Botulinum toxin for masseter hypertrophy
Fedorowicz, Z.; Zuuren, E.J. van; Schoones, J.
Citation
Fedorowicz, Z., Zuuren, E. J. van, & Schoones, J. (2013). Botulinum toxin for masseter
hypertrophy. Cochrane Database Of Systematic Reviews, (9).
doi:10.1002/14651858.CD007510.pub3
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Note: To cite this publication please use the final published version (if applicable).
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Botulinum toxin for masseter hypertrophy (Review)
Fedorowicz Z, van Zuuren EJ, Schoones J
Fedorowicz Z, van Zuuren EJ, Schoones J.
Botulinum toxin for masseter hypertrophy.
Cochrane Database of Systematic Reviews 2013, Issue 9. Art. No.: CD007510.
DOI: 10.1002/14651858.CD007510.pub3.
www.cochranelibrary.com
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TABLE OF CONTENTS
HEADER.........................................................................................................................................................................................................
ABSTRACT.....................................................................................................................................................................................................
PLAIN LANGUAGE SUMMARY.......................................................................................................................................................................
BACKGROUND..............................................................................................................................................................................................
OBJECTIVES..................................................................................................................................................................................................
METHODS.....................................................................................................................................................................................................
RESULTS........................................................................................................................................................................................................
Figure 1..................................................................................................................................................................................................
DISCUSSION..................................................................................................................................................................................................
AUTHORS' CONCLUSIONS...........................................................................................................................................................................
ACKNOWLEDGEMENTS................................................................................................................................................................................
REFERENCES................................................................................................................................................................................................
CHARACTERISTICS OF STUDIES..................................................................................................................................................................
APPENDICES.................................................................................................................................................................................................
WHAT'S NEW.................................................................................................................................................................................................
CONTRIBUTIONS OF AUTHORS...................................................................................................................................................................
DECLARATIONS OF INTEREST.....................................................................................................................................................................
SOURCES OF SUPPORT...............................................................................................................................................................................
DIFFERENCES BETWEEN PROTOCOL AND REVIEW....................................................................................................................................
INDEX TERMS...............................................................................................................................................................................................
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[Intervention Review]
Botulinum toxin for masseter hypertrophy
Zbys Fedorowicz1, Esther J van Zuuren2, Jan Schoones3
1UKCC (Bahrain Branch), The Cochrane Collaboration, Awali, Bahrain. 2Department of Dermatology, Leiden University Medical Center,
Leiden, Netherlands. 3Walaeus Library, Leiden University Medical Center, Leiden, Netherlands
Contact address: Zbys Fedorowicz, UKCC (Bahrain Branch), The Cochrane Collaboration, Box 25438, Awali, Bahrain.
zbysfedorowicz@gmail.com.
Editorial group: Cochrane Movement Disorders Group.
Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 9, 2013.
Citation: Fedorowicz Z, van Zuuren EJ, Schoones J. Botulinum toxin for masseter hypertrophy. Cochrane Database of Systematic
Reviews 2013, Issue 9. Art. No.: CD007510. DOI: 10.1002/14651858.CD007510.pub3.
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ABSTRACT
Background
Benign masseter muscle hypertrophy is an uncommon clinical phenomenon of uncertain aetiology which is characterised by a soft swelling
near the angle of the mandible. The swelling may on occasion be associated with facial pain and can be prominent enough to be considered
cosmetically disfiguring. Varying degrees of success have been reported for some of the treatment options for masseter hypertrophy, which
range from simple pharmacotherapy to more invasive surgical reduction. Injection of botulinum toxin type A into the masseter muscle
is generally considered a less invasive modality and has been advocated for cosmetic sculpting of the lower face. Botulinum toxin type
A is a powerful neurotoxin which is produced by the anaerobic organism Clostridium botulinum and when injected into a muscle causes
interference with the neurotransmitter mechanism producing selective paralysis and subsequent atrophy of the muscle.This review is an
update of a previously published Cochrane review.
Objectives
To assess the efficacy and safety of botulinum toxin type A compared to placebo or no treatment, for the management of benign bilateral
masseter hypertrophy.
Search methods
We searched the following databases from inception to April 2013: the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE
(via PubMed); EMBASE (via embase.com); Web of Science; CINAHL; Academic Search Premier (via EBSCOhost); ScienceDirect; LILACS (via
BIREME); PubMed Central and Google Scholar (from 1700 to 19 April 2013). We searched two bibliographic databases of regional journals
(IndMED and Iranmedex) which were expected to contain relevant trials. We also searched reference lists of relevant articles and contacted
investigators to identify additional published and unpublished studies.
Selection criteria
Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing intra-masseteric injections of botulinum toxin versus
placebo administered for cosmetic facial sculpting in individuals of any age with bilateral benign masseter hypertrophy, which had
been self-evaluated and confirmed by clinical and radiological examination were considered for inclusion. We excluded participants with
unilateral or compensatory contralateral masseter hypertrophy resulting from head and neck radiotherapy.
Data collection and analysis
Two review authors independently screened the search results. For future updates, two authors will independently extract data and assess
trial quality using the Cochrane risk of bias tool. Risk ratios (RR) and corresponding 95% confidence intervals (CI) will be calculated for all
dichotomous outcomes and the mean difference (MD) and 95% CI will be calculated for continuous outcomes.
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Main results
We retrieved 683 unique references to studies. After screening these references 660 were excluded for being non-applicable. We assessed
23 full text articles for eligibility and all of these studies were excluded from the review.
Authors' conclusions
We were unable to identify any RCTs or CCTs assessing the efficacy and safety of intra-masseteric injections of botulinum toxin for people
with bilateral benign masseter hypertrophy. The absence of high level evidence for the effectiveness of this intervention emphasises the
need for well-designed, adequately powered RCTs.
PLAIN LANGUAGE SUMMARY
Botulinum toxin type A for masseter hypertrophy
Masseter muscle hypertrophy occurs as a soft enlargement of the jaw muscles near the angle of the lower jaw and seldom presents a
major health problem. However, in some individuals the swelling can be associated with pain or may be so large that it causes facial
disfigurement. Although the cause of the condition is unclear it does appear to be more common in certain ethnic groups.
Symptoms such as pain can be treated with muscle relaxants and may also include bite adjustments or involve the use of splints on the
teeth. Surgical reduction of the jaw muscle or injections of botulinum toxin type A directly into the muscle are other treatment options.
Botulinum toxin type A is a powerful neurotoxin produced by the anaerobic organism Clostridium botulinum. When botulinum toxin type
A is injected into a muscle it causes interference with the neurotransmitter mechanism producing selective loss of muscle function and a
subsequent decrease in the mass of the muscle.
Although the use of botulinum toxin injections might appear to have certain advantages over surgery the authors of this review did not
find any high quality studies that evaluated the effectiveness and potential side effects of botulinum toxin type A for the management
of benign masseter hypertrophy. Well-designed randomised controlled trials are needed to assess the effectiveness and safety (i.e. side
effects) of this intervention.
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BACKGROUND
Aetiology and prevalence
Benign masseter muscle hypertrophy is an uncommon clinical
phenomenon of uncertain aetiology. It is characterised by a soft
swelling, near the angle of the mandible, which can be associated
with facial pain. The hypertrophy can be prominent enough to be
considered cosmetically disfiguring.
More than 250 cases of benign bilateral masseter muscle
hypertrophy have been reported since its first published
description (Legg 1880). Prevalence data are scarce but in a recent
study (Sannomya 2006) 90 (4%) of the patients with masseter
hypertrophy were less than 10 years old and 3% were over 40 years
of age (mean 30 years), with a male to female ratio of 1:1.
The aetiology of masseter muscle hypertrophy has been attributed
to a number of factors including: emotional stress, chronic bruxism,
masseteric hyper-function and para-function, and microtrauma
(Harriman 1996; Serrat 1998; Wilson 1990). It reportedly occurs
most frequently among pacific Asians and is associated with ethnic
characteristics (e.g. prominence of the mandibular angle) and
dietary habits (Jin Park 2007). The findings of several investigators
suggest that the increase in muscle size is not caused by work
hypertrophy but as a result of compensatory enlargement due to
lack of a certain type of muscle fibre (Jin Park 2007; Satoh 2001).
Tests have shown that the composition of muscle fibres in the
enlarged masseter is very different from that in muscles with 'work
hypertrophy' as well as that in normal masseter muscles (Satoh
2001), suggesting that the term 'hypertrophy' could be potentially
misleading.
Other possible causes and associations have been suggested
including: clenbuterol induced hypertrophy, overuse of anabolic
steroids (Skoura 2001), localised scleroderma and facial hemiatrophy (Kim 2000), and a multifactorial origin in combination with
a genetic basis (Giudice 1992). Benign masseter hypertrophy is also
compatible with a rare genetic condition known as hypertrophic
branchial myopathy (Kitagawa 2000).
Description of the condition
Cochrane Database of Systematic Reviews
Diagnosis cannot solely be based on clinical findings and there
are conflicting recommendations in the literature for investigating
patients presenting with benign bilateral masseter hypertrophy.
These recommendations include the following.
• Standard radiographs (not essential but can sometimes assist in
diagnosis).
• Computed tomographic (CT) scan, magnetic resonance imaging
(MRI) scan, or both (considered the gold standard in confirming
a clinical suspicion).
• Muscle biopsy.
• Morphometric analysis.
• Ultrasonographic measurement.
• Electromyographic measurement.
Description of the intervention
Treatment options
A range of treatment modalities have been reported with variable
degrees of success and failure. Treatment options include the
following.
1. Pharmacotherapy: anxiolytics, muscle relaxants and
antidepressants.
2. Dental restorations and occlusal adjustments to correct
premature contacts and malocclusions, and prevention of parafunctional habits with orthotic appliances.
3. Botulinum toxin type A injections into the muscle.
4. Radiofrequency volumetric reduction.
5. Intra-oral and extra-oral surgical reduction of masseter size,
removal of mandibular angle, neurectomy of the masseteric
nerve, and resection of the buccal fat pad.
How the intervention might work
Botulinum toxin type A (BtA) is a powerful neurotoxin produced
by the anaerobic organism Clostridium botulinum. When BtA
is injected into a muscle it causes interference with the
neurotransmitter mechanism producing selective paralysis and
subsequent atrophy of the muscle.
Signs and symptoms
Why it is important to do this review
Bilateral enlargement of the masseter muscles is often
accompanied by pain, which may be intermittent and can be
confused with pain arising from the parotid gland (Newton 1999;
Nishida 1995). Clinical examination usually reveals a soft tissue
mass near the angle of the mandible, which becomes more
prominent on clenching of the teeth (Sannomya 2006).
Surgery has historically been the standard treatment for cosmetic
reduction of masseter hypertrophy, but injection of BtA into the
muscle, which is generally considered to be a less invasive modality,
has more recently been advocated. This systematic review is an
update of a previously published Cochrane review (Al-Muharraqi
2009).
Limitation of the mouth opening has been reported in some
cases and particularly where the muscles are focally dystonic
with tension in the region of the hypertrophied muscle
(Papapetropoulos 2006). Midline deviation has also been observed
in some cases, as well as masseteric (hemi-masticatory) spasm
(Kim 2000). It has also been suggested that the hypertrophied
muscles of the jaw can lead to increased pressure in the temporomandibular joints (TMJ), which can generate severe pain and mimic
temporo-mandibular dysfunction syndrome (TMD) (Chikani 2003).
OBJECTIVES
To assess the efficacy and safety of botulinum toxin type A
compared to placebo or no treatment, for the management of
benign bilateral masseter hypertrophy.
Diagnosis
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METHODS
Criteria for considering studies for this review
Types of studies
Randomised controlled trials (RCTs) and controlled clinical trials
(CCTs) were considered for inclusion.
Types of participants
Individuals of any age with bilateral benign masseter hypertrophy
which has been self-evaluated and confirmed by clinical and
radiological examination were considered for inclusion. In view
of the possible clinical diversity in presentation, we excluded
studies involving participants with unilateral or compensatory
contra lateral masseter hypertrophy resulting from head and neck
radiotherapy from this review.
Types of interventions
Interventions included transcutaneous intra-masseteric injections
of botulinum toxin versus placebo or no treatment. We sought to
include studies in which the intervention had been administered
for cosmetic facial sculpting. We considered studies involving a
single injection cycle in addition to studies in which all participants
entered in to a trial had received repeat injections at similar time
periods.
Types of outcome measures
Cochrane Database of Systematic Reviews
• the Cochrane Central Register of Controlled Trials (CENTRAL)
(The Cochrane Library 2013, Issue 4). See Appendix 4
• CINAHL (from 1982 to 19 April 2013). See Appendix 5
• Academic Search Premier (via EBSCOhost) (from 1897 to 19 April
2013). See Appendix 6
• ScienceDirect (from 1823 to 19 April 2013). See Appendix 7
• LILACS (via BIREME) (from 1982 to 19 April 2013). See Appendix 8
• PubMed Central (from 1809 to 19 April 2013). See Appendix 9
• Google Scholar (from 1700 to 19 April 2013). See Appendix 10
Although we did not search the Cochrane Movement Disorders
Group Trials Register we clarified that it did not contain any relevant
studies.
We updated our search of IndMED, a bibliographic database of
Indian journals, available at (http://indmed.nic.in/) and a similar
Iranian database, Iranmedex, available at (www.iranmedex.com),
using free text terms appropriate for this review on 27 April 2013.
Searching other resources
We did not conduct any handsearching of journals but searched
the reference lists of relevant articles in addition to the review
authors' personal database of trial reports. We also contacted
a number of investigators by electronic mail to ask for details
of additional published and unpublished trials. There were no
language restrictions on included studies and we arranged to
translate any relevant non-English papers.
Assessment was to include a follow-up period of up to two years
after the intervention.
Data collection and analysis
Primary outcomes
Selection of studies
1. Self-assessed improvement in facial appearance and patient
satisfaction using any validated scale or questionnaire.
2. Patient-assessed improvement in pain or discomfort associated
with the temporo-mandibular joints or jaw muscles using any
recognised validated pain scale.
Two review authors (ZF and EvZ) independently assessed the
abstracts of studies resulting from the searches. We obtained
full copies of all relevant and potentially relevant studies, those
appearing to meet the inclusion criteria, and those for which there
were insufficient data in the title and abstract to make a clear
decision.The two review authors independently assessed the full
text papers and resolved any disagreement on the eligibility of
included studies through discussion and consensus. We excluded
all irrelevant records and noted details of the studies and the
reasons for their exclusion in the 'Characteristics of excluded
studies' table in RevMan 5.2 (RevMan 2012).
Secondary outcomes
1. Objective evaluation of the change in facial contour,
involving physical measurement. Change in facial contour
could be measured by clinical photography or radiological
measurement which could include three-dimensional
computed tomographic (CT) scans, magnetic resonance (MR)
imaging, or ultrasonographic measurements of the thickness of
the masseter muscle.
2. Adverse events including any specific adverse effects, systemic
or local toxicity, any clinically diagnosed hypersensitivity and
other unacceptable events associated with this treatment.
Data extraction and management
Electronic searches
The following methods of data extraction and management will
apply for subsequent updates, and when future studies are
identified. We will enter study details into the 'Characteristics of
included studies' table in RevMan 5.2. The review authors will
collect outcome data using a pre-determined form designed for this
purpose. Two authors (ZF and EvZ) will enter extracted data into
RevMan 5.2., data will only be included if there is an independently
reached consensus.
Databases searched
We will extract the following details.
We extended and updated the searches for the following databases:
1. Trial methods: (a) method of allocation, (b) masking of
participants, personnel and outcome assessors, (c) exclusion of
participants after randomisation and proportion and reasons for
losses at follow-up.
Search methods for identification of studies
• MEDLINE (via Pubmed) (1950 to 19 April 2013). See Appendix 1
• EMBASE (via embase.com) (from 1980 to 19 April 2013). See
Appendix 2
• Web of Science (from 1945 to 19 April 2013). See Appendix 3
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2. Participants: (a) country of origin and location (i.e. private clinic
or academic institute), (b) sample size, (c) age, (d) sex, (e)
inclusion and exclusion criteria.
3. Intervention: (a) type, dosage, route of administration, (b)
length of follow-up.
4. Control: (a) type, dosage, route of administration, (b) length of
follow-up.
5. Outcomes: (a) primary and secondary outcomes pre-specified in
the 'Types of outcome measures' section of this review.
If stated, we will record the sources of funding of any of the included
studies.
Assessment of risk of bias in included studies
If studies are included in future updates each review author
will grade the selected trials and assess every trial using a
simple contingency form following the domain-based evaluation
described in the Cochrane Handbook for Systematic Reviews of
Interventions 5.1.0 (Higgins 2011). We will compare the evaluations
and discuss and resolve any inconsistencies and disagreements.
The following domains will be rated separately for each of the
included studies as 'low risk of bias', 'high risk of bias', and 'unclear'
if the risk of bias was uncertain or unknown:
1.
2.
3.
4.
5.
6.
sequence generation;
allocation concealment;
blinding (of participants, personnel and outcome assessors);
incomplete outcome data;
selective outcome reporting;
other bias.
These assessments will be reported in the 'Risk of bias' table for
each individual study in the 'Characteristics of included studies'
section of the review.
We will also categorise and report the overall risk of bias of each of
the included studies according to the following:
• low risk of bias (plausible bias unlikely to seriously alter the
results) if all criteria were met;
• unclear risk of bias (plausible bias that raises some doubt about
the results) if one or more criteria were assessed as unclear; or
• high risk of bias (plausible bias that seriously weakens
confidence in the results) if one or more criteria were not met.
These assessments will be reported in the 'Risk of bias in included
studies' section of this review.
Measures of treatment effect
If studies are included in future updates we will conduct analysis at
the same level as the allocation. We will calculate risk ratios (RR)
and corresponding 95% confidence interval (CI) for all dichotomous
outcomes and the mean difference (MD) and 95% CI for continuous
outcomes. We will use RevMan 5 for data analysis. Unless stated
otherwise, we will use the Mantel-Haenzel method to calculate the
RR for dichotomous outcomes and MD for continuous outcomes.
As it is likely that the timing of outcome assessment will vary
between studies we will consider grouping the data according to
the following time-points: six months, one year and two years.
Cochrane Database of Systematic Reviews
Unit of analysis issues
We expect to include trials of participants with bilateral
hypertrophy in which the masseter muscles of an individual
participant were the units of randomisation and subsequent
analysis. We will analyse these data based on the advice provided
in sections 9.3.8 in the Cochrane Handbook for Systematic Reviews
of Interventions (Higgins 2011).
Dealing with missing data
If studies are included in future updates we will make attempts to
retrieve missing data from the investigators of the included trials,
and if unsuccessful or the discrepancies are significant, we will
provide a narrative synthesis of the data as reported.
Assessment of heterogeneity
If studies are included in future updates we will assess clinical
heterogeneity by examining the characteristics of the studies and
the similarity between types of participants, interventions and
outcomes. In view of the expectation of a degree of clinical
heterogeneity between the studies we will use a random-effects
model for statistical analyses. Statistical heterogeneity will be
assessed using the Chi2 test and the I2 statistic, where I2 values over
50% indicate moderate to high heterogeneity (Higgins 2011).
Assessment of reporting biases
if future updates include studies we will follow the
recommendations on testing for funnel plot asymmetry as
described in section 10.4.3.1 of the Cochrane Handbook for
Systematic Reviews of Interventions 5.1.0 (Higgins 2011) to assess
publication bias.
Data synthesis
If future updates include studies two review authors (ZF and
EvZ) will analyse the data and report the results as specified
in Chapter 9 of the Cochrane Handbook for Systematic Reviews
of Interventions Version 5.1.0 (Higgins 2011). Where appropriate,
we will calculate the pooled RR and 95% CI for dichotomous
outcomes and the pooled MD and 95% CI for continuous outcomes.
We will use the Mantel-Haenzel method for combining results
across studies using random-effects models. In the event that
there are insufficient clinically homogeneous trials for any specific
intervention or insufficient study data that can be pooled, we will
present a narrative synthesis.
Subgroup analysis and investigation of heterogeneity
If studies are included in future updates we will perform subgroup
analysis by dose (i.e. low dose of BtA compared to medium or high
doses). We define a low dose of BtA as ≤ 150 U per muscle and a
medium to high dose as > 150 U per muscle.
Sensitivity analysis
If future updates contain a sufficient number of included studies we
plan to conduct sensitivity analyses to assess the robustness of our
review results. We will do this by repeating the analyses excluding
studies with unclear or inadequate allocation concealment,
blinding of outcomes assessment and completeness of follow-up.
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RESULTS
Description of studies
Results of the search
A literature search conducted on April 19, 2013 identified
1147 records. After duplicates were removed, a total of 683
references remained for review of titles and abstracts (PubMed
258, EMBASE 361 (34 abstracts to conference proceedings), from
which 181 unique, Web of Science: 181 (8 abstracts to conference
proceedings), from which 41 unique, CENTRAL 105, from which
97 unique, CINAHL 23, from which 3 unique, Academic Search
Premier 55, from which 11 unique, ScienceDirect: 47, from which
10 unique, LILACS: 5, from which 3 unique, PubMed Central/
PMC: 54, from which 48 unique, Google Scholar: unknown set, 13
Cochrane Database of Systematic Reviews
unique), citations to Cochrane Review: through Web of Science:
2, from which 1 unique, citations from Cochrane Review: through
Web of Science: 30, from which 11 unique and citations to
Cochrane Review: through Google Scholar: 13, from which 6
unique). After examination of the titles and abstracts of these
references, we eliminated all but 23 and excluded them from
further review (see Figure 1). We obtained full text copies of those
remaining studies, translated them into the English language as
required and subjected them to further evaluation. We examined
the bibliographical references of these studies and, as with our
searches of the IndMED and Iranmedex databases, they did not
provide any further citations to potentially eligible studies. Two
authors, Zbys Fedorowicz (ZF) and Esther van Zuuren (EvZ),
independently assessed all of the full text papers, and resolved any
disagreement on their eligibility for this review through discussion
and consensus.
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Figure 1. Study flow diagram.
Included studies
Risk of bias in included studies
We retrieved a number of studies in our comprehensive search of
the literature but none were eligible and therefore no trials were
included in this review.
A risk of bias analysis was not carried out because no trials were
included in the review.
Excluded studies
We excluded all records which did not match our inclusion criteria
and noted the reasons for their exclusion in the 'Characteristics of
excluded studies' table.
Effects of interventions
None of the studies retrieved in our searches met our inclusion
criteria and therefore no data were available for analysis.
DISCUSSION
The comprehensive search used in this review provided a large
number of references to trials and thus the lack of relevant
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randomised controlled trials or controlled clinical trials as well
as any robust evidence to support or refute the effectiveness of
botulinum toxin for masseter hypertrophy, proved to be somewhat
disappointing. Over the last 10 years a number of case reports
and several recent cohort studies have sought to illustrate the
effectiveness of botulinum toxin type A injections for benign
masseter muscle hypertrophy, but questions remain unanswered
as to whether management options based on this intervention can
be considered both effective and safe.
AUTHORS' CONCLUSIONS
Implications for practice
A lack of consensus on the aetiology of benign masseter
hypertrophy together with an increasing concern about the longterm effects of botulinum toxin type A (BtA) would appear to
underline the fact that its therapeutic benefits remain unclear.
Therefore, before selecting this treatment option clinicians need to
carefully consider, and indeed discuss, not only its benefits but also
the possibility and implications of any potential harms with their
patients.
Implications for research
This systematic review on botulinum toxin for masseter
hypertrophy did not identify any eligible studies. This review
highlights the need for well-designed, adequately powered
randomised controlled trials to evaluate the efficacy and safety of
botulinum toxin for reducing the size and volume of the masseter
muscles in people diagnosed with bilateral benign masseter
Cochrane Database of Systematic Reviews
hypertrophy. Although further research is required, conducting
randomised controlled trials for this intervention will present
challenges in terms of the willingness of participants to be enrolled
into a trial where they may be allocated to an intervention
which will result in unilateral facial deformity for the duration
of the trial. Outcomes assessments in future trials should aim to
include both subjective and objective baseline and post treatment
evaluations, such as maximum bite force, clinical photography,
physical measurements of changes in facial contour, cephalometry
and electromyographic studies of masseter function. Any future
trials will also need to be rigorous in design and delivery, with
subsequent reporting to include high quality descriptions of all
aspects of methodology to enable appraisal and interpretation of
results, and conform with the Consolidated Standards of Reporting
Trials (CONSORT) statement (http://www.consortstatement.org/).
ACKNOWLEDGEMENTS
The review authors would like to acknowledge the assistance they
have received from members of the Cochrane Movement Disorders
Group and for the helpful comments on this review from the
referees. We would like to thank Emma Low of GKT Dental Institute,
King's College Hospital University of London, who provided us with
full text copies of many of the papers and Raphael F. de Souza of
the Department of Dental Materials and Prosthodontics, Ribeirão
Preto Dental School, University of São Paulo, Brazil who very kindly
ran all the searches for the original version of this review. The
authors would like to acknowledge the contribution of Mohammed
Al Muharraqi, Jaffer Al Bareeq, Reem Al Bareeq, and Mona Nasser to
earlier versions of this review.
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REFERENCES
References to studies excluded from this review
Ahn 2007 {published data only}
Ahn KY, Kim ST. The change of maximum bite force
after botulinum toxin type a injection for treating
masseteric hypertrophy. Plastic and Reconstructive Surgery
2007;120(6):1662-6.
Bhogal 2006 {published data only}
Bhogal PS, Hutton A, Monaghan A. A review of the current
uses of Botox for dentally-related procedures. Dental Update
2006;33(3):165-8.
Castro 2005 {published data only}
Castro WH, Gomez RS, Da Silva Oliveira J, Moura MD, Gomez RS.
Botulinum toxin type A in the management of masseter
muscle hypertrophy. Journal of Oral and Maxillofacial Surgery
2005;63(1):20-4.
Chikani 2003 {published data only}
Chikhani L, Dichamp J. Bruxism, temporo-mandibular
dysfunction and botulinum toxin. Annales de Réadaptation et de
Médecine Physique 2003;46(6):333-7.
Choe 2005 {published data only}
Choe SW, Cho WI, Lee CK, Seo SJ. Effects of botulinum toxin
type A on contouring of the lower face. Dermatologic Surgery
2005;31(5):502-7.
Collier 2009 {published data only}
Collier J, Zou L. Quantitative measurement of the response
of masseteric hypertrophy to treatment with botulinum
toxin type-A. British Journal of Oral and Maxillofacial Surgery
2009;47(7):e30.
Hui 2002 {published data only}
Hui AC. Botulinum toxin for treatment of masseteric
hypertrophy. Journal of Neurology 2002;249(3):345.
Işeri 2004 {published data only}
Işeri M, Işeri PK. Treatment of unilateral masseter hypertrophy
with botulinum toxin in two cases. Kulak Burun Boğaz Ihtisas
Dergisi 2004;12(3-4):99-102.
Jin 2010 {published data only}
Jin SP, Cho S, Youn C, Feneran A, Haw S, Bak H, et al.
Effectiveness of botulinum toxin type A and B in benign
masseteric hypertrophy. Journal of Dermatology 2010;37(Suppl
1):78.
Kane 2007 {published data only}
Kane MA. Botulinum toxin A for lower facial contouring: A
prospective study. Aesthetic Plastic Surgery 2007;31(5):452-3.
Kaynar 1997 {published data only}
Kaynar A, Parman Y, Poyanl A, Demirkol O, Birinci SH,
Minareci O, et al. Therapeutic use of botulinum toxin in the
treatment of masseter hypertrophy. International Journal of
Oral and Maxillofacial Surgery 1997;26(Suppl 1):116.
Kim 2003 {published data only}
Kim HJ, Yum KW, Lee SS, Heo MS, Seo K. Effects of botulinum
toxin type A on bilateral masseteric hypertrophy evaluated with
computed tomographic measurement. Dermatologic Surgery
2003;29(5):484-9.
Lee 2007 {published data only}
Lee CJ, Kim SG, Kim YJ, Han JY, Choi SH, Lee SI.
Electrophysiologic change and facial contour following
botulinum toxin A. Plastic and Reconstructive Surgery
2007;120(3):769-78.
Mischkowski 2005 {published data only}
Mischkowski RA, Siessegger M, Lazar F, Zöller JE.
Chemodenervation with botulinum toxin in masseteric
hypertrophy. Mund-, Kiefer- und Gesichtschirurgie
2005;9(2):101-8.
Moore 1994 {published data only}
Moore AP, Wood GD. The medical management of masseteric
hypertrophy with botulinum toxin type A. British Journal of Oral
and Maxillofacial Surgery 1994;32(1):26-8.
Niamtu 1999 {published data only}
Niamtu J. Aesthetic uses of botulinum toxin A. Journal of Oral
and Maxillofacial Surgery 1999;57(10):1228-33.
Park 2003 {published data only}
Park MY, Ahn KY, Jung DS. Botulinum toxin type A treatment
for contouring of the lower face. Dermatologic Surgery
2003;29(5):477-83.
Rogers 1995 {published data only}
Rogers BA, Whear NM. Medical management of masseteric
hypertrophy. Journal of Oral and Maxillofacial Surgery
1995;53(4):492.
Smyth 1994 {published data only}
Smyth AG. Botulinum toxin treatment of bilateral masseteric
hypertrophy. British Journal of Oral and Maxillofacial Surgery
1994;32(1):29-33.
To 2001 {published data only}
To EW, Ahuja AT, Ho WS, King WW, Wong WK, Pang PC, et al.
A prospective study of the effect of botulinum toxin A on
masseteric muscle hypertrophy with ultrasonographic and
electromyographic measurement. British Journal of Plastic
Surgery 2001;54(3):197-200.
von Lindern 2001 {published data only}
von Lindern JJ, Niederhagen B, Appel T, Bergé S, Reich RH.
Type A botulinum toxin for the treatment of hypertrophy of
the masseter and temporal muscles: an alternative treatment.
Plastic and Reconstructive Surgery 2001;107(2):327-32.
von Lindern 2003 {published data only}
von Lindern JJ, Niederhagen B, Bergé S, Appel T. Type A
botulinum toxin in the treatment of chronic facial pain
Botulinum toxin for masseter hypertrophy (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Trusted evidence.
Informed decisions.
Better health.
associated with masticatory hyperactivity. Journal of Oral and
Maxillofacial Surgery 2003;61(7):774-8.
Yu 2007 {published data only}
Yu CC, Chen PK, Chen YR. Botulinum toxin a for lower facial
contouring: a prospective study. Aesthetic Plastic Surgery
2007;31(5):445-51.
Additional references
Giudice 1992
Giudice M, Marra A, Barba A, Passariello N, D'Onofrio F.
Hypertrophy of the masseter: a rare case associated with
hypertrophic cardiomyopathy. Minerva Stomatologica
1992;41(11):535-42.
Harriman 1996
Harriman DG. The histochemistry of reactive masticatory
muscle hypertrophy. Muscle and Nerve 1996;19:1447-56.
Higgins 2011
Higgins JPT, Green S (editors). Cochrane Handbook for
Systematic Reviews of Interventions Version 5.1.0 [updated
March 2011]. The Cochrane Collaboration, 2011. Available from
www.cochrane-handbook.org.
Jin Park 2007
Jin Park Y, Woo Jo Y, Bang SI, Kim HJ, Lim SY, Mun GH, et
al. Radiofrequency volumetric reduction for masseteric
hypertrophy. Aesthetic Plastic Surgery 2007;31(1):42-52.
Kim 2000
Kim HJ, Jeon BS, Lee KW. Hemimasticatory spasm associated
with localized scleroderma and facial hemiatrophy. Archives of
Neurology 2000;57(4):576-80.
Kitagawa 2000
Kitagawa Y, Hashimoto K, Kuriyama M. Hypertrophic branchial
myopathy with uniform predominance of type 1 fibres. Case
report. Scandinavian Journal of Plastic and Reconstructive
Surgery and Hand Surgery 2000;34(4):391-6.
Legg 1880
Legg JW. Enlargement of the temporal and masseter muscles
on both sides. Transactions of the Pathological Society of London
1880;31:361-6.
Newton 1999
Newton JP, Cowpe JG, McClure IJ, Delday MI, Maltin CA.
Masseteric hypertrophy?: preliminary report. British Journal of
Oral and Maxillofacial Surgery 1999;37(5):405-8.
Cochrane Database of Systematic Reviews
Nishida 1995
Nishida M, Iizuka T. Intraoral removal of the enlarged
mandibular angle associated with masseteric hypertrophy.
Journal of Oral Maxillofacial Surgery 1995;53(12):1476-9.
Papapetropoulos 2006
Papapetropoulos S, Singer C. Eating dysfunction associated
with oromandibular dystonia: clinical characteristics and
treatment considerations. Head and Face Medicine 2006;7(2):47.
RevMan 2012 [Computer program]
The Nordic Cochrane Centre, The Cochrane Collaboration.
Review Manager (RevMan). Version 5.2. Copenhagen: The
Nordic Cochrane Centre, The Cochrane Collaboration, 2012.
Sannomya 2006
Sannomya EK, Gonçalves M, Cavalcanti MP. Masseter
muscle hypertrophy: case report. Brazilian Dental Journal
2006;17(4):347-50.
Satoh 2001
Satoh K, Yamaguchi T, Komatsu K, Inoue N, Minowa K,
Kanayama T, et al. Analyses of muscular activity, energy
metabolism, and muscle fiber type composition in a
patient with bilateral masseteric hypertrophy. Cranio
2001;19(4):294-301.
Serrat 1998
Serrat A, Garcia-Cantera JM, Redondo LM. Isolated unilateral
temporalis muscle hypertrophy. A case report. International
Journal of Oral Maxillofacial Surgery 1998;27(2):92-3.
Skoura 2001
Skoura C, Mourouzis C, Saranteas T, Chatzigianni E,
Tesseromatis C. Masseteric hypertrophy associated with
administration of anabolic steroids and unilateral mastication:
a case report. Oral Surgery, Oral Medicine, Oral Pathology, Oral
Radiology and Endodontics 2001;92(5):515-8.
Wilson 1990
Wilson PS, Brown AM. Unilateral temporalis muscle
hypertrophy: Case report. International Journal of Oral
Maxillofacial Surgery 1990;19(5):287-8.
References to other published versions of this review
Al-Muharraqi 2009
Al-Muharraqi MA, Fedorowicz Z, Al Bareeq J, Al Bareeq R,
Nasser M. Botulinum toxin for masseter hypertrophy.
Cochrane Database of Systematic Reviews 2009, Issue 1. [DOI:
10.1002/14651858.CD007510.pub2]
CHARACTERISTICS OF STUDIES
Characteristics of excluded studies [ordered by study ID]
Botulinum toxin for masseter hypertrophy (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Study
Reason for exclusion
Ahn 2007
Non relevant study design
Bhogal 2006
Review with no additional studies with the relevant study design
Castro 2005
Non relevant study design
Chikani 2003
Characteristics of participants do not match our inclusion criteria
Choe 2005
Non relevant study design
Collier 2009
No control group
Hui 2002
Letter, no relevant studies
Işeri 2004
Case study with no additional references to studies with the relevant study design
Jin 2010
Not placebo-controlled
Kane 2007
Comment on Yu 2007
Kaynar 1997
No control group
Kim 2003
Single intervention no control group
Lee 2007
Non relevant study design
Mischkowski 2005
Case series in German (translated by Mona Nasser)
Moore 1994
N of 1 study and results not generalisable
Niamtu 1999
Review, no additional studies with the relevant study design
Park 2003
No control group
Rogers 1995
Letter commenting on: Rocco R et al. Masseter hypertrophy: report of case and literature review.
Journal of Oral and Maxillofacial Surgery 1994 52(11):1199-202. No further studies matching the inclusion criteria
Smyth 1994
Non relevant study design
To 2001
Non relevant study design
von Lindern 2001
Non relevant study design
von Lindern 2003
No participants with masseter hypertrophy
Yu 2007
Non relevant study design
Botulinum toxin for masseter hypertrophy (Review)
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APPENDICES
Appendix 1. MEDLINE (via PubMed) search strategy
("masseter"[all fields] OR masseter*[all fields] OR (("masseter"[all fields] OR masseter*[all fields] OR "Masseter muscle"[mesh] OR
"Mandible"[mesh] OR "Facial Muscles"[mesh] OR masset*[all fields] OR "Masseter"[all fields] OR (("Face"[mesh] OR "face"[all fields]
OR "facial"[all fields]) AND ("Muscles"[mesh] OR "muscle"[all fields] OR "muscles"[all fields] OR Muscle*[all fields])) OR (Masseter* AND
Muscle*) OR Mandibl*[all fields] OR Myofac*[all fields]) AND ("Hypertrophy"[mesh] OR hypertrop*[all fields] OR enlarge*[all fields] OR
thick*[all fields])) OR "Myofascial Pain Syndromes"[Mesh]) AND ("Botulinum Toxins"[mesh] OR (Botul*[all fields] AND toxi*[all fields])
OR (Botul*[all fields] AND inject*[all fields]) OR "Botulinum"[all fields] OR Botulin*[all fields] OR "botox"[all fields] OR botox*[all fields]
OR "onabotulinumtoxinA"[Supplementary Concept] OR (("neurotoxins"[MeSH Terms] OR "neurotoxins"[all fields] OR "neurotoxin"[all
fields] OR "neurotoxins"[Pharmacological Action] OR neurotoxin*[all fields]) AND ("Clostridium"[mesh] OR "clostridium"[all fields] OR
Clostrid*[all fields])) OR "botulinal toxin"[all fields] OR "botulinium" OR botulinum OR "botulism toxin"[all fields] OR "botulism toxins"
OR "abobotulinumtoxin"[all fields] OR "azzalure"[all fields] OR "bocouture"[all fields] OR "BoNT A"[all fields] OR "BoNT serotype A"[all
fields] OR "botox" OR botox* OR "botulin A"[all fields] OR "botulin toxin a"[all fields] OR "BTXA"[all fields] OR "dysport"[all fields]
OR evabotulinum*[all fields] OR "incobotulinum"[all fields] OR incobotulin*[all fields] OR "nt 201"[all fields] OR "nt201"[all fields]
OR "oculinum"[all fields] OR "onabotulinum"[all fields] OR onabotulin*[all fields] OR "prosigne"[all fields] OR "reloxin"[all fields] OR
"vistabel"[all fields] OR "xeomin"[all fields] OR "BoNT B"[all fields] OR "myobloc"[all fields] OR "myoblock"[all fields] OR "neurobloc"[all
fields] OR rimabotulin*[all fields] OR "BoNT F"[all fields] OR "BoNT serotype F"[all fields] OR "BoNTF"[all fields] OR "exoenzyme C3"[all
fields] OR "bacterial toxin C3"[all fields] OR "dyslor"[all fields] OR "evabotulinum"[all fields] OR "onaclostox"[all fields] OR "purtox"[all
fields] OR "vistabex"[all fields] OR "rimabotulinum"[all fields])
((((Masseter muscle [mh]) OR Mandible [mh] OR (Facial Muscles [mh]) OR masset*) OR (((Face OR Facial) AND Muscle*) OR (Masseter* AND
Muscle*) OR Mandibl* OR (Myofac*))) AND (Hypertrophy [mh] OR hypertrop* OR enlarge* OR thick*) OR (Myofascial Pain Syndromes [Mesh]))
AND ((Botulinum Toxins [mh]) OR (Botul* AND toxi*) OR (Botul* AND inject*))
Appendix 2. EMBASE (via embase.com) search strategy
(masseter muscle/ OR masseter*.af OR (myofascial pain/ AND hypertrop*.af) OR ((exp hypertrophy/ OR hypertrop*.af OR enlarge*.af OR
thick*.af ) AND ((exp face/ OR facial.af OR face.af) AND muscle*.af) OR (masseter* AND muscle*).af OR mandibl*.af OR myofac*.af)) AND
(botulinum toxin/ OR botulinum toxin A/ OR botulinum toxin B/ OR botulinum toxin E/ OR botulinum toxin F/ OR ("botulinal toxin" OR
"botulinium" OR botulinum OR "botulism toxin" OR "botulism toxins" OR "abobotulinumtoxin" OR "azzalure" OR "bocouture" OR "BoNT
A" OR "BoNT serotype A" OR "botox" OR botox* OR "botulin A" OR "botulin toxin a" OR "BTXA" OR "dyslor" OR "dysport" OR "evabotulinum"
OR evabotulinum* OR "incobotulinum" OR incobotulin* OR "nt 201" OR "nt201" OR "oculinum" OR "onabotulinum" OR onabotulin* OR
"onaclostox" OR "prosigne" OR "purtox" OR "reloxin" OR "vistabel" OR "vistabex" OR "xeomin" OR "BoNT B" OR "myobloc" OR "myoblock"
OR "neurobloc" OR "rimabotulinum" OR rimabotulin* OR "BoNT F" OR "BoNT serotype F" OR "BoNTF" OR "exoenzyme C3" OR "bacterial
toxin C3").af OR (botul* AND (toxi* OR inject*)).af)
Appendix 3. Web of Science search strategy
TS=((*masseter* OR ("myofascial pain" AND hypertrop*) OR ((hypertrop* OR enlarge* OR thick*) AND ((facial OR face) AND muscle*) OR
(masseter* AND muscle*) OR mandibl* OR myofac*)) AND (*botulin* OR botulinum toxin OR botulinum toxin A OR botulinum toxin B OR
botulinum toxin E OR botulinum toxin F OR "botulinal toxin" OR "botulinium" OR botulinum OR "botulism toxin" OR "botulism toxins" OR
"abobotulinumtoxin" OR "azzalure" OR "bocouture" OR "BoNT A" OR "BoNT serotype A" OR "botox" OR botox* OR "botulin A" OR "botulin
toxin a" OR "BTXA" OR "dyslor" OR "dysport" OR "evabotulinum" OR evabotulinum* OR "incobotulinum" OR incobotulin* OR "nt 201" OR
"nt201" OR "oculinum" OR "onabotulinum" OR onabotulin* OR "onaclostox" OR "prosigne" OR "purtox" OR "reloxin" OR "vistabel" OR
"vistabex" OR "xeomin" OR "BoNT B" OR "myobloc" OR "myoblock" OR "neurobloc" OR "rimabotulinum" OR rimabotulin* OR "BoNT F"
OR "BoNT serotype F" OR "BoNTF" OR "exoenzyme C3" OR "bacterial toxin C3" OR (botul* AND (toxi* OR inject*))))
Plus citations to Cochrane Review and citations from Cochrane Review.
Appendix 4. CENTRAL search strategy
((masseter* OR ("myofascial pain" AND hypertrop*) OR ((hypertrop* OR enlarge* OR thick*) AND ((facial OR face) AND muscle*) OR
(masseter* AND muscle*) OR mandibl* OR myofac*)) AND (botulin* OR botulinum toxin OR botulinum toxin A OR botulinum toxin B OR
botulinum toxin E OR botulinum toxin F OR "botulinal toxin" OR "botulinium" OR botulinum OR "botulism toxin" OR "botulism toxins" OR
"abobotulinumtoxin" OR "azzalure" OR "bocouture" OR "BoNT A" OR "BoNT serotype A" OR "botox" OR botox* OR "botulin A" OR "botulin
toxin a" OR "BTXA" OR "dyslor" OR "dysport" OR "evabotulinum" OR evabotulinum* OR "incobotulinum" OR incobotulin* OR "nt 201" OR
"nt201" OR "oculinum" OR "onabotulinum" OR onabotulin* OR "onaclostox" OR "prosigne" OR "purtox" OR "reloxin" OR "vistabel" OR
"vistabex" OR "xeomin" OR "BoNT B" OR "myobloc" OR "myoblock" OR "neurobloc" OR "rimabotulinum" OR rimabotulin* OR "BoNT F"
OR "BoNT serotype F" OR "BoNTF" OR "exoenzyme C3" OR "bacterial toxin C3" OR (botul* AND (toxi* OR inject*))))
Appendix 5. CINAHL (via EbscoHost) search strategy
In fields: ti/ab/kw
Botulinum toxin for masseter hypertrophy (Review)
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((masseter* OR ("myofascial pain" AND hypertrop*) OR ((hypertrop* OR enlarge* OR thick*) AND ((facial OR face) AND muscle*) OR
(masseter* AND muscle*) OR mandibl* OR myofac*)) AND (botulin* OR botulinum toxin OR botulinum toxin A OR botulinum toxin B OR
botulinum toxin E OR botulinum toxin F OR "botulinal toxin" OR "botulinium" OR botulinum OR "botulism toxin" OR "botulism toxins" OR
"abobotulinumtoxin" OR "azzalure" OR "bocouture" OR "BoNT A" OR "BoNT serotype A" OR "botox" OR botox* OR "botulin A" OR "botulin
toxin a" OR "BTXA" OR "dyslor" OR "dysport" OR "evabotulinum" OR evabotulinum* OR "incobotulinum" OR incobotulin* OR "nt 201" OR
"nt201" OR "oculinum" OR "onabotulinum" OR onabotulin* OR "onaclostox" OR "prosigne" OR "purtox" OR "reloxin" OR "vistabel" OR
"vistabex" OR "xeomin" OR "BoNT B" OR "myobloc" OR "myoblock" OR "neurobloc" OR "rimabotulinum" OR rimabotulin* OR "BoNT F"
OR "BoNT serotype F" OR "BoNTF" OR "exoenzyme C3" OR "bacterial toxin C3" OR (botul* AND (toxi* OR inject*))))
Appendix 6. Academic Search Premier (via EbscoHost) search strategy
In fields: ti/ab/kw/su
((masseter* OR ("myofascial pain" AND hypertrop*) OR ((hypertrop* OR enlarge* OR thick*) AND ((facial OR face) AND muscle*) OR
(masseter* AND muscle*) OR mandibl* OR myofac*)) AND (botulin* OR botulinum toxin OR botulinum toxin A OR botulinum toxin B OR
botulinum toxin E OR botulinum toxin F OR "botulinal toxin" OR "botulinium" OR botulinum OR "botulism toxin" OR "botulism toxins" OR
"abobotulinumtoxin" OR "azzalure" OR "bocouture" OR "BoNT A" OR "BoNT serotype A" OR "botox" OR botox* OR "botulin A" OR "botulin
toxin a" OR "BTXA" OR "dyslor" OR "dysport" OR "evabotulinum" OR evabotulinum* OR "incobotulinum" OR incobotulin* OR "nt 201" OR
"nt201" OR "oculinum" OR "onabotulinum" OR onabotulin* OR "onaclostox" OR "prosigne" OR "purtox" OR "reloxin" OR "vistabel" OR
"vistabex" OR "xeomin" OR "BoNT B" OR "myobloc" OR "myoblock" OR "neurobloc" OR "rimabotulinum" OR rimabotulin* OR "BoNT F"
OR "BoNT serotype F" OR "BoNTF" OR "exoenzyme C3" OR "bacterial toxin C3" OR (botul* AND (toxi* OR inject*))))
Appendix 7. ScienceDirect search strategy
TITLE-ABSTR-KEY(((masseter* OR ("myofascial pain" AND hypertrop*) OR ((hypertrop* OR enlarge* OR thick*) AND ((facial OR face) AND
muscle*) OR (masseter* AND muscle*) OR mandibl* OR myofac*)) AND (botulin* OR botulinum toxin OR botulinum toxin A OR botulinum
toxin B OR botulinum toxin E OR botulinum toxin F OR "botulinal toxin" OR "botulinium" OR botulinum OR "botulism toxin" OR "botulism
toxins" OR "abobotulinumtoxin" OR "azzalure" OR "bocouture" OR "BoNT A" OR "BoNT serotype A" OR "botox" OR botox* OR "botulin
A" OR "botulin toxin a" OR "BTXA" OR "dyslor" OR "dysport" OR "evabotulinum" OR evabotulinum* OR "incobotulinum" OR incobotulin*
OR "nt 201" OR "nt201" OR "oculinum" OR "onabotulinum" OR onabotulin* OR "onaclostox" OR "prosigne" OR "purtox" OR "reloxin" OR
"vistabel" OR "vistabex" OR "xeomin" OR "BoNT B" OR "myobloc" OR "myoblock" OR "neurobloc" OR "rimabotulinum" OR rimabotulin*
OR "BoNT F" OR "BoNT serotype F" OR "BoNTF" OR "exoenzyme C3" OR "bacterial toxin C3" OR (botul* AND (toxi* OR inject*)))))
Appendix 8. LILACS (via Bireme) search strategy
masseter AND botulinum
Appendix 9. PubMed Central search strategy
masseter* AND (hypertrop* OR enlarge* OR thick*) AND (botulin* OR botulinum toxin OR botulinum toxin A OR botulinum toxin B OR
botulinum toxin E OR botulinum toxin F OR "botulinal toxin" OR "botulinium" OR botulinum OR "botulism toxin" OR "botulism toxins" OR
"abobotulinumtoxin" OR "azzalure" OR "bocouture" OR "BoNT A" OR "BoNT serotype A" OR "botox" OR botox* OR "botulin A" OR "botulin
toxin a" OR "BTXA" OR "dyslor" OR "dysport" OR "evabotulinum" OR evabotulinum* OR "incobotulinum" OR incobotulin* OR "nt 201" OR
"nt201" OR "oculinum" OR "onabotulinum" OR onabotulin* OR "onaclostox" OR "prosigne" OR "purtox" OR "reloxin" OR "vistabel" OR
"vistabex" OR "xeomin" OR "BoNT B" OR "myobloc" OR "myoblock" OR "neurobloc" OR "rimabotulinum" OR rimabotulin* OR "BoNT F"
OR "BoNT serotype F" OR "BoNTF" OR "exoenzyme C3" OR "bacterial toxin C3") AND (randomized OR randomised OR random OR RCT OR
RCTS OR trial OR trials OR placebo OR placebos OR compared OR comparison OR versus)
Appendix 10. Google Scholar search strategy
allintitle:masseter allintitle:botulinum
Plus: citations to Cochrane Review
WHAT'S NEW
Date
Event
Description
26 April 2013
New citation required but conclusions
have not changed
New authors added
26 April 2013
New search has been performed
Search strategy updated
Searches updated
Botulinum toxin for masseter hypertrophy (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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CONTRIBUTIONS OF AUTHORS
Zbys Fedorowicz (ZF), Esther van Zuuren (EvZ), Jan Schoones (JS) were responsible for:
Conducting all the searches for this update (JS)
•
•
•
•
•
•
•
•
organising the retrieval of papers;
writing to authors of papers for additional information;
screening search results;
screening retrieved papers against inclusion criteria;
appraising the quality of papers;
data collection for the review;
extracting data from papers; and
obtaining and screening data on unpublished studies.
ZF and EvZ were responsible for entering any extracted data into RevMan.
ZF and EvZ were responsible for the analysis and interpretation of data.
ZF was responsible for:
• designing the review;
• co-ordinating the review;and
• data management for the review.
All review authors contributed to writing the review.
ZF conceived the idea for the review and is the guarantor for the review.
DECLARATIONS OF INTEREST
There are no financial conflicts of interest and the authors declare that they do not have any associations with any parties who may have
vested interests in the results of this review.
SOURCES OF SUPPORT
Internal sources
• No sources of support, Netherlands.
External sources
• No sources of support, Netherlands.
DIFFERENCES BETWEEN PROTOCOL AND REVIEW
We added Adverse outcomes under 'Types of outcome measures'.
INDEX TERMS
Medical Subject Headings (MeSH)
Botulinum Toxins, Type A [*therapeutic use]; Hypertrophy [drug therapy]; Injections, Intramuscular; Masseter Muscle [*pathology];
Neuromuscular Agents [*therapeutic use]
MeSH check words
Humans
Botulinum toxin for masseter hypertrophy (Review)
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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