Home‐based chemically‐induced whitening (bleaching) of teeth in adults

Prashanti Eachempati; Sumanth Kumbargere Nagraj; Salian Kiran Kumar Krishanappa; Puneet Gupta; Ibrahim Ethem Yaylali

doi:10.1002/14651858.CD006202.pub2

. 2018 Dec 18;2018(12):CD006202. doi: 10.1002/14651858.CD006202.pub2

Home‐based chemically‐induced whitening (bleaching) of teeth in adults

Prashanti Eachempati ^1,^✉, Sumanth Kumbargere Nagraj ², Salian Kiran Kumar Krishanappa ¹, Puneet Gupta ³, Ibrahim Ethem Yaylali ⁴

Editor: Cochrane Oral Health Group

PMCID: PMC6517292 PMID: 30562408

Abstract

Background

With the increased demand for whiter teeth, home‐based bleaching products, either dentist‐prescribed or over‐the‐counter products have been exponentially increasing in the past few decades. This is an update of a Cochrane Review first published in 2006.

Objectives

To evaluate the effects of home‐based tooth whitening products with chemical bleaching action, dispensed by a dentist or over‐the‐counter.

Search methods

Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 12 June 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library (searched 12 June 2018), MEDLINE Ovid (1946 to 12 June 2018), and Embase Ovid (1980 to 12 June 2018). The US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (12 June 2018) and the World Health Organization International Clinical Trials Registry Platform (12 June 2018) were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.

Selection criteria

We included in our review randomised controlled trials (RCTs) which involved adults who were 18 years and above, and compared dentist‐dispensed or over‐the‐counter tooth whitening (bleaching) products with placebo or other comparable products.

Quasi‐randomised trials, combination of in‐office and home‐based treatments, and home‐based products having physical removal of stains were excluded.

Data collection and analysis

Two review authors independently selected trials. Two pairs of review authors independently extracted data and assessed risk of bias. We estimated risk ratios (RRs) for dichotomous data, and mean differences (MDs) or standardised mean difference (SMD) for continuous data, with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach.

Main results

We included 71 trials in the review with 26 studies (1398 participants) comparing a bleaching agent to placebo and 51 studies (2382 participants) comparing a bleaching agent to another bleaching agent. Two studies were at low overall risk of bias; two at high overall risk of bias; and the remaining 67 at unclear overall risk of bias.

The bleaching agents (carbamide peroxide (CP) gel in tray, hydrogen peroxide (HP) gel in tray, HP strips, CP paint‐on gel, HP paint‐on gel, sodium hexametaphosphate (SHMP) chewing gum, sodium tripolyphosphate (STPP) chewing gum, and HP mouthwash) at different concentrations with varying application times whitened teeth compared to placebo over a short time period (from 2 weeks to 6 months), however the certainty of the evidence is low to very low.

In trials comparing one bleaching agent to another, concentrations, application method and application times, and duration of use varied widely. Most of the comparisons were reported in single trials with small sample sizes and event rates and certainty of the evidence was assessed as low to very low. Therefore the evidence currently available is insufficient to draw reliable conclusions regarding the superiority of home‐based bleaching compositions or any particular method of application or concentration or application time or duration of use.

Tooth sensitivity and oral irritation were the most common side effects which were more prevalent with higher concentrations of active agents though the effects were mild and transient. Tooth whitening did not have any effect on oral health‐related quality of life.

Authors' conclusions

We found low to very low‐certainty evidence over short time periods to support the effectiveness of home‐based chemically‐induced bleaching methods compared to placebo for all the outcomes tested.

We were unable to draw any conclusions regarding the superiority of home‐based bleaching compositions or any particular method of application or concentration or application time or duration of use, as the overall evidence generated was of very low certainty. Well‐planned RCTs need to be conducted by standardising methods of application, concentrations, application times, and duration of treatment.

Plain language summary

Home‐based chemical bleaching of teeth in adults

Review question  What evidence is available regarding the different home‐based chemically‐induced bleaching agents in whitening teeth?

Background  There has been an increasing demand for whiter teeth. Home‐based whitening products with a bleaching action have become popular and are prescribed to people by the dentist or purchased over‐the‐counter. A variety of whitening products are available which include hydrogen peroxide, carbamide peroxide, sodium percarbonate, sodium hexametaphosphate, sodium tripolyphosphate, and calcium peroxide. These agents are supplied in different concentrations and are used with different methods of application (gel in tray, strips, paint‐on gel, chewing gum, and mouthwash), which have varying application times and duration of treatment.

Study characteristics  Authors from Cochrane Oral Health carried out this review of existing studies and the evidence is current up to 12 June 2018. We included 71 trials that involved 3780 adults who underwent tooth whitening procedures with various bleaching agents using different methods of application, length of application and duration of treatment. 26 studies compared a bleaching agent to placebo and 51 studies compared one bleaching agent to another bleaching agent.

Key results

The bleaching agents whitened teeth compared to placebo over a short time period (from 2 weeks to 6 months), however the certainty of the evidence is low to very low.

The evidence currently available is insufficient to draw reliable conclusions regarding the superiority of home‐based bleaching compositions or any particular method of application or concentration or application time or duration of use.

The most common adverse events were tooth sensitivity and oral irritation, which were reported with higher concentrations of active agents, although the effects were mild and transient.

Well‐planned randomised controlled trials need to be conducted by standardising methods of application, concentrations, application times and duration of treatment.

Certainty of evidence  The overall certainty of the evidence was low to very low for all comparisons. This was because most of the comparisons were reported in single trials with small sample sizes and event rates. There was an unclear risk of bias in most of the trials.

Summary of findings

Background

Aesthetic dentistry has received increased attention in recent years, especially because people are more concerned about the aesthetic appearance of their smile (Demarco 2009). Technological innovations in dentistry have been added due to patients' desire to improve aesthetics of their teeth, which is an important aspect of quality of life (Pinto 2014). A survey conducted in the UK revealed that 28% of adults were dissatisfied with their smile and among 3215 subjects examined, 50% had some kind of tooth discolouration (Joiner 2006). Another survey performed in the UK in 2004 suggested that the public is concerned about dental appearance in terms of tooth colours (Alkhatib 2004). Based on the survey conducted by the American Academy of Cosmetic Dentistry in 2012, discoloured, stained or yellow teeth were the main reason for an unattractive smile. The same survey reported that there was a 29% increase in patients receiving tooth whitening in a span of 1 year and was expected to increase to 45% and more in the years to come. 70% of patients who opted for bleaching were females. 75% of respondents reported the use of at‐home or over‐the‐counter whitening products. 18% of dentists in the US recommended a home‐based bleaching method (Whitening survey 2012).

With this increased demand for whiter teeth, tooth whitening products have been exponentially increasing in the past few decades. Presently, tooth whitening products are the most popularly marketed oral care products (Whitening survey 2012).

Description of the condition

Tooth discolouration can be described as any change in the colour or translucency of a tooth and can be classified based on aetiology as extrinsic or intrinsic discolourations. Extrinsic discolourations adhere to the tooth surface (superficial stains), while intrinsic discolourations are integrated in the structure of teeth (Demarco 2009). However, in some cases, both intrinsic and extrinsic discolourations may affect tooth enamel, dentine or pulp.

Extrinsic staining

This usually results from accumulation of chromatogenic substances on the external tooth surface. These include smoking, pigments in foods and beverages, and metals such as iron or copper which lead to dark, brownish discolourations. These stains are localised mainly in the pellicle and are either generated by the reaction between sugars and amino acids or acquired from the retention of exogenous chromophores in the pellicle (Viscio 2000). This reaction is called Maillard reaction or the non‐enzymatic browning reaction. Most extrinsic stains can be removed by routine prophylactic procedures. With time, these stains darken and become more persistent but they are highly responsive to bleaching.

Intrinsic staining

This can result from genetic disorders such as dentinogenesis imperfecta, amelogenesis imperfecta, thalassaemia, sickle cell anaemia, antibiotics such as tetracyclines, high levels of fluoride intake, dental caries, pulpal haemorrhage, pulpal necrosis, pulp tissue remnants, root filling materials/endodontic irrigation, or amalgam restorations (Nathoo 1997; Kim 2010; Belobrov 2011; Carey 2014; Kolosowski 2014). Likewise, high fevers during the time of a tooth development may cause enamel hypoplasia that leads to banding‐type discolourations on the affected tooth surface. Aging is another common cause of discolouration. Over time, dentine tends to darken due to the formation of secondary dentine and the overlying enamel becomes thinner. Intrinsic stains cannot be removed by regular prophylactic procedures. However, they can be reduced by bleaching with agents penetrating the enamel and dentine to oxidize the chromogens, in some conditions.

Description of the intervention

Tooth whitening or bleaching is a procedure most commonly employed by professionals and patients. It is considered the least invasive aesthetic treatment for improving the appearance of discoloured teeth (Pinto 2014). It may be accomplished by physical removal of the stain or a chemical reaction (bleaching) to lighten the tooth colour. The active ingredient in most chemically‐induced whitening products is hydrogen peroxide (H₂O₂) which is delivered as hydrogen peroxide (HP) or carbamide peroxide (CP). CP is a stable complex, which will break down to HP and urea, once in contact with water. The basic bleaching action is due to the HP, which can be explained in three phases (Joshi 2016):

initial phase: diffusion of HP through the inter‐prismatic spaces and circulation within the tooth for 2 weeks;
second phase: interaction of HP with organic chromophores which can be influenced by temperature, pH, light and metal cations (Kwon 2015);
third phase: colour change through an altered tooth surface.

Bleaching action reaches an end point which is known as inherent lightness potential for that tooth (Matis 2000). Usually if there is no improvement in the shade after 6 weeks of bleaching, irrespective of the bleaching agent and concentration, then bleaching is assumed to have reached its end point (Joshi 2016).

Types of dental bleaching procedures

Tooth discolourations can be improved by several methods such as internal bleaching for non‐vital teeth, or external bleaching for vital teeth (Joiner 2006) or a combination of techniques.

Internal bleaching/non‐vital bleaching

It consists of walking bleach and thermocatalytic bleaching techniques and is done after endodontic treatment by the dentist and comprises of in‐office techniques, which are not in the scope of this review.

External bleaching methods/vital bleaching

There are three fundamental approaches for bleaching vital teeth.

In‐office or power bleaching (not in the scope of this review).
At‐home or dentist‐supervised bleaching.
Consumer‐purchased or over‐the‐counter (OTC) products which are available in pharmacies or supermarkets without any prescription or professional monitoring.

(Other non‐dental products like malic acid found in juice of green apples or do‐it‐yourself whitening with strawberry and baking soda were reported (Kwon 2015) but are not in the scope of this review.)

This review includes only at‐home or dentist‐supervised bleaching and consumer‐purchased or OTC products.

Home‐based bleaching methods (dentist‐supervised and OTC)

A variety of peroxide compounds, including hydrogen peroxide (HP), carbamide peroxide (CP) or urea peroxide, sodium percarbonate (SPC), sodium hexametaphosphate (SHMP), sodium tripolyphosphate (STPP), and calcium peroxide have been used as active ingredients in home‐based bleaching methods. These agents are supplied in different concentrations, used with varying application times and duration of treatment (Alqahtani 2014), and delivered in various forms.

Gels in trays

Dentist‐supervised home‐use tooth bleaching with custom trays is the most common bleaching procedure dispensed by dentists to their patients. Usually, this treatment modality consists of fabrication of a custom tray with and without reservoirs (Javaheri 2000; Caballero 2006; Baroudi 2014).

Whitening strips

These strips mainly contain hydrogen peroxide as the active agent in different concentrations. They are applied directly to the tooth surfaces and are thin flexible polyethylene strips coated with the bleaching gel. Continued research led to the development of strip‐based whitening with very thin peroxide gels less than 0.20 mm in thickness (Perdigão 2004; Duschner 2006).

Disadvantages of the strip system are that it can reach only a finite number of teeth, cannot adapt well on malposed teeth, may interfere with speech patterns and can impinge on gingiva.

Paint‐on gels

Paint‐on gels or varnishes are barrier‐free whitening products that present hydrogen or carbamide peroxide in a suspension that is brushed by an applicator over the tooth surface and which adheres to enamel. Some paint‐on gels have sodium percarbonate as their active ingredient. This method has gained popularity since the consumer just needs to paint a thin layer of whitening gel on their teeth (similar to nail polish application on finger nails). The added advantage is that the users can scallop the product around the gingiva and apply it to an unlimited number of teeth, regardless of the position in the arch.

A disadvantage of this method is that lesser contact time of these agents to the tooth surface may result in reduced whitening of teeth. In addition, the applicator brush is re‐used and stored in the gel product which might lead to microbial contamination. Hence, some manufacturers supply disposable cotton bud applicators for this purpose (Goldstein 1995; Carey 2014).

Whitening mouthrinses

Whitening mouthrinses prevent stains and fight plaque build‐up. Generally, a low concentration of hydrogen peroxide (1.5%), sodium hexametaphosphate have been included in the formulation to protect the teeth surface from new stains (Lima 2012).

Whitening chewing gums

These are well accepted and enjoyed by many as a frequent activity among children and adults, therefore, may be a means for local drug administration into the oral cavity (Barabolak 1991). Chewing gum based products possess a number of therapeutic benefits, including increased saliva flow and removal of food debris, plaque and surface stains (Walters 2004). Baking soda (Mankodi 2001; Soparkar 2001), sodium hexametaphosphate (White 2002; Walters 2004), and sodium tripolyphosphate (Shellis 2005; Porciani 2010) have been reported as the active ingredients in chewing gums.

Whitening dentifrices

The active components of tooth whitening dentifrices include hydrogen peroxide or carbamide peroxide which break down the organic molecules of biological film (Horn 2014). Additionally, abrasives such as alumina, dicalcium phosphate dihydrate and silica are also present in the formulation to promote stain removal (Demarco 2009). Their stain removal ability is related to the large quantity of abrasives in their formulation, which remove superficial extrinsic stains. However, the toothpaste abrasiveness needs to be moderated in order to prevent excessive wear to the underlying enamel and dentine. Toothpastes containing blue covarine, a pigment, which increases the perception of tooth whiteness are available in the market as bleaching toothpastes (Dantas 2015). Whitening dentifrices with desensitizing agents (Po 2014) to reduce the adverse event of sensitivity or dentifrices with casein phosphopeptide‐amorphous calcium phosphate (CPP‐ACP) to remineralize the enamel have been in use (de Vasconcelos 2012).

Whitening dental floss

Whitening dental floss has been introduced to promote stain reduction around the interproximal and subgingival areas. The stain removal properties are associated with the presence of silica in the composition, which promotes a superficial surface abrasion during application in the interdental region (Demarco 2009).

Whitening dentifrices, floss and toothbrushes which involve an abrasive action are not included in this review.

All the above products are either prescribed by the dentist for use at home or purchased by the consumer over‐the‐counter without professional consultation. The permitted concentration of HP varies between countries.

The at‐home technique offers many advantages:

self‐administration by the patient
less chair‐side time
high degree of safety
fewer adverse effects
low cost.

However, there are certain disadvantages:

results dependent on active patient compliance and diligence of use
high dropout rates (Leonard 2003)
excessive use by overzealous patients leads to thermal sensitivity, reported to be as high as 67% (Haywood 1992).

How the intervention might work

General mechanism of action

Hydrogen peroxide and carbamide peroxide formulations used as gels in trays/strips/paint‐on gels and mouthrinses

Tooth stains consist of compounds that have colour or darker shades called chromogens. Bleaching mainly constitutes removal of stains by chemical degradation of these chromogens. It is hypothesized that the basic chemistry of peroxide‐based whitening agents is attributed to reaction of hydrogen peroxide with the chromogens. Carbamide peroxide is also an active ingredient in many whitening products. It is a stable complex which breaks down in contact with water to release hydrogen peroxide (10% CP on contact with water, gets converted to 3% HP and 7% urea).

Chromogens fall into two categories: large organic compounds that have conjugated double bonds in their chemical structure and metal containing compounds. Bleaching of the organic compounds by hydrogen peroxide involves reacting with the double bonds to oxidize the double bond.This causes the chromogen to become a lighter coloured compound. Other hypothesized mechanisms include oxidation of proteins within the tooth matrix.

Bleaching of the metallic compounds is much more difficult. There are some professional products that contain sodium hypochlorite (NaOCl) which react with the double bonds of the chromogen in much the same way as peroxide (Carey 2014).

Sodium percarbonate used in paint‐on gel

19% sodium percarbonate has been developed to deliver peroxide over a sustained period without a fixed barrier. The anhydrous system has peroxide bound in a silicone polymer suspension. Applied with a brush to the dried tooth surface, the suspension is designed to form an enamel adherent substantive film that hydrates overnight to slowly release peroxide into the tooth.

Sodium hexametaphosphate used in chewing gums

This active ingredient is a high molecular weight condensed phosphate analogue which inhibits stain chromogen adsorption reducing overall extrinsic staining.

Sodium tripolyphosphate (STPP) used in chewing gums

The inhibitory action of hydroxy apatite bound STPP on adsorption of salivary proteins, makes it an effective agent for inhibiting and removing dental stain.

Why it is important to do this review

The first published version of this Cochrane Review concluded that there was evidence that whitening products work when compared with placebo/no treatment (Hasson 2006). However, all trials in that review were short term and the majority of the included studies had low methodological quality (i.e. high risk of bias). Moreover, in the past 12 years there may have been additional randomised controlled trials published, which needed to be considered in the review. Therefore, there was a need to update this review to identify new evidence from pragmatic long‐term clinical trials and also to re‐look at the outcomes and comparisons used in the previous version.

Objectives

To evaluate the effects of home‐based tooth whitening products with chemical bleaching action, dispensed by a dentist or over‐the‐counter.

Methods

Criteria for considering studies for this review

Types of studies

Inclusion criteria

Randomised controlled clinical trials comparing dentist‐dispensed or over‐the‐counter (OTC) tooth whitening products (with chemical, bleaching action) with placebo or other comparable products.
Full reports (either published or obtained from the investigators) had to be available for inclusion in the review.
The application of tooth whitening products had to be exclusively carried out at home and outcome data had to be presented for tooth whitening, irrespective of the application time.

Exclusion criteria

Quasi‐randomised trials.

Types of participants

Home‐based whitening involving adults who were 18 years old and above were included in our review regardless of gender, race, profession, geographical location or baseline tooth shade. Because of issues related to compliance and ingestion of a bleaching agent in children and young adults, we decided to include trials including adults who were 18 years old and above.
We included participants with teeth stained because of tetracycline use and smoking.

Types of interventions

Inclusion criteria

We considered any intervention including home‐based chemically‐induced whitening with the following comparisons:

comparisons of different interventions (e.g. professional monitored versus over‐the‐counter; over‐the‐counter product A versus B; professional monitored technique A versus B);
intervention versus placebo or no treatment;
comparisons between different concentrations;
comparisons between different time periods of application.

Exclusion criteria

Combination of in‐office and home‐based treatments were excluded.
Home‐based products having an abrasive action or physical removal of stains were excluded from the review (e.g. whitening dentifrices, whitening dental floss).

Types of outcome measures

Primary outcomes

Two primary outcomes were of interest.

1. Tooth whitening ‐ assessed by the dentist using any relevant tool

The American Dental Association (ADA) acceptance programme guidelines for home‐based tooth whitening products specify the use of two main methods to measure tooth colour in bleaching studies:

value‐oriented shade guides (subjective measurement); and
electronic devices/colour measurement devices (objective measurement).

Value‐oriented shade guides

Traditionally, visual colour determination is used based on visual comparison of tooth with colour standards (also called shade guides). The most common shade guides are Vitapan classical and its derivatives like Vitapan 3D master, tooth guide, bleached guide and linear guide. Ordinal scale ranging from 1 to 16 has been suggested by the manufacturer with 1 representing the lightest shade and 16 representing the darker shade. However, some authors considered 1 as the darkest and 16 as the lighter shade. Some studies reported a scale below 1 and beyond 16 when the tooth shade was lighter than the lightest shade tab and darker than the darkest shade.

Trubyte Bioform shade guide has also been used by some authors using a scale from 1 to 24.

Electronic devices/colour measurement devices

Instruments for clinical shade matching encompass spectrophotometers, colorimeters and imaging systems. They provide a more objective measurement of whiteness compared to shade guides. For instrumental colour assessment of teeth the issue of suitable metric that corresponds to perpetual whiteness is important. Colourimeters, spectrophotometers, spectroradiometer and camera systems can allow computation of CIExyz or CIEL*a*b* values described by commission international deLE clariage (CIE 1978) an international standard for three dimensional colour space.

Using a calibration standard, red‐green‐blue values are determined and converted to L* a* b* values where L* represents the degree of lightness and b* represents degree of yellowness. Tooth whitening is characterised by negative or decreased b* values (reduction in yellowness) and positive or increased L* values (increased lightness). A composite colour W is used by some and derived from individual L* a* b* changes from baseline values. Some clinicians use E* which indicates composite colour change irrespective of the direction of change.

In our review we considered the composite score represented by W* or E* values wherever provided. In the absence of both, the value of L* is considered as it indicates a positive change towards increased lightness.

2. Tooth whitening ‐ reported by the patient using any relevant tool

Improvement in tooth whitening as reported by the patient using any tool was considered in this review. Some authors reported visual analogue scale (VAS) from 0 to 10 to record patient acceptance with 0 indicating best acceptance and 10 indicating no acceptance, while some others used the scale where 0 represents least satisfaction and 10 represents most satisfaction.

Other scores used were on an ordinal scale of 0 to 3 where 0 = no improvement in whiteness, 1 and 2 = moderate improvement, and 3 = improvement. In such cases, we combined 1, 2, and 3 as improvement in shade and counted them as events.

Secondary outcomes

Patient satisfaction or acceptability of the tooth whitening procedure (patient comfort).
Adverse effects: any side effects reported due to the bleaching procedure were considered in this review and described qualitatively.
Oral health‐related quality of life.

Search methods for identification of studies

Electronic searches

Cochrane Oral Health's Information Specialist conducted systematic searches in the following databases for randomised controlled trials and controlled clinical trials. There were no language, publication year or publication status restrictions:

Cochrane Oral Health's Trials Register (searched 12 June 2018) (Appendix 1);
Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library (searched 12 June 2018) (Appendix 2);
MEDLINE Ovid (1946 to 12 June 2018) (Appendix 3);
Embase Ovid (1980 to 12 June 2018) (Appendix 4).

Subject strategies were modelled on the search strategy designed for MEDLINE Ovid. Where appropriate, they were combined with subject strategy adaptations of the highly sensitive search strategy designed by Cochrane for identifying randomised controlled trials and controlled clinical trials as described in the Cochrane Handbook for Systematic Reviews of Interventions Chapter 6 (Lefebvre 2011).

Searching other resources

The following trial registries were searched for ongoing studies:

US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (clinicaltrials.gov; searched 12 June 2018) (Appendix 5);
World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch; searched 12 June 2018) (Appendix 6).

We searched the reference lists of included studies and relevant systematic reviews for further studies.

We did not perform a separate search for adverse effects of interventions used, we considered adverse effects described in included studies only.

Data collection and analysis

Selection of studies

Two review authors (Eachempati Prashanti (EP), Salian Kiran (SK)) independently screened the titles and abstracts from the electronic searches to identify potentially eligible studies. The search was designed to be sensitive and include controlled clinical trials, these were filtered out early in the selection process if they were not randomised. We obtained full‐text copies of all potentially eligible studies and two pairs of review authors (EP and Ibrahim Ethem (IE), SK and Puneet Gupta (PG)) further evaluated in detail the studies for inclusion. We recorded the reasons why studies did not meet the inclusion criteria in the 'Characteristics of excluded studies' table. We resolved any disagreements by discussion. When resolution was not possible, we consulted the arbiter (Sumanth Kumbargere Nagraj (SKN)). Articles in languages other than English were assessed by their abstracts where possible and if they appeared to be potentially eligible, we obtained and translated the full‐text article.

Data extraction and management

Two pairs of review authors (EP and IE, SK and PG) extracted the data independently, using a data extraction form specifically designed for this Cochrane Review. We resolved any disagreements by discussion. The two review authors independently checked data extraction forms obtained from translators and cross checked any doubtful aspects using Google translator. We entered all study details in the 'Characteristics of included studies' table in Review Manager 5 software (Review Manager 2014). We recorded the following details for each included trial.

Publication details like year of publication and language.
Demographic details of the report.
Inclusion and exclusion criteria.
Sample size.
Method of randomisation.
Allocation concealment.
Blinding.
Type of trial.
Method of assessing the outcome, and dropouts if any.
Type of intervention.
Details of the outcome reported.
Duration of follow‐up.
Results of the intervention.
Funding details.
Details about trials registration.
For obtaining additional data and clarifications, we contacted the authors of the included and excluded trials via email.

Assessment of risk of bias in included studies

We independently assessed the risk of bias in the included trials for seven domains: sequence generation; allocation concealment; performance bias and detection bias; incomplete outcome data; selective outcome reporting; and other biases. For each of these components, we assigned a judgement regarding the risk of bias as either 'high', 'low' or 'unclear', based on guidance in section 8.5.d of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We contacted the trial authors if details were missing in the publications or were unclear. We resolved disagreements through consensus. We recorded our judgements and justifications in 'Risk of bias' tables for each included study and generated a 'Risk of bias' summary figure. We used these judgements while grading of the overall quality of evidence for outcomes in the 'Summary of findings' tables for each comparison.

We summarised the risk of bias according to Higgins 2011 as follows:

Risk of bias	Interpretation	In outcome	In included studies
Low	Plausible bias unlikely to seriously alter the results	Low risk of bias for all key domains	Most information is from studies at low risk of bias
Unclear	Plausible bias that raises some doubt about the results	Unclear risk of bias for one or more key domains	Most information is from studies at low or unclear risk of bias
High	Plausible bias that seriously weakens confidence in the results	High risk of bias for one or more key domains	The proportion of information from studies at high risk of bias is sufficient to affect the interpretation of results

Trial	Interventions reported in the trials	Interventions considered in analyses	Reason
Aka 2017	Placebo 10% carbamide peroxide (Opalescence PF) gel in tray 6% hydrogen peroxide (Opalescence Go) gel in tray	Bleaching agent vs placebo 10% carbamide peroxide gel in tray vs placebo Bleaching agent vs bleaching agent 10% carbamide peroxide gel in tray vs 6% hydrogen peroxide gel in tray	Most commonly used concentrations
Alonso 2014	10% carbamide peroxide in tray 15% carbamide peroxide in tray 7.5% hydrogen peroxide in tray 9.5% hydrogen peroxide in tray	Bleaching agent vs bleaching agent 10% carbamide peroxide in tray vs 7.5% hydrogen peroxide in tray	Most commonly used concentrations
Bizhang 2007	6% hydrogen peroxide whitening strips 19% sodium percarbonate brush‐applied gel that dries to a film Placebo brush‐applied gel without peroxide	Bleaching agent vs placebo 6% hydrogen peroxide whitening strips vs placebo Bleaching agent vs bleaching agent 19% sodium percarbonate brush‐applied gel that dries to a film vs 6% hydrogen peroxide whitening strips	Most commonly used concentrations
Browning 2008	10% carbamide peroxide in tray 10% carbamide peroxide, 3% potassium nitrate in tray 10% carbamide peroxide, 0.5% potassium nitrate in tray 10% carbamide peroxide, 0.5% potassium nitrate, 0.25% sodium fluoride in tray Placebo	Bleaching agent vs placebo 10% carbamide peroxide, 0.5% potassium nitrate, 0.25% sodium fluoride in tray vs placebo Bleaching agent vs bleaching agent 10% carbamide peroxide in tray vs 10% carbamide peroxide, 0.5% potassium nitrate, 0.25% sodium fluoride in tray	Most commonly used concentrations
Gerlach 2000	5.3% hydrogen peroxide strips 10% carbamide peroxide gel in tray 15% carbamide peroxide gel in tray 20% carbamide peroxide gel in tray	Bleaching agent vs bleaching agent 5.3% hydrogen peroxide strips vs 10% carbamide peroxide gel in tray	Most commonly used concentrations
Hyland 2015	5% carbamide peroxide gel 10% carbamide peroxide gel Placebo	Bleaching agent vs placebo 5% carbamide peroxide gel vs placebo Bleaching agent vs bleaching agent 5% carbamide peroxide gel vs 10% carbamide peroxide gel	Most commonly used concentrations
Krause 2008	10% carbamide peroxide gel in tray 17% carbamide peroxide gel in tray 0% carbamide peroxide gel in tray (control)	Bleaching agent vs bleaching agent 10% carbamide peroxide gel in tray vs 17% carbamide peroxide gel in tray	Most commonly used concentrations
Li 2003	6.5% hydrogen peroxide strips 7.5% hydrogen peroxide gel in tray 16% carbamide peroxide gel in tray	Bleaching agent vs bleaching agent 6.5% hydrogen peroxide strips vs 16% carbamide peroxide gel in tray	Most commonly used concentrations
Li 2004	18% carbamide peroxide 2x paint‐on gel 18% carbamide peroxide 3x paint‐on gel 18% carbamide peroxide 4x paint‐on gel	Bleaching agent vs bleaching agent 18% carbamide peroxide 2x paint‐on gel vs 18% carbamide peroxide 4x paint‐on gel	Most commonly used concentrations
Matis 2006	10% carbamide peroxide gel in tray 15% carbamide peroxide gel in tray 20% carbamide peroxide gel in tray	Bleaching agent vs bleaching agent 10% carbamide peroxide gel in tray vs 15% carbamide peroxide gel in tray	Most commonly used concentrations
Wong 2004	6% hydrogen peroxide strips 18% carbamide peroxide paint‐on gel Placebo: non‐whitening toothpaste	Bleaching vs placebo 6% hydrogen peroxide strips vs placebo Bleaching agent vs bleaching agent 6% hydrogen peroxide strips vs 18% carbamide peroxide paint‐on gel	Most commonly used concentrations
Xu 2007	6% hydrogen peroxide strips 5.8% hydrogen peroxide paint‐on gel Placebo: negative control (water rinse)	Bleaching vs placebo 6% hydrogen peroxide strips vs placebo Bleaching agent vs bleaching agent 5.8% hydrogen peroxide paint‐on gel vs 6% hydrogen peroxide strips	Most commonly used concentrations

Carbamide peroxide (CP) gel in tray compared to placebo for whitening teeth
Patient or population: adults undergoing bleaching  Setting: home‐based  Intervention: CP gel in tray  Comparison: placebo
Tooth whitening ‐ assessed by the dentist
Comparison	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	Number of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with placebo	Risk with CP gel in tray
10% CP gel in tray versus placebo ‐ 6 months (higher RR indicates gel whiter)	Study population		RR 6.74  (3.15 to 14.40)	109  (2 RCTs)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
	107 per 1000	722 per 1000 (337 to 1000)
5% CP gel in tray versus placebo ‐ 2 weeks (higher shade indicates whiter)	The mean change in shade in the placebo group was 71.852	Mean difference in shade change is 4.56 units higher in the CP gel group  (1.52 higher to 7.59 higher)	‐	21  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
10% CP gel with desensitiser versus placebo ‐ 2 weeks (higher shade indicates whiter)	The mean change in shade in the placebo group was 9.40	Mean difference in shade change is 4.70 units higher in the CP gel group  (3.28 higher to 6.12 higher)	‐	37  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
10% CP gel (lighter shade) versus placebo ‐ 2 weeks (higher shade indicates whiter)	The mean change in shade in the placebo group was 1.40	Mean difference in shade change is 4.50 units higher in the CP gel group  (4.04 higher to 4.96 higher)	‐	179 teeth  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	Analysis done at tooth level
10% CP gel (medium dark shade) versus placebo ‐ 2 weeks (higher shade indicates whiter)	The mean change in shade in the placebo group was was 1.20	Mean difference in shade change is 9.30 units higher in the CP gel group  (8.75 higher to 9.85 higher)	‐	172 teeth  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	Analysis done at tooth level
10% CP gel (dark shade) versus placebo ‐ 2 weeks (higher shade indicates whiter)	The mean change in shade in the placebo group was 1.10	Mean difference in shade change is 10 units higher in the CP gel group  (9.44 higher to 10.56 higher)	‐	176 teeth  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	Analysis done at tooth level
Adverse effects
Main adverse events reported in majority of trials were mild and transient tooth sensitivity and oral irritation which occurred more in the intervention group compared to placebo
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)    CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio
GRADE Working Group grades of evidence  High certainty: we are very confident that the true effect lies close to that of the estimate of the effect  Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect  Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

Hydrogen peroxide (HP) gel in tray compared to placebo for whitening teeth
Patient or population: adults undergoing bleaching  Setting: home‐based  Intervention: HP gel in tray  Comparison: placebo
Tooth whitening ‐ assessed by the dentist
Comparison	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	Number of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with placebo	Risk with HP gel in tray
6% HP gel versus placebo ‐ 14 days (higher shade indicates whiter)	The mean change in shade in placebo group was 0.48	Mean difference in shade change is 3.08 units higher in the HP gel group  (2.28 higher to 3.88 higher)	‐	49  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
Adverse effects
Not reported
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)    CI: confidence interval; RCT: randomised controlled trial
GRADE Working Group grades of evidence  High certainty: we are very confident that the true effect lies close to that of the estimate of the effect  Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect  Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

Hydrogen peroxide (HP) strips compared to placebo for whitening teeth
Patient or population: adults undergoing bleaching  Setting: home‐based  Intervention: HP strips  Comparison: placebo
Tooth whitening ‐ assessed by the dentist
Comparison	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	Number of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
Comparison	Risk with placebo	Risk with HP strips	Relative effect  (95% CI)	Number of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
10% HP strip versus placebo ‐ day 8 (higher shade indicates whiter)	The mean change in shade in placebo group was 0.21	Mean difference in shade change is 2.24 units higher in the HP strip group  (1.72 higher to 2.76 higher)	‐	36  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
6% HP strip versus placebo ‐ 2 weeks (higher shade indicates whiter)	‐	Mean difference in shade change is 2.24 units higher in the HP strip group  (1.83 higher to 2.66 higher)	‐	195  (4 RCTs)	⊕⊕⊝⊝  LOW^{1, 2}	‐
10% HP strip versus placebo ‐ 15 days (higher shade indicates whiter)	The mean change in shade in placebo group was 0.90	Mean difference in shade change is 1.93 units higher in the HP strip group  (1.34 higher to 2.52 higher)	‐	40  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
14% HP strip versus placebo ‐ 3 weeks (higher shade indicates whiter)	The mean change in shade in placebo group was 1.90	Mean difference in shade change is 7.60 units higher in the HP strip group  (6.18 higher to 9.02 higher)	‐	28  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
6% HP strip versus placebo ‐ 6 weeks (higher shade indicates whiter)	The mean change in shade in placebo group was 1.82	Mean difference in shade change is 2.90 units higher in the HP strip group  (1.73 higher to 4.07 higher)	‐	37  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
14% HP strip versus placebo ‐ 6 weeks (higher shade indicates whiter)	The mean change in shade in placebo group was 0.45	Mean difference in shade change is 5.16 units higher in the HP strip group  (4.21 higher to 6.11 higher)	‐	35  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
5.3% HP strip versus placebo ‐ 6 months (higher shade indicates whiter)	The mean change in shade in placebo group was 1.02	Mean difference in shade change is 1.21 units higher in the HP strip group  (0.67 higher to 1.75 higher)	‐	52  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
Adverse effects
Main adverse events reported in majority of trials were mild and transient tooth sensitivity and oral irritation which occurred more in the intervention group compared to placebo
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)    CI: confidence interval; RCT: randomised controlled trial
GRADE Working Group grades of evidence  High certainty: we are very confident that the true effect lies close to that of the estimate of the effect  Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect  Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

Carbamide peroxide (CP) paint‐on gel compared to placebo for whitening teeth
Patient or population: adults undergoing bleaching  Setting: home‐based  Intervention: CP paint‐on gel  Comparison: placebo
Tooth whitening ‐ assessed by the dentist
Comparisons	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	Number of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with placebo	Risk with CP paint‐on
18% CP paint‐on gel versus placebo ‐ 3 weeks (higher shade indicates whiter)	The mean shade change in the placebo group was 0.34	Mean difference in the shade change was 3.50 higher in the CP paint‐on gel group  (3.12 higher to 3.88 higher)	‐	77  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
Adverse effects
Not reported
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)    CI: confidence interval; RCT: randomised controlled trial
GRADE Working Group grades of evidence  High certainty: we are very confident that the true effect lies close to that of the estimate of the effect  Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect  Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

Hydrogen peroxide (HP) paint‐on gel compared to placebo for whitening teeth
Patient or population: adults undergoing bleaching  Setting: home‐based  Intervention: HP paint‐on gel  Comparison: placebo
Tooth whitening ‐ assessed by the dentist
Comparisons	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	Number of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with placebo	Risk with HP paint‐on
6% HP paint‐on gel versus placebo ‐ 2 weeks (higher shade indicates whiter)	‐	SMD was 0.67 higher in HP paint‐on gel group  (0.19 higher to 1.14 higher)	‐	148  (2 RCTs)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
Adverse effects
Main adverse events reported in majority of trials were mild and transient tooth sensitivity and oral irritation which occurred more in the intervention group compared to placebo
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)    CI: confidence interval; RCT: randomised controlled trial; SMD: standardised mean difference
GRADE Working Group grades of evidence  High certainty: we are very confident that the true effect lies close to that of the estimate of the effect  Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect  Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

Sodium hexametaphosphate (SHMP) chewing gum compared to placebo for whitening teeth
Patient or population: adults undergoing bleaching  Setting: home‐based  Intervention: SHMP chewing gum  Comparison: placebo
Tooth whitening ‐ assessed by the dentist
Comparisons	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	Number of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with placebo	Risk with SHMP chewing gum
7.5% SHMP chewing gum versus placebo ‐ 2 days (higher shade indicates whiter)	The mean shade change in placebo gum was ‐4.28	Mean difference in the shade change was 0.89 higher in the SHMP chewing gum group  (0.77 higher to 1.01 higher)	‐	37  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
5.6% SHMP chewing gum versus placebo ‐ 3 days (higher shade indicates whiter)	The mean shade change in placebo gum was ‐7.27	Mean difference in the shade change was 2.60 higher in the SHMP chewing gum group  (1.45 higher to 3.75 higher)	‐	20  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
4% SHMP chewing gum versus placebo ‐ 12 weeks (higher shade indicates whiter)	The mean shade change in placebo gum was ‐1.27	Mean difference in the shade change was 0.14 lower in the SHMP chewing gum group  (0.38 lower to 0.10 higher)	‐	108  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
Adverse effects
Not reported
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)    CI: confidence interval; RCT: randomised controlled trial
GRADE Working Group grades of evidence  High certainty: we are very confident that the true effect lies close to that of the estimate of the effect  Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect  Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

Sodium tripolyphosphate (STPP) chewing gum compared to placebo for whitening teeth
Patient or population: adults undergoing bleaching  Setting: home‐based  Intervention: STPP chewing gum  Comparison: placebo
Tooth whitening ‐ assessed by the dentist
Comparisons	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	Number of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with placebo	Risk with STPP chewing gum
1% STPP chewing gum versus placebo ‐ 6 weeks (higher shade indicates whiter)	The mean shade change in placebo gum was ‐0.09	Mean difference in the shade change was 0.18 higher in the STPP chewing gum group (0.10 higher to 0.26 higher)	‐	108  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
Adverse effects
Not reported
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)    CI: confidence interval; RCT: randomised controlled trial
GRADE Working Group grades of evidence  High certainty: we are very confident that the true effect lies close to that of the estimate of the effect  Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect  Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

Hydrogen peroxide (HP) mouthwash compared to placebo for whitening teeth
Patient or population: adults undergoing bleaching  Setting: home‐based  Intervention: HP mouthwash  Comparison: placebo
Tooth whitening ‐ assessed by the dentist
Comparisons	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	Number of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with placebo	Risk with HP mouthwash
1.5% HP + 0.05% HF mouthwash versus placebo ‐ 6 months (higher OR indicates whiter)	Study population		OR 10.89  (5.08 to 23.35)	78  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	Log of odds ratio and SE were calculated and data analyzed using generic inverse variance method
	0 per 1000	0 per 1000  (0 to 0)
Adverse effects
Not reported
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)    CI: confidence interval; F: fluoride; OR: odds ratio; RCT: randomised controlled trial; SE: standard error
GRADE Working Group grades of evidence  High certainty: we are very confident that the true effect lies close to that of the estimate of the effect  Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect  Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

Carbamide peroxide (CP) paint‐on compared to CP paint‐on for whitening teeth
Patient or population: adults undergoing bleaching  Setting: home‐based  Intervention: CP paint‐on   Comparison: CP paint‐on
Tooth whitening ‐ assessed by the dentist
Comparisons	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	Number of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with 18% CP paint‐on	Risk with CP paint‐on
18% CP paint‐on 2x versus 18% CP paint‐on 4x ‐ 1 week (higher shade indicates whiter)	The mean shade change in the 18% CP paint‐on 2x group was ‐2.79	Mean difference in shade change was 1.39 higher in 18% CP paint‐on 4x group  (0.50 higher to 2.28 higher)	‐	69  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
18% CP paint‐on versus 16.40% CP paint‐on ‐ 2 weeks (higher shade indicates whiter)	The mean shade change in the 18% CP paint‐on group was 8.20	Mean difference in shade change was 0.70 lower in the 16.40% CP paint‐on group  (2.21 lower to 0.81 higher)	‐	93  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
Adverse effects
Very mild tooth sensitivity was found in the 4 times daily application group. Both gingival and tooth sensitivity were reported to be transient and caused none of the subjects to withdraw from the study
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)    CI: confidence interval; RCT: randomised controlled trial; 2x: twice; 4x: 4 times
GRADE Working Group grades of evidence  High certainty: we are very confident that the true effect lies close to that of the estimate of the effect  Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect  Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Tooth whitening ‐ assessed by the dentist	2	109	Risk Ratio (M‐H, Random, 95% CI)	6.74 [3.15, 14.40]
1.1 10% CP gel ‐ 6 months	2	109	Risk Ratio (M‐H, Random, 95% CI)	6.74 [3.15, 14.40]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Tooth whitening ‐ assessed by the dentist	2		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
1.1 6% HP ‐ 2 weeks	2	148	Std. Mean Difference (IV, Random, 95% CI)	0.67 [0.19, 1.14]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Tooth whitening ‐ assessed by the dentist	1		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
1.1 10% CP tray versus 10% CP tray ‐ 2 weeks	1	66	Risk Ratio (M‐H, Random, 95% CI)	1.03 [0.90, 1.18]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Tooth whitening ‐ assessed by the dentist	2		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
1.1 18% CP paint‐on versus 6% HP strip	2	102	Std. Mean Difference (IV, Random, 95% CI)	1.50 [1.06, 1.94]

Hydrogen peroxide (HP) paint‐on compared to HP paint‐on for whitening teeth
Patient or population: adults undergoing bleaching  Setting: home‐based  Intervention: HP paint‐on  Comparison: HP paint‐on
Tooth whitening ‐ assessed by the dentist
Comparison	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	Number of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with 6% HP paint‐on	Risk with 6% HP paint‐on with KF
6% HP paint‐on versus 6% HP paint‐on with KF (higher shade indicates whiter)	The mean shade change in the 6% HP paint‐on group was 2.70	Mean difference in shade change was 0.10 lower in 6% HP paint‐on with KF  (0.56 lower to 0.36 higher)	‐	67  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
Adverse effects
Tooth sensitivity was noted in both groups with no evidence of a difference
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)    CI: confidence interval; KF: potassium fluoride; RCT: randomised controlled trial
GRADE Working Group grades of evidence  High certainty: we are very confident that the true effect lies close to that of the estimate of the effect  Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect  Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

Sodium percarbonate (SPC) paint‐on compared to CP paint‐on for whitening teeth
Patient or population: adults undergoing bleaching  Setting: home‐based  Intervention: SPC paint‐on  Comparison: CP paint‐on
Tooth whitening ‐ assessed by the dentist
Comparison	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	Number of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with CP paint‐on	Risk with SPC paint‐on
19% SPC paint‐on versus 18% CP ‐ 14 days (higher shade indicates whiter)	The mean shade change in 18% CP paint‐on group was ‐0.55	Mean difference in shade change was 0.58 higher in the SPC paint‐on group  (0.95 lower to 0.21 lower)	‐	38  (1 RCT)	⊕⊝⊝⊝  VERY LOW^{1, 2}	‐
Adverse effects
1 subject in 19% SPC paint‐on group reported oral sensitivity. All adverse events were symptomatic and mild in severity
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)    CI: confidence interval; RCT: randomised controlled trial
GRADE Working Group grades of evidence  High certainty: we are very confident that the true effect lies close to that of the estimate of the effect  Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different  Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect  Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

Date	Event	Description
12 June 2018	New citation required and conclusions have changed	New authors. Review update including 46 new studies bringing the total to 71 included studies. Methods updated. 'Summary of findings' tables included. Conclusions changed.
12 June 2018	New search has been performed	Searches updated to 12 June 2018.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Tooth whitening ‐ assessed by the dentist	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
1.1 5% CP gel ‐ 2 weeks	1	21	Mean Difference (IV, Fixed, 95% CI)	4.56 [1.52, 7.59]
1.2 10% CP gel with desensitiser ‐ 2 weeks	1	37	Mean Difference (IV, Fixed, 95% CI)	4.70 [3.28, 6.12]
1.3 10% CP gel ‐ light shade ‐ 2 weeks	1	179	Mean Difference (IV, Fixed, 95% CI)	4.5 [4.04, 4.96]
1.4 10% CP gel ‐ medium dark shade ‐ 2 weeks	1	172	Mean Difference (IV, Fixed, 95% CI)	6.90 [6.35, 7.45]
1.5 10% CP gel ‐ darker shade ‐ 2 weeks	1	176	Mean Difference (IV, Fixed, 95% CI)	10.0 [9.44, 10.56]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Tooth whitening ‐ assessed by the dentist	1		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.1 6% HP gel ‐ 14 days	1	49	Mean Difference (IV, Random, 95% CI)	3.08 [2.28, 3.88]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Tooth whitening ‐ assessed by the dentist	3		Mean Difference (Random, 95% CI)	Subtotals only
1.1 7.5% SHMP gum ‐ 2 days	1	37	Mean Difference (Random, 95% CI)	0.89 [0.77, 1.01]
1.2 5.6% SHMP gum ‐ 3 days	1	20	Mean Difference (Random, 95% CI)	2.6 [1.45, 3.75]
1.3 4% SHMP gum ‐ 12 weeks	1	108	Mean Difference (Random, 95% CI)	‐0.14 [‐0.38, 0.10]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Tooth whitening ‐ assessed by the dentist	1		(Random, 95% CI)	Subtotals only
1.1 1.5% HP + 0.05% F ‐ 6 months	1	78	(Random, 95% CI)	10.89 [5.08, 23.35]

Methods	Title: evaluation of the efficacy and colour stability of 2 different at‐home bleaching systems on teeth of different shades Trial design: randomised, parallel‐group, controlled clinical trial Location: Izmir Katip Celebi University, Turkey Language: English Number of centres: 1 Recruitment period: January to July 2014 Funding source: not reported
Participants	Participants: 20 to 51 years old, mean age 26 years Total number: 200 Inclusion criteria: good general health adults 18+ no caries or restoration on the teeth permanent teeth availability for follow‐up at least 1 front teeth from each shade category Exclusion criteria: history of allergy tetracycline stain poor oral hygiene pregnant or lactating women having parafunctional habits current or previous use of bleaching orthodontic treatment hypersensitivity Number randomised: 92 (all patients had similar number of light, medium dark and dark shaded teeth) Method of randomisation: randomisation table Method of allocation concealment: not reported Method of blinding: not reported Number evaluated: 90
Interventions	Total number of intervention groups: 3 Group 1: placebo n = 31 Group 2: 10% carbamide peroxide gel (Opalescence PF) n = 30 Group 3: 6% hydrogen peroxide gel (Opalescence Go) n = 31 Duration of treatment: 14 days Each group was further divided based on the shade (tooth level analysis) Control group: light teeth n = 90, medium dark teeth n = 91, dark teeth n= 93 Experiment Group 2: light teeth n = 89, medium dark n = 81, dark teeth n = 83 Experiment Group 3: light teeth n = 91, medium teeth n = 88, dark teeth n = 81
Outcomes	Shade evaluation (dental spectrophotometer); tooth sensitivity, gingival irritation and patient satisfaction (self‐assessed using a 7‐point scale: 1 correlating to no sensitivity, no problems, or no satisfaction; 7 correlating to severe sensitivity, problems, or satisfaction
Notes	Sample size calculation: given Adverse effects: tooth sensitivity and irritation Key conclusions of the study authors: "A pre‐loaded tray system may be used for dental bleaching, but it is still less effective than conventional 10% carbamide peroxide system, irrespective of the initial shade. Bleaching was more effective with dark teeth compared to light teeth. Patient satisfaction was higher in 10% CP group compared to 6% HP" Correspondence required: no Contact: Department of Restorative Dentistry, Faculty of Dentistry, Izmir Katip Celebi University, Izmir, Turkey
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The patients were randomly assigned to one of the two treatment groups and a control group using a randomization table…"
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not mentioned
Blinding of outcome assessment (detection bias)   All outcomes	High risk	Assessed as at high risk of bias due to the lack of clarity of how teeth were selected for outcome assessment
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: "2 patients from 6% HP/Go groups with 6 light shades of teeth did not attend the 6 months visit" Comment: Plausible effect size (difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size
Selective reporting (reporting bias)	Low risk	All outcomes described were reported. Conclusions are in accordance with the results
Other bias	Low risk	None

Methods	Title: comparison of the clinical efficacy and safety of carbamide peroxide and hydrogen peroxide in at‐home bleaching gels Trial design: split‐mouth randomised controlled trial Location: not reported Language: English Number of centres: 1 Recruitment period: not reported Funding source: not reported
Participants	Participants: 18 to 50 years, mean age: 31.8 years Total number: 16 Inclusion criteria: subject availability to attend the control visits good overall general health a minimum of 24 natural teeth, including at least 4 molars (excluding third molars) willingness to refrain from the use of any type of mouthrinse during participation in the study Exclusion criteria: medication; need of antibiotic prophylactic therapy to receive dental treatment smoking habit pregnant or breastfeeding presence of active cavities; anterior sector restorations covering > 1/6 of the labial surface anterior teeth with root canal treatment crowns or veneers on anterior teeth a Löe‐Silness Gingival Index 25 above 1 stains confirmed to be due to tetracycline Number randomised: 16 Method of randomisation: not reported Method of allocation concealment: not reported Method of blinding: not reported Number evaluated: 16
Interventions	Total number of intervention groups: 2 3.5% hydrogen peroxide gel + 5% potassium nitrate 10% carbamide peroxide gel Duration of treatment: 3 hours a day on each arch, renew the gel every hour for 4 weeks
Outcomes	Change in tooth colour Vita shade guide: B1 lightest (1) – C4 darkest (16) Dental sensitivity: a scale of 4 levels, absence of sensitivity (grade 0), slight sensitivity not necessitating suspension of treatment (grade 1), sensitivity that forced suspension of treatment for 1 day (grade 2), sensitivity that led to suspension of treatment for more than 1 day (grade 3) Gingival irritation: present or absent
Notes	Sample size calculation: not reported Adverse effects: sensitivity Health‐related quality of life: not reported Key conclusions of the study authors: "Under the conditions of this study, no statistically significant differences were detected between 3.5% hydrogen peroxide containing 5% potassium nitrate (FKD) and the 10% carbamide peroxide‐based product (Opalescence)" Correspondence required: no Contact: Victor Alonso de la Peña; victorap@mundo‐r.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Both groups applied the products on a random basis"
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not mentioned
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Not mentioned
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All 16 patients completed the study
Selective reporting (reporting bias)	Low risk	All outcomes described were reported. Conclusions are in accordance with the results
Other bias	Low risk	None

Methods	Title: randomised clinical trial on the efficacy and safety of 4 professional at home tooth whitening gels Trial design: randomised controlled clinical trial Location: Faculty of Medicine and Dentistry, Santiago de Compostela, Spain Language: English Number of centres: 1 Recruitment period: not reported Funding source: not reported
Participants	Participants: mean age 25.9 years Total number: 96 Inclusion criteria: 18 years and older minimum 24 natural teeth, with incisor, canine and premolars in both arches absence of periodontal disease and gingival recession availability to complete the study Exclusion criteria: systemic illness antibiotic prophylaxis pregnant and breastfeeding women tumours of hard and soft palate presence of restoration xerostomia, smokers fluoride supplements and desensitizing agents removable prosthesis previous history of bleaching Number randomised: 96 Method of randomisation: based on alphabetical order Method of allocation concealment: not reported Method of blinding: not reported Number evaluated: 96
Interventions	Total number of intervention groups: 4 10% carbamide peroxide 15% carbamide peroxide 7.5% hydrogen peroxide 9.5% hydrogen peroxide Duration of treatment: 2 weeks
Outcomes	Change in colour Vita shade guide arranged from lightest to darkest B1 (1) to C4 (16). And change in score was recorded ΔL, a, b were recorded (b*: decreased b indicates reduced yellowness; ΔL: increased ΔL is increased brightness) Sensitivity: 0 = none, 1 = mild, 2 = moderate, 3 = considerable, 4 = severe
Notes	Sample size calculation: not reported Adverse effects: sensitivity Health‐related quality of life: not reported Key conclusions of the study authors: "There were no differences in the degree of whitening among the different products. With all of the products there was an increase in L, a decrease in chromatic intensity (C), and an increase in the value (tone) or hue (h*)" Contact: Dr Teijeiro; victorap@mundo‐r.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "...they were randomly divided into 4 groups of 24 individuals by alphabetical order"
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Quote: "this was controlled, parallel, randomized one centre…" However, method of blinding is not mentioned
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Quote: "this was controlled, parallel, randomized one centre…" However, method of blinding is not mentioned
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: "All 96 participants completed the study"
Selective reporting (reporting bias)	Low risk	All outcomes described were reported. Conclusions are in accordance with the results
Other bias	Low risk	None

PERMALINK

Home‐based chemically‐induced whitening (bleaching) of teeth in adults

Prashanti Eachempati

Sumanth Kumbargere Nagraj

Salian Kiran Kumar Krishanappa

Puneet Gupta

Ibrahim Ethem Yaylali

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Background

Description of the condition

Extrinsic staining

Intrinsic staining

Description of the intervention

Types of dental bleaching procedures

Internal bleaching/non‐vital bleaching

External bleaching methods/vital bleaching

Home‐based bleaching methods (dentist‐supervised and OTC)

Gels in trays

Whitening strips

Paint‐on gels

Whitening mouthrinses

Whitening chewing gums

Whitening dentifrices

Whitening dental floss

How the intervention might work

General mechanism of action

Hydrogen peroxide and carbamide peroxide formulations used as gels in trays/strips/paint‐on gels and mouthrinses

Sodium percarbonate used in paint‐on gel

Sodium hexametaphosphate used in chewing gums

Sodium tripolyphosphate (STPP) used in chewing gums

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Inclusion criteria

Exclusion criteria

Types of participants

Types of interventions

Inclusion criteria

Exclusion criteria

Types of outcome measures

Primary outcomes

1. Tooth whitening ‐ assessed by the dentist using any relevant tool

Value‐oriented shade guides

Electronic devices/colour measurement devices

2. Tooth whitening ‐ reported by the patient using any relevant tool

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Population

Method

Outcome measures

Sensitivity analysis

Summary of findings and assessment of the certainty of the evidence

Results

Description of studies

Results of the search

1.

Methods	Title: a clinical comparison of 2 over‐the‐counter bleaching systems Trial design: examiner‐blinded, split‐mouth randomised controlled trial Location: Freiburg, Germany Language: German (translates to English using Google translate) Number of centres: 1 Recruitment period: not reported Funding source: not reported
Participants	Participants: 21 to 36 years old. Mean age: 25.5 years Total number: 26 Inclusion criteria: A3 or darker shade presence of anterior teeth to premolar Number randomised: 26 Method of randomisation: not reported Method of allocation concealment: not reported Method of blinding: not reported Number evaluated: 20
Interventions	Total number of intervention groups: 2 5.9% hydrogen peroxide gel 5.9% hydrogen peroxide strips Duration of treatment: 32 days
Outcomes	Improvement in tooth shade Vita shade guide: C1 lightest (1) to B4 darkest (16)
Notes	Sample size calculation: not reported Adverse effects: hypersensitivity Health‐related quality of life: not reported Key conclusions of the study authors: "The subjects teeth treated with the strips‐system exhibited a 6.0 +/‐ 0.0 mean shade scores improvement compared to baseline (53.7 cycles; 1610.3 min), and the subjects teeth treated with the gel‐system exhibited a 3.3 +/‐ 1.4 mean shade scores improvement (64.6 cycles; 969.0 min). However, both treatments were able to whiten teeth statistically significantly compared to baseline. Side effects caused by the 2 systems were minimal and reversible. None of the teeth studied showed detectible enamel surface changes in the subsequent SEM analysis. Both methods were well accepted" Contact: Thorsten.auschill@uniklini‐freiburg.de
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote:"...subjects were randomly assigned to one of two groups." However, method is not reported
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not done
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Quote: "Examiner‐blinded split‐mouth randomised controlled trial." However, method is not reported
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: "6 out of 26 patients no longer appeared for follow‐up" Comment: as each group had 20 participants (split‐mouth trial) we rated it as low risk according to Higgins 2011 Section 8.5.d. Missing outcome data balanced in numbers across intervention groups
Selective reporting (reporting bias)	Low risk	All outcomes described were reported. Conclusions are in accordance with the results
Other bias	Low risk	None

Methods	Title: randomised clinical trial of the efficacy, tolerability, and long‐term colour stability of 2 bleaching techniques: 18‐month follow‐up Trial design: 2‐cell, parallel, examiner‐blinded, randomised controlled trial Location: Albert‐Ludwigs‐University, Freiburg, Germany Language: English Number of centres: 1 Recruitment period: not reported Funding source: Colgate Palmolive
Participants	Participants: 18 to 56 years old, mean age: 33.08 years Total number: 30 Inclusion criteria: maxillary central incisor with A3 or darker shade free of restorations no prior bleaching Exclusion criteria: fixed orthodontic appliance tooth hypersensitivity Number randomised: 30 Method of randomisation: a computer‐based randomisation Method of allocation concealment: not reported Method of blinding: personal examiner blinding done by coding which was only known to statistician Number evaluated: 28. 2 dropouts at follow‐up
Interventions	Total number of intervention groups: 2 Tray group: 5% hydrogen peroxide Strip group: 5.3% hydrogen peroxide Duration of treatment: 14 days
Outcomes	Improvement in tooth shade Vita shade guide: ranked from lightest B1 (1) to darkest C4 (16); mean score for anterior teeth was calculated Adverse effects. Patient recorded: mild, moderate and severe Patient acceptance, gingival irritation, sensitivity VAS scale: 0 (best acceptance) to 10 (no acceptance)
Notes	Sample size calculation: not reported Adverse effects: sensitivity Key conclusions of the study authors: "Both bleaching techniques (the tray technique with 5.0% hydrogen peroxide and the strip technique with 5.3% hydrogen peroxide) demonstrated similar success. Although a significant relapse in tooth shade was observed over an 18‐month post bleaching period, treated teeth were still significantly lighter compared to baseline. Adverse effects were minimal and reversible. Patient acceptance was statistically significantly higher in the tray group compared with the strip group" Correspondence required: no Contact: Dr Thorsten M Auschill; auschill@med.uni‐marburg.de
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A computer‐based randomisation scheme (generated before starting the study) allocated patients…"
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Quote: "2‐cell, parallel, examiner‐blinded, randomised controlled trial." However, method is not mentioned
Blinding of outcome assessment (detection bias)   All outcomes	Low risk	Quote: "..examiners, who were blinded to the treatment modality and period, subjectively measured.. Personal blinding done by coding which was only known to statistician"
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: "2 had to be classified as dropouts for that single visit. Thus, 28 subjects were available at the 18‐month follow‐up" Comment: as each group had 14 participants each we considered it as low risk according to Higgins 2011 Section 8.5.d. Missing outcome data balanced in numbers across intervention groups
Selective reporting (reporting bias)	Low risk	All outcomes described were reported. Conclusions are in accordance with the results
Other bias	Low risk	None

Methods	Title: clinical response of 2 brush‐applied peroxide whitening systems Trial design: double‐blinded, randomised, controlled, parallel‐group trial Location: university Language: English Number of centres: 1 Recruitment period: not reported Funding source: Colgate Palmolive
Participants	Participants: 18 to 48 years old, mean age: 23 years Total number: 38 Inclusion criteria: healthy adults who provided informed consent Exclusion criteria: poor general and oral health prior bleaching patients with orthodontic appliances and restorations in their maxillary anterior teeth patients with tooth sensitivity Number randomised: 38 Method of randomisation: not reported Method of allocation concealment: not reported Method of blinding: similar packet kits Number evaluated: 38
Interventions	Total number of intervention groups: 2 18% carbamide peroxide 19% sodium percarbonate (2 brush‐applied whitening kits) Duration of treatment: 14 days
Outcomes	Improvement in tooth colour b: decreased b indicates reduced yellowness ΔL: increased ΔL is increased brightness ΔW: negative ΔW indicates colour closer to white
Notes	Sample size calculation: not reported Adverse effects: sensitivity and gingival irritation Health‐related quality of life: not reported Key conclusions of the study authors: "Crest Night Effect provided significant and meaningful improvement in colour after 14 days... Both products were tolerated" Correspondence required: no Contact: A Barlow; barlow.ap@pg.com
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote:"double‐blind, randomised, controlled, parallel‐group clinical trial." However, method of randomisation not reported
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding of participants and personnel (performance bias)   All outcomes	Low risk	Quote: "Participants were supplied with blinded study kit boxes"
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Quote: "double‐blind, randomised, controlled, parallel‐group clinical trial." However, method of blinding not reported
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No dropouts reported
Selective reporting (reporting bias)	Low risk	All outcomes described were reported. Conclusions are in accordance with the results
Other bias	Low risk	None

Methods	Title: at‐home vital bleaching: a comparison of hydrogen peroxide and carbamide peroxide treatments Trial design: randomised controlled trial Location: not reported Language: English Number of centres: 1 Recruitment period: not reported Funding source: not reported
Participants	Participants: age not reported Total number: 6 Inclusion criteria: not reported Exclusion criteria: not reported Number randomised: 6 Method of randomisation: not reported Method of allocation concealment: not reported Method of blinding: not reported Number evaluated: 6
Interventions	Total number of intervention groups: 2 10% carbamide peroxide: 20 to 28 days 3.5% hydrogen peroxide: 28 days Duration of treatment: 20 to 28 days
Outcomes	Improvement in tooth shade
Notes	Sample size calculation: not reported Adverse effects: sensitivity Health‐related quality of life: not reported Key conclusions of the study authors: "In carbamide peroxide group, the daily length of application was 2 hours. In the first case the treatment lasted for 24 days, there was no pre‐ or post‐operative sensitivity and the tooth shade changed from A4 (canines) – A3.5 (incisors) to A2 (canines) – A1 (incisors). In hydrogen peroxide the duration of treatment was similar (28 days), no sensitivity was shown during treatment and the shade changed from A3.5 (canines) – A3 (incisors) to A1. Case 3 presented a change in shade from A4 (canines) – A3 (incisors) to A2 (canines) – A1 (incisors) after only 20 days; in this case the patient did mention slight sensitivity in the anterior mandibular teeth throughout the treatment" Correspondence required: no Contact: Professor Dr Forner Navarro; forner@uv.es
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "They were randomly assigned to the two treatment groups." However, the method is not mentioned
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not mentioned
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Not mentioned
Incomplete outcome data (attrition bias)   All outcomes	Low risk	All subjects completed the trial
Selective reporting (reporting bias)	Low risk	All outcomes described were reported. Conclusions are in accordance with the results
Other bias	Low risk	None

Methods	Title: a chewing gum containing 7.5% sodium hexametaphosphate inhibits stain deposition compared with a placebo chewing gum Trial design: cross‐over randomised controlled trial Location: USA Language: English Number of centres: 1 Recruitment period: not reported Funding source: Procter & Gamble
Participants	Participants: 18 to 70 years old. Mean age: 39.1 years Total number: 20 Inclusion criteria: 16 natural teeth with minimum 7 anterior teeth Exclusion criteria: previous history of hypersensitivity to test products multiple restorations fixed prosthesis temporomandibular joint disfunction Number randomised: 19 Method of randomisation: not reported Method of allocation concealment: not reported Method of blinding: not reported Number evaluated: 18
Interventions	Total number of intervention groups: 2 (cross‐over) 7.5% sodium hexametaphosphate chewing gum Placebo Duration of treatment: 2 weeks with 78 hours washout time
Outcomes	Improvement in tooth shade: reduction in stain ΔL, a, b values were recorded. Increase in L and reduction in b indicated whitening
Notes	Sample size calculation: not reported Adverse effects: not reported Health‐related quality of life: not reported Key conclusions of the study authors: "Sodium hexametaphosphate delivered from a chewing gum prevents dental stain formation and facilitates stain removal, which leads to a perceptible whitening benefit" Correspondence required: no Contact: Dr Aron RB, Procter and Gamble Company, Healthcare Research Center, Manson, Ohio, USA
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Subjects were randomly assigned to one of two treatment groups." However, method was not reported
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Quote: "Randomised, double‐blinded cross‐over trial." However, method was not reported
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Quote: "Randomised, double‐blinded cross‐over trial." However, method was not reported
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: "1 woman abandoned the study" Comment: plausible effect size (difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size
Selective reporting (reporting bias)	Low risk	All outcomes described were reported. Conclusions are in accordance with the results
Other bias	Low risk	None

Methods	Title: clinical trial of long‐term colour stability of hydrogen peroxide strips and sodium percarbonate film Trial design: randomised, placebo‐controlled trial Location: Berlin, Germany Language: English Number of centres: 1 Recruitment period: not reported Funding source: not reported
Participants	Participants: 18 to 60 years old, mean age: 30 years Total number: 72 Inclusion criteria: healthy adults with at least 16 natural teeth including 4 maxillary incisors tooth shade score of A2 Exclusion criteria: prior bleaching history current sensitivity acute dental treatment needs Number randomised: 72 Method of randomisation: not reported Method of allocation concealment: not reported Method of blinding: blinded test kits Number evaluated: 70
Interventions	Total number of intervention groups: 3 6% hydrogen peroxide whitening strips 19% sodium percarbonate brush‐applied gel that dries to a film Placebo brush‐applied gel without peroxide Duration of treatment: 2 weeks
Outcomes	Improvement in tooth shade Tooth whitening was characterized by decreased b* (reduction in yellowness) and increased ΔL* (increased brightness)
Notes	Sample size calculation: not reported Adverse effects: tooth sensitivity and oral irritation Health‐related quality of life: not reported Key conclusions of the study authors: "6% hydrogen peroxide whitening strips yielded significant (P < 0.02) initial whitening relative to baseline, placebo and a 19% sodium percarbonate, brush‐applied film. All treatments were well‐tolerated, both peroxide‐containing systems exhibited appreciable color retention throughout the 18‐month post‐treatment period, and here were no meaningful, persistent adverse events seen with long‐term follow‐up" Correspondence required: no Contact: Dr Mozhgan Bizhang; mozhgan.bizhang@med.uni‐duesseldorf.de
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "A total of 72 subjects from the greater Berlin metropolitan area were randomised equally to the strip, film and placebo groups." However, the method is not mentioned
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding of participants and personnel (performance bias)   All outcomes	Low risk	Quote: "Products were dispensed in a blinded subject kit box"
Blinding of outcome assessment (detection bias)   All outcomes	Low risk	Quote: "With the examiners still blinded as to treatment, these subjects (strip and film groups) were evaluated at post‐treatment months 12, 15, 16, and 18"
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: "With respect to subject disposition, 71 subjects completed the end‐of‐treatment visit, and 70 (97%) completed the month 6 …" Comment: 2 dropouts were noted. Plausible effect size (difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size
Selective reporting (reporting bias)	Low risk	All outcomes described were reported. Conclusions are in accordance with the results
Other bias	Low risk	None

Methods	Title: a randomised controlled trial of home bleaching of tetracycline‐stained teeth Trial design: randomised, examiner‐blinded controlled trial Location: University of Hong Kong Language: English Number of centres: 1 Recruitment period: not reported Funding source: not reported
Participants	Participants: tray group: mean age 28.7 years; strip group: mean age 30.4 years Total number: 36 Inclusion criteria: tetracycline stained teeth maxillary anterior teeth sound or minimally restored able to attend 4‐month review Exclusion criteria: subjects under 18 medically unfit pregnant or lactating uncontrolled oral disease or infection history of tooth whitening treatment smoker allergy to hydrogen peroxide or carbamide peroxide Number randomised: 26 Method of randomisation: coin toss Method of allocation concealment: not reported Method of blinding: not reported Number evaluated: 24 (2 dropouts (1 for each group) at follow‐up)
Interventions	Total number of intervention groups: 2 Tray: 15% carbamide peroxide Strip: 6.5% hydrogen peroxide Duration of treatment: 3 months
Outcomes	Improvement in tooth colour a, b and ΔL were recorded Whitening benefit was represented by negative b* (yellowness reduction), and positive ΔL (increasing lightness)
Notes	Sample size calculation: done Adverse effects: sensitivity Health‐related quality of life: not reported Key conclusions of the study authors: "Both groups experienced noticeable and significant ΔLab* improvement at the end of the trial in comparison to the baseline. Significant improvement was observed in the first month for the tray group and in the first 2 months for the strip group (P < 0.05). While greater lightness improvement was observed in the tray group over the strip group in the first month, the opposite was noticed in the second month. There was no difference between 2 groups at the end of this trial and no adverse reactions were observed" Correspondence required: no Contact: Dr Botelho MG; botelho@hku.hk
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Participants were randomly assigned to either group….. tossing coin"
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Quote: "Participants were clinically review by one reviewer who was blinded to their treatment." However, method of blinding is not reported
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Quote: "Participants were clinically review by one reviewer who was blinded to their treatment." However, method of blinding is not reported
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: "..each group had 1 participant that did not attend 2 months review" Comment: missing outcome data balanced in numbers across intervention groups
Selective reporting (reporting bias)	Low risk	All outcomes described were reported. Conclusions are in accordance with the results
Other bias	Low risk	None

Methods	Title: comparison of traditional and low sensitivity whiteners Trial design: double‐blinded, placebo‐controlled clinical trial Location: Department of Restorative Dentistry, Indiana University School of Dentistry, USA Language: English Number of centres: 1 Recruitment period: not reported Funding source: not reported
Participants	Participants: adults Total number: 91 Inclusion criteria: adults with no significant medical problems maxillary cuspids, lateral incisors and central incisors had to be shade A3 or darker Exclusion criteria: active caries, defective restorations untreated periodontal disease Number randomised: 91 Method of randomisation: not reported Method of allocation concealment: not reported Method of blinding: not reported Number evaluated: 91
Interventions	Total number of intervention groups: 5 Experimental 1: 10% carbamide peroxide Experimental 2: 10% carbamide peroxide, 3% potassium nitrate Experimental 3: 10% carbamide peroxide, 0.5% potassium nitrate Experimental 4: 10% carbamide peroxide, 0.5% potassium nitrate, 0.25% sodium fluoride Group 5: placebo Duration of treatment: 11 weeks
Outcomes	Change in tooth shade. Vita shade guide lightest C1 (16) to B4 (1)
Notes	Sample size calculation: not reported Adverse effects: tooth, hard and soft tissue sensitivity Health‐related quality of life: not reported Key conclusions of the study authors: "Participants using one of the two whiteners with 0.5% potassium nitrate had sensitivity levels equivalent to those using the placebo. Relative to the whitening agent with no desensitising agent, the addition of 0.5% potassium nitrate resulted in a significant reduction in the number of days of sensitivity experienced by participants. When compared to the whitener without any potassium nitrate, the addition of 3% potassium nitrate did not result in a significant reduction in the number of days of sensitivity. The addition of potassium nitrate did not result in any significant change in bleaching efficacy" Correspondence required: no Contact: William D Browning; lewis46@iupui.edu
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "placebo‐controlled, double‐blind randomised clinical trial compared..." However, method not mentioned
Allocation concealment (selection bias)	Unclear risk	Method not mentioned
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Quote: "Neither the participant nor the operator was aware which material was received." However, method is not mentioned
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Quote: "Neither the participant nor the operator was aware which material was received." However, method is not mentioned
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No dropouts are mentioned
Selective reporting (reporting bias)	Low risk	All outcomes described were reported. Conclusions are in accordance with the results
Other bias	Low risk	None

Methods	Title: vital tooth whitening effects on oral health–related quality of life in older adults Trial design: single‐blinded, randomised, pre–test, multiple post–test design Location: Hampton Roads area of Virginia, USA Language: English Number of centres: 1 Recruitment period: not reported Funding source: not reported
Participants	Participants: 50 years old and above Total number: 62 Inclusion criteria: 50 years old and older good general health, possessing cognitive ability physical dexterity to perform daily oral care have at least 8 natural anterior teeth free from composite restorations, crowns, veneers no full or partial dentures and endodontic treatment refrain from using any over–the–counter tooth whitening products for the duration of the study Exclusion criteria: visible calculus deposits on labial or lingual surfaces of anterior teeth severe tooth sensitivity professional whitening within the past 3 years Number randomised: 62 Method of randomisation: not reported Method of allocation concealment: not reported Method of blinding: participants were assigned a number after being randomly assigned to a group Number evaluated: 53
Interventions	Total number of intervention groups: 2 Control: placebo Experimental: 14% hydrogen peroxide Duration of treatment: 3 weeks
Outcomes	Trubyte New Hue Vitality Scale: 12 shades numbered from 1 to 12, with 1 being the lightest and 12 being the darkest Tooth Colour Satisfaction Scale (TCSS): very satisfied (5 points), satisfied (4 points), neither satisfied nor dissatisfied (3 points), dissatisfied (2 points) and very dissatisfied (1 point) Oral Health Impact Profile (OHIP): 5‐point Likert scale: very often (5 points), fairly often (4 points), occasionally (3 points), hardly ever (2 points), never (1 point) Additional Questions Survey (AQS): none (1 point), 1 to 2 (2 points), 3 to 4 (3 points), 5 to 6 (4 points) and 7 or more (5 points)
Notes	Sample size calculation: not reported Adverse effects: sensitivity Health‐related quality of life: reported Key conclusions of the study authors: "The older adults who whitened their teeth experienced an increased satisfaction with their tooth colour as evidenced by the TCSS. Tooth whitening was not associated with improvements in overall OHRQoL, or its functional factors, psychological disabilities, psychological discomforts, physical disabilities and social disabilities subscales. Tooth whitening did affect the handicap subscale, which demonstrated that persons who experienced tooth whitening were more willing to work due to a perceived increase in health. Tooth whitening did affect the physical pain subscale, which demonstrated a lower OHRQoL for participants. Older adults who whitened their teeth reported fewer social activities 3 months after the initial post–testing. Regression analysis relating tooth colour satisfaction with overall OHRQoL revealed a significant correlation between tooth colour satisfaction and overall OHIP for the experimental group" Correspondence required: no Contact: Ann M Bruhn; abruhn@odu.edu
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "62 participants 50 years of age and older were enrolled and randomly assigned to 1 of 2 groups by research assistants." However, the method is not mentioned
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Not mentioned
Blinding of outcome assessment (detection bias)   All outcomes	Low risk	Quote: "Clinicians collecting data were unaware of participant group status, since the participants were assigned a number after being randomly assigned to"
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Quote: "A total of 53 participants completed the study" Comment: 9 dropouts were noted. Reason for dropouts not mentioned
Selective reporting (reporting bias)	Low risk	All outcomes described were reported. Conclusions are in accordance with the results
Other bias	Low risk	None

Methods	Title: a 6‐month study of 2 self‐applied tooth whitening products containing carbamide peroxide Trial design: double‐blinded, randomised, controlled, parallel‐group clinical trial Location: not reported Language: English Number of centres: not reported Recruitment period: not reported Funding source: Colgate Palmolive
Participants	Participants: 18 to 70 years old Total number: 95 Inclusion criteria: male and female subjects ranging in age from 18 to 70 years inclusive good general and oral health all maxillary anterior teeth present availability for the 6‐month duration of the study a minimum Vita shade of A3 on 1 or more upper central incisors Exclusion criteria: presence of orthodontic appliances or any anterior tooth with a prosthetic crown or veneer tumours or significant pathology of the soft or hard tissues of the oral cavity moderate or advanced periodontal disease, rampant caries or any condition that the dental examiner considered exclusionary from the study 5 or more carious lesions requiring immediate care participation in any other study within 30 days preceding the clinical study pregnant or lactating females a history of allergies to tooth whitening products, personal care consumer products or their ingredients restorations on the teeth to be scored Number randomised: 95 Method of randomisation: not reported Method of allocation concealment: not reported Method of blinding: not reported Number evaluated: 93, 2 dropouts
Interventions	Total number of intervention groups: 2 18% (Group 1) carbamide peroxide 16.4% (Group 2) carbamide peroxide Duration of treatment: 2 weeks
Outcomes	Improvement in tooth shade The shade guide was arranged with the 16‐shade tabs in order from B1 (1) to C4 (16) Gingival score: Loë and Silness Gingival Index Gingival and teeth sensitivity score: 0 none ‐ 5 severe
Notes	Sample size calculation: not reported Adverse effects: sensitivity Health‐related quality of life: not reported Key conclusions of the study authors: "Both products effectively whitened teeth with a treatment time of 2‐weeks. The different concentrations tested were equally effective in improving whiteness. The whitening systems tested produced little tooth or gingival sensitivity. Some whitening benefit is sustained for at least 6 months after cessation of treatment" Correspondence required: no Contact: Paul A Brunton; paul.brunton@man.ac.uk
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "double‐blinded, randomised, controlled, parallel‐group clinical trial." However, method of randomisation not reported
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding of participants and personnel (performance bias)   All outcomes	Unclear risk	Quote: "double‐blinded, randomised, controlled, parallel‐group clinical trial." However, method of blinding not reported
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Quote: "double‐blinded, randomised, controlled, parallel‐group clinical trial." However, method of blinding not reported
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Quote: "2 subjects failed to complete the 2‐week study (1 from each group) for reasons unrelated to the study" Comment: missing outcome data balanced in numbers across intervention groups
Selective reporting (reporting bias)	Low risk	All outcomes described were reported. Conclusions are in accordance with the results
Other bias	Low risk	None