More quit smoking with new drug than bupropion
Satisfaction reduced with new smoking cessation drug |
Varenicline, a partial agonist of the a4b2 nicotinic acetylcholine receptor, is better at helping people to stop smoking and to stay abstinent than both placebo and bupropion SR, according to three studies conducted by the Varenicline Phase 3 Study Group and published in JAMA last week.
Two of the studies randomised around 1,000 participants to receive 12
weeks of varenicline 1mg twice daily, placebo or bupropion SR 150mg twice
daily, plus weekly brief smoking cessation counselling. Follow-up was
for 52 weeks. The third study looked at maintenance therapy by giving
1,210 participants 12 weeks of open-label varenicline plus 12 weeks of
additional treatment or placebo.
In one of the comparison trials (JAMA 2006;296:56) the short-term and
long-term efficacy of varenicline exceeded that of bupropion SR and placebo.
During the last four weeks of treatment, 43.9 per cent of participants
in the varenicline group stopped smoking compared with 17.6 per cent
in the placebo group (odds ratio 3.85, 95 per cent confidence interval
2.69–5.50; P<0.001) and 29.8 per cent in the bupropion group
(OR 1.90, CI 1.38–2.62; P<0.001).
At 24 weeks, 29.7 per cent in the varenicline group were abstinent compared
with 13.2 per cent in the placebo group (OR 2.83, CI 1.91–4.19; P<0.001) and 20.2 per cent in the bupropion group (OR 1.69, CI 1.19–2.42; P=0.003).
At 52 weeks, the abstinence figures were 23 per cent in the varenicline
group compared with 10.3 per cent in the placebo group (OR
2.66, CI 1.72–4.11; P<0.001) and 14.6 per cent in the bupropion
group (OR 1.77, CI 1.19–2.63; P=0.004).
The second comparison trial (ibid, p47) yielded similar results except
that varenicline was not significantly more efficacious than bupropion
at week 52 (21.9 per cent versus 16.1 per cent; P=0.057). The researchers
explain that partial agonists can work by two mechanisms. By partially
activating the a4b2 nicotinic acetylcholine receptor they can alleviate
craving mechanisms and, by occupying part of the receptors and blocking
nicotine binding, they can reduce smoking satisfaction. Both of these
effects were observed in this trial, they say.
The maintenance study (ibid, p64)
showed that, during the treatment phase, the abstinence rate was higher
in the varenicline group than in the placebo
group (70.5 per cent versus 49.6 per cent, OR 2.48, CI 1.95–3.16; P<0.001).
This difference was maintained at 52-week follow-up (P=0.02).
The most frequent adverse effect to varenicline reported in the three
trials was nausea, which occurred in about 30 per cent of participants.
JAMA editorial comment
The authors of an accompanying editorial (ibid,
p94), believe that the relapse prevention results reported in
the maintenance
study are probably more optimistic than would occur in the real
world since they only take into account people who had quit at
12 weeks. “By eliminating participants who failed to quit
smoking in the open label phase, the authors have eliminated one
third of individuals for whom this drug does not appear to be effective,” they
say. “Varenicline definitely is not a panacea for smoking
cessation,” they add. However, they acknowledge that varenicline
represents a third class of drugs, with a different mechanism of
action to nicotine replacement therapy and bupropion, and which
studies have shown is associated with better quit rates than placebo,
and may produce better quit rates than bupropion. |
|
The
Pharmaceutical Journal
Acrobat
Reader