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Operative Dentistry, 2016, 41-4, 341-356

Literature Review

At-home vs In-office Bleaching:

A Systematic Review and
Meta-analysis
JL de Geus  LM Wambier  S Kossatz
AD Loguercio  A Reis

Clinical Relevance
Although there is a general concept that at-home dental bleaching is more effective and
yields less tooth sensitivity than in-office bleaching, this study could not confirm this due to
the high variability of protocols in both bleaching techniques.

SUMMARY Library in Dentistry, Cochrane Library, and

Objective: A systematic review and meta-anal- System for Information on Grey Literature in
ysis were performed to evaluate the risk and Europe without restrictions. The annual con-
ference of the International Association for
intensity of tooth sensitivity during in-office
Dental Research abstracts (1990-2014) and un-
and at-home bleaching in adult patients. The
published and ongoing trials registry were
efficacy of dental bleaching was also evaluat-
also searched. Dissertations and theses were
ed. searched using the ProQuest Dissertations and
Methods: A comprehensive search was per- Periódicos Capes Theses databases. Only ran-
formed in the MEDLINE via PubMed, Scopus, domized clinical trials that compared the
Web of Science, Latin American and Caribbean prevalence or intensity of tooth sensitivity
Health Sciences Literature database, Brazilian during in-office and at-home bleaching in
adult patients were included and studies that
Juliana L. de Geus, MS, Restorative Dentistry, State evaluated the efficacy of these dental bleach-
University of Ponta Grossa, Ponta Grossa, Brazil
ing techniques, in terms of shade guide units
Leticia M. Wambier, MS, Restorative Dentistry, State Uni- (DSGU) and in terms of color difference mea-
versity of Ponta Grossa, Ponta Grossa, Brazil sured with a spectrophotometer (DE*).
Stella Kossatz, DDS, PhD, Restorative Dentistry, State
University of Ponta Grossa, Ponta Grossa, Brazil
Results: After the removal of duplicates, 1139
articles were identified. After title and ab-
Alessandro D. Loguercio, DDS, PhD, Restorative Dentistry,
State University of Ponta Grossa, Ponta Grossa, Brazil
stract screening, 29 studies remained. Fifteen
studies were further excluded, whereas 12
*Alessandra Reis, DDS, PhD, Restorative Dentistry, State
studies remained for qualitative analyses and
University Ponta Grossa, Ponta Grossa, Brazil
8 for the meta-analysis of the primary and
*Corresponding author: Rua Carlos Cavalcanti, 4748, Bloco
secondary outcomes. No significant difference
M, Sala G4A, Uvaranas, PR 84030-900, Brazil; e-mail:
reis_ale@hotmail.com in the risk/intensity of tooth sensitivity or in
bleaching efficacy was observed in the present
DOI: 10.2341/15-287-LIT
study.
342 Operative Dentistry

Conclusion: In an overall comparison of at- immediate and long-term results for both tech-
home and in-office bleaching, no differences niques.30,31
were detected, either regarding risk/intensity In face of conflicting results published in the
of tooth sensitivity or the effectiveness of the literature, the aim of this systematic review of the
bleaching treatment. This comparison, howev- literature was to determine whether there are
er, does not take into consideration variations evidence-based differences in sensitivity and efficacy
in the protocols (daily usage time, number of between in-office and at-home bleaching techniques.
bleaching sessions, and product concentra- For this, the following PICO question (Population,
tion) of the bleaching techniques in the studies Intervention, Comparison and Outcome) was an-
included.
swered: is the risk and intensity of tooth sensitivity,
as well as bleaching efficacy, in adults that under-
INTRODUCTION
went in-office bleaching different from those that
Public demand for esthetic dentistry, including underwent at-home bleaching?
dental bleaching, has increased in recent years.1 In
such context, clinicians are acutely aware of the METHODS
importance of dental bleaching in daily clinical
Protocol and Registration
practice.
This study protocol was registered at the Interna-
Nowadays, there are two types of dentist-super-
tional Prospective Register of Systematic Reviews
vised techniques: at-home or in-office bleaching.
(PROSPERO - CRD42015015564) and followed the
Although at-home bleaching has been the most
recommendations of the Preferred Reporting Items
frequent treatment for vital teeth, some patients do
for Systematic Reviews and Meta-Analyses (PRIS-
not want to use a bleaching tray on a daily basis for
MA) statement for report.32
several weeks; so they request in-office bleaching,
which produces more immediate results.2,3
Information Sources and Search Strategy
Although several clinical studies have proven the
The controlled vocabulary (MeSH terms) and free
effectiveness of in-office and at-home bleaching,4-10
keyword in the search strategy were defined based
tooth sensitivity is a very common side effect11 for
on the following PICOS question:
both bleaching approaches. It affects between 37%
and 90% of the patients undergoing at-home bleach-
ing6,9,12-17 and between 16.7% and 100% of the 1. Population (P): adult patients that underwent
patients using in-office bleaching.13,18-20 Although vital tooth bleaching.
tooth sensitivity of at-home bleaching is reported to 2. Intervention (I): in-office bleaching.
be mild,12,13,21 the intensity of tooth sensitivity after 3. Comparison (C): dentist-supervised at-home
in-office bleaching is usually moderate7,22-24 and in bleaching.
some cases so severe that patients eventually 4. The outcome (O): risk and intensity of tooth
abandon the procedure.25 Some authors speculate sensitivity during dental bleaching; color change
that such an adverse effect may be due to the release in shade guide units (DSGU) and in in terms of
of inflammatory mediators such as cyclooxygenase color difference measured with a spectrophotom-
and lipoxygenases on the dental pulp.26 eter (DE*) will be the secondary outcomes.
5. Study design (S): randomized clinical trials
The high number of bleaching gels and protocols (RCTs).
evaluated in randomized clinical trials4-7,9,13 inhibits
clinicians from reaching a clear conclusion about To identify trials to be included for this review, the
which protocol presents increased risk and intensity electronic databases such as MEDLINE via PubMed,
of tooth sensitivity. Some studies report higher tooth Scopus, Web of Science, Latin American and Carib-
sensitivity of in-office bleaching than at-home bean Health Sciences Literature database (LILACS),
bleaching,5,13 whereas others report similar tooth Brazilian Library in Dentistry (BBO), and Cochrane
sensitivity27,28 or higher tooth sensitivity of the at- Library (Table 1) were searched. The reference lists
home protocol than the in-office bleaching.7 Similar of all primary studies were hand searched for
controversy exists in terms of bleaching efficacy. additional relevant publications and the related
There are some authors that believe that at-home articles link of each primary study in the PubMed
bleaching provide better and more stable whitening database without restrictions to publication date or
than the in-office protocol.29 Others showed similar languages.
de Geus & Others: At-home vs In-office Bleaching: a review 343

Other sources were also used to identify more were extracted directly into a single data collection
articles. The abstracts of the annual conference of form to avoid overlapping data. When data were not
the International Association for Dental Research reported in the studies, authors were contacted by
and their regional divisions (1990-2014) were email at least twice to request the missing information.
searched. The grey literature using the database When data from multiple bleaching sessions were
System for Information on Grey Literature in provided, an average of the figures for each bleach-
Europe and dissertations and theses using the ing protocol was obtained. When more than one
ProQuest Dissertations and Theses Full text data- bleaching agent from the same bleaching protocol
base, as well as the Periódicos Capes Theses was included in the study, their values were merged
database, were explored. to make a single entry. Concerning color change, the
To locate unpublished and ongoing trials related to data that represented the immediate result (up to
the review question, the following clinical trials three months after bleaching) were used.
registries were searched: Current Controlled Trials
(www.controlled-trials.com), International Clinical Risk of Bias in Individual Studies
trials registry platform (http://apps.who.int/
Quality assessments of the selected trials were
trialsearch/), ClinicalTrials.gov (www.clinicaltrials.
carried out by two independent reviewers, using
gov), Rebec (www.rebec.gov.br), and EU Clinical
the Cochrane Collaboration’s tool for assessing risk
Trials Register (https://www.clinicaltrialsregister.eu).
of bias in randomized trials.33 The assessment
criteria contain six items: sequence generation,
Eligibility Criteria
allocation concealment, blinding of the outcome
Parallel and split-mouth RCTs that compared in- assessors, incomplete outcome data, selective out-
office vs at-home bleaching in adult patients of any come reporting, and other possible sources of bias.
age group were included. No controlled clinical During data selection and quality assessment, any
trials, editorial letters, pilot studies, historical disagreements between the reviewers were solved
reviews, in vitro studies, cohort, and observational through discussion, and if needed, by consulting a
and descriptive studies, such as case reports and third reviewer.
case series, were excluded.
For each aspect of the quality assessment, the risk of
Additionally, RCT studies were excluded if 1) bias was scored following recommendations as de-
studies compared only in-office or only at-home scribed in the Cochrane Handbook for Systematic
bleaching treatments; 2) studies whose participants reviews of Interventions 5.1.0 (http://handbook.
took analgesics or anti-inflammatory drugs before or cochrane.org). At domain level, the judgment for each
during bleaching treatment; 3) studies that always entry involved recording ‘‘yes,’’ indicating low risk of
used desensitizers before and after bleaching; and 4) bias, ‘‘no,’’ indicating high risk of bias, and ‘‘unclear,’’
studies in which the at-home protocol was performed indicating either lack of information or uncertainty
with over-the-counter products. over the potential for bias. At the study level, the study
was considered to be at ‘‘low’’ risk of bias if all key
Study Selection and Data Collection Process domains for each outcome were at low risk of bias. If
Initially, the articles were selected by title and one or more key domains (see below) were judged as
abstracts according to the previously described search ‘‘unclear’’ or at ‘‘high’’ risk of bias, the study as a whole
strategy. Articles that appeared in more than one was considered at high risk of bias. When the study
database were considered only once. Full-text articles was judged as unclear in its key domains, authors were
were also obtained when the title and abstract contacted to obtain more information and to allow a
presented insufficient information to make a clear definitive yes or no judgment.
decision. Subsequently two reviewers classified those For the patient-centered outcomes (risk and
that met the inclusion criteria. To handle such a large intensity of tooth sensitivity) and for color change
number of studies, a study ID for each eligible study in DE*, studies were considered to be at low risk of
was used, combining first author and year of publica- bias if there were adequate sequence generation and
tion. Relevant information about the study design, allocation concealment (key domains). Patient blind-
participants, interventions, and outcomes were extract- ing was not considered a key domain as patients
ed using customized extraction forms by three authors. could easily identify the different bleaching proto-
If there were multiple reports of the same study (ie, cols. Examiner blinding was not essential for
reports with different follow-ups), data from all reports evaluation of color in DE* as the previous knowledge
344 Operative Dentistry

Table 1: Electronic Database and Search Strategy

Pubmed (23/December/2014)
#1 (tooth discoloration[MeSH Terms]) OR‘‘tooth staining"[Title/ #2 (peroxides[MeSH Terms]) OR tooth bleaching[MeSH Terms])
Abstract]) OR‘‘stained tooth"[Title/Abstract]) OR‘‘stained teeth"[Title/ OR bleaching agents[MeSH Terms]) OR tooth bleaching
Abstract]) OR‘‘tooth discoloration"[Title/Abstract]) OR‘‘tooth agents[MeSH Terms]) OR hydrogen peroxide[MeSH Terms]) OR
discolouration"[Title/Abstract]) OR‘‘discolored tooth"[Title/Abstract]) carbamide peroxide[Supplementary Concept]) OR‘‘tooth
OR‘‘discoloured tooth"[Title/Abstract]) OR‘‘discolored teeth"[Title/ bleaching"[Title/Abstract]) OR‘‘tooth whitening"[Title/Abstract])
Abstract]) OR‘‘discoloured teeth"[Title/Abstract]) OR‘‘dental bleaching"[Title/Abstract]) OR‘‘dental whitening"[Title/
Abstract]) OR whitening[Title/Abstract]) OR bleaching[Title/
Abstract]) OR‘‘bleaching agents"[Title/Abstract]) OR‘‘bleaching
systems"[Title/Abstract]) OR‘‘whitening agents"[Title/Abstract])
OR‘‘whitening systems"[Title/Abstract]) OR‘‘bleaching
techniques"[Title/Abstract]) OR‘‘whitening techniques"[Title/
Abstract]) OR‘‘hydrogen peroxide"[Title/Abstract]) OR‘‘carbamide
peroxide"[Title/Abstract]) OR‘‘power bleaching"[Title/Abstract])
OR‘‘in-office bleaching"[Title/Abstract]) OR‘‘in-office vital
bleaching"[Title/Abstract]) OR‘‘vital bleaching"[Title/Abstract])
OR‘‘vital whitening"[Title/Abstract]) OR‘‘professional bleaching"[Title/
Abstract]) OR‘‘professional whitening"[Title/Abstract]) OR‘‘home-
use"[Title/Abstract]) OR‘‘home bleaching"[Title/Abstract]) OR‘‘home
whitening"[Title/Abstract]) OR‘‘at-home bleaching"[Title/Abstract])
OR‘‘at-home whitening"[Title/Abstract]) OR‘‘home-care
bleaching"[Title/Abstract]) OR‘‘home-applied bleaching"[Title/
Abstract]) OR‘‘nightguard vital bleaching"[Title/Abstract]) OR‘‘night-
guard vital bleaching"[Title/Abstract])
#1 AND #2
Scopus (23/December/2014)
#1 ( TITLE-ABS-KEY (‘‘tooth discoloration’’) OR TITLE-ABS-KEY #2 ( TITLE-ABS-KEY ( peroxides ) OR TITLE-ABS-KEY (‘‘hydrogen
(‘‘tooth staining’’) OR TITLE-ABS-KEY (‘‘discolored tooth’’) OR peroxide’’) OR TITLE-ABS-KEY (‘‘carbamide peroxide’’) OR TITLE-
TITLE-ABS-KEY (‘‘stained tooth’’) ABS-KEY (‘‘tooth bleaching agent’’) OR TITLE-ABS-KEY (‘‘dental
bleaching’’) OR TITLE-ABS-KEY (‘‘tooth whitening’’) OR TITLE-
ABS-KEY (‘‘bleaching system’’) OR TITLE-ABS-KEY (‘‘whitening
system’’) OR TITLE-ABS-KEY (‘‘power bleaching’’) OR TITLE-ABS-
KEY (‘‘in-office bleaching’’) OR TITLE-ABS-KEY (‘‘vital bleaching’’)
OR TITLE-ABS-KEY (‘‘vital whitening’’) OR TITLE-ABS-KEY
(‘‘professional bleaching’’) OR TITLE-ABS-KEY (‘‘professional
whitening’’) OR TITLE-ABS-KEY (‘‘home-use’’) OR TITLE-ABS-
KEY (‘‘at-home bleaching’’) OR TITLE-ABS-KEY (‘‘at-home
whitening’’) OR TITLE-ABS-KEY (‘‘home-care bleaching’’) OR
TITLE-ABS-KEY (‘‘home-applied bleaching’’) OR TITLE-ABS-KEY
(‘‘nightguard vital bleaching’’)
#1 AND #2
Web of Science (27/December/2014)
#1 Topic: (‘‘tooth discolo*ration’’) OR Topic: (‘‘discolo*red teeth’’) #2 Topic: (peroxides) OR Topic: (‘‘tooth bleaching’’) OR Topic:
OR Topic: (‘‘discolo*red tooth’’) OR Topic: (‘‘tooth staining’’) OR (‘‘bleaching agents’’) OR Topic: (‘‘tooth bleaching agents’’) OR
Topic: (‘‘stained teeth’’) OR Topic: (‘‘stained tooth’’) Topic: (‘‘hydrogen peroxide’’) OR Topic: (‘‘carbamide peroxide’’) OR
Topic: (‘‘dental bleaching’’) OR Topic: (‘‘tooth whitening’’) OR Topic:
(‘‘dental whitening’’) OR Topic: (‘‘vital bleaching’’) OR Topic: (‘‘vital
whitening’’) OR Topic: (whitening) OR Topic: (bleaching) OR Topic:
(‘‘bleaching techniques’’) OR Topic: (‘‘bleaching systems’’) OR
Topic: (‘‘whitening systems’’) OR Topic: (‘‘professional whitening’’)
OR Topic: (‘‘professional bleaching’’) OR Topic: (‘‘power
bleaching’’) OR Topic: (‘‘in office bleaching’’) OR Topic: (‘‘in office
vital bleaching’’) OR Topic: (‘‘home use’’) OR Topic: (‘‘at home
bleaching’’) OR Topic: (‘‘at home whitening’’) OR Topic: (‘‘home
applied bleaching’’) OR (‘‘home whitening’’) OR Topic: (‘‘home
bleaching’’) OR Topic: (‘‘night guard vital bleaching’’) OR Topic:
(‘‘home care bleaching’’)
de Geus & Others: At-home vs In-office Bleaching: a review 345

Table 1: Continued.
Pubmed (23/December/2014)
#1 AND #2
LILACS and BBO (27/December/2014)
#1 (MH:‘‘tooth discoloration’’OR‘‘tooth staining’’OR‘‘dicolored #2 (MH: peroxides OR MH:‘‘tooth bleaching agents’’OR MH:‘‘tooth
tooth’’OR‘‘discolored teeth’’OR‘‘tooth discolouration’’OR‘‘discoloured bleaching’’OR MH:‘‘bleaching agents’’OR MH:‘‘hydrogen
teeth’’OR‘‘discoloured tooth’’OR‘‘stained tooth’’OR‘‘stained peroxide’’OR‘‘carbamide peroxide’’OR‘‘peróxido de
teeth’’OR‘‘descoloração dental’’OR‘‘manchamento carbamida’’OR‘‘dental bleaching’’OR‘‘clareamento
dental’’OR‘‘dentes escuros’’OR‘‘escurecimento dental’’OR‘‘dientes dental’’OR‘‘blanqueamiento dental’’OR‘‘in office
oscuros’’OR‘‘manchas en los dientes’’OR‘‘oscurecimiento dental’’) bleaching’’OR‘‘clareamento de consultório’’OR‘‘blanqueamiento en
oficina’’OR‘‘blanqueamiento dental de oficina’’OR‘‘tooth
whitening’’OR‘‘power bleaching’’OR‘‘dental whitening’’OR‘‘bleaching
systems’’OR‘‘whitening systems’’OR‘‘sistemas clareadores’’OR‘‘vital
bleaching’’OR‘‘clareamento em dentes vitais’’OR‘‘blanqueamiento
en dientes vitales’’OR‘‘in office vital bleaching’’OR‘‘professional
bleaching’’OR‘‘professional whitening’’OR‘‘clareamento
professional’’OR‘‘blanqueamiento professional’’OR‘‘vital
whitening’’OR‘‘home-use’’OR‘‘at home bleaching’’OR‘‘at home
whitening’’OR‘‘clareamento caseiro’’OR‘‘blanqueamiento en
casa’’OR‘‘home-applied bleaching’’OR‘‘home whitening’’OR‘‘home
bleaching’’OR‘‘nigthguard vital bleaching’’OR‘‘night guard vital
bleaching’’OR‘‘home care bleaching’’)
#1 AND #2
Cochrane Library (15/December/2014)
#1 MeSH descriptor: [Tooth Discoloration] explode all trees
#2‘‘tooth staining’’:ti,ab,kw or‘‘discolored tooth’’:ti,ab,kw or‘‘tooth discoloration’’:ti,ab,kw or‘‘discolored teeth’’:ti,ab,kw or‘‘tooth
discolouration’’:ti,ab,kw (Word variations have been searched)
#3‘‘discoloured tooth’’:ti,ab,kw or‘‘discoloured teeth’’:ti,ab,kw or‘‘stained tooth’’:ti,ab,kw or‘‘stained teeth’’:ti,ab,kw (Word variations have been
searched)
#4 #1 or #2 or #3
#5 MeSH descriptor: [Peroxides] explode all trees
#6 MeSH descriptor: [Tooth Bleaching Agents] explode all trees
#7 MeSH descriptor: [Bleaching Agents] explode all trees
#8 MeSH descriptor: [Hydrogen Peroxide] explode all trees
#9‘‘carbamide peroxide’’:ti,ab,kw or‘‘dental bleaching’’:ti,ab,kw or‘‘in-office bleaching’’:ti,ab,kw or‘‘tooth whitening’’:ti,ab,kw or‘‘power
bleaching’’:ti,ab,kw (Word variations have been searched)
#10‘‘bleaching techniques’’:ti,ab,kw or whitening:ti,ab,kw or bleaching:ti,ab,kw or‘‘dental whitening’’:ti,ab,kw or‘‘bleaching systems’’:ti,ab,kw
(Word variations have been searched)
#11‘‘whitening systems’’:ti,ab,kw or‘‘vital bleaching’’:ti,ab,kw or‘‘in-office vital bleaching’’:ti,ab,kw or‘‘professional bleaching’’:ti,ab,kw
or‘‘professional whitening’’:ti,ab,kw (Word variations have been searched)
#12‘‘vital whitening’’:ti,ab,kw or‘‘home-use’’:ti,ab,kw or‘‘at-home whitening’’:ti,ab,kw or‘‘at-home bleaching’’:ti,ab,kw or‘‘home-applied
bleaching’’:ti,ab,kw (Word variations have been searched)
#13‘‘home whitening’’:ti,ab,kw or‘‘home bleaching’’:ti,ab,kw or‘‘nightguard vital bleaching’’:ti,ab,kw or‘‘night-guard vital bleaching’’:ti,ab,kw
or‘‘home-care bleaching’’:ti,ab,kw (Word variations have been searched)
#14 #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13
#15 #4 and #14

of the treatment would not affect the results Copenhagen, Denmark). Data from eligible studies
produced by the instrument. However, examiner were either dichotomous (absolute risk of tooth
blinding was considered to be essential in the sensitivity) or continuous (intensity of tooth sensi-
subjective color assessment performed with shade tivity, DSGU, and DE*).
guide units. Therefore, for color change in DSGU, Only studies classified at low risk of bias in the key
three items of the Cochrane tool as key domains domains were used in the meta-analysis. The
were considered: adequate sequence generation, outcomes were summarized by calculating the
allocation concealment, and examiner blinding. Hedge’s g standardized mean difference for the
continuous data and the odds ratio along with the
Summary Measures and Synthesis of Results 95% confidence interval for the dichotomous data.
Data were analyzed using Revman 5 (Review When matched data were available (split-mouth
Manager Version 5, The Cochrane Collaboration, and crossover designs), an external correlation of 0.5
346 Operative Dentistry

Figure 1. Flow diagram of study

identification.

was imputed among data from both groups, as this USA). No subgroup analysis was performed. Sensi-
information was not available in any of the studies. tivity analyses were also conducted to investigate the
Sensitivity analyses using lower (0.1) and higher reasons for high heterogeneity whenever detected.
(0.9) external correlations were performed to check
the impact of such imputation in all meta-analysis. RESULTS
The random-effects models were used. Heterogene-
Study Selection
ity was assessed using the Cochran Q test and I2
statistics. All analyses were conducted using CMA After the database screening and removal of dupli-
software (version 3, Biostat, Englewood, New Jersey, cates, 1139 studies were identified (Figure 1). After
de Geus & Others: At-home vs In-office Bleaching: a review 347

title screening, 29 studies remained, and this Assessment of the Risk of Bias
number was reduced to 12 after careful examination The selected studies risk of bias is presented in
of the abstracts. Figure 2. Few full-text studies reported the method
of randomization, allocation concealment, and
Characteristics of Included Articles whether or not the examiner was blinded during
The characteristics of the 12 studies selected are color assessment in shade guide units.
listed in Table 2. The parallel study design was E-mails were sent to authors of nine stud-
predominantly used in these studies.7,13,27,30,34-36 ies4,5,7,13,27,34-37 to request further information. Re-
Some of the studies used the split-mouth de- sponses were obtained from the authors of eight
sign.4,5,28,31,37 studies.4,5,7,13,27,34-36
Six of the 12 studies used a 0-10 visual analog In summary, from the 12 studies, 313,36,37 were
scale for pain evaluation,4,5,13,28,34,35 and 3 studies considered to be at high/unclear risk of bias in the
used a 0-4 numeric rating scale.7,27,30 One study just key domains of the Cochrane risk of bias tool,
evaluated the risk of tooth sensitivity.37 Two studies yielding 9 studies4,5,7,27,28,30,31,34,35 that met the best
did not evaluate tooth sensitivity.31,36 requirement features (randomization and allocation
For color evaluation, ten studies used a shade concealment) for meta-analysis of risk and intensity
guide.4,5,7,27,28,30,31,34,36,37 Six of these 12 studies of tooth sensitivity and color change in DE*.
added an objective instrument (spectrophotometer From the 12 studies, 413,35-37 were considered to be
or colorimeter) for color assessment.4,5,27,28,31,36 at high/unclear risk of bias in the key domains of the
Color slide photography was used in one study34 Cochrane risk of bias tool, yielding 8 stud-
and photography in two others.27,37 Two studies did ies4,5,7,27,28,30,31,34 that met the best requirement
not evaluate the color.13,35 features (randomization, allocation concealment,
The number of patients per group included in and blinding) for meta-analysis of DSGU. Although
these studies ranged from 10 to 30. In 2 of the 12 the study of Giachetti and others31 was classified at
articles, most participants were male5,31; in 3 low risk of bias, the authors did not evaluate color
articles, females predominated.7,28,30 Seven studies change in shade guide units or DE*, which is the
did not report this information. reason why the study was not included in the meta-
Regarding the bleaching protocol (Table 2), nine analyses of color change. Additionally, this study did
studies used 10% carbamide peroxide for at-home not evaluate bleaching-induced tooth sensitivity;
bleaching.4,5,7,13,27,30,31,34,37 Carbamide peroxide therefore, it was not included in the meta-analyses
with different concentrations, such as 15%, 28 of tooth sensitivity.
16%,35 20%,7 and 32%,36 was also used for at-home
bleaching. For in-office bleaching, the majority of Meta-analysis
studies used 35% hydrogen peroxide.4,7,13,27,30,34,35,37 All meta-analysis was performed on studies classi-
Only three studies used 38% hydrogen peroxide for fied as low risk of bias in the key domains and from
this bleaching modality.7,28,31 Two studies used 25% which the information about the outcome could be
hydrogen peroxide for this technique.5,36 extracted.
The daily time use of the at-home bleaching gel Risk of Tooth Sensitivity—This analysis was based
varied from 3 to 10 minutes, and the number of days on five studies.4,5,7,28,30 The odds ratio was 2.186,
varied from 6 to 28 days. The application protocol of with a 95% confidence interval of 0.63-7.53
the in-office bleaching was quite variable. Most of (p=0.215). Based on these studies, a significant
the studies applied the product for 20-45 minutes in statistical difference between the groups could not
each clinical session.4,7,13,27,28,30,31,35,37 However, be identified (Figure 3). Data were heterogeneous (v2
variations in this protocol were observed, with test, p,0.001; I2=87.8%; Figure 3), which means
applications lasting 1534 or 60 minutes5,36 in each that all studies included in the analysis did not share
session (Table 2). Half of the studies performed two a common effect size. Through a sensitivity analysis,
to three bleaching sessions,4,7,13,27,30,37 with some the high heterogeneity of this outcome was caused by
exceptions. Some studies performed only one in- the study of Basting and others.7 By removing this
office bleaching session,5,28,31,35,36and another study study from the present meta-analysis, the heteroge-
performed a variable number of clinical sessions to neity was seen not to be significant, and the overall
reach the patient’s satisfaction34 (Table 2). odds ratio was shown as significant, with a lower
348 Operative Dentistry

Table 2: Summary of the Studies Selected for This Systematic Review

Study ID Study design Method of color Subjects’ age in No. of subjects No. patients
[setting] assessment mean 6 SD (male [%]) [drop-outs]
[range] (yr)
Acosta 199937 Split mouth [n.r.] Shade guide unit (Vitapan n.r. 6 n.r. [15-20] n.r. 20 [n.r.]
classical) and photography

Auschill 200534 Parallel [University] Shade guide unit (Vitapan 29.8 6 n.r. [n.r.] n.r. 39 [0]
classical) and color slide
photography

Basting 20127 Parallel [n.r.] Shade guide unit (Vitapan n.r. 6 n.r. [18-42] 18 [19] 94 [13]
classical)

Bernardon 20104 Split mouth [n.r.] Shade guide unit (Vitapan n.r. 6 n.r. [n.r.] n.r. 90 [n.r.]
classical) and
spectrophotometer
(Easyshade)
da Costa 20105 Split mouth [n.r.] Shade guide unit (Vita n.r. [23-57] 12 [60] 20 [0]
Bleachedguide) and
spectrophotometer
(Easyshade)
de Almeida 201213 Parallel [n.r.] n.r. n.r.6 n.r. [18-28] n.r. 40 [0]

Giachetti 201031 Split mouth Spectrophotometer 22 6 1.4 [20-25] 10 [59] 17 [1]

[University] (Easyshade)

Kim-Pusateri 200936 Parallel [n.r.] Shade guide unit (Trubyte n.r. 6 n.r. [n.r.] n.r. 24 [n.r.]
Bioform) and colorimeter
(ShadeVision)

Moghadam 201328 Split mouth [n.r.] Shade guide unit (Vitapan n.r. 6 n.r. [18-55] 8 [40] 20 [n.r.]
classical and Vitapan 3D
Master) and
spectrophotometer
(Easyshade)
Pintado-Palomino Parallel [University] n.r. n.r. 6 n.r. [18-40] n.r. 113 [n.r.]
201535

Tay 201230 Parallel [University] Shade guide unit (Vitapan AH: 21 6 3.8 AH: 14 [47] 60 [0]
classical) IO: 21 6 3.2 IO: 8 [27]

Zekonis 200327 Parallel [university] Shade guide unit (Trubyte n.r. 6 n.r. [n.r.g n.r. 20 [1]
Bioform), clinical
photographs and
colorimeter (Chroma
meter)
de Geus & Others: At-home vs In-office Bleaching: a review 349

Table 2: Extended.
Study ID Bleaching Groups/materials Bleaching Outcomes evaluated
tray protocol Color Tooth sensitivity Gingival
change irritation
Acosta 199937 n.r. AH: 10% CPa AH: during night [10 DSGU Absolute risk n.r.
IO: 35% HPb days]
IO: 20-30 min [3
sessions]
Auschill 200534 With AH: 10% CPc AH: 8h daily DSGU VAS 0-10 Absolute risk
reservoirs IO: 38% HPd (number of cycles
needed for therapy
success)
IO: 15-min; 1 cycle
per appointment
(number of cycles
needed for therapy
success)
Basting 20127 Without AH1: 10% CPc AH: 2 h daily [21 DSGU Absolute risk and n.r.
reservoirs AH2: 20% CPe days] NRS 0-3
IO1: 38% HPd IO1: 3 3 15 min [3
IO2: 35% HPf sessions]
IO2: 30 min [3
sessions]
Bernardon 20104 Without AH: 10% CPg vs. AH: 8 h daily [21 DSGU VAS 0-10 n.r.
reservoirs IOL: 35% HPh days] and DE*
IO vs IOL IO: 3 3 15 min [2
AH vs AH þ IO sessions]
da Costa 20105 n.r. AH: 3% CPi AH: 8 h daily [6 DSGU Absolute risk and VAS 0-10
IO: 25% HPj days] and DE* VAS 0-10
IO: 4 3 15 min [1
session]
de Almeida 201213 With AH: 10% CPg AH: 4 h daily [21 n.r. Absolute risk and n.r.
reservoirs IO: 35% HPk days] VAS 0-10
IOL1: 35% HPk IO: 3 3 10 min [3
IOL2: 35% HPk sessions]
Giachetti 201031 n.r. AH: 10% CPc AH: 6-8 h daily [14 Whitening n.r. n.r.
IO: 38% HPd days] index
IO: 2 3 10 min [1
session]
Kim-Pusateri 200936 n.r. AH1: 32% CPl AH1: 3 min daily [28 DSGU n.r. n.r.
AH2: 32% CPl days] and DE*
IO: 25% HPm AH2: 15 min daily
IOL: 25% HPm [28 days]
IO: 2 3 30 min [1
session]
Moghadam 201328 With AH: 15% CPn AH: 4 h daily [14 DE* Absolute risk and n.r.
reservoirs IO: 38% HPd days] VAS 0-10
IO: 3 3 15 min [1
session]

Pintado-Palomino n.r. AH: 16% CPo AH: 4 h daily [14 n.r. VAS 0-10 n.r.
201535 IO: 35% HPk days]
IO: 3 3 15 min [1
session]
Tay 201230 Without AH: 10% CPg AH: 6 h daily [28 DSGU Absolute risk and n.r.
reservoirs IO: 35% HPk days] NRS 0-4
IO: 3 3 15 min [2
sessions]
Zekonis 200327 With AH: 10% CPc AH: 8 – 10 h or DSGU Absolute risk and NRS 0-4
reservoirs IO: 35% HPp during night [14 and DE* NRS 0-4 scale scale
days]
IO: 3 3 10 min [2
sessions]
350 Operative Dentistry

Table 2: Continued.

Abbreviations: AH, at-home bleaching; CP, carbamide peroxide; HP, hydrogen peroxide; IO, in-office bleaching; n.r., not reported; SD, standard deviation; VAS, Visual
Analog Scale: a 10-cm horizontal line with words ‘‘no pain’’ at one end and ‘‘worst pain’’ at the opposite end; VRS, Visual Rating Scale: none, mild, moderate,
considerate, severe; DSGU, shade guide units; DE* (color difference measured with a spectrophotometer).
a
NightWhite Excel 10%, Discus DentaL, Culver City, CA, USA;
b
Superoxol 35%, Moyco Union Broach-Thompson, Montgomeryville, Penn, USA;
c
Opalescence 10%, Ultradent, South Jordan, UT, USA;
d
Opalescence XtraBoost 38%, Ultradent, South Jordan, UT, USA;
e
Opalescence 20%, Ultradent, South Jordan, UT, USA;
f
Pola Office 35%, SDI, Bayswater, Victoria, Australia;
g
Whineness Perfect 10%, FGM, Joinville, SC, Brazil;
h
Whiteness HPMaxx 35%, FGM, Joinville, SC, Brazil;
i
NightWhite Excel 3%, Discus DentaL, Culver City, CA, USA;
j
Zoom AP 25%, Discus Dental, Culver City, CA, USA;
k
Whineness HP 35%, FGM, Joinville, SC, Brazil;
l
Sapphire take-home 32%, DenMat, Lompoc, CA, USA;
m
Sapphire Chairside 25%, DenMat, Lompoc, CA, USA;
n
Opalescence 15%, Ultradent, South Jordan, UT, USA;
o
Whineness Perfect 16%, FGM, Joinville, SC, Brasil;
p
StarBrite 35%, Interdent, Los Angeles, CA.

Figure 2. Summary of the risk of

bias assessment according to the
Cochrane Collaboration tool. Under-
lined authors provided extra informa-
tion by e-mail to allow assessment of
the risk of bias.
de Geus & Others: At-home vs In-office Bleaching: a review 351

Figure 3. Forest plot of the risk of

tooth sensitivity for in-office vs at-
home bleaching.

chance of tooth sensitivity for the at-home bleaching confidence interval varying from 0.42 to 2.09
protocol (data not shown). (p=0.193). This provides evidence that there is no
difference in the intensity of tooth sensitivity
Intensity of Tooth Sensitivity—This analysis was between the two bleaching protocols (Figure 4). Data
based on five studies.4,7,30,34,35 The Hedge’s g were heterogeneous (v2 test, p,0.001; I2=95.6%;
standardized difference in means was 0.823, with a Figure 4), which means that all studies included in

Figure 4. Forest plot of the intensity

of tooth sensitivity for in-office vs at-
home bleaching.
352 Operative Dentistry

Figure 5. Forest plot of the color

change in shade guide units for in-
office vs at-home bleaching.

the analysis did not share a common effect size. Data were heterogeneous (v2 test, p=0.01; I2=72%;
Through a sensitivity analysis, no study that was Figure 5), which means that all studies included in the
responsible for such high heterogeneity was identi- analysis did not share a common effect size. Through a
fied, and the reduced number of studies prevented us sensitivity analysis, no study that was responsible for
from performing meta-regression or subgroup anal- such high heterogeneity could be identified.
ysis. Color Change in DE*—This analysis was based on
Color Change in DSGU—This analysis was based four studies.4,5,27,28 The Hedge’s g standardized
on four studies.4,7,27,30 The Hedge’s g standardized difference in means was 0.260, with a confidence
difference in means was 0.184, with a confidence interval varying from 0.77 to 0.22 (p=0.292). This
interval varying from 0.66 to 0.29 (p=0.451). This showed that there was no difference in the color
showed that there was no difference in the color change measured with a spectrophotometer (Figure
change measured in shade guide units (Figure 5). 6). Data were heterogeneous (v2 test, p=0.05;

Figure 6. Forest plot of the color

change in DE* for in-office vs at-home
bleaching.
de Geus & Others: At-home vs In-office Bleaching: a review 353

I2=62.8%; Figure 6), which means that all studies and intensity of tooth sensitivity in earlier clinical
included in the analysis did not share a common trials comprising in-office and at-home bleach-
effect size. ing.22,45-48
Sensitivity Analysis for Imputations—For the The similar results in terms of color change were
matched data (split-mouth designs), the change of somehow expected, as bleaching is a time- and
the external correlation for extreme conditions (0.1 concentration-dependent procedure.49,50 The use of
and 0.9) did not affect the results of any of the meta- low concentration products can reach similar whiten-
analysis run for this study. The low number of ing degree as high concentration products as long as
studies included in all meta-analyses prevented us they are used for longer periods. Cardoso and others51
from evaluating the impact of some predictors on the showed that different application times of the at-
estimates. home bleaching gel may reach equally satisfactory
A high heterogeneity of the risk of tooth sensitivity results in relation to efficacy of bleaching treatment
and color change in shade guide units was caused by as long as the shorter application times are compen-
the study of Basting and others.7 By removing this sated for by prolonging the number of treatment days.
study from the present meta-analysis, no heteroge- In agreement with such findings are the studies that
neity was detected, and the I2 was reduced by half, compared both techniques and assessed the patient’s
with no change in the overall Hedge’s g effect size satisfaction. These studies reported similar overall
(data not shown). satisfaction in terms of comfort and whitening
results,4,5,31 demonstrating that both techniques can
DISCUSSION yield satisfactory bleaching efficacy.
The most important advantage of proper randomi- Nonetheless, the similarity in outcomes between
zation is that it balances both known and unknown techniques should be interpreted with caution due to
prognostic factors in the assignment of treatments. two reasons: 1) a low number of studies included in
Besides randomization, allocation concealment is the meta-analyses and 2) the high heterogeneity of
equally important as it protects the randomization the studies detected by the v2 statistics. When facing
process, so that the treatment to be allocated is not meta-analyses with high heterogeneity, more impor-
known before the patient is enrolled into the study. tant than the discussion of the summary outcomes
The adequate management of these two domains and the overall results is the identification of factors
minimizes selection bias.38 responsible for such heterogeneity.52
This is the reason why only studies classified as The low number of studies identified in the
low risk of bias of these domains were included in the literature search and included in the meta-analysis
meta-analyses. There is abundant evidence that the prevented us from evaluating the impact of such
proper conduction of these steps in RCTs reduces the variants (different protocols, concentration of the
possibility of systematic errors39,40; studies with low bleaching agents, product brand and composition,
methodologic quality tend to overestimate the re- etc) on the outcomes through a meta-regression. It is
sults, favoring the intervention under testing.41,42 generally assumed that there should be 10 studies
for every predictor to be included in a meta-
In the present study, no significant difference
regression.52
between techniques in any of the comparisons was
found. An increased risk and intensity of tooth The high heterogeneity observed in this study is
sensitivity for the in-office bleaching were expected, probably due to the different in-office and at-home
due to the use of bleaching agents in concentrations bleaching protocols, varied number of clinical ses-
much higher than that used in the at-home proto- sions, and different concentrations of bleaching gels
col.1,43,44 However, due to the large variation of among the RCTs. For instance, the use of a single
bleaching protocols and concentrations of the bleach- bleaching session5,28,31 or even shorter application
ing products, this association was not observed. times of 10-20 minutes31,34 were reported in many
This similarity in risk and intensity of tooth clinical studies of in-office bleaching. Such degree of
sensitivity could be partially explained by the fact variation was also detected for at-home bleaching.
that most of the studies used at-home and in-office The daily use time ranged from 27 to 10 hours4,27 for
bleaching agents with potassium nitrate and sodium 6,5 14,27,28,31 and 21-28 days.4,7,30
fluoride4,7,27,28,30,34,35 or at least sodium fluoride5,7 in Additionally, in some studies, a fair comparison
their composition. Potassium nitrate and sodium between in-office bleaching and at-home bleaching
fluoride were already associated with reduced risk was not performed. One week of at-home bleaching
354 Operative Dentistry

with 10% or 16% carbamide peroxide gel usually methods to evaluate color change can also be
results in a change of two to four shade guide reported, as well as changes in L*, a*, and b*, this
units,4,5,12,27,37 which is approximately equivalent to should be accompanied by reports of the changes in
the change reported after a single in-office bleaching shade guide units and in DE* so that the study
session with 35% hydrogen peroxide gel.4,27,53,54 becomes comparable with other clinical studies.
Therefore, comparing a single in-office bleaching This is the reason why the study of Giachetti and
session with a 14-day at-home protocol28,31,35 will others,31 even after being classified at low risk of
certainly favor the at-home bleaching in terms of bias, was not included in any of the meta-analysis
color change and may even minimize the tooth of color change.
sensitivity of in-office bleaching. In the same line,
there were studies comparing two in-office bleaching CONCLUSIONS
sessions with three-week at-home bleaching4 and
also two in-office bleaching sessions with a four-week Neither the risk/intensity of tooth sensitivity nor the
at-home bleaching.30 effectiveness of the bleaching treatment was influ-
enced by the choice of bleaching technique. Howev-
In regard to the heterogeneity of the studies, it is er, this should be interpreted with caution as it
worth mentioning that in two of the four meta- represents an overall comparison without taking
analyses, the high heterogeneity was mainly deter- into consideration variations in the protocols (daily
mined by the study of Basting and others.7 Most in- use time, number of bleaching sessions, and product
office bleaching gels are delivered at low pH because
concentration) of the bleaching techniques in the
they are more stable as acid solutions than as base
studies included.
solutions.55,56 However, in the specific study of
Basting and others,7 the authors used two in-office
bleaching gels: one with an alkaline pH and the Acknowledgments
other with an acidic pH. The gel with an alkaline pH This study was conducted during the doctoral stage of Juliana
showed a very low risk of tooth sensitivity. Although Larocca de Geus under the supervision of Prof. Alessandra
Reis. The authors of this study would like to thank the
this is an unusual finding, it may be explained by following authors who kindly provided information not
differences in the decomposition kinetics of the available in their full texts: Bruce A. Matis, Daniele
hydrogen peroxide at different pHs. Scaminaci, Juliana da Costa, Jussara Bernardon, Roberta T.
Basting, Sebastian Ciancio, Thorsten Auschill. This study was
While it is in an acidic solution, oxygen free partially supported by the National Council for Scientific and
radicals and hydroxyl anions are produced, but an Technological Development from the Brazilian Government,
under grants 304105/2013-9 and 301891/2010-9.
alkaline solution has a higher concentration of
perhydroxyl ions.57 In an alkaline media, the
Regulatory Statement
dissociation of hydrogen peroxide (HP) into free
radicals is the greatest, as the dissociation constant This study protocol was registered at the PROSPERO
(CRD42015015564), and followed the recommendations of
(pKa) of the HP is around 11.5. HP in a pH of 9 the PRISMA statement for report.
dissociated 2.7 times more than it did in a pH of
4.4.55 Thus, if more HP dissociates into free radicals Conflict of Interest
within the dental structure, less surplus of HP is The authors of this manuscript certify that they have no
available to travel within dentin and reach the pulp proprietary, financial, or other personal interest of any nature
chamber. This low diffusion of HP into the pulp or kind in any product, service, and/or company that is
chamber when using an alkaline in-office gel was presented in this article.
demonstrated in an in vitro study.58 This may
(Accepted 22 December 2015)
explain the very low risk of tooth sensitivity of one
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