Abstract
Background
Silver acetate produces an unpleasant taste when combined with cigarettes, thereby producing an aversive stimulus. It has been marketed in various forms with the aim of extinguishing the urge to smoke, by pairing the urge with an unpleasant stimulus.
Objectives
The aim of this review was to determine the effectiveness of silver acetate products (gum, lozenge, spray) in promoting smoking cessation.
Search methods
We searched the Cochrane Tobacco Addiction Group specialised trials register. Most recent search was in July 2012.
Selection criteria
We included randomised trials of silver acetate for smoking cessation with reports of smoking status at least six months after the beginning of treatment.
Data collection and analysis
We extracted data in duplicate on the type of subjects, the dose and form of silver acetate, the outcome measures, method of randomisation, and completeness of follow‐up.
The main outcome measure was biochemically validated abstinence from smoking after at least six months follow‐up in patients smoking at baseline. Subjects lost to follow‐up were counted as continuing smokers. Where appropriate, we performed meta‐analysis using a fixed effects model.
Main results
Two studies provided long‐term follow‐up data on patients randomised to silver acetate or placebo. In one of these studies, there was a third arm, randomised to 2mg nicotine gum. The pooled risk ratio for quitting for silver acetate vs placebo was 1.04 (95% confidence interval 0.69 to 1.57).
Authors' conclusions
Existing trials show little evidence for a specific effect of silver acetate in promoting smoking cessation. The confidence intervals for the ratio are quite wide. However, the upper limit of the confidence intervals for a positive effect equates to an absolute increase in the smoking cessation rate of about 4%. Any effect of this agent is therefore likely to be smaller than nicotine replacement therapy. The lack of effect of silver acetate may reflect poor compliance with a treatment whose rationale is to create an unpleasant stimulus.
Plain language summary
Does silver acetate help people stop smoking
Silver acetate products (gum, lozenge, and spray) produce an unpleasant metallic taste when combined with cigarettes, so they are used as a form of aversion therapy for smoking. However, the review of trials found little evidence to show that silver acetate helps smokers quit. Any beneficial effect of silver acetate is likely to be very small, and less than the effect already proven for nicotine replacement therapy.
Background
Silver acetate preparations produce an unpleasant, metallic taste when combined with cigarettes. Their use for smoking cessation is based on the principles of aversive conditioning, and is analogous to the use of disulfiram (Antabuse) for alcoholism. That is, an aversive stimulus (in this case taste) is systematically paired with a behaviour (smoking) that the subject wishes to stop. Various silver acetate products are available including lozenges, gum and sprays. The aim of treatment is to encourage smokers to use silver acetate, so that the act of smoking becomes unpleasant, and the urge to smoke therefore diminished, or ideally, extinguished. Excessive ingestion of silver can lead to the rare condition of argyrism. To avoid this, a total dose of silver no greater than 756mg is recommended, and this limits the duration of silver acetate treatment.
Objectives
To review the randomised evidence for the effectiveness of silver acetate in promoting smoking cessation.
Methods
Criteria for considering studies for this review
Types of studies
Randomised controlled trials which report smoking status at least six months after intervention. Studies reporting follow‐up between 3 and 6 months only were reviewed, but data were not included in pooled analyses.
Types of participants
Adult patients who smoke.
Types of interventions
All randomised controlled comparisons of silver acetate with placebo, or with other smoking cessation treatments were included. Silver acetate products included lozenges, gums and sprays.
Types of outcome measures
The main outcome measure was sustained abstinence from smoking at 6 to12 months. Only participants who met criteria for biochemically validated cessation were counted as quitters.
Search methods for identification of studies
We searched the Tobacco Addiction Review Group specialised register for trials, using the term 'silver acetate' in the title or abstract, or as a keyword. This register has been developed from regular electronic searches of MEDLINE, EMBASE and PsycINFO, together with handsearching of specialist journals, conference proceedings and reference lists of previous trials and overviews. The most recent search for trials was in July 2102 when the Register included the results of searches of the Cochrane Central Register of Controlled trials (CENTRAL), issue 7, 2012; MEDLINE (via OVID) to update 20120622; EMBASE (via OVID) to week 201227; and PsycINFO (via OVID) to update 20120625. See the Tobacco Addiction Group Module in the Cochrane Library for full search strategies and list of other resources searched. We also searched Clinicaltrials.gov using the terms 'silver acetate' and 'smoking'.
Data collection and analysis
All potentially eligible studies were reviewed by two authors (TL and LS). Data were abstracted onto a data form which detailed the methods of recruitment and randomisation, types of participants, interventions and outcomes. A record was made of whether abstinence was confirmed biochemically.
Trial results were expressed as risk ratios (number of quitters in intervention group/total randomised to intervention)/(number of quitters in control group/total randomised to control). Pooled effects were estimated using a Mantel‐Haenszel fixed‐effect model (Deeks 2011).
Results
Description of studies
Two randomised trials with follow‐up greater than six months were identified. In the first (Jensen 1990) 6mg silver acetate chewing gum was compared to 2mg nicotine gum, and to ordinary chewing gum in a three armed, randomised, open study. In the second (Hymowitz 1996), 2.5mg silver acetate lozenges were compared to placebo lozenges in a randomised double‐blind study. A third study (Malcolm 1986) was reviewed. In this study, participants were randomised to silver acetate chewing gum or placebo. This study was excluded from formal analysis because the maximum follow‐up was only four months.
Risk of bias in included studies
The studies were judged on their attempts to control bias in allocation, assessment and analysis. All three were randomised, though the precise method of randomisation was not stated in any of the studies. One (Jensen 1990) was not blinded. Each of three studies reviewed confirmed abstinence with biochemical verification. In all studies, smokers lost to follow‐up were counted as continuing smokers in the analysis.
Effects of interventions
Two studies provided long‐term follow‐up of patients randomised to silver acetate or placebo. In the first (Jensen 1990), there were no significant differences in smoking status between patients randomised to silver acetate chewing gum, nicotine gum or ordinary chewing gum. In the second (Hymowitz 1996), 11/ 239 subjects randomised to silver acetate lozenges had quit at one year, compared to 9/241 randomised to placebo. The combined estimate for the risk ratio for quitting was 1.04 (95% confidence interval 0.69 to 1.57).
In the comparison between silver acetate and nicotine gum in Jensen 1990 the risk ratio was 0.98 95% (CI 0.69 to 1.39).
In one further study (Malcolm 1986) 9/127 randomised to silver acetate gum quit, compared to 4/142 randomised to placebo. This study was not included in meta‐analysis because follow‐up was only four months.
In all trials, the total dose of silver acetate was restricted to reduce the chance of developing the rare outcome of argyrism (silver deposition in body tissues), and no subject suffered this side‐effect. The main adverse effects reported were those expected from this aversive stimulus; unpleasant tastes and sensations in the mouth, and gastrointestinal disturbances.
Discussion
There is little evidence for a specific effect of silver acetate in promoting smoking cessation. The confidence intervals for the pooled risk ratio are quite wide, because the total number of subjects studied with long‐term follow‐up is relatively small. The upper limit of the confidence intervals for a positive effect equates to an absolute increase in smoking cessation rate of about 4%. Such an effect would, of course, be worth having. However, given that other smoking cessation interventions produce effects comparable to or larger than this (Stead 2008; Cahill 2012), proving or disproving a small effect of silver acetate is unlikely to have much clinical relevance. In a direct comparison between silver acetate and nicotine gum, no advantages were seen for either product over the other, but the numbers studied were small (Jensen 1990).
In part, the results may reflect the difficulties of complying with a treatment whose rationale is to create an unpleasant stimulus.
A recent laboratory based study (Rose 2010) assessed the effect of silver acetate on the taste of nicotine‐containing or denicotinized cigarettes, and nicotine inhaler. Silver acetate mouth wash made the taste of both types of cigarette less pleasant but did not affect the taste of the inhaler, implying that silver acetate interacts with components other than nicotine. The authors suggest that silver acetate could potentially be used in combination with NRT products to reduce the chance that a recent quitter who slipped and tried a cigarette would relapse completely.
Authors' conclusions
Implications for practice.
Although a possible small effect of silver acetate in promoting smoking cessation has not been disproved, any such effect is likely to be very small, and less than that proven for nicotine replacement therapy. There is therefore little role for silver acetate for promoting smoking cessation in the clinical setting.
Implications for research.
Further research on silver acetate for smoking cessation is unlikely to be helpful.
What's new
| Date | Event | Description |
|---|---|---|
| 14 August 2012 | New search has been performed | Searches updated. No new studies included. Effect sizes now expressed as risk ratios and pooled using a Mantel‐Haenszel fixed‐effect model. |
| 14 August 2012 | New citation required but conclusions have not changed | No change to conclusions. |
History
Protocol first published: Issue 3, 1997 Review first published: Issue 3, 1997
| Date | Event | Description |
|---|---|---|
| 8 January 2009 | New search has been performed | No new trials found |
| 29 October 2008 | Amended | Converted to new review format. |
| 26 April 2006 | New search has been performed | Searches updated, no new trials found. |
| 14 May 2003 | New search has been performed | Searches updated, no new trials found. |
Acknowledgements
None
Data and analyses
Comparison 1. Silver acetate vs placebo.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Sustained abstinence at 12 months | 2 | 785 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.04 [0.69, 1.57] |
1.1. Analysis.
Comparison 1 Silver acetate vs placebo, Outcome 1 Sustained abstinence at 12 months.
Comparison 2. Silver acetate vs nicotine gum.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Sustained abstinence at 12 months | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Totals not selected |
2.1. Analysis.
Comparison 2 Silver acetate vs nicotine gum, Outcome 1 Sustained abstinence at 12 months.
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Hymowitz 1996.
| Methods | Randomised, double‐blind trial. Country: USA | |
| Participants | Adult smokers of more than 10 cigarettes/day. Motivated volunteers recruited by advertisement. | |
| Interventions | 2.5mg silver acetate lozenge vs placebo lozenge. To be used six times daily for 3 weeks. Successful quitters were given further lozenges to assist relapse prevention. All participants received self‐help materials, videos and follow‐up visits. | |
| Outcomes | Sustained abstinence at 12 months, validated by urinary cotinine/expired carbon monoxide. | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomised, method not described |
| Allocation concealment (selection bias) | Unclear risk | No details reported |
Jensen 1990.
| Methods | Randomised, open, controlled trial. Country: Denmark | |
| Participants | 496 motivated adult smokers, smoking >10 cigarettes/day for >5years. | |
| Interventions | 1. 6mg Silver acetate chewing gum, up to six pieces daily. 2. 2 mg Nicotine chewing gum 3. Ordinary chewing gum The gums were recommended for six weeks, with a reducing dose for a further six weeks. Treatments were not blinded. | |
| Outcomes | Sustained abstinence at one year, validated by expired carbon monoxide. | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomised to 24 smaller groups, each group then randomly allocated to treatment |
| Allocation concealment (selection bias) | Unclear risk | No details reported |
Malcolm 1986.
| Methods | Randomised, double‐blind trial, method of randomisation not stated Country: USA | |
| Participants | Adult smokers, at least 1 pack/day for 2 years. Motivated volunteers who responded to an advertisement. | |
| Interventions | Chewing gum (Tabmit) containing 6mg of silver acetate vs placebo gum. To be chewed six times daily for 3 weeks | |
| Outcomes | Sustained abstinence at 4 months, validated by serum metabolites. | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomised, method not described |
| Allocation concealment (selection bias) | Unclear risk | No details reported |
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| Hymowitz 1993 | A trial of 2.5 mg silver acetate lozenges vs placebo for smoking cessation with three week follow‐up. Smokers who successfully quit were then randomised to silver acetate vs placebo for relapse prevention, and followed to one year. Excluded because does not present long‐term follow‐up of the initial randomisation to silver acetate or placebo for cessation. |
| Morrow 1993 | A randomised controlled trial among 42 patients in US family practice, comparing silver acetate spray with placebo. Excluded on the grounds that follow‐up less than six months (3 months). |
| Rose 2010 | Laboratory study, cessation not an outcome. |
| Rosenberg 1977 | Randomised trial of silver acetate gum vs placebo gum. Excluded because follow‐up only four weeks. |
| Zmeili 1999 | Silver nitrate mouthwash. Excluded because follow‐up only six weeks post treatment. |
Contributions of authors
TL extracted data and wrote the review. LS assisted in identifying studies and data extraction.
Sources of support
Internal sources
Department of Primary Care Health Sciences, University of Oxford, UK.
National School for Health Research School for Primary Care Research, UK.
External sources
NHS Research and Development Fund, UK.
Declarations of interest
None
New search for studies and content updated (no change to conclusions)
References
References to studies included in this review
Hymowitz 1996 {published data only}
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