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International Journal of Clinical... Jul 2017The objective of this systematic review was to describe the efficacy, tolerability, and safety of valbenazine for the treatment of tardive dyskinesia (TD). (Review)
Review
Valbenazine for tardive dyskinesia: A systematic review of the efficacy and safety profile for this newly approved novel medication-What is the number needed to treat, number needed to harm and likelihood to be helped or harmed?
OBJECTIVE
The objective of this systematic review was to describe the efficacy, tolerability, and safety of valbenazine for the treatment of tardive dyskinesia (TD).
DATA SOURCES
The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/ and http://www.clinicaltrials.gov, for the search terms 'valbenazine' OR 'NBI-98854', and by also querying the EMBASE (Elsevier) commercial database for clinical poster abstracts, and by asking the manufacturer for copies of posters presented at congresses. Product labeling provided additional information.
STUDY SELECTION
All available clinical reports of studies were identified.
DATA EXTRACTION
Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports and other sources of information.
DATA SYNTHESIS
Valbenazine, a reversible inhibitor of Vesicular Monoamine Transporter Type 2 (VMAT2), received approval for the treatment of TD in adults based on a clinical trial development programme that included three 6-week parallel group, randomised, placebo-controlled studies, including one Phase III trial described in product labeling. The recommended dose for valbenazine is 80 mg/d. The percentage of responders in the Phase III acute study, as defined by ≥50% reduction from baseline in the Abnormal Involuntary Movement Scale dyskinesia score was 40.0% for valbenazine 80 mg/d vs 8.7% for placebo, yielding a NNT of 4 (95% CI 3-6). As pooled from available data, discontinuation rates because of an adverse event were 2.9% for valbenazine-treated patients vs 1.6% for placebo-treated patients, resulting in a NNH of 76 (ns). The only adverse event that met the threshold of incidence ≥5% for valbenazine and a rate of ≥2 times than that observed with placebo was somnolence (somnolence, fatigue, sedation), with rates of 10.9% for valbenazine (all doses) vs 4.2% for placebo, resulting in a NNH of 15 (95% CI 9-52). An additional warning and precaution is that valbenazine can prolong the ECG QT interval, however, the valbenazine product label does not contain any bolded boxed warnings or contraindications.
CONCLUSIONS
Valbenazine is presently the only US Food and Drug Administration-approved agent specifically indicated for the treatment of TD. Valbenazine is about 15 times more likely to result in a response than in a discontinuation because of an adverse event. Head-to-head comparisons with other VMAT2 inhibitors among patients with TD in the 'real world' are needed.
Topics: Central Nervous System Agents; Humans; Numbers Needed To Treat; Tardive Dyskinesia; Tetrabenazine; Treatment Outcome; Valine
PubMed: 28497864
DOI: 10.1111/ijcp.12964 -
The relationship between allergic diseases and tic disorders: A systematic review and meta-analysis.Neuroscience and Biobehavioral Reviews Jan 2022This systematic review aims to 1) explore the association between tic disorders (TD) and allergic diseases (AD), 2) judge whether patients with a diagnosis of TD are... (Meta-Analysis)
Meta-Analysis Review
This systematic review aims to 1) explore the association between tic disorders (TD) and allergic diseases (AD), 2) judge whether patients with a diagnosis of TD are prone to suffer from a specific AD, by compiling the literature and analyzing the evidence. A literature search was conducted in PubMed and Embase database on February 24, 2021. The inclusion criteria for the literature were all comparative studies that reported TD patients were diagnosed with allergic illness as well. We identified that TD is positively associated with asthma, allergic rhinitis and allergic conjunctivitis, respectively. Especially, provisional tic disorder (PTD) patients might be more likely to suffer from these three AD, although it is still difficult to accurately predict which specific AD is prone to be accompanied by a specific TD. Shared genetic and etiological factors are suggested responsible for the AD-TD association. Large prospective cohort studies in future might shed light on a deep understanding of the relationship between immune disorders and tics.
Topics: Asthma; Humans; Prospective Studies; Rhinitis, Allergic; Tic Disorders; Tics
PubMed: 34883165
DOI: 10.1016/j.neubiorev.2021.12.004 -
Journal of Neurology Apr 2022The best choice between levodopa alone and levodopa sparing medications for early Parkinson's disease (PD) remains controversial. We aimed to evaluate the effect and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The best choice between levodopa alone and levodopa sparing medications for early Parkinson's disease (PD) remains controversial. We aimed to evaluate the effect and safety of levodopa alone and levodopa sparing therapy in symptom relief, neuroimage results and complications.
METHODS
A systematic search was performed in PubMed, The Cochrane Library, EMBASE, and Web of Science for randomized controlled trials of early PD patients comparing levodopa-alone with levodopa-sparing therapy. The mean difference (MD) and the risk ratio (RR) were meta-analyzed.
RESULTS
Twenty-three articles with 4913 patients were included. Significantly greater benefit was detected for the levodopa group in the changes of Unified Parkinson's Disease Rating Scale part II (p < 0.00001), III (p < 0.00001), and total (p < 0.00001) scores, and the between-group MD in part III score increased over time. The loss of the radioligands uptake in levodopa-alone group was also increasingly greater over time. Patients treated with levodopa alone were at higher risk for wearing-off (p < 0.001) and dyskinesia (p < 0.001), but the RR for dyskinesia between the two groups decreased after 2 years of follow-up.
CONCLUSION
Levodopa-alone therapy might be superior in motor symptom relief than levodopa-sparing therapy for early PD patients, and the motor advantage of levodopa-alone might grow over time. Sparing therapy might be associated with less risk of wearing-off and dyskinesia, but the events between the two groups might not be different in the long run. Overall, levodopa alone therapy might bring more net benefit to early PD patients compared with levodopa sparing strategies. The clinical and imaging findings are conflicting, which requires further investigation.
Topics: Antiparkinson Agents; Dyskinesia, Drug-Induced; Humans; Levodopa; Parkinson Disease
PubMed: 34652505
DOI: 10.1007/s00415-021-10830-0 -
Movement Disorders : Official Journal... Dec 2013Treatment effect in Huntington disease (HD) clinical trials has relied on primary outcome measures such as total motor score or functional rating scales. However, these... (Meta-Analysis)
Meta-Analysis Review
Treatment effect in Huntington disease (HD) clinical trials has relied on primary outcome measures such as total motor score or functional rating scales. However, these measures have limited sensitivity, particularly in pre- to early stages of the disease. We performed a systematic review of HD clinical studies to identify endpoints that correlate with disease severity. Using standard HD keywords and terms, we identified 749 published studies from 1993 to 2011 based on the availability of demographic, biochemical, and clinical measures. The average and variability of each measure was abstracted and stratified according to pre-far, pre-close, early, mild, moderate, and severe HD stages. A fixed-effect meta-analysis on selected variables was conducted at various disease stages. A total of 1,801 different clinical variables and treatment outcomes were identified. Unified Huntington Disease Rating Scale (UHDRS) Motor, UHDRS Independence, and Trail B showed a trend toward separation between HD stages. Other measures, such as UHDRS Apathy, Verbal Fluency, and Symbol Digit, could only distinguish between pre- and early stages of disease and later stages, whereas other measures showed little correlation with increasing HD stages. Using cross-sectional data from published HD clinical trials, we have identified potential endpoints that could be used to track HD disease progression and treatment effect. Longitudinal studies, such as TRACK-HD, are critical for assessing the value of potential markers of disease progression for use in future HD therapeutic trials. A list of variables, references used in this meta-analysis, and database is available at http://www.cmmt.ubc.ca/research/investigators/leavitt/publications.
Topics: Biomedical Research; Databases, Bibliographic; Humans; Huntington Disease
PubMed: 24142393
DOI: 10.1002/mds.25663 -
Neuroscience Letters Mar 2022As an adenosine receptor A2A antagonist, istradefylline is used as an adjunctive agent of levodopa to improve motor symptoms in advanced Parkinson's disease (PD)... (Meta-Analysis)
Meta-Analysis
As an adenosine receptor A2A antagonist, istradefylline is used as an adjunctive agent of levodopa to improve motor symptoms in advanced Parkinson's disease (PD) patients. In this study, we re-evaluated the effects of istradefylline on treating the motor symptoms of PD patients. We performed a literature search up to November 2021 from electronic databases. Eligible studies were synthesized for efficacy, tolerability, OFF time, Unified Parkinson's Disease Rating Scale part III score, ON state with dyskinesia, and the incidence of treatment-emergent adverse events. As a result, nine clinical studies with 2727 subjects on istradefylline treatment for PD patients were included. Our results showed that compared to placebo, istradefylline exhibited a statically significant difference in efficacy (1.39 [1.15 to 1.69]; p = 0.001), decreasing OFF time (-0.58 [-1.01 to - 0.16]; p = 0.007), and improving ON state with dyskinesia (0.69 [0.02 to 1.37]; p = 0.043). For tolerability, UPDRS III, and adverse effects, there was no significant difference between istradefylline and placebo. In conclusion, the results suggest that istradefylline exhibits an efficient and well-tolerated role in treating PD patients. Randomized controlled trials and long-term studies are still required to investigate the effects of istradefylline on motor and non-motor symptoms of PD in future research.
Topics: Adenosine A2 Receptor Antagonists; Antiparkinson Agents; Dyskinesias; Humans; Levodopa; Parkinson Disease; Purines; Treatment Outcome
PubMed: 35149201
DOI: 10.1016/j.neulet.2022.136515 -
Journal of Parkinson's Disease 2022Long-term levodopa administration for treating Parkinson's disease (PD) may shorten the duration of effect and cause dyskinesias, inducing the need for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Long-term levodopa administration for treating Parkinson's disease (PD) may shorten the duration of effect and cause dyskinesias, inducing the need for catechol-O-methyltransferase (COMT) inhibitors as adjuvant therapy.
OBJECTIVE
We provide pooled scientific evidence highlighting the efficacy and safety of opicapone, a newly approved COMT inhibitor, as an adjuvant to levodopa.
METHODS
We searched Ovid Medline, Embase, and Cochrane databases for relevant reports. Efficacy and safety were evaluated as off-time reduction and risk ratio (RR) of dyskinesia, respectively. Data were independently extracted using predefined criteria. Selected placebo-controlled trials were divided into double-blind and open-label periods. Using a random-effects model, the mean difference (MD) of the off-time reduction (efficacy), RR for the occurrence of dyskinesia, and on-time without/with troublesome dyskinesia (TD; safety assessment) were compared between opicapone and placebo groups.
RESULTS
Five studies from three randomized controlled trials were included, and a meta-analysis was performed with 407 patients receiving opicapone 50 mg and 402 patients receiving placebo. Compared with the placebo, opicapone (50 mg) reduced off-time by 49.91 min during the double-blind period (95% confidence intervals [CIs] = -71.39, -28.43; I2 = 0%). The RR of dyskinesia was 3.43 times greater in the opicapone 50 mg group than in the placebo group (95% CI = 2.14, 5.51; I = 0%). Compared with the placebo, opicapone increased the on-time without TD by 44.62 min (95% CI = 22.60, 66.64; I2 = 0%); the on-time increase with TD did not differ between treatments.
CONCLUSION
Opicapone can play a positive role as an adjuvant to levodopa in patients with PD by reducing off-time and prolonging on-time without PD.
Topics: Antiparkinson Agents; Catechol O-Methyltransferase; Catechol O-Methyltransferase Inhibitors; Dyskinesias; Humans; Levodopa; Oxadiazoles; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 35180134
DOI: 10.3233/JPD-213057 -
Developmental Medicine and Child... Aug 2017To identify and systematically review the psychometric properties and clinical utility of dystonia and choreoathetosis scales reported for children with cerebral palsy... (Review)
Review
AIM
To identify and systematically review the psychometric properties and clinical utility of dystonia and choreoathetosis scales reported for children with cerebral palsy (CP).
METHOD
Six electronic databases were searched for dystonia and choreoathetosis scales with original psychometric data for children with CP aged 0 to 18 years.
RESULTS
Thirty-four papers met the inclusion criteria, which contained six scales purported to measure dystonia and/or choreoathetosis in children with CP: the Burke-Fahn-Marsden Dystonia Rating Scale; Barry-Albright Dystonia Scale; Unified Dystonia Rating Scale; Movement Disorder-Childhood Rating Scale; Movement Disorder-Childhood Rating Scale 0-3 Years; and the Dyskinesia Impairment Scale.
INTERPRETATION
Each scale provides useful information about dyskinesia, with most focusing on dystonia. The Barry-Albright Dystonia Scale, which was designed for CP, is the most commonly reported scale and least complex to use clinically. The Dyskinesia Impairment Scale is the only tool to consider both dystonia and choreoathetosis in CP. All tools are designed to classify movement disorders at the level of body functions and structures, rather than activity limitations or participation restrictions, although many provide some insight into the impact of dystonia on activities. Further studies are required to fully examine the validity, reliability, responsiveness, and clinical utility of each scale specifically for children with CP.
Topics: Adolescent; Athetosis; Cerebral Palsy; Child; Child, Preschool; Chorea; Dystonic Disorders; Humans; Infant; Severity of Illness Index
PubMed: 28485494
DOI: 10.1111/dmcn.13452 -
Cerebellum (London, England) Jun 2024Spinocerebellar ataxias (SCAs) are a heterogenous group of rare neurodegenerative conditions sharing an autosomal dominant pattern of inheritance. More than 40 SCAs have... (Review)
Review
Spinocerebellar ataxias (SCAs) are a heterogenous group of rare neurodegenerative conditions sharing an autosomal dominant pattern of inheritance. More than 40 SCAs have been genetically determined. However, a systematic review of SCA epidemiology in Europe is still missing. Here we performed a narrative review of the literature on the epidemiology of the most common SCAs in Europe. PubMed, Embase, and MEDLINE were searched from inception until 1 April 2023. All English peer-reviewed articles published were considered and then filtered by abstract examination and subsequently by full text reading. A total of 917 original articles were retrieved. According to the inclusion criteria and after reviewing references for useful papers, a total of 35 articles were included in the review. Overall, SCA3 is the most frequent spinocerebellar ataxia in Europe. Its frequency is strikingly higher in Portugal, followed by Germany, France, and Netherlands. None or few cases were described in Italy, Russia, Poland, Serbia, Finland, and Norway. SCA1 and SCA2 globally displayed similar frequencies, and are more prevalent in Italy, United Kingdom, Poland, Serbia, and France.
Topics: Humans; Spinocerebellar Ataxias; Europe; Prevalence
PubMed: 37698771
DOI: 10.1007/s12311-023-01600-x -
The Cochrane Database of Systematic... 2000Since the 1950s neuroleptic medication has been extensively used to treat people with chronic mental illnesses, such as schizophrenia. These drugs, however, have been... (Review)
Review
BACKGROUND
Since the 1950s neuroleptic medication has been extensively used to treat people with chronic mental illnesses, such as schizophrenia. These drugs, however, have been also associated with a wide range of adverse effects, including movement disorders such as tardive dyskinesia (TD). Various strategies have been examined to reduce a person's cumulative exposure to neuroleptics. These studies include dose reduction, intermittent dosing strategies, such as drug holidays, and neuroleptic cessation.
OBJECTIVES
To determine whether, for those people with both schizophrenia (or other chronic mental illnesses) and tardive dyskinesia (TD), a reduction or cessation of neuroleptic drugs was associated with reduction in TD symptoms. A secondary objective was to determine whether the use of specific neuroleptics for similar groups of people could be a treatment for already established TD.
SEARCH STRATEGY
Electronic searches of Biological Abstracts (1982-1997), Cochrane Schizophrenia Group's Register of trials (1997), EMBASE (1980-1997), LILACS (1982-1996), MEDLINE (1966-1997), PsycLIT (1974-1997), and SCISEARCH (1997) were undertaken. References of all identified studies were searched for further trial citations. Principal authors of trials were contacted.
SELECTION CRITERIA
Reports were included if they assessed the treatment of neuroleptic-induced tardive dyskinesia in people with schizophrenia or other chronic mental illnesses and already established TD, who had been randomly allocated to (a) neuroleptic cessation (placebo or no intervention) versus neuroleptic maintenance; b. neuroleptic reduction (including intermittent strategies) versus neuroleptic maintenance; or c. specific neuroleptics for the treatment of TD versus placebo or no intervention.
DATA COLLECTION AND ANALYSIS
The reviewers extracted the data independently and the Odds Ratio (95% CI) or the average difference (95% CI) were estimated. The reviewers assumed that people who dropped out had no improvement.
MAIN RESULTS
Two trials were able to be included in this review. Sixty two were excluded and 16 are awaiting assessment. Seven trials are still pending classification. No randomised controlled trial-derived data were available to clarify the role of neuroleptics as treatments for TD. This includes the atypical antipsychotics including clozapine. Despite neuroleptic cessation being a frequently first-line recommendation, there were no RCT-derived data to support this. Two studies ( approximately approximately Cookson 1987 approximately approximately , approximately approximately Kane 1983 approximately approximately ) found a reduction in TD associated with neuroleptic reduction.
REVIEWER'S CONCLUSIONS
The lack of evidence to support the efficacy of neuroleptic cessation as a treatment for TD, combined with the accumulating evidence of an increased risk of relapse should antipsychotic drugs be reduced, makes this intervention a hazardous treatment for TD. Dose reduction may offer some benefit as a treatment for TD compared to standard levels of neuroleptic use. There is a need to evaluate the utility of clozapine and the 'atypical' antipsychotics as treatments for established TD.
Topics: Antipsychotic Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Dyskinesia, Drug-Induced; Humans; Mental Disorders; Schizophrenia
PubMed: 10796546
DOI: 10.1002/14651858.CD000459 -
PloS One 2017A number of genetic loci were found to be associated with dystonia. Quite a few studies have been contacted to examine possible contribution of TOR1A variants to the... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
A number of genetic loci were found to be associated with dystonia. Quite a few studies have been contacted to examine possible contribution of TOR1A variants to the risk of dystonia, but their results remain conflicting. The aim of the present study was to systematically evaluate the effect of TOR1A gene SNPs on dystonia and its phenotypic subtypes regarding the body distribution.
METHODS
We performed a systematic review of Pubmed database to identify all available studies that reported genotype frequencies of TOR1A SNPs in dystonia. In total 16 studies were included in the quantitative analysis. Odds ratios (ORs) were calculated in each study to estimate the influence of TOR1A SNPs genotypes on the risk of dystonia. The fixed-effects model and the random effects model, in case of high heterogeneity, for recessive and dominant mode of inheritance as well as the free generalized odds ratio (ORG) model were used to calculate both the pooled point estimate in each study and the overall estimates.
RESULTS
Rs1182 was found to be associated with focal dystonia in recessive mode of inheritance [Odds Ratio, OR (95% confidence interval, C.I.): 1.83 (1.14-2.93), Pz = 0.01]. In addition, rs1801968 was associated with writer's cramp in both recessive and dominant modes [OR (95%C.I.): 5.99 (2.08-17.21), Pz = 0.00009] and [2.48 (1.36-4.51), Pz = 0.003) respectively and in model free-approach [ORG (95%C.I.): 2.58 (1.45-4.58)].
CONCLUSIONS
Our meta-analysis revealed a significant implication of rs1182 and rs1801968 TOR1A variants in the development of focal dystonia and writer's cramp respectively. TOR1A gene variants seem to be implicated in dystonia phenotype.
Topics: Databases, Factual; Dystonia; Dystonic Disorders; Genetic Predisposition to Disease; Humans; Molecular Chaperones; Odds Ratio; Polymorphism, Single Nucleotide
PubMed: 28081261
DOI: 10.1371/journal.pone.0169934