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Systematic review

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Effect of botulinum toxin type A on muscular temporomandibular disorder: A systematic review and meta-analysis of randomized controlled trials.

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Authors Li K , Tan K , Yacovelli A , Bi WG
Journal Journal of oral rehabilitation
Year 2023
Links Pubmed DOI

This article includes 19 Primary studies 15 Primary studies (19 references)

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BACKGROUND: Botulinum toxin type A (BTX-A) is increasingly used to manage painful temporomandibular disorders (TMD). However, the effect of BTX-A on muscular TMD remains unclear. OBJECTIVE: To assess the efficacy, safety and optimal dose of BTX-A for treating TMD. METHODS: We conducted systematic literature searches in MEDLINE, Embase, Web of Science, ClinicalTrials.gov and Cochrane Library until March 2023. We extracted data from randomized controlled trials (RCTs) that evaluated the efficacy and safety of BTX-A in treating muscular TMD. We performed a meta-analysis using a random-effects model. RESULTS: Fifteen RCTs involving 504 participants met the inclusion criteria. BTX-A was significantly more effective than placebo in reducing pain intensity, as measured on a 0-10 scale, at 1 month (MD [95% CI] = -1.92 [-2.87, -0.98], p < .0001) and 6 months (MD [95% CI] -2.08, [-3.19 to -0.98]; p = .0002). A higher dosage of BTX-A (60-100 U bilaterally) was associated with a greater reduction in pain at 6 months (MD [95% CI] = -2.98 [-3.52, -2.44]; p < .001). BTX-A also resulted in decreased masseter muscle intensity (μV) (MD [95% CI] = -44.43 [-71.33, -17.53]; p = .001) at 1 month and occlusal force (kg) at 3 months (MD [95% CI] = -30.29 [-48.22 to -12.37]; p = .0009). There was no significant difference in adverse events between BTX-A and placebo. CONCLUSIONS: BTX-A is a safe and effective treatment for reducing pain and improving temporomandibular muscle and joint function in muscular TMD patients. A bilateral dose of 60-100 U might be an optimal choice for treating muscular TMD pain.

Systematic review

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Botulinum Toxin for Treating Temporomandibular Disorders: What is the Evidence?

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Journal Journal of oral & facial pain and headache
Year 2022
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This article includes 24 Primary studies 24 Primary studies (24 references)

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AIMS: To systematically review the scientific literature for evidence concerning the clinical use of botulinum toxin (BTX) for the management of various temporomandibular disorders (TMDs). METHODS: A comprehensive literature search was conducted in the Medline, Web of Science, and Cochrane Library databases to find randomized clinical trials (RCT) published between 2000 and the end of April 2021 investigating the use of BTX to treat TMDs. The selected articles were reviewed and tabulated according to the PICO (patients/problem/population, intervention, comparison, outcome) format. RESULTS: A total of 24 RCTs were selected. Nine articles used BTX injections to treat myofascial pain, 4 to treat temporomandibular joint (TMJ) articular TMDs, 8 for the management of bruxism, and 3 to treat masseter hypertrophy. A total of 411 patients were treated by injection of BTX. Wide variability was found in the methods of injection and in the doses injected. Many trials concluded superiority of BTX injections over placebo for reducing TMD pain levels and improving maximum mouth opening; however, this was not universal. CONCLUSION: There is good scientific evidence to support the use of BTX injections for treatment of masseter hypertrophy and equivocal evidence for myogenous TMDs, but very little for TMJ articular disorders. Studies with improved methodologic design are needed to gain better insight into the utility and effectiveness of BTX injections for treating both myogenous and TMJ articular TMDs and to establish suitable protocols for treating different TMDs.

Systematic review

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Clinical efficacy of local injection therapies for lateral epicondylitis: A systematic review and network meta-analysis.

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Journal Caspian journal of internal medicine
Year 2022
Links Pubmed DOI PubMed Central

This article includes 31 Primary studies 31 Primary studies (31 references)

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BACKGROUND: We aimed to compare the efficacy of local injection therapies for lateral epicondylitis in a Bayesian framework. METHODS: We searched the Embase, PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, and ProQuest, for randomized controlled trials published from inception to February 2021 in any languages. The injection therapies included corticosteroids (CSs), autologous blood (AB), botulinum toxin (BT), and platelet-rich plasma (PRP). Placebo was the reference group for comparison. The study outcomes were pain, function, and strength, at 1, 3 and 6 months after injection. RESULTS: Thirty-one trials were finally included in this network meta-analysis, comprising 1,948 patients. In the first month of treatment, CS and BT were more efficacious than placebo in terms of pain reduction, and CS was superior to BT. In the same follow-up time, CS was also superior to placebo in terms of functional improvement. In the third month of treatment, BT was the only intervention that was more efficient than placebo in pain relief. With regard to functional improvement, none of the treatments significantly had a higher effectiveness than placebo in the same period. Moreover, no therapies were found to be more efficient than placebo in the sixth month of treatment in terms of any study outcomes. In addition, we did not identify an intervention superior to placebo regarding strength improvement outcome in any times of follow-up. CONCLUSION: CSs and BT are efficient in improving clinical outcomes of lateral epicondylitis in the short term. Also, the efficacy of CSs seems to be greater than BT. On the other hand, AB and PRP were not significantly more efficient than placebo in any times of follow-up.

Systematic review

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Efficacy of botulinum-A for nocturnal bruxism pain and the occurrence of bruxism events: A meta analysis and systematic review

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Journal British Journal of Oral and Maxillofacial Surgery
Year 2022
Links Pubmed DOI https://www.sciencedirect.com/science/article/pii/S0266435621001121

This article includes 6 Primary studies 6 Primary studies (6 references)

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PURPOSE: The purpose of this study is to explore the treatment efficacy of botulinum-A (BTX-A) in nocturnal bruxism. MATERIALS AND METHODS: Five electronic databases (PubMed, Web of Science, Cochrane, Embase and Clinical Trials) were searched to identify related randomized controlled trials through September 1, 2020. Five evaluation indexes were extracted, namely, the pain at rest and at chewing (PR and PC), the number of bruxism events (NBEs) and the self-assessment by patients (SA), to assess the treatment efficacy of BTX-A in bruxism. All data analyses were conducted using Review Manager (Version 5.3; The Cochrane Collaboration, London, United Kingdom). RESULT: Six studies were included in this review. The sample was composed of 148 participants. Compared with the placebo group, the BTX-A group showed the significantly improved the PR index scores (MD, 1.16 cm; 95%CI, 0.65 to 1.67 cm; P < 0.00001), slightly improved the PC index scores (SMD, 0.25; 95%CI -0.14 to 0.64; P = 0.21), and the NBEs were significantly decreased in the before-injection group compared with that in the after-injection group (MD, 1.72; 95%CI, 0.60 to 2.85; P = 0.003). CONCLUSIONS: The results of this study suggest that BTX-A possesses significant therapeutic efficiency for the relief of pain and events of bruxism. However, whether the events of bruxism would recur or rebound after botulinum toxin injection needs more follow-up clinical evidence.

Systematic review

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Clinical outcomes of botulinum toxin type A injections in the management of primary bruxism in adults: A systematic review.

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Journal The Journal of prosthetic dentistry
Year 2021
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This article includes 10 Primary studies 10 Primary studies (10 references)

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STATEMENT OF PROBLEM: Botulinum toxin has been used for various therapeutic and esthetic purposes for nearly 4 decades and has shown positive outcomes in patients with bruxism. However, the effectiveness of botulinum toxin injections as an alternative to traditional therapies in the management of primary bruxism is still unclear. PURPOSE: The purpose of this systematic review was to analyze the clinical outcomes of the use of botulinum toxin type A injections in the management of primary bruxism in adults. MATERIAL AND METHODS: Databases such as PubMed, Web of Science, Scopus, LILIACS, Cochrane Library, and Open Grey Literature were searched without language or date restrictions until October 6, 2019. Using Mendeley Desktop software to organize the references, 2 independent researchers selected the published clinical studies (Study type) on the improvement of symptoms (Outcome) in human adults with primary bruxism (Participants/Population) who received botulinum toxin type A injections (Intervention), placebo injections, saline injections, no injections, or other treatments (Comparator(s)/Control) for the management of bruxism. RESULTS: A total of 601 references were initially obtained from the 6 databases. Six randomized clinical trials and 4 case series were selected and critically appraised according to the Fowkes and Fulton guidelines. Heterogeneity among the studies did not allow for a meta-analysis. All studies supported the efficacy and safety of botulinum toxin injections in reducing the symptoms of primary bruxism. CONCLUSIONS: Botulinum toxin type A injections are effective in the treatment of the symptoms of primary bruxism in adults. Randomized clinical trials are still needed to establish a protocol for using botulinum toxin as an alternative to traditional therapies in the management of primary bruxism.

Systematic review

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The effect of botulinum toxin injections on bruxism: A systematic review.

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Authors Ågren M , Sahin C , Pettersson M
Journal Journal of oral rehabilitation
Year 2020
Links Pubmed DOI

This article includes 4 Primary studies 4 Primary studies (4 references)

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Botulinum neurotoxins are produced by the gram-positive anaerobic bacteria Clostridium botulinum, of which several different serotypes have been identified 1,2 . Botulinum neurotoxin type A (BTA) is clinically used the most due to the longer duration of its effect 3,4 and is the focus of this article. One of the first to investigate BTA was Brooks, as he in 1953, showed that when injecting BTA in muscle tissue it inhibited the release of Acetylcholine (ACh) at the neuromuscular junction and rendered motor nerve filaments unexcitable 3 . It has since been shown that BTA inhibits synaptosomal nerve-associated protein 25 (SNAP-25), a protein involved in the release of ACh filled vesicles into the synaptic cleft through the assembly of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors (SNARE) complex, which is necessary for docking and fusing neurotransmitter vesicles with neuronal membranes.

Systematic review

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Botulinum neurotoxin injections for muscle-based (dystonia and spasticity) and non-muscle-based (neuropathic pain) pain disorders: a meta-analytic study.

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Journal Journal of neural transmission (Vienna, Austria : 1996)
Year 2020
Links Pubmed DOI www.epistemonikos.org

This article includes 25 Primary studies 25 Primary studies (25 references)

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Apart from the known efficacy of Botulinum Neurotoxin Type A (BoNT/A) in hyperactive striated and smooth muscles, different pain states have become potential targets of toxin effects. This present study determined the comparative toxin effectiveness in pain reduction among those patients injected with BoNT/A in muscle-based and in non-muscle-based conditions. Randomized controlled trials (RCTs) on the effect of BoNT/A on selected pain conditions were included. The conditions were spasticity and dystonia for muscle-based pain. For non-muscle-based pain, conditions included were painful diabetic neuropathy (PDN), post-herpetic neuralgia (PHN), trigeminal neuralgia (TN), complex regional pain syndrome (CRPS), and spinal cord injury (SCI). In view of possibly differing pathophysiology, myofascial pain, temporomandibular joint (TMJ), other joint or tendon pains, cervicogenic and lumbar pains, migraine and visceral pain syndromes were excluded. Standardized mean difference was used as the effect measure and computed with STATA. 25 RCTs were analyzed. Pooled estimates showed significantly lower pain score in the Treatment group (z = 5.23, p < 0.01, 95% CI = - 0.75, - 0.34). Subgroup analyses showed that BoNT/A significantly reduced both muscle-based (z = 3.78, p < 0.01, 95% CI = - 0.72, - 0.23) and non-muscle-based (z = 3.37, p = 0.001, 95% CI = - 1.00, - 0.27) pain. Meta-regression using four covariates namely dosage, route, frequency and duration was done which revealed that dosage significantly affects standardized mean differences, while the other three covariates were insignificant. The joint F-test was found to be insignificant (p value = 0.1182). The application of the model with these covariates does not significantly explain the derived heterogeneity of standardized mean differences. In conclusion, BoNT/A can be effectively used in muscle-based and non-muscle-based pain disorders. We detected no difference between the presence and magnitude of pain relief favoring muscle-based compared to non-muscle-based pain. Thus, we cannot say whether or not there might be independent mechanisms of toxin-induced pain relief for pain generated from either muscle or nerve hyperactivity.

Systematic review

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Botulinum toxin in the management of temporomandibular disorders: a systematic review

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Journal Br. J. Oral Maxillofac. Surg.
Year 2020
Links Pubmed DOI

This article includes 7 Primary studies 7 Primary studies (7 references)

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The aim of this review was to critically investigate and assess the evidence relating to the use and efficacy of botulinum toxin (BTX) in the management of temporomandibular joint disorders (TMD) and masticatory myofascial pain. A comprehensive search was conducted of PubMed, Scopus, Embase, and Cochrane CENTRAL, to find relevant studies from the last 30 years up to the end of July 2018. Seven were identified. Three showed a significant reduction in pain between the BTX and placebo groups and one showed a clinical, but not a significant, difference. In one that compared BTX with another novel treatment, myofascial pain reduced equally in both groups, and in the remaining two there was no significant difference in pain reduction between the BTX and control groups. Of the four studies that assessed mouth opening, two reported that BTX had resulted in a slight improvement; one reported no improvement, and the other a worsening of the condition. A meta-analysis was not possible because of the considerable variation in the studies' designs, the heterogeneity between the groups, and the different assessment tools used. Despite showing benefits, consensus on the therapeutic benefit of BTX in the management of myofascial TMD is lacking. Further randomised controlled trials with larger sample sizes, minimal bias, and longer follow-up periods are now needed.

Systematic review

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Botulinum toxin type A for painful temporomandibular disorders: systematic review and meta-analysis.

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Journal The journal of pain : official journal of the American Pain Society
Year 2020
Links Pubmed DOI

This article includes 6 Primary studies 6 Primary studies (6 references)

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This systematic review investigated the effectiveness and safety of botulinum toxin type A (BTX-A) for painful temporomandibular disorders. We searched for randomized controlled trials (RCTs) in ten databases, from inception to February 12, 2019 (MEDLINE, EMBASE, CENTRAL, LILACS, BBO, Web of Science, Scopus, ClinicalTrials.gov, WHO and OpenGrey). We included 12 RCTs that compared BTX-A versus inactive or active interventions. BTX-A was slightly more effective than placebo for pain reduction at one month: mean difference (MD) -1.74 points (0 to 10 scale), 95% confidence interval (CI) -2.94 to -0.54, 3 RCTs, 60 participants, I-square (I2) = 0%. However, there were no significant differences at three and six months. BTX-A was similar to no treatment for pain reduction at three and six months. BTX-A was more effective than conventional treatment and low level laser therapy for pain reduction at one, six and 12 months, but less effective than facial manipulation for pain reduction at three months. BTX-A was not associated with a significant increase in the risk of adverse events. The quality of the evidence was low and results are insufficient to support the use of BTX-A for painful temporomandibular disorders. High quality RCTs are needed to increase confidence in effect estimates. PERSPECTIVE: BTX-A for painful temporomandibular disorders appears to be well tolerated. For pain reduction, BTX-A is slightly more effective than placebo only at one month; conventional treatment and low-level laser at one, six and 12 months. Low quality evidence limits the applicability of these findings and precludes recommendations for practice.

Systematic review

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Needling therapies in the management of myofascial pain of the masticatory muscles: a network meta-analysis of randomized clinical trials.

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Journal Journal of oral rehabilitation
Year 2020
Links Pubmed DOI

This article includes 20 Primary studies 20 Primary studies (20 references)

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OBJECTIVE: A network meta-analysis (NMA) of randomized clinical trials (RCTs) was performed aiming to compare the treatment outcome of dry needling, acupuncture, or wet needling using different substances in managing myofascial pain of the masticatory muscles (TMD-M). METHOD: An electronic search was undertaken to identify RCTs published until September 2019, comparing dry needling, acupuncture, or wet needling using local anaesthesia (LA), botulinum toxin-A (BTX-A), granisetron, platelet-rich plasma (PRP) or passive placebo versus real active placebo in patients with TMD-M. RCTs meeting the inclusion criteria were stratified according to the follow-up time; immediate post-treatment to 3 weeks, and one to 6 months post-treatment. Outcome variables were post-treatment pain intensity, increased mouth opening (MMO) and pressure threshold pain (PPT). The quality of evidence was rated according to Cochrane's tool for assessing risk of bias. Mean difference (MD) was used to analyzed via frequentist NMA using STATA software. RESULTS: Twenty-two RCTs involving 959 patients were included. The quality of evidence of the included studies was low or very low. There was significant pain decrease after PRP when compared to an active/passive placebo and acupuncture. There was a significant improvement of MMO after LA (MD=3.65; CI: 1.18-6.1) and dry needling therapy (MD= 2.37; CI: 0.66-4) versus placebo. The three highest-ranked treatments for short-term post-treatment pain reduction in TMD-M (1 to 20 days) were PRP (95.8%), followed by LA (62.5%), and dry needling (57.1%), whereas the three highest-ranked treatments at intermediate-term follow-up (1 to 6 months) were LA (90.2%), dry needling (66.1%), and BTX-A (52.1%) (all very low quality evidence). LA (96.4%) was the most effective treatment regarding the increase of MMO followed by dry needling (72.4%). CONCLUSION: Based on this NMA, one can conclude that the effectiveness of needling therapy did not depend on needling type (dry or wet) or needling substance. The outcome this NMA suggests that LA, BTX-A, granisetron and PRP hold some promise as injection therapies, but no definite conclusions can be drawn due to the low-quality of evidence of the included studies. This NMA did not provide enough support for any of the needling therapies for TMD-M.