バレニクリンに関するまとめの論文

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2010年12月20日(Mon) 17:07

[Intervention Review]
Nicotine receptor partial agonists for smoking cessation (Archive)

Kate Cahill1, Lindsay F Stead1, Tim Lancaster1

1Department of Primary Health Care, University of Oxford, Oxford, UK

Contact address: Kate Cahill, Department of Primary Health Care, University of Oxford,
Rosemary Rue Building, Old Road Campus, Oxford, OX3 7LF, UK. kate.cahill@dphpc.ox.ac.uk.

Editorial group: Cochrane Tobacco Addiction Group.
Publication status and date: Edited (no change to conclusions), published in Issue 1, 2009.
Review content assessed as up-to-date: 14 March 2008.

Citation: Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking
cessation. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD006103.
DOI: 10.1002/14651858.CD006103.pub3.

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Abstract

Background
Nicotine receptor partial agonists may help people to stop smoking 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 have now been published or are currently 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 latest search was in March 2008.

Selection criteria
We included randomized controlled trials which compared the treatment drug with placebo.
We also included comparisons with bupropion and nicotine patches 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 to produce a risk ratio, using the Mantel-Haenszel fixed-effect model.

Main results
We found seven trials of varenicline compared with placebo for smoking cessation; three of
these also included a bupropion experimental arm. We found one relapse prevention trial,
comparing varenicline with placebo. We also found one open-label trial comparing varenicline
with nicotine replacement therapy. The nine trials covered 7267 participants, 4744 of whom
used varenicline. We identified one trial of cytisine (Tabex) for inclusion.

The pooled risk ratio (RR) for continuous abstinence at six months or longer for varenicline
versus placebo was 2.33 (95% confidence interval [CI] 1.95 to 2.80). The pooled RR for
varenicline versus bupropion at one year was 1.52 (95% CI 1.22 to 1.88). The RR for
varenicline versus NRT at one year was 1.31 (95% CI 1.01 to 1.71). The two trials which
tested the use of varenicline beyond the 12-week standard regimen found the drug to be
well-tolerated during long-term use. The main adverse effect of varenicline was nausea,
which was mostly at mild to moderate levels and usually subsided over time. Post-marketing
safety data suggest that varenicline may be associated with depressed mood, agitation, and
suicidal behaviour or ideation. The labelling of varenicline has been amended, and the FDA
is conducting a safety review.

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 RR of 1.61 (95% CI 1.24 to 2.08).

Authors' conclusions
Varenicline increased the chances of successful long-term smoking cessation between two-
and threefold compared with pharmacologically unassisted quit attempts. More participants
quit successfully with varenicline than with bupropion. One open-label trial of varenicline
versus nicotine replacement therapy demonstrated a modest benefit of varenicline. The effectiveness
of varenicline as an aid to relapse prevention has not been clearly established. The main
adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to
subside over time. Possible links with serious adverse events, including depressed mood,
agitation and suicidal thoughts, are currently under review.

There is a need for independent community-based trials of varenicline, to test its efficacy
and safety in smokers with varying co-morbidities and risk patterns. There is a need for further
trials of the efficacy of treatment extended beyond 12 weeks. Cytisine may also increase the
chances of quitting, but the evidence at present is inconclusive.

Plain language summary (簡単なまとめ)

Can nicotine receptor partial agonists, including varenicline and cytisine, help people to stop smoking
The treatment aims to reduce withdrawal symptoms and smoking satisfaction. We found nine randomized
controlled trials of varenicline, covering more than 7000 participants. Three of the trials included
a direct comparison with bupropion. One trial was a comparison between varenicline and nicotine patches.
From these data, varenicline increased the chances of quitting between two- and three-fold compared
with placebo. The number of people stopping smoking with varenicline was higher than with bupropion.
The trial with nicotine patches showed a modest benefit of varenicline over the patches. The main
adverse effect of varenicline was nausea, but this was mostly at mild or moderate levels and usually
subsided over time. There are recent concerns that varenicline may be linked with depressed mood,
agitation or suicidal thinking and behaviour in some smokers.
The evidence on cytisine is limited at present, and no firm conclusions can yet be drawn about its
effectiveness as an aid to quitting.


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