Loe H, Theilade E, Jensen SB Experimental gingivitis in man. J Periodontol. 1965; 36:177-187
Theilade E, Wright WH, Jensen SB, Loe H Experimental gingivitis in man. II. A longitudinal clinical and bacteriological investigation. J Periodontal Res. 1966; 1:1-13
Loe H, Anerud A, Boysen H, Morrison E Natural history of periodontal disease in man. Rapid, moderate and no loss of attachment in Sri Lankan laborers 14 to 46 years of age. J Clin Periodontol. 1986; 13:431-445
Baelum V, van Palenstein HW, Hugoson A, Yee R, Fejerskov O A global perspective on changes in the burden of caries and periodontitis: implications for dentistry. J Oral Rehabil. 2007; 34:(12)872-906
Kassebaum NJ, Bernabé E, Dahiya M, Bhandari B, Murray CJ, Marcenes W Global burden of severe periodontitis in 1990–2010: a systematic review and meta-regression. J Dent Res. 2014; 93:(11)1045-1053
Rosling B, Serino G, Hellstrom MK, Socransky SS, Lindhe J Longitudinal periodontal tissue alterations during supportive therapy. Findings from subjects with normal and high susceptibility to periodontal disease. J Clin Periodontol. 2001; 28:241-249
Preventive behaviour and risks to oral health – a report from the Adult Dental Health Survey 2009. 2011.
Loe H, Schiott CR The effect of mouthrinses and topical application of chlorhexidine on the development of dental plaque and gingivitis in man. J Periodontal Res. 1970; 5:79-83
Van Strydonck DA, Slot DE, Van der Velden U, Van der Weijden F Effect of a chlorhexidine mouthrinse on plaque, gingival inflammation and staining in gingivitis patients: a systematic review. J Clin Periodontol. 2012; 39:(11)1042-1055
Jones CG Chlorhexidine: is it still the gold standard?. Periodontol 2000. 1997; 15:55-62
Hoffmann T, Bruhn G, Richter S, Netuschil L, Brecx M Clinical controlled study on plaque and gingivitis reduction under long-term use of low-dose chlorhexidine solutions in a population exhibiting good oral hygiene. Clin Oral Investig. 2001; 5:89-95
Leyes Borrajo JL, Garcia VL, Lopez CG, Rodriguez-Nuñez I, Garcia FM, Gallas TM Efficacy of chlorhexidine mouthrinses with and without alcohol: a clinical study. J Periodontol. 2002; 73:317-321
Loe H, Schiott CR, Karring G, Karring T Two years oral use of chlorhexidine in man. I. General design and clinical effects. J Periodontal Res. 1976; 11:135-144
Lang NP, Hase JC, Grassi M, Hammerle CH, Weigel C, Kelty E Plaque formation and gingivitis after supervised mouthrinsing with 0.2% delmopinol hydrochloride, 0.2% chlorhexidine digluconate and placebo for 6 months. Oral Dis. 1998; 4:105-113
Addy M Oral hygiene products: potential for harm to oral and systemic health?. Periodontol 2000. 2008; 48:54-65
Segreto VA, Collins EM, Beiswanger BB, Delarosa M, Isaacs RL, Lang NP A comparison of mouthrinses containing 2 concentrations of chlorhexidine. J Periodontal Res. 1986; 21:23-32
Van der Weijden GA, Ten Heggeler JM, Slot DE, Rosema NA, Van der Velden U Parotid gland swelling following mouthrinse use. Int J Dent Hyg. 2010; 8:276-279
Pemberton MN, Gibson J Chlorhexidine and hypersensitivity reactions in dentistry. Br Dent J. 2012; 213:(11)547-550
Barkvoll P, Rolla G, Svendsen K Interaction between chlorhexidine digluconate and sodium lauryl sulfate in vivo. J Clin Periodontol. 1989; 16:593-595
Kato T, Iijima H, Ishihara K, Kaneko T, Hirai K, Naito Y Antibacterial effects of Listerine on oral bacteria. Bull Tokyo Dent Coll. 1990; 31:301-307
Gunsolley JC A meta-analysis of six-month studies of antiplaque and antigingivitis agents. J Am Dent Assoc. 2006; 137:1649-1657
van Leeuwen MPC, Slot DE, Van der Weijden GA Essential oils compared to chlorhexidine with respect to plaque and parameters of gingival inflammation: a systematic review. J Periodontol. 2011; 82:174-194
Marchetti E, Mummolo S, Di Mattia J, Casalena F, Di Martino S, Mattei A, Marzo G Efficacy of essential oil mouthwash with and without alcohol: a 3-Day plaque accumulation model. Trials. 2011; 12
Sharma NC, Charles CH, Qaqish JG, Galustians HJ, Zhao Q, Kumar LD Comparative effectiveness of an essential oil mouthrinse and dental floss in controlling interproximal gingivitis and plaque. Am J Dent. 2002; 15:351-355
Bauroth K, Charles CH, Mankodi SM, Simmons K, Zhao Q, Kumar LD The efficacy of an essential oil antiseptic mouthrinse vs. dental floss in controlling interproximal gingivitis: a comparative study. J Am Dent Assoc. 2003; 134:359-365
Finkelstein P, Yost KG, Grossman E Mechanical devices versus antimicrobial rinses in plaque and gingivitis reduction. Clin Prev Dent. 1990; 12:8-11
Adams D, Addy M Mouthrinses. Adv Dent Res. 1994; 8:291-301
Roberts WR, Addy M Comparison of the in vivo and in vitro antibacterial properties of antiseptic mouthrinses containing chlorhexidine, alexidine, cetyl pyridinium chloride and hexetidine. Relevance to mode of action. J Clin Periodontol. 1981; 8:295-310
Haps S, Slot DE, Berchier CE, Van der Weijden GA The effect of cetylpyridinium chloride-containing mouth rinses as adjuncts to toothbrushing on plaque and parameters of gingival inflammation: a systematic review. Int J Dent Hyg. 2008; 6:290-303
Addy M, Moran J, Newcombe RG Meta-analyses of studies of 0.2% delmopinol mouth rinse as an adjunct to gingival health and plaque control measures. J Clin Periodontol. 2007; 34:58-65
Hase JC, Edwardsson S, Rundegren J, Attström R, Kelty E 6-month use of 0.2% delmopinol hydrochloride in comparison with 0.2% chlorhexidine digluconate and placebo (II). Effect on plaque and salivary microflora. J Clin Periodontol. 1998; 25:(11 Pt 1)841-849
Zanatta FB, Antoniazzi RP, Rösing CK The effect of 0.12% chlorhexidine digluconate rinsing on previously plaque-covered surfaces: a randomized, controlled clinical trial. J Periodontol. 2007; 78:2127-2134
Pan PC, Harper S, Ricci-Nittel D, Lux R, Shi W In vitro evidence for efficacy of antimicrobial mouthrinses. J Dent. 2010; 38:16-20
Robinson C Mass transfer of therapeutics through natural human plaque biofilms: a model for therapeutic delivery to pathological bacterial biofilms. Arch Oral Biol. 2011; 56:829-836
Neely AL Essential oil mouthwash (EOMW) may be equivalent to chlorhexidine (CHX) for long-term control of gingival inflammation but CHX appears to perform better than EOMW in plaque control. J Evid Base Dent Pract. 2011; 11:171-174
This article will focus on the antiplaque efficacy of mouthwashes. An antiplaque agent inhibits the formation of plaque and also reduces gingivitis. There is good evidence that chlorhexidine digluconate, used in the correct concentrations, is the gold standard agent against which all others should be measured. It does, however, have some unwanted side-effects. One of the major problems for antiplaque mouthwashes is that they have a much reduced effect on established plaque within the oral environment. Although they can flow into the biofilm channels and kill bacteria in the superficial layers of dental plaque, they cannot penetrate the biomass and inhibit the pathogenic bacteria adjacent to the tooth surface and gingival margin. There is no evidence that they prevent the progression of periodontitis.
CPD/Clinical Relevance: The evidence supporting the use of ‘over the counter’ antiplaque mouthwashes is evaluated. This provides guidance for dentists and dental care professionals of when it is appropriate to recommend mouthwash use to their patients.
Article
There are various reasons why a patient may wish to use a mouthwash. These include:
Having fresh breath;
Finding flossing difficult;
To kill bacteria;
Because of bleeding gums; or
To prevent decay.
A member of the dental profession might consider recommending the use of a mouthwash as an antiplaque agent, to deliver topical fluoride, to combat oral malodour or for a patient with a dry mouth. For members of the public the array of mouthwashes available and the claims made by manufacturers can be confusing. A newspaper article raised the question ‘Mouthwash or hogwash: experts argue that not only is a mouthwash useless, it can also be harmful to your health' (Times newspaper 15 September 2008). The aim of this series of papers is to review the available evidence for the efficacy of ‘over the counter’ mouthwashes and to give guidance for dentists and dental care professionals of when it is appropriate to recommend mouthwash use to their patients.
Evidence regarding mouthwashes may be divided into:
Antiplaque efficacy;
Caries prevention;
Antihalitosis efficacy;
Dry mouth relief;
Safety.
This narrative review will be split into three parts. The first part will focus on antiplaque efficacy of mouthwashes. The second part will address caries prevention, antihalitosis efficacy and dry mouth relief. The third part will cover safety of mouthwashes.
Antiplaque efficacy
Background
Experimental gingivitis studies conducted in the 1960s showed that the accumulation of dental plaque leads to the development of chronic gingivitis1,2 (Figure 1). The consensus is that, without treatment, chronic gingivitis will, ultimately, proceed to chronic periodontitis in a majority of the population3 (Figure 2). The severity of periodontitis is determined by other factors including those listed in Table 1.4 It is estimated that between 5 and 15% of the population worldwide are affected by severe periodontitis.5,6,7 It has been shown that improvement in plaque control can reduce the prevalence of gingivitis (Figure 3) and periodontitis6 and that thorough supragingival scaling and root surface debridement, together with good oral hygiene, may arrest periodontitis8 (Figure 4).
Figure 1. Plaque infected dentition with signs of chronic gingivitis.Figure 2. Signs of chronic gingivitis and chronic periodontitis.
Factors affecting the severity of periodontitis
Cigarette smoking
Diabetes mellitus
Genes
Socioeconomic status
Osteoporosis
Stress
Alcohol
Diet
Obesity
Exercise
Figure 3. Chronic gingivitis (a) before and (b) after non-surgical treatment. (Reproduced by kind permission of Dr Bill Jenkins.)Figure 4. Generalized chronic gingivitis and aggressive periodontitis (a) before and (b) after non-surgical treatment (with acknowledgment to Dr Frank van Schaik and Mr Dimitri van Hezik, dental technician, for the new crowns). In Figure 4b gingival recession around LR4, LR2 and LL1 has been caused by overbrushing.
Rationale for the use of mouthwashes
Although supragingival dental plaque can be effectively removed using either manual or electric toothbrushes and interdental cleaning aids, the most recent data available from the Adult Dental Health Survey showed that the oral hygiene of the UK population was poor.9 Of dentate adults, 66% and, on average, 23% of all teeth, had visible plaque present and 68% of adults had calculus deposits visible in at least one sextant. Of those subjects, 64% who said that they cleaned twice a day, and 61% of those who attended regularly for a check-up had visible plaque present.9 When subjects who cleaned their teeth were asked if they used additional methods to supplement oral hygiene, 31% indicated that they used a mouthwash. Mouthwash use decreased with advancing age and there was no difference between the sexes or between different socio-economic groups. The percentage of subjects using a mouthwash had increased over the years (1988: 10%; 1998: 23%; 2009: 31%). Interestingly the percentage flossing had decreased since 1998 (1988: 21%; 1998: 28%; 2009: 22%).9 This may reflect the public's perception, encouraged by the manufacturers, that mouthwash use can replace the need to floss or the use of interdental brushes. The most recent survey excluded data from Scotland.
Antiseptics present in mouthwashes are effective in vitro against the bacteria found within dental plaque, when they are in a planktonic form, and can show both bacteriostatic and bacteriocidal activity. Mouthwashes have a number of advantages:
They are available without prescription;
They have a good safety record;
No significant bacterial resistance has been reported; and
They require little skill and motivation on behalf of the patient.
Antiplaque agents
An antiplaque agent reduces the amount of dental plaque to such an extent that it inhibits the development of gingivitis. Most of the research into the clinical efficacy of antiplaque agents has focused on their effect on levels of plaque and gingival inflammation. One of the most important characteristics of an antiplaque agent is its persistence of action or substantivity. This depends on its ability to adsorb to oral surfaces and remain active for a prolonged period. Available antiplaque agents are listed in Table 2.
The use of chlorhexidine digluconate-containing mouthwashes in preventing plaque formation is supported by a huge body of scientific evidence over decades.10,11 Chlorhexidine is active against Gram +ve and Gram –ve bacteria, fungi, yeast and viruses. It has 12 hours substantivity and shows both bacteriostatic and bacteriocidal activity, depending on concentration. It has been demonstrated in experimental gingivitis studies that rinsing with chlorhexidine mouthwash for one minute twice daily can completely inhibit plaque formation and gingivitis10 (Table 3). Prescribed in the following formulations and doses it is the gold standard antiplaque agent against which all others are compared:12
10 ml of 0.2% equivalent to 20 mg twice per day;
15 ml of 0.12% equivalent to 18 mg twice per day.
Characteristics of chlorhexidine
Substantivity of 12 hours
Active against Gm +ve and Gm −ve bacteria, fungi, yeast and viruses
Bacteriostatic and bacteriocidal
Shown to completely inhibit plaque formation and gingivitis when used in the correct formulation
Evidence supporting the clinical antiplaque effectiveness of lower concentrations is weak.13 However, it has been shown that an alcohol-free 0.12% chlorhexidine-containing mouthwash was as effective as the same mouthwash also containing 11% alcohol, compared with a placebo.14
Side-effects
Chlorhexidine is considered to be safe because of its dicationic nature which inhibits absorption through the skin, mucous membranes and the gut. Therefore, no systemic toxicity has been reported. There are no publications recording bacterial resistance or superinfection following its use. However, there are some side-effects which contra-indicate prolonged use (Table 4).
Side-effects of chlorhexidine
Extrinsic staining of oral surfaces
Taste disturbance
Burning sensation
Mucosal erosion
Parotid swelling
Immediate hypersensitivity reaction
Staining occurs as a result of dietary chromogens binding to chlorhexidine which is bound to the oral surfaces (Figure 5). Staining occurs with all correctly formulated products.11 Long-term use of chlorhexidine has been reported to result in more calculus formation than a placebo mouthrinse.15,16 It has been suggested that this could arise because chlorhexidine increases pellicle thickness by precipitating salivary proteins. It may also precipitate phosphate and then calcium onto the pellicle.17 If a burning sensation or mucosal erosion arises, the patient can be advised to double dilute to reduce the concentration of chlorhexidine, ensuring that the dose remains the same.18
Figure 5. Staining due to long-term use of chlorhexidine.
In rare cases, parotid swelling has been observed. If this occurs the patient should be advised to discontinue use of the mouthwash. One report has indicated that this problem is not specific to chlorhexidine mouthwash and may be caused by the method of rinsing, but this needs to be confirmed in larger studies.19 It has also been reported that, in rare cases, chlorhexidine may give rise to significant immediate hypersensitivity which very rarely may lead to a severe anaphylactic reaction.20
Sodium lauryl sulphate, an anionic detergent found in most toothpastes, inhibits the action of chlorhexidine by binding to the molecule.21 For this reason, patients should be advised to leave an interval of an hour between using the mouthwash and toothbrushing.
The clinical applications and misuse of chlorhexidine mouthwash are listed in Table 5.
Clinical applications of chlorhexidine
Short term use for specific problems
Post oral or periodontal surgery
For use by physically or mentally disabled patients; although use of a chlorhexidine spray may be more effective because of an inability to rinse effectively
Misuse
Use in patients with plaque-infected dentitions (Zanatta et al 200734)
Using once per day when pharmacological considerations require twice daily use
Using two or three times a week
Essential oils
Listerine® (Johnson and Johnson) is a widely used hydro-alcohol based mouthwash containing essential oils in the following concentrations: thymol (0.064%); eucalyptol (0.092%); menthol (0.042%); and methyl salicylate (0.060%). In most of the products, alcohol is used to solubilize the essential oils and alcohol content varies between 21% and 27%, depending on the formulation. In 2009, the manufacturers launched an alcohol-free version of Listerine® which contains propylene glycol as the solubilizing agent. The antiplaque effect of Listerine® is not as great as chlorhexidine.22 Gunsolley conducted a systematic review and meta-analysis of studies of a minimum of six months' duration.23 He found that in studies comparing the two agents, chlorhexidine mouthwash was significantly more effective at reducing plaque than Listerine®. When the placebo effect was removed, chlorhexidine reduced plaque by 40% and essential oils by 27%. Although chlorhexidine mouthwash was also more effective at reducing gingivitis (28% compared with 18% for essential oils), the difference between the two agents was not significant. These findings were confirmed in another systematic review and a series of meta-analyses, which investigated differences in plaque index, gingival index and gingival bleeding between the two mouthwashes used daily for less than four weeks and more than or equal to four weeks.24 The authors also investigated differences in calculus index and staining index and found chlorhexidine showed higher scores than the essential oil mouthwash for both these indices. However, a meta-analysis of studies including calculus indices could not be performed because none of the studies met the required criteria.24 A clinical trial investigated the antiplaque effect of alcohol-free compared with alcohol-containing essential oil mouthwash. The authors found that the alcohol-free mouthwash was less effective at reducing plaque formation over a three-day period than the alcohol containing one.25
It has been claimed that an essential oil mouthwash could be used as an alternative to flossing because it shows at least equivalent benefit to flossing in plaque reduction and bleeding on probing in six-month clinical trials.26,27 Both these studies were funded by the manufacturer which may introduce bias. The purpose of both flossing and toothbrushing is to disrupt early plaque formation when the biofilm is thin. If an antiplaque-containing mouthwash can substitute for brushing in preventing plaque formation, we would expect it also to be able to substitute for flossing. However, penetration of the mouthwash into interdental niches may be inhibited by the presence of impacted food.28 It is therefore difficult to understand how an antiplaque mouthwash used for 30 to 60 seconds could reduce plaque burden interdentally to the same extent as mechanical removal of plaque by flossing.
Side-effects
Initial use often induces a burning sensation and it has a bitter taste. It does not cause staining and does not appear to induce resistant strains of pathogenic bacteria in longer-term studies.29
Cetyl pyridinium chloride
Cetyl pyridinium chloride is a quaternary ammonium compound commonly found in many branded mouthwashes. It is monocationic in nature and shows similar antimicrobial activity to chlorhexidine in vitro. However, despite initially appearing to be adsorbed to oral surfaces better than chlorhexidine, cetyl pyridinium chloride has much reduced substantivity.30
Two systematic reviews have been conducted investigating the efficacy of mouthwashes containing cetyl pyridinium chloride.23,31 The first restricted studies to a minimum of six months' duration. Four studies showed a statistically significant plaque-inhibitory effect and three did not. Overall, little evidence of an antiplaque or antigingivitis effect was demonstrated. The test for heterogeneity between the studies was positive. In particular, different concentrations of cetyl pyridinium chloride were used in different studies ranging from 0.01–0.1%.23 The second systematic review restricted studies to a minimum of four weeks' duration. Eight studies were included. The authors concluded that mouthwashes containing cetyl pyridinium chloride, used as adjuncts to either supervised or unsupervised oral hygiene, had a small but significant effect in reducing plaque and gingivitis compared with toothbrushing alone or in combination with a placebo rinse.31 It is difficult to understand how they reached this conclusion based on the data presented in the paper and the discussion. They discuss the heterogeneity between studies in both the concentration of the cetyl pyridinium chloride products evaluated and in the results obtained. In addition, six of the studies included in the review had authors from industry or were industry-funded, leading to conflicts of interest which may have caused bias.31
Side-effects
Cetyl pyridinium chloride has shown no long-term disruption to the normal oral flora. It does produce staining because of its cationic nature but not to the same degree as chlorhexidine. It is also inactivated by sodium lauryl sulphate in the same way as chlorhexidine.
Delmopinol hydrochloride
Delmopinol hydrochloride (0.2%) mouthwash is a third generation antiplaque agent which has been available on the continent for some years. It has almost no bacteriostatic or bacteriocidal activity in vitro or in vivo. Delmopinol's mechanism of action is to interfere with plaque matrix formation and prevent attachment and adherence of bacteria to the acquired pellicle.
During the 1990s, the manufacturers of this product commissioned eight clinical trials of the adjunctive effect of 0.2% delmopinol mouthwash on usual oral hygiene. Meta-analyses of these trials were conducted in 2007.32 Seven independent research groups conducted the studies but only three of the studies have been published in the scientific literature. The authors of the meta-analyses of the supervised and unsupervised studies concluded that the mouthwash had an adjunctive effect in reducing plaque and gingivitis. The differences in reduction in plaque, bleeding and gingival inflammation between the delmopinol and the placebo mouthwashes were highly statistically significant. The reduction in plaque index overall was around 35% compared with the placebo. However, the reduction in bleeding, and in the gingival index were very small across all of the studies and of doubtful clinical significance. Two of the published studies compared 0.2% delmopinol with 0.2% chlorhexidine, as well as the placebo rinse. The authors found that delmopinol reduced the plaque index and percentage bleeding on probing by around half as much as chlorhexidine.16,33
Side-effects
One of the most commonly reported adverse events when using delmopinol is transient anaesthesia of the tongue which showed similar incidence to chlorhexidine.32 Taste disturbance was also an unwanted side-effect and was reported at similar levels to chlorhexidine use.16 Tooth and tongue staining have been reported but were at least 50% less than with chlorhexidine.16
Other relevant issues
One of the major problems for antiplaque mouthwashes is that they have a much reduced effect on established plaque.34 An in vitro study has investigated the antimicrobial effects of mouthwashes on saliva-derived plaque biofilms in both static and flow through systems.35 In the static system, it was shown that Listerine® was more effective than chlorhexidine and cetyl pyridium chloride at killing bacteria within 16–18 hour biofilms.35 For 65 hour biofilms twice daily, 30-second treatments resulted in antibacterial effects of 21.3% (±3.1%) for Listerine® and 23.1 (±5.5%) for chlorhexidine, which were significantly different from the control (p<0.001 for both agents). In the flow through system, Listerine® and chlorhexidine showed equivalent effects, which were significantly greater than cetyl pyridium chloride and chlorhexidine combined, and water.35 In a series of elegant studies, Robinson used the ‘Leeds in situ device' for undisturbed plaque biofilm collection, which may better represent plaque located in inaccessible interdental areas.36 They showed that antiplaque agents can only penetrate around a third to half of the way from the surface into the plaque biofilm after 30 seconds' and two minutes' immersion. The agents flowed into the biofilm channels and were able to kill bacteria in the superficial layers of dental plaque, but only fluoride was able to penetrate deep into the biomass after 30 minutes' exposure. Because of this inability to penetrate deep into the plaque biomass, mouthwashes may have little effect on the pathogenic bacteria adjacent to the tooth surface and gingival margin, which may explain the following:
There is sparse evidence that using mouthwashes on a regular basis instead of subgingival debridement has any effect on preventing the progression of periodontitis;
There is no evidence that sporadic use of antiplaque mouthwashes has any clinical benefit to patients.37
Conclusions
The systematic reviews and meta-analyses which have been conducted into mouthwash efficacy have highlighted the heterogeneity between studies, which makes conclusions regarding the comparison of different agents less reliable.23,24 Standardization of methodology in clinical trials would increase the number of studies eligible to be included in meta-analyses and provide better estimates of the effect of chlorhexidine compared with other agents.38 Good plaque control is essential for periodontal health. Although mouthwashes have been shown to have varying degrees of antiplaque efficacy, because of the possible side-effects, it is sensible to restrict their use for the treatment of specific problems on a short-term basis. The best method of personal plaque control remains mechanical removal using toothbrushes and other aids for interdental cleaning, including floss and interproximal brushes.38
An enhanced oral hygiene behaviour change strategy (Oral Hygiene TIPPS) was described in the recent guidance document on The Prevention and Treatment of Periodontal Diseases in Primary Care published by The Scottish Dental Clinical Effectiveness Programme (SDCEP). The guidance document can be downloaded free of charge from the SDCEP website (www.sdcep.org.uk).
