Issue 38.
Bupropion to aid smoking
cessation
This article summarises a recent Drugs and Therapeutics
Bulletin article. As the topic is an important one we have given this quite a
lot of space.
Around 1 in 4 adults in the UK smoke cigarettes and about
two-thirds say they would like to give them up. However, giving up permanently
is difficult, and each year, only about 2% of all smokers manage to do so.
Bupropion (Zyban-Glaxo Wellcome) has recently been licensed “as an aid to
smoking cessation in combination with motivational support”. The
manufacturer claims that there is evidence that the drug is “almost twice as
effective as a nicotine patch in achieving smoking abstinence at one year”.
Here, we assess the efficacy and safety of bupropion in helping people stop
smoking.
The efficacy of bupropion as an aid to smoking cessation
has been investigated in two randomised, double-blind, placebo-controlled
trials. Smokers were recruited via advertisements in the media (a method
thought more likely to attract smokers highly motivated to quit). Recruits
were initially smoking at least 15 cigarettes daily. Exclusion criteria
included serious or unstable medical or psychiatric disorders, including
depression or alcohol dependence.
The participants received trial treatment in conjunction
with individual regular brief counselling. Their self-reports of smoking
cessation were verified by measuring carbon monoxide content in expired air.
In the first study the proportion of smokers who had
continuously abstained in the placebo group (10.5%) was lower but not
statistically significantly so to that in the bupropion 100mg (13.7%) and
150mg groups (18.3%), but significantly lower than that in the 300mg group
(24.4%).
At 12 months, the point-prevalence smoking cessation rate
(the proportion of participants who had not smoked during the previous 7 days)
was again lower but not significantly so in those who received placebo (12.4%)
and bupropion 100mg (19.6%), but significantly greater in those who received
bupropion 150mg (22.9%) or 300mg (23.1%). The study did not report continuous
abstinence rates at 12 months, a measure conventionally used in smoking
cessation studies and a more reliable indicator of long-term treatment
effectiveness.
The second study randomised 893 smokers to one of four
treatments for 9 weeks (oral and patch); oral bupropion 300mg daily plus
placebo patch; nicotine skin patch (Habitrol, marketed in the UK as Nicotinell)
plus oral placebo; or combined bupropion 300mg daily plus the nicotine patch.
At 12 months, the point-prevalence rate of abstinence with bupropion alone
(30.3%) was around double that seen with nicotine patch alone (16.4%) or
placebo (15.6%). Continuous abstinence rates at 12 months did not differ
significantly between the two bupropion groups (18.4% with bupropion alone vs
22.5% with bupropion plus nicotine patch), and these rates were higher than in
the other two groups (9.8% with nicotine patch alone and 5.6% with placebo).
A meta-analysis of continuous abstinence rates from one of the published
trials and
from two unpublished trials (involving a total of 235
patients), together with 12-month point-prevalence rates from the other
published trial, gave an estimated odds ratio of 2.7 (95% CI 1.9-3.9) for
achieving abstinence from smoking at 12 months with bupropion relative to
placebo. However, this result should be viewed with caution given the
heterogeneous and unpublished data used to generate it.
Bupropion is contraindicated in patients with epilepsy
(past or present) and should be used with “extreme caution” in patients
who have conditions predisposing to a lowered seizure threshold (eg history of
head trauma); are at an increased risk of seizures (eg diabetics treated with
hypoglycaemics or insulin, patients taking stimulants or appetite suppressants
or because of alcohol abuse); or are taking drugs that lower seizure threshold
(e.g. theophylline, antipsychotics, antidepressants and systemic
corticosteroids).
Bupropion is also contraindicated in pregnancy and in those
with a history of anorexia nervosa or bulimia, severe hepatic cirrhosis, or a
history of bipolar disorder. Bupropion should not be used together with a
monoamine-oxidase inhibitor (MAOI), including selegiline; at least 14 days
should elapse between discontinuation of MAOI therapy and starting bupropion.
Oral bupropion is available on the NHS as a
prescription-only medicine. When used in a specialist setting and in
conjunction with regular counselling, bupropion is at least twice as effective
as placebo in helping patients to stop smoking.
Bupropion should therefore only be used in conjunction with
expert counselling, for example, from a specialist clinic. At present, there
is no clear evidence to favour bupropion over NRT in terms of efficacy. Choice
may depend on the unwanted effects and drug interaction profiles of bupropion
and nicotine preparations and also on the cost of these treatments as well as
that of any specialist counselling.
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Grey literature and Meta-analyses
The Lancet had a recent article on this subject.
Missing out evidence from the grey literature in a
meta-analysis may introduce biases and threaten the validity of the findings.
A study set out to examine whether exclusion of grey literature, compared with
its inclusion in meta-analysis, provided different estimates of the
effectiveness of interventions assessed in randomised trials.
From a random sample of 135 meta-analyses, it identified
and retrieved 33 publications that included both grey and published primary
studies. The 33 publications contributed 41 separate meta-analyses from
several disease areas. General characteristics of the meta-analyses and
associated studies and outcome data at the trial level were collected. They
explored the effects of the inclusion of grey literature on the quantitative
results using logistic-regression analyses.
33% of the meta-analyses were found to include some form of
grey literature. The grey literature, when included, accounted for between
4.5% and 75% of the studies On average, published work, compared with grey
literature, gave 15% larger estimates of the effect of the intervention by
15%. Excluding abstracts from the analysis further compounded the exaggeration
.
The exclusion of grey literature from meta-analyses can
lead to exaggerated estimates of intervention effectiveness. In general,
meta-analysts should attempt to identify, retrieve, and include all reports,
grey and published, that meet predefined inclusion criteria.
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