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CoDAS Oct 2018Investigate the association between levodopa therapy and vocal characteristics in Parkinson's disease patients. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Investigate the association between levodopa therapy and vocal characteristics in Parkinson's disease patients.
SEARCH STRATEGY
Studies published at MEDLINE, LILACS, and SciELO, from 1960 to December 2016. A systematic review and meta-analysis was performed using the following keywords: Parkinson's disease; levodopa; L-dopa; voice; speech disorders; dysphonia; dysarthria. After analyzing titles and abstracts, two independent reviewers selected all clinical trials that met the eligibility criteria and selected the articles and the data recorded in a previously standardized table.
SELECTION CRITERIA
Trials published in English between 1960 and December 2016 individuals with clinical diagnosis of Parkinson's disease; use of levodopa therapy in stable doses; acoustic analysis combined or not with auditory-perceptual analysis to evaluate the vocal parameters under investigation.
DATA ANALYSIS
The following vocal parameters were analyzed: fundamental frequency (F 0), jitter, and vocal intensity. Standardized mean differences (SMD) were calculated using the Comprehensive Meta-analysis V2 software.
RESULTS
Nine articles met the eligibility criteria and were selected, with a total of 119 individuals. From these, six articles with 83 individuals were included in the meta-analysis. During the levodopa therapy "on" state, modifications in F 0 (SMD=0.39; 95% CI - 0.21-0.57) and jitter (SMD=0.23; 95% CI - 0.02-0.45) were observed. Vocal intensity was not affected (SMD=0.09; 95% CI - 0.22-0.39) by levodopa ingestion. Data of the included studies were controversial in the auditory-perceptual analysis of voice.
CONCLUSION
Levodopa therapy modifies F0 and jitter. No changes in vocal intensity were observed in either the "on" or "off" states of levodopa therapy.
Topics: Antiparkinson Agents; Dysarthria; Dysphonia; Female; Humans; Levodopa; Male; Parkinson Disease; Speech Production Measurement; Voice; Voice Quality
PubMed: 30304100
DOI: 10.1590/2317-1782/20182017200 -
Journal of Comparative Effectiveness... Aug 2022To assess the clinical efficacy and safety profile of opicapone (25 and 50 mg once daily) versus placebo. Levodopa-treated adults with Parkinson's disease. A... (Meta-Analysis)
Meta-Analysis Review
To assess the clinical efficacy and safety profile of opicapone (25 and 50 mg once daily) versus placebo. Levodopa-treated adults with Parkinson's disease. A systematic review and meta-analysis were conducted. Opicapone provided a greater reduction in the absolute OFF-time, increased the chances of ≥1-h reduction in the OFF-time and ≥1-h increase in the ON-time compared with placebo. Receiving opicapone more often facilitated levodopa dose reduction versus placebo. There were no differences in the occurrence of adverse events (severe and leading to drug discontinuation), but receiving opicapone increased the frequency of dyskinesia. Opicapone demonstrated superior clinical efficacy to placebo, with a comparable general safety profile.
Topics: Adult; Antiparkinson Agents; Catechol O-Methyltransferase Inhibitors; Double-Blind Method; Humans; Levodopa; Oxadiazoles; Parkinson Disease
PubMed: 35758044
DOI: 10.2217/cer-2022-0031 -
Frontiers in Aging Neuroscience 2022Pharmacotherapy is the first-line treatment option for Parkinson's disease, and levodopa is considered the most effective drug for managing motor symptoms. However, side... (Review)
Review
BACKGROUND
Pharmacotherapy is the first-line treatment option for Parkinson's disease, and levodopa is considered the most effective drug for managing motor symptoms. However, side effects such as motor fluctuation and dyskinesia have been associated with levodopa treatment. For these conditions, alternative therapies, including invasive and non-invasive medical devices, may be helpful. This review sheds light on current progress in the development of devices to alleviate motor symptoms in Parkinson's disease.
METHODS
We first conducted a narrative literature review to obtain an overview of current invasive and non-invasive medical devices and thereafter performed a systematic review of recent randomized controlled trials (RCTs) of these devices.
RESULTS
Our review revealed different characteristics of each device and their effectiveness for motor symptoms. Although invasive medical devices are usually highly effective, surgical procedures can be burdensome for patients and have serious side effects. In contrast, non-pharmacological/non-surgical devices have fewer complications. RCTs of non-invasive devices, especially non-invasive brain stimulation and mechanical peripheral stimulation devices, have proven effectiveness on motor symptoms. Nearly no non-invasive devices have yet received Food and Drug Administration certification or a CE mark.
CONCLUSION
Invasive and non-invasive medical devices have unique characteristics, and several RCTs have been conducted for each device. Invasive devices are more effective, while non-invasive devices are less effective and have lower hurdles and risks. It is important to understand the characteristics of each device and capitalize on these.
PubMed: 35462692
DOI: 10.3389/fnagi.2022.807909 -
The Cochrane Database of Systematic... 2001Long term levodopa therapy in Parkinson's disease is associated with the development of motor complications including abnormal involuntary movements and a shortening... (Review)
Review
BACKGROUND
Long term levodopa therapy in Parkinson's disease is associated with the development of motor complications including abnormal involuntary movements and a shortening response to each dose (wearing off phenomenon). It is thought that dopamine agonists can reduce the duration of immobile off periods and the need for levodopa therapy whilst maintaining or improving motor impairments and only minimally increasing dopaminergic adverse events.
OBJECTIVES
To compare the efficacy and safety of adjuvant cabergoline therapy versus bromocriptine in patients with Parkinson's disease, already established on levodopa and suffering from motor complications.
SEARCH STRATEGY
Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Pharmacia Upjohn Limited.
SELECTION CRITERIA
Randomised controlled trials of cabergoline versus bromocriptine in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy.
DATA COLLECTION AND ANALYSIS
Data were abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, off time measurements and the frequency of withdrawals and adverse events.
MAIN RESULTS
Cabergoline has been compared with bromocriptine in five randomised, double-blind, parallel group studies including 1071 patients. Only one of the phase II studies was medium term (36 weeks), the others all being short term (12 -15 weeks). The non-significant difference in off time reduction produced by cabergoline compared with bromocriptine was 0.29 hours/day in favour of the former (weighted mean difference; 95% CI -0.10, 0.68; p = 0.15). Dyskinesia reported as an adverse event was significantly increased with cabergoline compared with bromocriptine (Peto odds ratio 1.57; 95% CI 1.05, 2.35; p = 0.03). Motor impairment and disability were measured in four of the studies using the UPDRS rating scale but the small differences in UPDRS ADL (part II) and motor (part III) scores were not statistically significant in any study. Similarly, no significant difference in Schwab and England score was seen. The number of patients rated as much or very much improved on a clinician's global impression scale was similar with both agonists. Levodopa dose reduction was no different between cabergoline and bromocriptine. There was more confusion with cabergoline (Peto odds ratio 2.02; 95% CI 1.09, 3.76; p = 0.03). Otherwise, dopaminergic adverse events were comparable with these agonists and no significant difference in all cause withdrawal rate was found.
REVIEWER'S CONCLUSIONS
Cabergoline produces similar benefits to bromocriptine in off time reduction, motor impairment and disability ratings, and levodopa dose reduction over the first three months of therapy. Dyskinesia and confusion were increased with cabergoline but otherwise the frequency of adverse events and withdrawals from treatment were similar with the two agonists.
Topics: Antiparkinson Agents; Bromocriptine; Cabergoline; Dopamine Agonists; Dyskinesia, Drug-Induced; Ergolines; Humans; Levodopa; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 11279721
DOI: 10.1002/14651858.CD001519 -
The Cochrane Database of Systematic... Oct 2004As Parkinson's disease progresses the control of the symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
As Parkinson's disease progresses the control of the symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of the levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase.
OBJECTIVES
To compare the efficacy and safety of adjuvant COMT inhibitor therapy versus active comparators in patients with Parkinson's disease, already established on levodopa and suffering from motor complications.
SEARCH STRATEGY
Electronic searches of the Cochrane Controlled Trials Register (The Cochrane Library Issue 1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of COMT inhibitors were contacted.
SELECTION CRITERIA
Randomised controlled trials of adjuvant COMT inhibitor therapy versus an active comparator in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy.
DATA COLLECTION AND ANALYSIS
Data was abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events.
MAIN RESULTS
Two trials were found that examined the efficacy of a COMT inhibitor against an active comparator (n = 349). Koller 1998 compared the efficacy of tolcapone versus pergolide (n = 203) over 12 weeks and TSG 1999 compared the efficacy of tolcapone versus bromocriptine (n = 146) over 8 weeks. No trials were found that compared entacapone with active comparators. Tolcapone produced similar benefits to bromocriptine in 'off' time reduction, motor impairment and disability ratings over three months of therapy. Tolcapone produced a greater reduction in levodopa dosage than bromocriptine. Tolcapone produced similar benefits to pergolide in levodopa dose reduction, motor impairment and disability ratings, and in generic health-related quality of life scales over the first two months of therapy. Tolcapone produced a greater improvement in the disease-specific quality of life scale PDQ-39 than pergolide. Nausea, constipation and orthostatic complaints were greater with agonist therapy, but otherwise the frequency of adverse events and withdrawals from treatment were similar with the two classes of adjuvant medication. One patient had significantly elevated liver enzymes whilst on tolcapone, but otherwise the frequency of adverse events and withdrawals from treatment were similar.
REVIEWERS' CONCLUSIONS
The two trials comparing tolcapone with the dopamine agonists bromocriptine and pergolide were underpowered to detect clinically relevant differences between them. This is based on medium-term evidence. No evidence was found comparing entacapone with active comparators. Further larger and longer-term trials are required to compare tolcapone with entacapone and COMT inhibitor therapy with alternative adjuvant classes of drug in later Parkinson's disease such as dopamine agonists and monoamine oxidase inhibitors.
Topics: Antiparkinson Agents; Benzophenones; Bromocriptine; Catechol O-Methyltransferase Inhibitors; Dopamine Agonists; Humans; Levodopa; Nitrophenols; Parkinson Disease; Pergolide; Tolcapone
PubMed: 15495118
DOI: 10.1002/14651858.CD004553.pub2 -
Translational Neurodegeneration 2015To assess the association between Parkinson's disease (PD) and melanoma via systematic review and meta-analysis.
OBJECTIVE
To assess the association between Parkinson's disease (PD) and melanoma via systematic review and meta-analysis.
METHODS
Comprehensive search in PubMed, Web of Science, Embase and four China databases (SinoMed, WanFang data, CNKI and VIP database) of epidemiologic evidences on PD and melanoma published before April 30, 2015. Studies which reported risk estimates of melanoma among PD patients or risk estimates of PD in patients with melanoma were included. Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated by random-effects models. Heterogeneity across studies was assessed using Cochran Q and I(2) statistics. Subgroup analyses and sensitivity analyses were conducted to evaluate sources of heterogeneity. Subgroup analyses were done according to temporal relationship, geographic region and gender respectively. We assessed publication bias using the Begg and Egger test. In addition, study appraisal was done using a scale for observational studies to ensure the quality of evidence.
RESULTS
We identified 24 eligible studies on PD and melanoma with a total number of 292,275 PD patients: the pooled OR was 1.83 (95 % CI 1.46-2.30) overall, subgroup analyses by temporal relationship showed that risk of melanoma after PD diagnosis was significantly higher (OR 2.43, 95 % CI 1.77-3.32), but not before the diagnosis of PD (OR 1.09, 95 % CI 0.78-1.54). Subgroup analysis by geographic region showed that increased risk of melanoma in PD was found both in Europe (OR 1.44, 95 % CI 1.22-1.70) and in North America (OR 2.64, 95 % CI 1.63-4.28). Gender-specific subgroup analyses did not show difference between men (OR 1.64, 95 % CI 1.27-2.13) and women (OR 1.38, 95 % CI 1.04-1.82) in the risk of melanoma. In addition, we found the risk of non-melanoma skin cancers in PD was slightly higher (OR 1.20, 95 % CI 1.11-1.29) than general population. It was impossible to evaluate the association between PD and melanoma according to use of levodopa or gene polymorphism via meta-analysis since few observational or cohort studies have focused on it.
CONCLUSIONS
An association between PD and melanoma was confirmed. Most of the evidences were of high quality, and the conclusion was robust. Further research is needed to explore the mechanisms underlying this relationship.
PubMed: 26535116
DOI: 10.1186/s40035-015-0044-y -
Stereotactic and Functional Neurosurgery 2010The purpose of the present article is a systematic review of the proposed medical or surgical treatments in patients in chronic vegetative state (VS) or minimally... (Review)
Review
BACKGROUND/AIMS
The purpose of the present article is a systematic review of the proposed medical or surgical treatments in patients in chronic vegetative state (VS) or minimally conscious state (MCS), as well as of their mechanisms of action and limitations.
METHODS
For this review, we have agreed to include patients in VS or MCS having persisted for over 6 months in posttraumatic cases, and over 3 months in nontraumatic cases, before the time of intervention. Searches were independently conducted by 2 investigators between May 2009 and September 2009 in the following databases: Medline, Web of Science and the Cochrane Library. The electronic search was complemented by cross-checking the references of all relevant articles. Overall, 16 papers were eligible for this systematic review.
RESULTS
According to the 16 eligible studies, medical management by dopaminergic agents (levodopa, amantadine), zolpidem and median nerve stimulation, or surgical management by deep brain stimulation, extradural cortical stimulation, spinal cord stimulation and intrathecal baclofen have shown to improve the level of consciousness in certain cases.
CONCLUSION
The treatments proposed for disorders of consciousness have not yet gained the level of 'evidence-based treatments'; moreover, the studies to date have led to inconclusiveness. The published therapeutic responses must be substantiated by further clinical studies of sound methodology.
Topics: Baclofen; Consciousness; Electric Stimulation Therapy; Humans; Persistent Vegetative State; Pyridines; Treatment Outcome; Zolpidem
PubMed: 20460949
DOI: 10.1159/000314354 -
The Cochrane Database of Systematic... 2000To compare the efficacy and safety of adjuvant pramipexole therapy versus inactive placebo in patients with Parkinson's disease, already established on levodopa. (Review)
Review
OBJECTIVES
To compare the efficacy and safety of adjuvant pramipexole therapy versus inactive placebo in patients with Parkinson's disease, already established on levodopa.
SEARCH STRATEGY
Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Pharmacia Upjohn and Boehringer Ingelheim.
SELECTION CRITERIA
Randomised controlled trials of pramipexole versus placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy.
DATA COLLECTION AND ANALYSIS
Data was abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of drop outs and adverse events.
MAIN RESULTS
Four randomised controlled trials have compared pramipexole with placebo in 669 patients with later Parkinson's disease. Two phase III studies were medium term (24 weeks maintenance period) and 2 phase II studies were short term (4 weeks maintenance period). The reduction in off time was significantly greater with pramipexole compared with placebo (weighted mean difference 1.8 hours; 1.2, 2.3 95% CI). No significant changes were noted in a dyskinesia rating scale in any of the 4 studies, but dyskinesia as an adverse event was reported more frequently with pramipexole. A significant improvement occurred in UPDRS complication score (part IV) in 2 studies but not in the remaining trials. Statistically significant improvements in UPDRS ADL score occurred with pramipexole in all studies. Significant improvements in UPDRS motor scores in the on state were reported in 3 of the 4 studies. Levodopa dose reduction was allowed in 3 studies and meta-analysis shows a significant difference in favour of pramipexole (weighted mean difference 115 mg; 87, 143 95% CI). Trends toward a higher incidence of dopaminergic adverse events with pramipexole only reached statistical significance regarding hallucinations. There were significantly fewer withdrawals from pramipexole.
REVIEWER'S CONCLUSIONS
Pramipexole can be used to reduce off time, improve motor impairments and disability and reduce levodopa dose at the expense of increased dyskinetic adverse events. This conclusion is based on short and medium term trials (up to 24 weeks). Further trials are required to directly compare the newer with the older dopamine agonists.
Topics: Antiparkinson Agents; Benzothiazoles; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dopamine Agonists; Humans; Levodopa; Pramipexole; Randomized Controlled Trials as Topic; Thiazoles
PubMed: 10908540
DOI: 10.1002/14651858.CD002261 -
Neurology Apr 2014To determine the efficacy of medical marijuana in several neurologic conditions. (Review)
Review
Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology.
OBJECTIVE
To determine the efficacy of medical marijuana in several neurologic conditions.
METHODS
We performed a systematic review of medical marijuana (1948-November 2013) to address treatment of symptoms of multiple sclerosis (MS), epilepsy, and movement disorders. We graded the studies according to the American Academy of Neurology classification scheme for therapeutic articles.
RESULTS
Thirty-four studies met inclusion criteria; 8 were rated as Class I.
CONCLUSIONS
The following were studied in patients with MS: (1) Spasticity: oral cannabis extract (OCE) is effective, and nabiximols and tetrahydrocannabinol (THC) are probably effective, for reducing patient-centered measures; it is possible both OCE and THC are effective for reducing both patient-centered and objective measures at 1 year. (2) Central pain or painful spasms (including spasticity-related pain, excluding neuropathic pain): OCE is effective; THC and nabiximols are probably effective. (3) Urinary dysfunction: nabiximols is probably effective for reducing bladder voids/day; THC and OCE are probably ineffective for reducing bladder complaints. (4) Tremor: THC and OCE are probably ineffective; nabiximols is possibly ineffective. (5) Other neurologic conditions: OCE is probably ineffective for treating levodopa-induced dyskinesias in patients with Parkinson disease. Oral cannabinoids are of unknown efficacy in non-chorea-related symptoms of Huntington disease, Tourette syndrome, cervical dystonia, and epilepsy. The risks and benefits of medical marijuana should be weighed carefully. Risk of serious adverse psychopathologic effects was nearly 1%. Comparative effectiveness of medical marijuana vs other therapies is unknown for these indications.
Topics: Academies and Institutes; Guidelines as Topic; Humans; Medical Marijuana; Nervous System Diseases; Retrospective Studies; United States
PubMed: 24778283
DOI: 10.1212/WNL.0000000000000363 -
The Cochrane Database of Systematic... Oct 2007Drugs that mimic dopamine, such as bromocriptine (BR), were introduced as monotherapy or in combination with levodopa (LD) in the hope that this approach would prevent... (Review)
Review
BACKGROUND
Drugs that mimic dopamine, such as bromocriptine (BR), were introduced as monotherapy or in combination with levodopa (LD) in the hope that this approach would prevent or delay the onset of motor complications in patients with Parkinson's disease (PD). However, hitherto, the role of BR has remained controversial. We present a systematic review of all randomised controlled trials (RCTs) of BR/LD combination therapy compared with LD monotherapy in PD.
OBJECTIVES
To assess the efficacy and safety of BR/LD combination therapy in delaying the onset of motor complications associated with LD monotherapy in patients with PD.
SEARCH STRATEGY
We searched the Movement Disorders Group trials register which includes MEDLINE and EMBASE; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); handsearched appropriate neurology journals, symposia reports, PD handbooks and reference lists of reviews found by the search-strategy. We also contacted Sandoz -now Novartis- (manufacturer of BR) and PPD Pharmaco and contacted colleagues who had co-ordinated trials on BR.
SELECTION CRITERIA
RCTs were eligible for inclusion if they evaluated the efficacy of BR/LD combination therapy for delaying the onset of motor complications compared with LD monotherapy in patients with PD. Outcome measures evaluated included the occurrence and severity of motor complications, impairment and disability scores, side effects and dropouts.
DATA COLLECTION AND ANALYSIS
To determine the feasibility of a quantitative systematic review two independent reviewers evaluated the methodological quality of identified trials and extracted data from the trials.
MAIN RESULTS
The methodological quality of seven trials showed important shortcomings. All studies failed adequately to describe randomisation procedures. Only three were carried out according to a double-blind design. Differences were found between studies concerning the mean age of the participants, the BR titration phase, the maximum achieved daily dose of LD (62.5 to 1000 mg) and BR (5 to 50 mg), and the applied outcomes. Our results show no evidence of consistent differences between treatment groups concerning the occurrence and severity of motor complications, scores of impairment and disability, or the occurrence of side effects.
AUTHORS' CONCLUSIONS
This systematic review revealed no evidence to support the use of early BR/LD combination therapy as a strategy to prevent or delay the onset of motor complications in the treatment of PD.
Topics: Antiparkinson Agents; Bromocriptine; Combined Modality Therapy; Humans; Levodopa; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 17943795
DOI: 10.1002/14651858.CD003634.pub2