Pharmacological therapy is relatively cost-effective whenadded to smoking cessation counsellingAbstracted from: Song F, Raftery J, Aveyard P et al. Cost-effectiveness of pharmacological interventions for smoking cessation: aliterature review and a decision analytical analysis. Med Dec Making 2002; 22: S26 ^S37.
sustained release bupropion are pharmacological agents tal cost per life-year saved ($US for year 2000).
that may help people quit smoking. Numerous studieshave suggested that these treatments have modestbene¢ts, but their relative cost-e¡ectiveness remainsuncertain.
cost-e¡ective for smoking cessation. No published stu-dies evaluated the cost-e¡ectiveness of sustained release bupropion relative to other pharmacological options.
ness of nicotine replacement therapy and sustained re- Compared with advice or counselling alone, the lease bupropion for smoking cessation.
incremental cost per life-year saved is US$920 to $2150for bupropion; US$1441 to $3455 for nicotine replace-ment therapy, and US$1282 to $2836 for nicotine repla- Systematic review with cost-e¡ectiveness cement therapy plus bupropion (Table 1).
analysis based on a decision analytic model from theUK National Health Service perspective.
vice or smoking cessation counselling, nicotine replace- National Health Services Economic Evaluation Data- ment therapy and sustained release bupropion are base at the University of York, MEDLINE, the internet more cost-e¡ective than many accepted healthcare and reference lists from retrieved articles.
Source of funding: UK National Health Service Research and Development HealthTechnology Assessment Programme.
were considered most relevant if they estimated thecost-e¡ectiveness of nicotine replacement therapy in Correspondence to: F Song, Department of Public Health and the United Kingdom. Studies of pharmacological Epidemiology, University of Birmingham, UK.
interventions in other countries were also eligible. Theauthors do not describe the data extraction process.
Incremental cost-e¡ectiveness of pharmacological options for smoking cessation Point estimate of incremental cost compared with Brief advice plus nicotine replacement therapy Brief advice plus sustained release bupropion Brief advice plus nicotine replacement plus bupropion Counselling plus nicotine replacement therapy Counselling plus nicotine replacement plus bupropion Evidence-based Healthcare (2003) 7, 44 ^ 46 1462-9410/03/$ - see front matter & 2003 Elsevier Science Ltd. All rights reserved other pharmacological interventions, such as anxiolytics, lobe-line, mecamylamine, opioid antagonists and silver acetate, re- Smoking cessation has a long history. Anti-smoking campaigns mains equivocal at best. The clinical usefulness of such have been reported asfar back asthe 17th and 18th centuries. It treatmentsmay be limited by their adverse effect profile. It is isonly recently, however, that nicotine hasbeen accepted asthe therefore likely that nicotine replacement therapy and bupropion principal addictive component of tobacco. We now realise that will remain the first-line pharmacological interventions in the smoking initiation will result in addiction in many cases.1 This commentary providesa context for Song'spaper, before examin- Within the United Kingdom, both of these products have re- ing itsimplicationsfor policy and practice.
cently become available on National Health Service prescription.
It iswell established that smoking isunhealthy. The seminal An overwhelming majority of GPs(96%) and practice nurs work of Doll and Peto and othersin the United Statesin the (99%) accept that intervening in smoking is part of their role.4 1950s found an association between cigarette smoking and lung Most patients (80%) see their GP at least once each year. Never- cancer. Epidemiological studies suggest that smoking is asso- theless, only 29% of smokers who have seen their GP in the pre- ciated with a number of other adverse health consequences. In- viousyear recall having been given advice to stop smoking. If this creased mortality and morbidity in smokers is a consequence of isa true reflection of practice, thismay be because GPsare keen the variouscomponentsof cigarette smoke, and there isnow a to avoid negative responses from patients and to maintain good far clearer understanding of the biological basis of these associa- relationships. It may also be because GPs' main focus is the treat- tions. More than one quarter of adults in the United Kingdom ment of disease and their ethos is one of solving patients' com- smoke 15 or more cigarettes a day, while approximately 15% of plaints. GPs' attitudes towards smoking cessation medication children aged between 11 and 15 yearssmoke once a week or contrast with their perceived role in smoking cessation. In a sur- more. About 70% of adult smokers report that they are keen to vey published in October 2001, 43% felt that bupropion should stop, and one third of smokers make at least one attempt to stop not be available on NHS prescription and 50% thought that nico- in any given year. Only 2% of smokers, however, successfully stop tine replacement therapy should not be available.The reasons for smoking every year. Those who continue to smoke may be more thiscould include failure to accept that nicotine dependence isa addicted. Tobacco use is implicated in the deaths of around genuine medical disorder, a lack of sympathy for a 'self-inflicted' 120,000 people in the United Kingdom every year, or about 330 condition or low absolute efficacy rates.
every day. Thisamountsto approximately 20% of all deaths Most importantly in relation to this paper by Song and collea- Roughly half of regular cigarette smokers will die prematurely as gues, previous surveys have found that many GPs do not think a consequence of smoking. One quarter of regular smokers die that nicotine replacement therapy iscost-effective. Thismay be before the age of 70, losing on average 23 years of life. Smoking because of the low absolute success rates achieved. In general, is the single greatest cause of preventable illness and early death helping smokers to quit is somewhat thankless, and lives saved in the United Kingdom, dwarfing other causes such as traffic ac- in this way are less visible than those in the field of acute disease.
cidents.One point is central, however: it is never too late to stop, There isa need to make evidence about the cost-effectivenessof regardless of lifetime exposure to smoking.
pharmacological smoking cessation aids explicit and accessible to Meta-analyses of clinical trials suggest that the principal phar- those who can promote these aids. While studies of the cost-ef- fectiveness of nicotine replacement therapies are not new, the therapy2 and bupropion,3 are effective. Nicotine replacement evidence for the cost-effectiveness of bupropion is more limited, therapy isbased on a substitution therapy model, while bupro- ashighlighted in thispaper by Song and colleagues. The paper pion'smechanism of action remainssomewhat uncertain. The provides estimates of the cost-effectiveness of nicotine replace- substitution model suggests that withdrawal symptoms following ment therapy and bupropion in addition to (a doctor's) advice.
cessation are a consequence of nicotine deprivation.Thus, by re- Thisishighly relevant to both general practice and pharmacolo- placing some of the nicotine normally taken in while smoking, gical interventionsdelivered in other contexts, such assmoking withdrawal effects can be reduced and the likelihood of success- cessation clinics, where the intensity of advice or counselling may fully stopping smoking increased. This is the most commonly used pharmacological intervention for nicotine dependence.
Efforts to quantify the cost-effectiveness of medical interven- Nevertheless, it is not clear precisely how nicotine replacement tions rest on a number of critical assumptions, which may be therapy works. Even the most rapidly delivered nicotine replace- more or less robust.This should not deter the reader. It is impor- ment doesnot mimic the arterial spike produced by smoking a tant to place a particular intervention in the context of a variety cigarette, which providesmuch of the reinforcing and addicting of medical interventionsfrom a variety of settings. Similar as- potential. Venouslevelsof nicotine are approximately half of sumptions are made in different cost-effectiveness analyses, so those achieved during moderately heavy smoking, however, and it isvalid to compare the cost-effectivenessof variousstrategies.
appear to offer some relief. Stronger doses and combined mod- The wealth of data on nicotine replacement therapy meansthat alitiesof nicotine replacement are being investigated, but are not these estimates are likely to be robust.The evidence base for bu- currently recommended in the product licences.
propion ismore limited.The evidence for combination therapy is The value of sustained release bupropion (Zyban) was first re- cognised in the United States during its use as an atypical antide- As in all such analyses, the principal outcome measure is cost pressant. A number of anecdotal reports from those using the per life year saved.This does not take into account the impact of drug suggested that smoking cravings reduced. The main draw- smoking cessation on long-term medical expenditure. Given the back is an elevated risk of seizures, estimated to be about 1 in chronic nature of smoking-related diseases, the impacts on 1000 (as with many other antidepressants). The seizure risk can long-term expenditure are likely to be relatively great. Thisis be reduced by not prescribing it to people with the relevant con- offset by a failure to include estimates of long-term relapse, the traindications, but this reduces the number who might benefit infrastructural costs of smoking cessation services and so on.
Nevertheless, the conclusion that nicotine replacement therapy Overall, there isgood evidence for the efficacy of both nicotine and buproprion are relatively cost-effective is sound and prob- replacement therapy and bupropion.3 Evidence for the efficacy of 2003 Elsevier Science Ltd. All rights reserved Evidence-based Healthcare (2003) 7, 44 ^ 46 Pharmacological therapiesstill only confer relatively modest benefitsover brief interventionsand individual counselling.2,3There is scope to develop more effective smoking cessation stra- 1. Munafo¤ MR, Drury M, Wakely G, Chambers R. Smoking cessa- tegies. One strategy is to 'individualise' therapy by tailoring it to tion in primary care. Oxford: Radcliffe Medical Press, 2002.
the individual motivational and psychological characteristics of a 2. Silagy C, LancasterT, Stead L et al. Nicotine replacement ther- apy for smoking cessation (Cochrane Review). In: The smoker.5 These individual characteristics may be measured in ad- Cochrane Library, Issue 1. Oxford: Update Software, 2002.
vance using computer-based systems. Such interventions can 3. HughesJR, Stead LF, LancasterT. Antidepressantsfor smoking potentially be delivered on a large scale.6 Compared to standar- cessation (Cochrane Review). In: The Cochrane Library, Issue dised interventions, tailored interventions have been found to yield higher long-term quit rates.7 Tailored interventionsmay also 4. McEwen A, West R. Smoking cessation activities by general have cost implications, although a recent trial found that a tai- practitionersand practice nurses.Tob Control 2000; 10: 232^ lored letter wasno more cost-effective than a non-tailored let- 5. Velicer WF, Prochaska JO, Bellis JM et al. An expert system A more recent development isthe area of pharmacogenetics, intervention for smoking cessation. Addict Behav 1993; 18: which offersthe possibility of tailoring pharmacological interven- tionsto an individual'sgenotype. In the future, a relatively small 6. Lichtenstein E, Glasgow RE. Smoking cessation: what have we set of genes could be used to classify smokers according to the learned over the past decade? J Consulting Clin Psychol 2002; molecular basis for their addiction.9 At present, there is limited data about the efficacy of pharmacological interventionsin indi- 7. Velicer WF, Prochaska JO, Fava JL et al. Interactive versus non- vidualswith different genotypes, but it remainsan area of inter- interactive interventions and dose-response relationships for est, particularly in relation to genes affecting dopaminergic stage-matched smoking cessation programs in a managed care function which may influence the development of reward and in- setting. Health Psychol.1999; 18: 21^28.
8. Lennox AS, Osman LM, Reiter E et al. Cost effectiveness of In the near future, it islikely that research will examine tai- computer tailored and non-tailored smoking cessation letters lored interventionsand novel pharmacological interventions in general practice: randomised controlled trial. BMJ 2001;322: 1396.
such as nicotine vaccines and combination therapies. With these 9. Walton R, Johnstone E, Munafo¤ MR et al. Molecular basis of increasingly intensive and tailored interventions, we will be tar- tobacco addiction and progress towards personalised therapy.
geting resistant and dependent smokers.We will need to remem- ber this when considering the relative cost-effectiveness ofdifferent interventionsasthe target populationsin each casemay be somewhat different.
Evidence-based Healthcare (2003) 7, 44 ^ 46 & 2003 Elsevier Science Ltd. All rights reserved


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Mk-801 improves retention in aged rats: implications for altered neural plasticity in age-related memory deficits

Neurobiology of Learning and Memory 71, 194 –206 (1999) Article ID nlme.1998.3864, available online at on Implications for Altered Neural Plasticity Department of Pharmacology, College of Medicine, University of Kentucky, Alterations in N -methyl-D-aspartate receptor (NMDAR)-dependent synaptic plas-ticity, characteristic of aged rodents, may contribute to im

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