BACKGROUND: Nicotine receptor partial agonists may help smokers to quit by a 
combination of maintaining moderate levels of dopamine to counteract withdrawal 
symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an 
antagonist). Varenicline was developed as a nicotine receptor partial agonist 
from cytisine, a drug widely used in central and eastern Europe for smoking 
cessation. The first trial reports of varenicline were released in 2006, and 
further trials are underway.
OBJECTIVES: The primary objective of this review is to assess the efficacy and 
tolerability of nicotine receptor partial agonists, including varenicline and 
cytisine, for smoking cessation.
SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group's specialised 
register for trials, using the terms ('varenicline' or 'cytisine' or 'Tabex' or 
'nicotine receptor partial agonist') and 'smoking' in the title or abstract, or 
as keywords. We also searched MEDLINE, EMBASE, PsycINFO and CINAHL using MeSH 
terms and free text, and we contacted authors of trial reports for additional 
information where necessary. The last search was in October 2006.
SELECTION CRITERIA: We included randomized controlled trials which compared the 
treatment drug with placebo. We also included comparisons with bupropion where 
available. We excluded trials which did not report a minimum follow-up period of 
six months from start of treatment.
DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of 
participants, the dose and duration of treatment, the outcome measures, the 
randomization procedure, concealment of allocation, and completeness of follow 
up. The main outcome measured was abstinence from smoking after at least six 
months from the beginning of treatment. We used the most rigorous definition of 
abstinence, and preferred biochemically validated rates where they were 
reported. Where appropriate we performed meta-analysis using the Mantel-Haenszel 
fixed-effect model.
MAIN RESULTS: We found five trials of varenicline compared with placebo for 
smoking cessation; three of these also included a bupropion experimental arm. We 
also found one relapse prevention trial, comparing varenicline with placebo. The 
six trials covered 4924 participants, 2451 of whom used varenicline. We 
identified one trial of cytisine (Tabex) for inclusion. The pooled odds ratio 
(OR) for continuous abstinence at 12 months for varenicline versus placebo was 
3.22 (95% confidence interval [CI] 2.43 to 4.27). The pooled OR for varenicline 
versus bupropion was 1.66 (95% CI 1.28 to 2.16). The main adverse effect of 
varenicline was nausea, which was mostly at mild to moderate levels and usually 
subsided over time. The two trials which tested the use of varenicline beyond 
the 12-week standard regimen found the drug to be well-tolerated and effective 
during long-term use. The one cytisine trial included in this review found that 
more participants taking cytisine stopped smoking compared with placebo at 
two-year follow up, with an OR of 1.77 (95% CI 1.30 to 2.40).
AUTHORS' CONCLUSIONS: Varenicline increased the odds of successful long-term 
smoking cessation approximately threefold compared with pharmacologically 
unassisted quit attempts. In trials reported so far, more participants quit 
successfully with varenicline than with bupropion. The effectiveness of 
varenicline as an aid to relapse prevention has not been clearly established. 
The main adverse effect of varenciline is nausea, but this is mostly at mild to 
moderate levels and tends to reduce with habituation. There is a need for 
independent trials of varenicline versus placebo, to test the early findings. 
There is also a need for direct comparisons with nicotine replacement therapy, 
and for further trials with bupropion, to establish the relative efficacy of the 
treatments.Cytisine may also increase the chances of quitting, but the evidence 
at present is inconclusive.