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de Almeida et al. | Journal of Clinical and Translational Research 2024; 10(4): 237-245 239
collected information. A careful analysis was performed to check most effective medication in relieving short-[15,16,18] and
for disagreements between the authors. Any disagreements long-term [5,9] symptoms, either topically or systemically.
were resolved through discussion with a third author (J.S.V.) Glenny’s scale and AMSTAR 2 were used to assess the
until a consensus was reached. The Cohen’s Kappa coefficient methodological quality of the included studies. AMSTAR 2 is
indicated an intra-examiner agreement of 0.92 and an inter- a significant revision of the original AMSTAR tool [22], rating
examiner agreement of 0.90. overall confidence in the review results as high, moderate, low,
and critically low. The reliability index of the included studies
2.5. Quality assessment of the studies was high for two studies [17,20] and critically low for six
The methodological quality of the included systematic studies [5,9,15,16,18,19]. Two studies were considered to have
reviews was analyzed using the Assessment of Multiple moderate quality of evidence (based on GRADE) [17,20].
Systematic Reviews (AMSTAR 2) tool [22]. This tool consists The score range for Glenny’s scale [23] was between 9 and
of 16 questions that analyze the methodology of systematic 15 (moderate to high quality); Item 4 of Glenny’s scale did not
reviews of randomized and non-randomized studies, with apply to any of the studies (Table 3). It should be noted that
responses categorized as “Yes,” “Partial Yes,” or “No.” A some revisions did not clarify if two reviewers conducted the
systematic review is considered well done when all items on the article peer review process. However, the selection of articles
checklist are answered with “Yes.” by at least two reviewers was addressed in subsequent studies.
Systematic reviews were designated as high-quality when The aspects that presented the most significant deficiency of
they have no weaknesses or non-critical weaknesses; moderate information were the search for published and unpublished
quality when the reviews have more weaknesses but no critical literature (item 4), the search in all languages (item 5), and the
flaws; low quality when the reviews have one critical flaw and assessment of heterogeneity and discussion of the reasons for
the variation (item 14) (Table 3).
may not provide an accurate and comprehensive summary of
available studies addressing the PICOT question; and critically 4. Discussion
low-quality when the reviews have more than one critical flaw
and should not be used to provide an accurate and comprehensive In this umbrella review, we aimed to evaluate the therapeutic
summary of the available studies. modalities for the relief of BMS symptoms. We found that
Glenny’s scale [23] was applied to analyze the included several treatment strategies could be effective in some groups of
studies. The scale consists of 15 items that assess the structure patients with BMS, such as clonazepam [5,9,15,16,18], α-lipoic
of the topics covered, formulation of the PICOT question, and acid [5,15,16,18], capsaicin [5,18], and psychotherapy [18], in
interpretation of the data. Scoring was performed as follows: addition to treatment with placebo [19,20].
each item with a “Yes” answer was assigned one point, and the The different treatments reflect the heterogeneity of the studies,
total score obtained can range from 0 – 15 points. A score of especially the methodology. Low sample size [16,18,19,20],
10 – 15 indicates high quality, 5 – 9 points indicates medium short follow-up [5,9], lack of comparison of several therapeutic
quality, and 0 – 4 points indicate low quality. agent arms with placebo [17,19,20], and high variability of the
To increase the ability to evaluate evidence and support scales used to assess pain reduction [5,9,15-20] are limitations
clinical recommendations more robustly, each study was found in the selected studies. These factors demonstrate
categorized based on the overall risk category and classified as heterogeneous methodologies that make it challenging to
low, unclear, or high risk. The quality of all included articles was compare the effects of interventions.
assessed based on Grading of Recommendations, Assessment, Through the data collected, we conclude that the topical
Development, and Evaluations (GRADE) [24]. use of clonazepam is a suitable and effective alternative for
relieving symptoms of BMS. This efficacy may be related to its
3. Results anxiolytic properties that potentiate the action of the inhibitory
γ-aminobutyric acid (GABA) neurotransmitter [25,26].
A total of 298 articles were found in the databases. After Systemic clonazepam induces central nervous system inhibition
duplicate studies were excluded, the titles and abstracts were due to its anticonvulsant action, leading to muscle relaxation,
reviewed to match the eligibility criteria. A total of 23 articles sedation, and tranquilization [25-27]. When used as a topical
were selected for full-text review, and eight studies were finally medication, clonazepam reduces BMS symptoms without
selected for analysis in this umbrella review. The reasons for causing the adverse effects associated with systemic use, such
exclusion from the studies are listed in Figure 1. as drowsiness, fatigue, and headache [27]. Besides that, among
The characteristics of the systematic reviews are described the current evidence, the psychological effects of BMS should
in Table 1. Results of the quality assessment of the systematic be considered during clinical management. In some studies, the
reviews (AMSTAR 2, GRADE, and Glenny’s scale) are comparison of medication and/or non-pharmacological therapy
described in Tables 2 and 3. between two groups revealed no difference compared to the use
Therapeutic modalities for the relief of BMS symptoms of placebo, with no influence on treatment results [17,19,20].
include the use of pharmacological (clonazepam) and non- Regarding non-pharmacological therapy, the use of herbal
pharmacological (psychotherapy and placebo) measures. medicines, such as 0.02% capsaicin, reduces the symptoms
Among all therapeutic managements, clonazepam was the of BMS and may be valuable in establishing treatment for the

DOI: http://doi.org/10.36922/jctr.24.00018