Chantix is a partial agonist of nicotinic acetylcholine receptors; it works in part by decreasing the pleasure response to smoking.  In Eastern Europe, a related drug called cytisine has been used for smoking cessation for some time.  Cytisine has the same mechanism of action as Chantix but is sold as a generic agent and is much cheaper.  Both agents work differently from nicotine replacement therapy (e.g., gum or patches), which directly supply nicotine to the body.

A study published this week in NEJM compared the effectiveness of cytisine versus nicotine replacement therapy for smoking cessation.  1300 adult smokers in New Zealand were randomized to receive either cytisine for 25 days or nicotine replacement therapy for 8 weeks.  Participants also received behavioral support.  The primary outcome was self-reported continuous abstinence after one month.

At one month, 40% of participants in the cytisine group reported continuous abstinence, as compared to 31% of those on nicotine replacement therapy (absolute difference of 9.3 percentage points; 95% confidence interval 4.2 to 14.5; number needed to treat = 11).  Abstinence was also higher with cytisine than with nicotine replacement therapy at two and six months.  And, time to relapse (resumption of smoking) was longer for patients in the cytisine group as compared to the nicotine replacement group (53 versus 11 days; hazard ratio 0.8, P=0.001).

Not surprisingly, whether patients were compliant with therapy made a difference.  In the cytisine group, the median time to relapse was 127 days among compliant participants, versus only 20 days among those who were non-compliant (P<0.001).  Unfortunately, compliance rates weren’t great – only 53% in the cytisine group, and 67% in the nicotine replacement therapy group.

There were more self-reported adverse events with cytisine than nicotine replacement therapy, with an incidence rate ratio of 1.7 (P<0.001).  The most commonly reported events were nausea and vomiting and sleep disorders.  The authors note, “The higher proportion of adverse events in the cytisine group may be due to reporting bias, since the known side effects of nicotine-replacement therapy could have been regarded as ‘normal’ by participants in the nicotine replacement therapy group who had previously received such therapy and could therefore have gone unreported.”

Today, cytisine use is mostly limited to Eastern Europe.  Considering it is much less expensive than Chantix ($20-$30 for the recommended 25 day treatment course of cytisine versus $500 for 12 weeks of Chantix), if cytisine is indeed more effective than nicotine replacement therapy, as the findings of this study suggests, then introducing it to a broader market could yield tremendous value.

What is your current approach to smoking cessation?  What has been your experience with Chantix?  If cytisine becomes available to you, how do you anticipate it will fit into your treatment algorithm? 

For more on this topic, view the NEJM Quick Take animation, narrated by editor-in-chief Jeffrey Drazen.

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