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The Cochrane Database of Systematic... Jan 2017Motor neuron disease (MND), which is also known as amyotrophic lateral sclerosis (ALS), causes a wide range of symptoms but the evidence base for the effectiveness of... (Review)
Review
BACKGROUND
Motor neuron disease (MND), which is also known as amyotrophic lateral sclerosis (ALS), causes a wide range of symptoms but the evidence base for the effectiveness of the symptomatic treatment therapies is limited.
OBJECTIVES
To summarise the evidence from Cochrane Systematic Reviews of all symptomatic treatments for MND.
METHODS
We searched the Cochrane Database of Systematic Reviews (CDSR) on 15 November 2016 for systematic reviews of symptomatic treatments for MND. We assessed the methodological quality of the included reviews using the Assessment of Multiple Systematic Reviews (AMSTAR) tool and the GRADE approach. We followed standard Cochrane study (review) selection and data extraction procedures. We reported findings narratively and in tables.
MAIN RESULTS
We included nine Cochrane Systematic Reviews of interventions to treat symptoms in people with MND. Three were empty reviews with no included randomised controlled trials (RCTs); however, all three reported on non-RCT evidence and the remaining six included mostly one or two studies. We deemed all of the included reviews of high methodological quality. Drug therapy for painThere is no RCT evidence in a Cochrane Systematic Review exploring the efficacy of drug therapy for pain in MND. Treatment for crampsThere is evidence (13 RCTs, N = 4012) that for the treatment of cramps in MND, compared to placebo:- memantine and tetrahydrocannabinol (THC) are probably ineffective (moderate-quality evidence);- vitamin E may have little or no effect (low-quality evidence); and- the effects of L-threonine, gabapentin, xaliproden, riluzole, and baclofen are uncertain as the evidence is either very low quality or the trial specified the outcome but did not report numerical data.The review reported adverse effects of riluzole, but it is not clear whether other interventions had adverse effects. Treatment for spasticityIt is uncertain whether an endurance-based exercise programme improved spasticity or quality of life, measured at three months after the programme, as the quality of evidence is very low (1 RCT, comparison "usual activities", N = 25). The review did not evaluate other approaches, such as use of baclofen as no RCTs were available. Mechanical ventilation for supporting respiratory functionNon-invasive ventilation (NIV) probably improves median survival and quality of life in people with respiratory insufficiency and normal to moderately impaired bulbar function compared to standard care, and improves quality of life but not survival for people with poor bulbar function (1 RCT, N = 41, moderate-quality evidence; a second RCT did not provide data). The review did not evaluate other approaches such as tracheostomy-assisted ('invasive') ventilation, or assess timing of NIV initiation. Treatment for sialorrhoeaA single session of botulinum toxin type B injections to parotid and submandibular glands probably improves sialorrhoea and quality of life at up to 4 weeks compared to placebo injections, but not at 8 or 12 weeks after the injections (moderate-quality evidence from 1 placebo-controlled RCT, N = 20). The review authors found no trials of other approaches. Enteral tube feeding for supporting nutritionThere is no RCT evidence in a Cochrane Systematic Review to support benefit or harms of enteral tube feeding in supporting nutrition in MND. Repetitive transcranial magnetic stimulationIt is uncertain whether repetitive transcranial magnetic stimulation (rTMS) improves disability or limitation in activity in MND in comparison with sham rTMS (3 RCTs, very low quality evidence, N = 50). Therapeutic exerciseThere is evidence that exercise may improve disability in MND at three months after the exercise programme, but not quality of life, in comparison with "usual activities" or "usual care" including stretching (2 RCTs, low-quality evidence, N = 43). Multidisciplinary careThere is no RCT evidence in a Cochrane Systematic Review to demonstrate any benefit or harm for multidisciplinary care in MND.None of the reviews, other than the review of treatment for cramps, reported that adverse events occurred. However, the trials were too small for reliable adverse event reporting.
AUTHORS' CONCLUSIONS
This overview has highlighted the lack of robust evidence in Cochrane Systematic Reviews on interventions to manage symptoms resulting from MND. It is important to recognise that clinical trials may fail to demonstrate efficacy of an intervention for reasons other than a true lack of efficacy, for example because of insufficient statistical power, the wrong choice of dose, insensitive outcome measures or inappropriate participant eligibility. The trials were mostly too small to reliably assess adverse effects of the treatments. The nature of MND makes it difficult to research clinically accepted or recommended practice, regardless of the level of evidence supporting the practice. It would not be ethical, for example, to design a placebo-controlled trial for treatment of pain in MND or to withhold multidisciplinary care where such care is available. It is therefore highly unlikely that there will ever be classically designed placebo-controlled RCTs in these areas.We need more research with appropriate study designs, robust methodology, and of sufficient duration to address the changing needs-of people with MND and their caregivers-associated with MND disease progression and mortality. There is a significant gap in studies assessing the effectiveness of interventions for symptoms relating to MND, such as pseudobulbar emotional lability and cognitive and behavioural difficulties. Future studies should use appropriate outcome measures that are reliable, have internal and external validity, and are sensitive to change in what is being measured (such as quality of life).
Topics: Amyotrophic Lateral Sclerosis; Enteral Nutrition; Exercise Therapy; Humans; Motor Neuron Disease; Muscle Cramp; Muscle Spasticity; Noninvasive Ventilation; Pain; Respiratory Insufficiency; Review Literature as Topic; Sialorrhea; Transcranial Magnetic Stimulation
PubMed: 28072907
DOI: 10.1002/14651858.CD011776.pub2 -
The Cochrane Database of Systematic... May 2022Motor neuron disease (MND), also known as amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative condition that may cause dysphagia, as well as limb... (Review)
Review
BACKGROUND
Motor neuron disease (MND), also known as amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative condition that may cause dysphagia, as well as limb weakness, dysarthria, emotional lability, and respiratory failure. Since normal salivary production is 0.5 L to 1.5 L daily, loss of salivary clearance due to dysphagia leads to salivary pooling and sialorrhea, often resulting in distress and inconvenience to people with MND. This is an update of a review first published in 2011.
OBJECTIVES
To assess the effects of treatments for sialorrhea in MND, including medications, radiotherapy and surgery.
SEARCH METHODS
On 27 August 2021, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, AMED, CINAHL, ClinicalTrials.gov and the WHO ICTRP. We checked the bibliographies of the identified randomized trials and contacted trial authors as needed. We contacted known experts in the field to identify further published and unpublished papers.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) and quasi-RCTs, including cross-over trials, on any intervention for sialorrhea and related symptoms, compared with each other, placebo or no intervention, in people with ALS/MND.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We identified four RCTs involving 110 participants with MND who were described as having intractable sialorrhea or bulbar dysfunction. A well-designed study of botulinum toxin B compared to placebo injected into the parotid and submandibular glands of 20 participants showed that botulinum toxin B may produce participant-reported improvement in sialorrhea, but the confidence interval (CI) was also consistent with no effect. Six of nine participants in the botulinum group and two of nine participants in the placebo group reported improvement (risk ratio (RR) 3.00, 95% CI 0.81 to 11.08; 1 RCT; 18 participants; low-certainty evidence). An objective measure indicated that botulinum toxin B probably reduced saliva production (in mL/5 min) at eight weeks compared to placebo (MD -0.50, 95% CI -1.07 to 0.07; 18 participants, moderate-certainty evidence). Botulinum toxin B may have little to no effect on quality of life, measured on the Schedule for Evaluation of Individual Quality of Life direct weighting scale (SEIQoL-DW; 0-100, higher values indicate better quality of life) (MD -2.50, 95% CI -17.34 to 12.34; 1 RCT; 17 participants; low-certainty evidence). The rate of adverse events may be similar with botulinum toxin B and placebo (20 participants; low-certainty evidence). Trialists did not consider any serious events to be related to treatment. A randomized pilot study of botulinum toxin A or radiotherapy in 20 participants, which was at high risk of bias, provided very low-certainty evidence on the primary outcome of the Drool Rating Scale (DRS; range 8 to 39 points, higher scores indicate worse drooling) at 12 weeks (effect size -4.8, 95% CI -10.59 to 0.92; P = 0.09; 1 RCT; 16 participants). Quality of life was not measured. Evidence for adverse events, measured immediately after treatment (RR 7.00, 95% CI 1.04 to 46.95; 20 participants), and after four weeks (when two people in each group had viscous saliva) was also very uncertain. A phase 2, randomized, placebo-controlled cross-over study of 20 mg dextromethorphan hydrobromide and 10 mg quinidine sulfate (DMQ) found that DMQ may produce a participant-reported improvement in sialorrhea, indicated by a slight improvement (decrease) in mean scores for the primary outcome, the Center for Neurologic Study Bulbar Function Scale (CNS-BFS). Mean total CNS-BFS (range 21 (no symptoms) to 112 (maximum symptoms)) was 53.45 (standard error (SE) 1.07) for the DMQ treatment period and 59.31 (SE 1.10) for the placebo period (mean difference) MD -5.85, 95% CI -8.77 to -2.93) with a slight decrease in the CNS-BFS sialorrhea subscale score (range 7 (no symptoms) to 35 (maximum symptoms)) compared to placebo (MD -1.52, 95% CI -2.52 to -0.52) (1 RCT; 60 participants; moderate-certainty evidence). The trial did not report an objective measure of saliva production or measure quality of life. The study was at an unclear risk of bias. Adverse events were similar to other trials of DMQ, and may occur at a similar rate as placebo (moderate-certainty evidence, 60 participants), with the most common side effects being constipation, diarrhea, nausea, and dizziness. Nausea and diarrhea on DMQ treatment resulted in one withdrawal. A randomized, double-blind, placebo-controlled cross-over study of scopolamine (hyoscine), administered using a skin patch, involved 10 randomized participants, of whom eight provided efficacy data. The participants were unrepresentative of clinic cohorts under routine clinical care as they had feeding tubes and tracheostomy ventilation, and the study was at high risk of bias. The trial provided very low-certainty evidence on sialorrhea in the short term (7 days' treatment, measured on the Amyotrophic Lateral Scelerosis Functional Rating Scale-Revised (ALSFRS-R) saliva item (P = 0.572)), and the amount of saliva production in the short term, as indicated by the weight of a cotton roll (P = 0.674), or daily oral suction volume (P = 0.69). Quality of life was not measured. Adverse events evidence was also very uncertain. One person treated with scopolamine had a dry mouth and one died of aspiration pneumonia considered unrelated to treatment.
AUTHORS' CONCLUSIONS
There is some low-certainty or moderate-certainty evidence for the use of botulinum toxin B injections to salivary glands and moderate-certainty evidence for the use of oral dextromethorphan with quinidine (DMQ) for the treatment of sialorrhea in MND. Evidence on radiotherapy versus botulinum toxin A injections, and scopolamine patches is too uncertain for any conclusions to be drawn. Further research is required on treatments for sialorrhea. Data are needed on the problem of sialorrhea in MND and its measurement, both by participant self-report measures and objective tests. These will allow the development of better RCTs.
Topics: Amyotrophic Lateral Sclerosis; Botulinum Toxins, Type A; Clinical Trials, Phase II as Topic; Deglutition Disorders; Diarrhea; Humans; Motor Neuron Disease; Nausea; Randomized Controlled Trials as Topic; Saliva; Scopolamine Derivatives; Sialorrhea
PubMed: 35593746
DOI: 10.1002/14651858.CD006981.pub3 -
Developmental Medicine and Child... Nov 2019To determine the prevalence of drooling, swallowing, and feeding problems in persons with cerebral palsy (CP) across the lifespan. (Meta-Analysis)
Meta-Analysis
AIM
To determine the prevalence of drooling, swallowing, and feeding problems in persons with cerebral palsy (CP) across the lifespan.
METHOD
A systematic review was conducted using five different databases (AMED, CINAHL, Embase, MEDLINE, and PubMed). The selection process was completed by two independent researchers and the methodological quality of included studies was assessed using the STROBE and AXIS guidelines. Meta-analyses were conducted to determine pooled prevalence estimates of drooling, swallowing, and feeding problems with stratified group analyses by type of assessment and Gross Motor Function Classification System level.
RESULTS
A total of 42 studies were included. Substantial variations in selected outcome measures and variables were observed, and data on adults were limited. Pooled prevalence estimates determined by meta-analyses were as high as 44.0% (95% confidence interval [CI] 35.6-52.7) for drooling, 50.4% (95% CI 36.0-64.8) for swallowing problems, and 53.5% (95% CI 40.7-65.9) for feeding problems. Group analyses for type of assessments were non-significant; however, more severely impaired functioning in CP was associated with concomitant problems of increased drooling, swallowing, and feeding.
INTERPRETATION
Drooling, swallowing, and feeding problems are very common in people with CP. Consequently, they experience increased risks of malnutrition and dehydration, aspiration pneumonia, and poor quality of life.
WHAT THIS PAPER ADDS
Drooling, swallowing, and feeding problems are very common in persons with cerebral palsy (CP). The prevalence of drooling, swallowing, and feeding problems is 44.0%, 50.4%, and 53.5% respectively. There are limited data on the prevalence of drooling, swallowing, and feeding problems in adults. Higher Gross Motor Function Classification System levels are associated with higher prevalence of drooling, swallowing, and feeding problems. There is increased risk for malnutrition, dehydration, aspiration pneumonia, and poor quality of life in CP.
Topics: Cerebral Palsy; Deglutition Disorders; Feeding and Eating Disorders; Humans; Longevity; Prevalence; Quality of Life; Sialorrhea
PubMed: 31328797
DOI: 10.1111/dmcn.14316 -
Drugs in R&D Mar 2017Medication-induced salivary gland dysfunction (MISGD), xerostomia (sensation of oral dryness), and subjective sialorrhea cause significant morbidity and impair quality... (Review)
Review
A Guide to Medications Inducing Salivary Gland Dysfunction, Xerostomia, and Subjective Sialorrhea: A Systematic Review Sponsored by the World Workshop on Oral Medicine VI.
BACKGROUND
Medication-induced salivary gland dysfunction (MISGD), xerostomia (sensation of oral dryness), and subjective sialorrhea cause significant morbidity and impair quality of life. However, no evidence-based lists of the medications that cause these disorders exist.
OBJECTIVE
Our objective was to compile a list of medications affecting salivary gland function and inducing xerostomia or subjective sialorrhea.
DATA SOURCES
Electronic databases were searched for relevant articles published until June 2013. Of 3867 screened records, 269 had an acceptable degree of relevance, quality of methodology, and strength of evidence. We found 56 chemical substances with a higher level of evidence and 50 with a moderate level of evidence of causing the above-mentioned disorders. At the first level of the Anatomical Therapeutic Chemical (ATC) classification system, 9 of 14 anatomical groups were represented, mainly the alimentary, cardiovascular, genitourinary, nervous, and respiratory systems. Management strategies include substitution or discontinuation of medications whenever possible, oral or systemic therapy with sialogogues, administration of saliva substitutes, and use of electro-stimulating devices.
LIMITATIONS
While xerostomia was a commonly reported outcome, objectively measured salivary flow rate was rarely reported. Moreover, xerostomia was mostly assessed as an adverse effect rather than the primary outcome of medication use. This study may not include some medications that could cause xerostomia when administered in conjunction with others or for which xerostomia as an adverse reaction has not been reported in the literature or was not detected in our search.
CONCLUSIONS
We compiled a comprehensive list of medications with documented effects on salivary gland function or symptoms that may assist practitioners in assessing patients who complain of dry mouth while taking medications. The list may also prove useful in helping practitioners anticipate adverse effects and consider alternative medications.
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Oral Medicine; Salivary Glands; Sialorrhea; Xerostomia
PubMed: 27853957
DOI: 10.1007/s40268-016-0153-9 -
European Journal of Pediatrics Jul 2022Drooling, or sialorrhea, is a common condition in patients with cerebral palsy, rare diseases, and neurodevelopmental disorders. The goal of this review was to identify... (Review)
Review
Drooling, or sialorrhea, is a common condition in patients with cerebral palsy, rare diseases, and neurodevelopmental disorders. The goal of this review was to identify the different properties of sialorrhea outcome measures in children. Four databases were analysed in search of sialorrhea measurement tools, and the review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. The COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) checklist was used for quality appraisal of the outcome measures. The initial search yielded 891 articles, 430 of which were duplicates. Thus, 461 full-text articles were evaluated. Among these, 21 met the inclusion criteria, reporting 19 different outcome measures that encompassed both quantitative measures and parent/proxy questionnaires. Conclusions: Among the outcome measures found through this review, the 5-min Drooling Quotient can objectively discriminate sialorrhea frequency in patients with developmental disabilities. The Drooling Impact Scale can be used to evaluate changes after treatment. The modified drooling questionnaire can measure sialorrhea severity and its social acceptability. To date, the tests proposed in this review are the only tools displaying adequate measurement properties. The acquisition of new data about reliability, validity, and responsiveness of these tests will confirm our findings. What is Known: • Although sialorrhea is a recognized problem in children with disabilities, especially those with cerebral palsy (CP), there is a lack of confidence among physicians in measuring sialorrhea. What is New: • Few sialorrhea measures are available for clinicians that may guide decision-making and at the same time have strong evidence to provide confidence in the results. • A combination of both quantitative measures and parent/proxy questionnaires might provide an adequate measurement of sialorrhea in children.
Topics: Cerebral Palsy; Child; Humans; Outcome Assessment, Health Care; Reproducibility of Results; Sialorrhea; Surveys and Questionnaires
PubMed: 35441248
DOI: 10.1007/s00431-022-04460-5 -
International Journal of Environmental... May 2023(1) Background: Immunological laboratory testing is known to be complex, and it is usually performed in tertiary referral centers. Many criticalities affect diagnostic... (Review)
Review
(1) Background: Immunological laboratory testing is known to be complex, and it is usually performed in tertiary referral centers. Many criticalities affect diagnostic immunological testing, such as limited availability, the need for specifically trained laboratory staff, and potential difficulties in collecting blood samples, especially in the most vulnerable patients, i.e., the elderly and children. For this reason, the identification of a new feasible and reliable methodology for autoantibody detection is urgently needed. (2) Methods: We designed a systematic review to investigate the available literature on the utilization of saliva samples for immunological testing. (3) Results: A total of 170 articles were identified. Eighteen studies met the inclusion criteria, accounting for 1059 patients and 671 controls. The saliva collection method was mostly represented by passive drooling (11/18, 61%), and the most frequently described methodology for antibody detection was ELISA (12/18, 67%). The analysis included 392 patients with rheumatoid arthritis, 161 with systemic lupus erythematosus, 131 with type 1 diabetes mellitus, 116 with primary biliary cholangitis, 100 with pemphigus vulgaris, 50 with bullous pemphigoids, 49 with Sjogren syndrome, 39 with celiac disease, 10 with primary antiphospholipid syndromes, 8 with undifferentiated connective tissue disease, 2 with systemic sclerosis, and 1 with autoimmune thyroiditis. The majority of the reviewed studies involved adequate controls, and saliva testing allowed for a clear distinction of patients (10/12 studies, 83%). More than half of the papers showed a correlation between saliva and serum results (10/18, 55%) for autoantibody detection, with varying rates of correlation, sensitivity, and specificity. Interestingly, many papers showed a correlation between saliva antibody results and clinical manifestations. (4) Conclusions: Saliva testing might represent an appealing alternative to serum-based testing for autoantibody detection, considering the correspondence with serum testing results and the correlation with clinical manifestations. Nonetheless, standardization of sample collection processing, maintenance, and detection methodology has yet to be fully addressed.
Topics: Child; Humans; Aged; Saliva; Lupus Erythematosus, Systemic; Sjogren's Syndrome; Autoantibodies; Arthritis, Rheumatoid
PubMed: 37239511
DOI: 10.3390/ijerph20105782 -
Frontiers in Neurology 2022The prevalence and associated factors of dysphagia in Parkinson's disease (PD) are different in studies conducted in different countries. The purpose of our systematic...
BACKGROUND
The prevalence and associated factors of dysphagia in Parkinson's disease (PD) are different in studies conducted in different countries. The purpose of our systematic review and meta-analysis was to evaluate the prevalence of dysphagia in PD and to clarify its associated factors.
METHODS
Two researchers systematically searched PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang Database, SinoMed and VIP databases and manually searched references in the retrieved articles to identify potential research subjects. The last search was conducted on June 28, 2022. Finally, a total of 58 studies including 60 observations with 20,530 PD patients were included in our meta-analysis.
RESULTS
The meta-analysis estimated that the pooled prevalence rate of dysphagia in PD was 36.9% (95% CI: 30.7-43.6%) and instrumental examination showed a higher prevalence (57.3%, 95% CI: 44.3-69.1%). Oceania showed the highest prevalence of dysphagia in PD (56.3%) compared to Africa (39.5%), Asia (38.6%), Europe (36.1%) and America (28.9%). Dysphagia in PD was associated with older age, lower body mass index, longer disease duration, higher Hoehn and Yahr stage and levodopa equivalent daily dose, PIGD subtype, severe motor symptoms, drooling and higher levels of depression, and lower quality of life.
CONCLUSIONS
In conclusion, our meta-analysis showed that dysphagia occurs in more than one-third of PD patients and was associated with several demographic characteristics and PD-related characteristics, motor symptoms, non-motor symptoms, as well as decreased quality of life. It deserves early screening, diagnosis, and treatment in clinical practice to prevent serious complications from dysphagia.
PubMed: 36277913
DOI: 10.3389/fneur.2022.1000527 -
Journal of Clinical Movement Disorders 2017The aim of this study was to examine the efficacy, safety and dosing practices of rimabotulinumtoxinB (BoNT-B) for the treatment of patients with sialorrhea based on a... (Review)
Review
OBJECTIVE
The aim of this study was to examine the efficacy, safety and dosing practices of rimabotulinumtoxinB (BoNT-B) for the treatment of patients with sialorrhea based on a systematic review of clinical trials.
METHODS
A systematic literature review was performed to identify randomized controlled trials and other comparative clinical studies of BoNT-B for the treatment of sialorrhea published in English between January 1999 and December 2015. Medical literature databases (PubMed, Cochrane Library, and EMBASE) were searched and a total of 41 records were identified. Of these, six primary publications that evaluated BoNT-B for the treatment of sialorrhea met criteria and were included in the final data report.
SYNTHESIS
Total BoNT-B doses ranged from 1500 to 4000 units for sialorrhea. Most of the studies in sialorrhea showed statistically significant benefits of BoNT-B versus placebo (range 4-19.2 weeks). BoNT-B was generally well tolerated across the individual studies; most adverse events reported were considered unrelated to treatment. Adverse events considered potentially associated with BoNT-B included: dry mouth, change in saliva thickness, mild transient dysphagia, mild weakness of chewing and diarrhea.
CONCLUSIONS
BoNT-B significantly reduces sialorrhea at doses between 1500 and 4000 units. The relatively mild dose-dependent adverse events suggest both direct and remote toxin effects.
PubMed: 28593050
DOI: 10.1186/s40734-017-0055-1 -
BMC Pharmacology & Toxicology Oct 2023Botulinum toxin (BoNT) injection is an important adjunctive method to treat sialorrhea. The purpose of this systematic review was to analyze the effect and safety of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Botulinum toxin (BoNT) injection is an important adjunctive method to treat sialorrhea. The purpose of this systematic review was to analyze the effect and safety of BoNT injections in the intervention of sialorrhea with Parkinson's disease (PD).
METHODS
We searched PubMed, Web Of Science (WOS), Scopus, Cochrane CENTRAL, and Embase from inception until April 2022. Randomized controlled trials or randomized crossover trials comparing BoNT with placebo in sialorrhea with PD were eligible. PRISMA guidelines were used to carry out the meta-analysis. The Drooling Severity Frequency Scale (DSFS) score and the number of adverse events (AEs) were the primary and secondary outcomes, respectively. Standardized mean differences (SMDs) and risk differences (RDs) are used to express continuous and categorical outcomes, respectively. Heterogeneity among these studies was evaluated using I tests. We used the GRADE tool to assess the certainty of evidence (COE).
RESULTS
Eight articles involving 259 patients compared BoNT injections with a placebo for PD with sialorrhea. This meta-analysis showed a significant reduction in DSFS scores between BoNT injections and placebo (SMD=-0.98; 95% CI, -1.27 to 0.70, p<0.001; COE: high). This meta-analysis showed a significant difference in AEs between BoNT injections and placebo (RD=0.15; 95% CI, 0.05 to 0.24, p=0.002; COE: low).
CONCLUSIONS
The pooled results suggest that BoNT injections have some effect on DSFS scores with sialorrhea caused by PD. There are also mild adverse events, which generally recover within a week or so. The results indicate that BoNT injection is one of the treatments for sialorrhea caused by PD, but we need to pay attention to adverse events. In addition, the follow-up time was extended to observe oral hygiene, ulceration or dental caries, and digestive function.
TRIAL REGISTRATION
Our review protocol was registered on PROSPERO (42021288334).
Topics: Humans; Botulinum Toxins, Type A; Sialorrhea; Parkinson Disease; Dental Caries; Treatment Outcome
PubMed: 37828600
DOI: 10.1186/s40360-023-00694-7 -
The Cochrane Database of Systematic... Jun 2016Autism spectrum disorders (ASD) include autistic disorder, Asperger's disorder and pervasive developmental disorder - not otherwise specified (PDD-NOS). Antipsychotics... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Autism spectrum disorders (ASD) include autistic disorder, Asperger's disorder and pervasive developmental disorder - not otherwise specified (PDD-NOS). Antipsychotics have been used as a medication intervention for irritability related to ASD. Aripiprazole, a third-generation, atypical antipsychotic, is a relatively new drug that has a unique mechanism of action different from that of other antipsychotics. This review updates a previous Cochrane review on the safety and efficacy of aripiprazole for individuals with ASD, published in 2011 (Ching 2011).
OBJECTIVES
To assess the safety and efficacy of aripiprazole as medication treatment for individuals with ASD.
SEARCH METHODS
In October 2015, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and seven other databases as well as two trial registers. We searched for records published in 1990 or later, as this was the year aripiprazole became available.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of aripiprazole (administered orally and at any dosage) versus placebo for treatment of individuals with a diagnosis of ASD.
DATA COLLECTION AND ANALYSIS
Two review authors independently collected, evaluated and analysed data. We performed meta-analysis for primary and secondary outcomes, when possible. We used the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach to rate the overall quality of the evidence.
MAIN RESULTS
We included three trials in this review. Two were included in the previous published review, and the results of one, placebo-controlled discontinuation study were added to this review. Although we searched for studies across age groups, we found only studies conducted in children and youth. Included trials had low risk of bias across most domains. High risk of bias was seen in only one trial with incomplete outcome data. We judged the overall quality of the evidence for most outcomes to be moderate.Two RCTs with similar methods evaluated use of aripiprazole for a duration of eight weeks in 316 children/adolescents with ASD. Meta-analysis of study results revealed a mean improvement of -6.17 points on the Aberrant Behavior Checklist (ABC) - Irritability subscale (95% confidence intervals (CIs) -9.07 to -3.26, two studies, 308 children/adolescents, moderate-quality evidence), -7.93 points on the ABC - Hyperactivity subscale (95% CI -10.98 to -4.88, two studies, 308 children/adolescents, moderate-quality evidence) and -2.66 points on the ABC - Stereotypy subscale (95% CI -3.55 to -1.77, two studies, 308 children/adolescents, moderate-quality evidence) in children/adolescents taking aripiprazole relative to children/adolescents taking placebo. In terms of side effects, children/adolescents taking aripiprazole had a greater increase in weight, with a mean increase of 1.13 kg relative to placebo (95% CI 0.71 to 1.54, two studies, 308 children/adolescents, moderate-quality evidence), and had a higher risk ratio (RR) for sedation (RR 4.28, 95% CI 1.58 to 11.60, two studies, 313 children/adolescents, moderate-quality evidence) and tremor (RR 10.26, 95% CI 1.37 to 76.63, two studies, 313 children/adolescents, moderate-quality evidence). A randomised, placebo-controlled discontinuation study found that 35% of children/adolescents randomised to continue intervention with aripiprazole relapsed with respect to their symptoms of irritability, compared with 52% of children/adolescents randomised to placebo, for a hazard ratio of 0.57 (95% CI 0.28 to 1.12, 85 children/adolescents, low-quality evidence).All three included trials were supported by Bristol-Myers Squibb (Princeton, NJ) and Otsuka Pharmaceutical Company, Ltd. (Tokyo, Japan), with editorial support provided by Ogilvy Healthworld Medical Education and Bristol-Myers Squibb.
AUTHORS' CONCLUSIONS
Evidence from two RCTs suggests that aripiprazole can be effective as a short-term medication intervention for some behavioural aspects of ASD in children/adolescents. After a short-term medication intervention with aripiprazole, children/adolescents showed less irritability and hyperactivity and fewer stereotypies (repetitive, purposeless actions). However, notable side effects, such as weight gain, sedation, drooling and tremor, must be considered. One long-term, placebo discontinuation study found that relapse rates did not differ between children/adolescents randomised to continue aripiprazole versus children/adolescents randomised to receive placebo, suggesting that re-evaluation of aripiprazole use after a period of stabilisation in irritability symptoms is warranted. Studies included in this review used criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (APA 2000) for ASD diagnosis; however, the diagnostic criteria for ASD changed significantly with release of the fifth edition of the DSM (DSM-5) in 2013 (APA 2013).
Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Child Development Disorders, Pervasive; Female; Humans; Hyperkinesis; Irritable Mood; Male; Randomized Controlled Trials as Topic
PubMed: 27344135
DOI: 10.1002/14651858.CD009043.pub3