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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 -
Brazilian Journal of Biology = Revista... 2017The treatment of sialorrhea is necessary for the constant risks posed by hypersalivation. A new therapeutic option comes up with the application of botulinum toxin in...
The treatment of sialorrhea is necessary for the constant risks posed by hypersalivation. A new therapeutic option comes up with the application of botulinum toxin in salivary glands. However, little is known about its mechanism of action in glandular tissue. Based on the above, this work had the objective to systematically review the literature about the action of botulinum toxin on submandibular and parotid salivary glands tissues. Electronic search was performed in databases of great relevance for this study (PubMed, SciELO, HighWire, Crossref, Scopus, Science Direct, MEDLINE, OLDMEDLINE, Serials Database, NLM Catalog, LILACS and IBECS). Inclusion and exclusion criteria for articles were established, and a total number of 14 articles were selected and used. There are few publications that clarify how the salivary gland acini behave with application of botulinum toxin. Although, the immunohistochemical findings were consistent among authors, showing weak immunoreactivity in glands treated with botulinum toxin. Histometric data are divergent, requiring more detailed studies to answer the questions about the efficacy and safety of botulinum toxin in salivary glands.
Topics: Animals; Botulinum Toxins, Type A; Rabbits; Rats; Salivary Glands; Sialorrhea
PubMed: 27599097
DOI: 10.1590/1519-6984.11115 -
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 -
Clinical Otolaryngology : Official... Aug 2017Child maltreatment is persistently under-recognised. Given that a third of maltreated children may return with serious or fatal injuries, it is imperative that... (Review)
Review
BACKGROUND
Child maltreatment is persistently under-recognised. Given that a third of maltreated children may return with serious or fatal injuries, it is imperative that otolaryngologists who are in frequent contact with children are able to detect maltreatment at first presentation.
OBJECTIVE OF REVIEW
This review aims to identify ENT injuries, signs or symptoms that are indicative of physical abuse or fabricated or induced illness (child maltreatment).
TYPE OF REVIEW
Systematic review.
SEARCH STRATEGY
An all-language search, developed in Medline Ovid and consisting of 76 key words, was conducted of published and grey literature across 10 databases from inception to July 2015, for primary observational studies involving children aged <18 years.
EVALUATION METHOD
Each relevant article underwent two independent reviews with full critical appraisal, applying strict quality standards.
RESULTS
Of the 2448 studies identified and screened, 371 underwent full review, resulting in 38 included studies that detailed 122 maltreated children. Pharyngeal perforations (n = 20) were the most frequent abusive ENT injury, predominantly affecting neonates and infants, presenting with dysphagia, drooling, haemoptysis and surgical emphysema. At least 52% of children with abusive pharyngeal injuries had additional co-existent injuries. The majority of ear injuries were inflicted to the external ear (n = 11) and included auricular deformity, abrasions, petechiae, lacerations and burns. Fabricated or induced illness cases presented most commonly with recurrent, unexplained otorrhoea or ENT lesions that failed to heal despite appropriate therapy.
CONCLUSIONS
All clinicians should be familiar with the signs of child maltreatment. Pharyngeal injuries, or injuries to the external ear, presenting in young children without an explicit history of witnessed injury should prompt a child protection referral for full evaluation. Likewise, children who present with recurrent, or apparently intractable symptoms and signs despite appropriate treatment, should raise the possibility of fabricated or induced illness, and discussion with a child protection specialist is advised. Early recognition of possible child maltreatment and instigation of appropriate safeguarding measures are essential to prevent repetition and escalation of injury. This is of paramount importance to otolaryngologists, who have the potential to identify these children in their practice.
Topics: Adolescent; Child; Child Abuse; Child, Preschool; Ear; Humans; Infant; Infant, Newborn; Otolaryngology; Pharynx
PubMed: 27148702
DOI: 10.1111/coa.12668 -
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 -
Epilepsia Dec 2015Topiramate (TPM) is an antiepileptic drug that is also used for other indications (e.g., migraine). Adverse event (AE) data from epilepsy trials could be supplemented by... (Review)
Review
OBJECTIVE
Topiramate (TPM) is an antiepileptic drug that is also used for other indications (e.g., migraine). Adverse event (AE) data from epilepsy trials could be supplemented by data from trials in other indications. Combining data across trials and indications is a novel method for evaluating AEs. We conducted a multiple-indications review by systematically reviewing randomized placebo-controlled trials of TPM, to compare the nervous system AEs of TPM in epilepsy with those in other indications.
METHODS
Randomized placebo-controlled trials of TPM including patients with any indication were included. We searched Cochrane Central Register of Controlled Trials (Issue 2, 2012) and MEDLINE (1966-February 2012). Two authors assessed eligibility and risk of bias, and extracted data. For each reported nervous system AE, we extracted event rates, applied random-effects inverse-variance meta-analysis (pooling within-indications then across-indications), and assessed within- and across-indication heterogeneity.
RESULTS
Ninety trials, including 16 epilepsy trials, were included. A difference was detected between TPM and placebo for three events (i.e., drooling, dysgeusia, and hypoesthesia) that were not reported in epilepsy trials but were reported by other trials. A difference between TPM and placebo was detected for speech disorder using epilepsy trials but not when combining all trials. For two events (i.e., cognitive disorder and "language problems"), no difference was detected between TPM and placebo when using epilepsy trials alone, but a difference was identified using all trials. A difference was detected between TPM and placebo for six events (i.e., ataxia, disturbance in attention, dizziness, memory impairment, paraesthesia, and somnolence) when using epilepsy trials alone, and using all trials.
SIGNIFICANCE
Including trials of any indication enabled detection of differences that would have been missed using epilepsy trials alone. Multiple-indications reviews can improve the synthesis of AEs for antiepileptic drugs.
Topics: Anticonvulsants; Epilepsy; Fructose; Humans; Randomized Controlled Trials as Topic; Topiramate
PubMed: 26662191
DOI: 10.1111/epi.13209 -
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 -
Bipolar Disorders May 2015To evaluate the efficacy and safety of clozapine for treatment-resistant bipolar disorder (TRBD). (Review)
Review
OBJECTIVE
To evaluate the efficacy and safety of clozapine for treatment-resistant bipolar disorder (TRBD).
METHODS
A systematic review of randomized controlled studies, open-label prospective studies, and retrospective studies of patients with TRBD was carried out. Interventions included clozapine monotherapy or clozapine combined with other medications. Outcome measures were efficacy and adverse drug reactions (ADRs).
RESULTS
Fifteen clinical trials with a total sample of 1,044 patients met the inclusion criteria. Clozapine monotherapy or clozapine combined with other treatments for TRBD was associated with improvement in: (i) symptoms of mania, depression, rapid cycling, and psychotic symptoms, with many patients with TRBD achieving a remission or response; (ii) the number and duration of hospitalizations, the number of psychotropic co-medications, and the number of hospital visits for somatic reasons for intentional self-harm/overdose; (iii) suicidal ideation and aggressive behavior; and (iv) social functioning. In addition, patients with TRBD showed greater clinical improvement in long-term follow-up when compared with published schizophrenia data. Sedation (12%), constipation (5.0%), sialorrhea (5.2%), weight gain (4%), and body ache/pain (2%) were the commonly reported ADRs; however, these symptoms but did not usually require drug discontinuation. The percentage of severe ADRs reported, such as leukopenia (2%), agranulocytosis (0.3%), and seizure (0.5%), appeared to be lower than those reported in the published schizophrenia literature.
CONCLUSION
The limited current evidence supports the concept that clozapine may be both an effective and a relatively safe medication for TRBD.
Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans
PubMed: 25346322
DOI: 10.1111/bdi.12272 -
Dysphagia Aug 2014Difficulty in managing oral secretions is commonly experienced by patients with amyotrophic lateral sclerosis (ALS)/motor neurone disease (MND) and associated bulbar... (Review)
Review
Difficulty in managing oral secretions is commonly experienced by patients with amyotrophic lateral sclerosis (ALS)/motor neurone disease (MND) and associated bulbar weakness including dysphagia. There are no definitive evidence-based treatment guidelines to manage the distressing symptom of drooling. We reviewed the evidence for the effectiveness of botulinum toxin injections to reduce saliva in ALS/MND. The search strategy was conducted in four stages: (1) electronic search of relevant databases, (2) hand searches of all international ALS/MND symposium journals, (3) email request to MND care centres in the UK and Ireland, and (4) hand searching of reference lists. All studies were critically appraised and relevant data extracted. Botulinum toxin type A and type B were analysed separately. Due to heterogeneity, it was not possible to calculate a pooled estimate of effect. Twelve studies met the inclusion criteria (9 for type A and 3 for type B). Only two randomised controlled trials were identified. Study sample sizes were small with a mean of 12.5 subjects. The most frequently reported outcomes were weight of cotton rolls and number of tissues used. All studies claimed the intervention tested was effective, but only seven studies (4 for type A and 3 for type B) reported statistically significant differences. Although there is evidence to suggest that botulinum toxin B can reduce drooling, the evidence base is limited by a lack of randomized controlled trials. Evidence to support the use of botulinum toxin A is weaker. Larger trials will help remove the uncertainty practitioners face in treating this disabling symptom.
Topics: Amyotrophic Lateral Sclerosis; Botulinum Toxins, Type A; Humans; Injections; Neurotoxins; Sialorrhea; Treatment Outcome
PubMed: 24847964
DOI: 10.1007/s00455-014-9535-8 -
Research in Developmental Disabilities Mar 2014The management of problem behaviours (PB) in individuals with intellectual disabilities (ID), developmental disabilities (DD) and/or autistic spectrum disorders (ASD)... (Review)
Review
The effectiveness of aripiprazole in the management of problem behaviour in people with intellectual disabilities, developmental disabilities and/or autistic spectrum disorder--a systematic review.
The management of problem behaviours (PB) in individuals with intellectual disabilities (ID), developmental disabilities (DD) and/or autistic spectrum disorders (ASD) can be challenging. Antipsychotic medications are commonly prescribed where other strategies have failed. A systematic review (SR) was conducted to establish the research evidence for the efficacy of aripiprazole in the management of PB in adults and children with ID, DD and/or ASD. Although included studies supported the efficacy of aripiprazole for this indication, the overall quality of studies was poor. Of the 20 studies included in this systematic review there were only two randomised controlled trials (RCTs) on children with ASD and/or ID/DD, both of which were conducted by the pharmaceutical company that manufactures aripiprazole, and it is not clear whether a number of same participants were included in both RCTs. One of the RCTs was extended into an open label long term follow up, which showed that aripiprazole's efficacy lasted over 52 weeks and the adverse effects were tolerable. Four studies were open label prospective studies, 11 were retrospective case reports which included four single case reports, and two were prospective case series. Most studies reported adverse effects from aripiprazole in the form of weight gain, increased appetite, sedation, tiredness, drooling and tremor. However, aripiprazole improved serum prolactin level in some participants and overall did not show any adverse effect on QTc interval. There is a need for more carefully designed RCTs into the use of aripiprazole in the management of PB in people with ID/DD and/or ASD, which should be carried out independent of pharmaceutical companies.
Topics: Aggression; Antipsychotic Agents; Aripiprazole; Child Development Disorders, Pervasive; Developmental Disabilities; Humans; Intellectual Disability; Mental Disorders; Piperazines; Quinolones; Self-Injurious Behavior; Treatment Outcome
PubMed: 24405794
DOI: 10.1016/j.ridd.2013.12.004