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The Laryngoscope Jan 2016Up to 80% of patients with Parkinson disease and 30% of patients with amyotrophic lateral sclerosis (ALS) suffer from sialorrhea. Patients who fail medical and surgical... (Review)
Review
PURPOSE
Up to 80% of patients with Parkinson disease and 30% of patients with amyotrophic lateral sclerosis (ALS) suffer from sialorrhea. Patients who fail medical and surgical therapy should be considered for external beam radiation therapy (EBRT). In this study, we conduct a systematic review to determine the dose and techniques used that result in greatest efficacy and lowest toxicity for the administration of EBRT in patients with Parkinson disease or ALS-associated sialorrhea.
METHODS AND MATERIALS
This review included 216 patients from four prospective and six retrospective studies published from 1998 to 2014, with ALS or Parkinson disease who were treated with electron or photon EBRT for sialorrhea.
RESULTS
A total of 216 patients were treated with EBRT from 10 studies. The indication for EBRT was failure of alternative medical treatment in all ALS patients. For patients with Parkinson disease, EBRT was the primary mode of treatment in 68% of cases. Overall, 176 (81%) of 216 patients treated with EBRT for sialorrhea reported symptomatic improvement from baseline. The most common target was the inferior two-thirds of the bilateral parotid glands and the entire bilateral submandibular glands. The total number of patients who experienced short-term toxicity was 86 of 216 patients (40%). The total number of patients who experienced long-term toxicity was 24 of 207 (12%).
CONCLUSIONS
EBRT is an effective treatment for sialorrhea in patients suffering from ALS or Parkinson disease. Treatment to the bilateral submandibular glands and caudal parotid glands is the most common field arrangement.
Topics: Amyotrophic Lateral Sclerosis; Humans; Parkinson Disease; Salivary Glands; Sialorrhea
PubMed: 26152655
DOI: 10.1002/lary.25444 -
Pharmaceuticals (Basel, Switzerland) Jul 2022Clozapine is the gold standard for treatment-resistant schizophrenia. Serious and even life-threatening adverse effects, mostly granulocytopenia, myocarditis, and... (Review)
Review
Clozapine is the gold standard for treatment-resistant schizophrenia. Serious and even life-threatening adverse effects, mostly granulocytopenia, myocarditis, and constipation, are of great clinical concern and constitute a barrier to prescribing clozapine, thus depriving many eligible patients of a lifesaving treatment option. Interestingly, clozapine presents variable pharmacokinetics affected by numerous parameters, leading to significant inter- and intra-individual variation. Therefore, therapeutic drug monitoring of plasma clozapine levels confers a significant benefit in everyday clinical practice by increasing the confidence of the prescribing doctor to the drug and the adherence of the patient to the treatment, mainly by ensuring effective treatment and limited dose-related side effects. In the present systematic review, we aimed at identifying how a full range of adverse effects relates to plasma clozapine levels, using the Jadad grading system for assessing the quality of the available clinical evidence. Our findings indicate that EEG slowing, obsessive-compulsive symptoms, heart rate variability, hyperinsulinemia, metabolic syndrome, and constipation correlate to plasma clozapine levels, whereas QTc, myocarditis, sudden death, leucopenia, neutropenia, sialorrhea, are rather unrelated. Rapid dose escalation at the initiation of treatment might contribute to the emergence of myocarditis, or leucopenia. Strategies for managing adverse effects are different in these conditions and are discussed accordingly.
PubMed: 35890117
DOI: 10.3390/ph15070817 -
Journal of Clinical Neuroscience :... May 2018Sialorrhea is a common distress associated with certain neurological disorders. The aim of this study is to compare the pharmacological agents used for treating... (Meta-Analysis)
Meta-Analysis Review
Sialorrhea is a common distress associated with certain neurological disorders. The aim of this study is to compare the pharmacological agents used for treating sialorrhea by network meta-analysis. Electronic databases were searched for randomized clinical trials comparing active drugs with either placebo or other active drugs. Total drooling scores was the primary outcome measure. Inverse variance heterogeneity model was used for both direct and mixed treatment comparison analysis. Twenty one studies were included in the systematic review and 15 in the meta-analysis. Compared to placebo, benztropine, botulinum toxins A and B are associated with a significant reduction in the frequency and severity of drooling both in the overall neurological disorders as well as for children with cerebral palsy. Only botulinum toxin A and B were associated with significant therapeutic effects in Parkinson's disease. Benztropine and botulinum toxins A and B were observed to be effective in reducing sialorrhea associated with neurological disorders.
Topics: Benztropine; Botulinum Toxins, Type A; Child; Child, Preschool; Female; Glycopyrrolate; Humans; Muscarinic Antagonists; Nervous System Diseases; Network Meta-Analysis; Randomized Controlled Trials as Topic; Scopolamine; Sialorrhea
PubMed: 29475576
DOI: 10.1016/j.jocn.2018.02.011 -
Schizophrenia Research Jun 2024To synthesize the information relevant for clinical practice on clozapine-antidepressant co-prescription concerning pharmacokinetic drug-drug interactions (DDI), adverse...
OBJECTIVES
To synthesize the information relevant for clinical practice on clozapine-antidepressant co-prescription concerning pharmacokinetic drug-drug interactions (DDI), adverse drug reactions (ADRs) associated with the co-prescription, antidepressant add-on for clozapine-resistant symptoms and antidepressant add-on for clozapine-induced ADRs.
METHODS
Articles were identified with MEDLINE, Web of Sciences and PsycINFO search from inception through April 2023. Data were synthesized narratively.
RESULTS
ADRs are most often induced by the co-prescription of antidepressants that inhibit CYP enzymes (fluvoxamine, fluoxetine, paroxetine). Fluvoxamine add-on is hazardous because of its potent inhibition of clozapine metabolism and has few indications (lowering daily number of clozapine tablets, reducing norclozapine-induced metabolic disturbances and other dose-dependent clozapine-induced ADRs). ADR frequency may be reduced by therapeutic drug monitoring and knowledge of other factors impacting clozapine metabolism (pneumonia, inflammation, smoking, etc.). Improvement of negative symptoms is the most documented beneficial effect of antidepressant add-on for clozapine-resistant psychotic symptoms. The add-on antidepressant should be chosen according to its safety profile regarding DDI with clozapine: antidepressants inhibiting clozapine metabolism or increasing the anticholinergic load should be avoided. Other indications of antidepressant add-on (affective or obsessive compulsive symptoms, sialorrhea, and enuresis) are poorly documented.
CONCLUSION
Antidepressant add-on to clozapine is associated with potential benefits in clozapine users as this strategy may contribute to reduce the burden of clozapine-resistant symptoms or of clozapine-induced ADRs. Further studies are needed to determine whether antidepressant add-on can reduce the risk of clozapine discontinuation.
Topics: Clozapine; Humans; Drug Interactions; Antidepressive Agents; Antipsychotic Agents; Drug Therapy, Combination; Schizophrenia
PubMed: 37852856
DOI: 10.1016/j.schres.2023.10.003 -
Paediatrics & Child Health May 2022Sialorrhea in children can be associated with adverse physical and social effects. Treatment using anticholinergic medications has been shown to offer symptomatic...
BACKGROUND
Sialorrhea in children can be associated with adverse physical and social effects. Treatment using anticholinergic medications has been shown to offer symptomatic relief, but there is no consensus regarding which treatment is the most efficacious.
OBJECTIVE
To examine the effectiveness of anticholinergic medications for sialorrhea in children.
METHODS
A systematic review was carried out in Medline, EMBASE, Cochrane, Scopus, and the Web of Science from inception until April 29, 2020. Studies reporting original data on the efficacy of anticholinergic medications in the management of sialorrhea in children aged 0 to 17 years of age were included. This review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards. Data on study design, setting, population, pharmacologic intervention(s), comparator(s), outcomes, and results were extracted and summarized.
RESULTS
The search strategy identified 2,800 studies of which 27 articles were included in the synthesis, including five randomized controlled trials. Each anticholinergic undergoing experimental study (glycopyrrolate, scopolamine/hyoscine, trihexyphenidyl/benzhexol, benztropine, and atropine) showed evidence of efficacy. Adverse side effects were common. Significant heterogeneity exists in the studies' methodology and the variability of outcome measures used between studies precluded a meta-analysis.
CONCLUSIONS
Glycopyrrolate, scopolamine/hyoscine, trihexyphenidyl/benzhexol, benztropine, and atropine have all shown efficacy in the treatment of sialorrhea in children. The small number of reports and the variability in study design precluded a meta-analysis. More studies are needed with uniformity in outcome measures to help guide evidence-based decision making. A guidance table is presented.
PubMed: 35599670
DOI: 10.1093/pch/pxab051 -
International Journal of Clinical... Jun 2024To describe the efficacy of atropine in controlling salivary flow in patients with sialorrhea or drooling. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To describe the efficacy of atropine in controlling salivary flow in patients with sialorrhea or drooling.
MATERIALS AND METHODS
We included randomized controlled studies, quasi-randomized trials, case reports, clinical trials, systematic reviews, and meta-analyses assessing the use of atropine in patients with sialorrhea or drooling. The endpoints were reduction in salivary flow rate, amount of saliva secreted, reduction in clinical symptoms of sialorrhea, death rattle intensity, or reduction in drooling intensity as measured by an objective scale such as the drooling intensity scale.
RESULTS
A total of 56 studies with 2,378 patients were included in the systematic review. The underlying disease states included brain injury, amyotrophic lateral sclerosis, cerebral palsy, clozapine- and perphenazine-induced sialorrhea, Parkinson's disease, and terminal illness. The routes of atropine administration included sublingual, intravenous, subcutaneous, oral tablet or solution, and direct injection of atropine into parotid glands or at the base of the tongue. The generalized estimated equation regression models showed that sublingual administration is superior to oral and subcutaneous routes.
CONCLUSION
Atropine is efficacious in managing sialorrhea in most disease states. Sublingual administration of atropine is superior to other routes of administration in reducing salivary flow in patients with sialorrhea.
Topics: Sialorrhea; Humans; Atropine; Treatment Outcome; Salivation
PubMed: 38577753
DOI: 10.5414/CP204538 -
Children (Basel, Switzerland) Nov 2022Functional Chewing Training (FuCT) was designed as a holistic approach to improve chewing function by providing postural alignment, sensory and motor training, and food... (Review)
Review
Evaluation of the Effectiveness of Functional Chewing Training Compared with Standard Treatment in a Population of Children with Cerebral Palsy: A Systematic Review of Randomized Controlled Trials.
BACKGROUND
Functional Chewing Training (FuCT) was designed as a holistic approach to improve chewing function by providing postural alignment, sensory and motor training, and food and environmental adjustments. The aim of this systematic review was to evaluate the effectiveness of FuCT in improving chewing function and the severity of tongue thrust and drooling in children with cerebral palsy as compared with standard treatment.
METHODS
We conducted a systematic review of randomized controlled trials. The search was performed between October 2021 and January 2022 using the following databases: PubMed, Scopus, Web of Science, and CINAHL. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
The initial search yielded 56 articles. After reading the studies in full, 3 articles were chosen based on the inclusion criteria. Included participants were people with PCI; the studies reported a sample size ranging from 40-80 individuals, one study was on a pediatric population, while the others on adults. The selected studies were then evaluated using Jadad and PEDro scales.
CONCLUSION
Our study confirmed the value of FuCT in improving chewing function and the severity of tongue thrust and drooling. Our results may be useful in optimizing appropriate therapeutic management.
PubMed: 36553319
DOI: 10.3390/children9121876 -
Expert Opinion on Drug Safety May 2016Antipsychotic co-treatment is common in schizophrenia, despite lacking evidence for its efficacy and safety. Areas: We conducted a systematic search of... (Comparative Study)
Comparative Study Meta-Analysis Review
INTRODUCTION
Antipsychotic co-treatment is common in schizophrenia, despite lacking evidence for its efficacy and safety. Areas: We conducted a systematic search of PubMed/PsycInfo/CJN/WangFan/CBM without language restrictions from database inception until 05/25/2015 for randomized trials comparing antipsychotic monotherapy with antipsychotic co-treatment in ≥20 adults with schizophrenia reporting meta-analyzable adverse events (AEs) data. Meta-analyzing 67 studies (n=4,861, duration=10.3±5.2 weeks), antipsychotic co-treatment was similar to monotherapy regarding intolerability-related discontinuation (risk ratio (RR)=0.84, 95% confidence interval (CI)=0.53-1.33, p=0.455). While incidence of ≥1 AE was lower with antipsychotic co-treatment (RR=0.77, 95%CI=0.66-0.90, p=0.001), these results were solely driven by open-label and efficacy-focused studies. Adjunctive D2-antagonists lead to less nausea (RR=0.220, 95%CI=0.06-0.87, p=0.030) and insomnia (RR=0.26, 95%CI=0.08-0.86, p=0.028), but higher prolactin (SMD=2.20, 95%CI=0.43-3.96, p=0.015). Conversely, adjunctive partial D2-agonists (aripiprazole=100%) resulted in lower electrocardiogram abnormalities (RR=0.43, 95%CI=0.25-0.73, p=0.002), constipation (RR=0.45, 95%CI=0.25-0.79, p=0.006), drooling/hypersalivation (RR=0.14, 95%CI=0.07-0.29, p<0.001), prolactin (SMD=-1.77, 95%CI=-2.38, -1.15, p<0.001), total and LDL-cholesterol (SMD=-0.33, 95%CI=-0.55, -0.11, p=0.003; SMD=-0.33, 95%CI=-0.54, -0.10, p=0.004).
EXPERT OPINION
No double-blind evidence for altered AE burden associated with antipsychotic co-treatment was found. However, AEs were insufficiently and incompletely reported and follow-up duration was modest. Adjunctive partial D2-agonists might be beneficial for counteracting several AEs. High-quality, long-term studies that comprehensively assess AEs are needed.
Topics: Adult; Antipsychotic Agents; Dopamine D2 Receptor Antagonists; Drug Partial Agonism; Drug Therapy, Combination; Humans; Randomized Controlled Trials as Topic; Receptors, Dopamine D2; Schizophrenia
PubMed: 26967126
DOI: 10.1517/14740338.2016.1165668 -
Journal of Clinical Medicine Mar 2019The main objective was to assess the efficacy of botulinum toxin-based treatment for sialorrhea in adult patients with Parkinson's disease. The search was performed by... (Review)
Review
The main objective was to assess the efficacy of botulinum toxin-based treatment for sialorrhea in adult patients with Parkinson's disease. The search was performed by using the Medline-PubMed, EMBASE and Cochrane Library databases from January 2000⁻December 2017, in English/Spanish in patients with Parkinson's disease and sialorrhea. The methodological quality of trials was carried out by following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria and the Newcastle⁻Ottawa Scale (NOS). Finally, a total of 21 articles were identified as fulfilling the inclusion criteria. There is no consensus regarding the site of injection of the toxin (single or multiple points), toxin dose or follow-up period. In all cases there was a reduction of sialorrhea. Treatment safety increases with the use of ultrasonography. Effects approximately occur at one week post-injection and for 3⁻5 months. Botulinum toxin is an effective therapeutic strategy or option in treating sialorrhea in adult patients with Parkinson's disease. More studies with a better design, larger samples and a longer follow-up period are required to confirm these data.
PubMed: 30845700
DOI: 10.3390/jcm8030317 -
The Laryngoscope Jul 2024Sialorrhea, also known as drooling, hypersalivation, or ptyalism, has a significant impact on the medical and psychosocial well-being of children. Onabotulinum toxin A... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Sialorrhea, also known as drooling, hypersalivation, or ptyalism, has a significant impact on the medical and psychosocial well-being of children. Onabotulinum toxin A (BoNT-A) is the most commonly used botulinum toxin worldwide for the treatment of sialorrhea in children.
OBJECTIVES
To conduct a comprehensive systematic review and meta-analysis to assess the clinical efficacy and potential adverse effects of BoNT-A as a treatment for drooling in children.
METHODS
Cochrane, Embase, and Medline databases were systematically searched (up to May 2023). Out of 535 identified publications, 20 were found eligible for inclusion. A systematic review and meta-analysis were performed to determine the efficacy of BoNT-A treatment in children in reducing the frequency and severity of drooling.
RESULTS
Out of the 20 studies included, a meta-analysis was conducted on the complete dataset of eight studies involving 131 patients. BoNT-A was found to significantly decrease the severity of drooling in patients with sialorrhea (standardized mean difference [SMD], -2.07; 95% confidence interval [CI], -2.91 to -1.23; p < 0.0001) when compared with the conditions before injections using random-effects models. Six studies out of 20 reported dysphagia as an adverse effect after injection. Other side effects included thickness of saliva and pain at the site of injection.
CONCLUSION
BoNT-A is a clinically effective therapy that improves drooling severity in children with sialorrhea. Although there were some adverse side effects reported, they were transient and not severe. Future studies are needed to further evaluate the best techniques and to identify the ideal dosages required to achieve the optimal outcomes. Laryngoscope, 134:3012-3017, 2024.
Topics: Humans; Sialorrhea; Botulinum Toxins, Type A; Child; Neuromuscular Agents; Treatment Outcome; Child, Preschool; Adolescent; Male; Female
PubMed: 38294288
DOI: 10.1002/lary.31277