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Clinical Therapeutics May 2012Levodopa is considered the gold standard therapy for Parkinson's disease (PD). Aspiration pneumonia is the most frequent cause of death among PD patients. Asymptomatic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Levodopa is considered the gold standard therapy for Parkinson's disease (PD). Aspiration pneumonia is the most frequent cause of death among PD patients. Asymptomatic respiratory impairment can be detected even in the initial stages of the disease course; however, there is no conclusive evidence regarding the efficacy of levodopa, the main therapeutic drug for PD, to enhance pulmonary function in these patients.
OBJECTIVE
The aim of this systematic review and meta-analysis was to evaluate the effects of levodopa therapy on respiratory parameters in patients with PD.
METHODS
After a comprehensive and systematic literature search in the electronic databases MEDLINE, Embase, the Cochrane Library, and Web of Science, all trials referring to levodopa and respiratory function that met the eligibility criteria were included in the analysis. Considered outcomes were forced vital capacity (FVC), forced expiratory volume in 1 second (FEV(1)), the ratio between FEV(1) and FVC (FEV(1)/FVC), and peak expiratory flow (PEF). The fixed effects model was used to assess the weighted mean difference, and heterogeneity between studies was calculated with the I(2) test.
RESULTS
Four clinical trials comprising 73 patients and assessing the effects of levodopa on pulmonary function in patients with PD were included in the analysis. Pooled data showed that levodopa significantly improved FVC (SMD, 0.40; P = 0.02) and PEF (standard mean difference, 0.39; P = 0.03). No significant change was observed with FEV(1) (SMD, 0.34; P = 0.05) or the FEV(1)/FVC ratio (standard mean difference, -0.08; P = 0.66) after levodopa therapy.
CONCLUSIONS
The results of this systematic review suggest that levodopa therapy improved FVC and PEF, whereas no changes were observed in FEV(1) and FEV(1)/FVC. These findings may provide some indirect evidence regarding the efficacy of levodopa in restrictive parameters of pulmonary function.
Topics: Antiparkinson Agents; Forced Expiratory Volume; Humans; Levodopa; Lung Diseases; Models, Statistical; Parkinson Disease; Peak Expiratory Flow Rate; Vital Capacity
PubMed: 22465616
DOI: 10.1016/j.clinthera.2012.03.001 -
Archives of Gerontology and Geriatrics 2021We investigated the efficacy and acceptability of pharmacotherapy for dementia with Lewy bodies (DLB) while simultaneously considering the neuropsychiatric symptoms... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
We investigated the efficacy and acceptability of pharmacotherapy for dementia with Lewy bodies (DLB) while simultaneously considering the neuropsychiatric symptoms (NPS), cognitive function, motor symptoms, and acceptability.
METHODS
Electronic databases were searched from inception through June 5, 2019, for randomized controlled trials (RCTs) and open-label trials (OLTs) in patients with DLB. We performed a pairwise conventional meta-analysis (PWMA) and network meta-analysis (NMA) within a frequentist framework. The main outcomes were mean change scores in NPS, general cognition, motor symptoms and acceptability. The effect sizes and odds ratios with 95% confidence intervals (CIs) were calculated. This study was registered with PROSPERO (CRD42018096996).
RESULTS
In total, we included 29 studies (9 RCTs and 20 OLTs). In the NMA with 9 RCTs, both high- (mean difference [MD] 2.00, 95% CIs, 0.69 to 3.31) and low-dose (1.86, 0.58 to 3.15) donepezil were associated with a greater cognitive improvement than placebo. High-dose zonisamide was associated with greater motor symptom improvement ( -4.10, -7.03 to -1.17]). No medications reached statistical significance regarding improving neuropsychiatric symptoms or developing intolerable adverse effects as compared to placebo. In the second NMA, with 29 studies as an exploratory analysis, aripiprazole and yokukansan may be effective for neuropsychiatric symptoms, while levodopa may be associated with cognitive impairment.
CONCLUSIONS
We report the most comprehensive evidence for the selection of pharmacotherapy for treating different clusters of DLB-related symptoms. Due to the limited availability of RCTs on DLB, more well-conducted RCTs are needed for MMA to warrant clinical efficacy in the future.
Topics: Cognition; Humans; Lewy Body Disease; Network Meta-Analysis; Treatment Outcome
PubMed: 34256210
DOI: 10.1016/j.archger.2021.104474 -
Neurological Sciences : Official... May 2014L-dopa-induced dyskinesias (LIDs) are abnormal involuntary movements (AIM) that develop with long-term L-dopa therapy for Parkinson's disease (PD). In this study, we... (Meta-Analysis)
Meta-Analysis Review
L-dopa-induced dyskinesias (LIDs) are abnormal involuntary movements (AIM) that develop with long-term L-dopa therapy for Parkinson's disease (PD). In this study, we used these tools to describe the efficacy of nicotine reduced LID in animal models of PD. Studies were identified by electronic searching of six online databases up to September of 2013 to identify preclinical trials involving nicotine for LID in animal model. Data were extracted for AIM compared with LID animals. Pre-specified subgroup analysis was carried out according to method of model, gender, anesthetic used, and species. Combined standardized mean difference (SMD) estimates and 95 % confidence intervals (CIs) were calculated using a random-effects model. Eleven studies involving 181 animals which described the effect of nicotine on LID were included in the meta-analysis. Nicotine was efficacious in reducing total AIM compared with control group (SMD -3.77, 95 % CI -5.30 to -2.23, P < 0.00001). Meanwhile, four studies showed certain effects of nicotine for improving the axial AIM (SMD -2.21, 95 % CI -4.17 to -0.24, P = 0.03); oral AIM and forelimb AIM were obvious improved in six studies in the nicotine group (SMD -3.00, 95 % CI -4.55 to -1.44, P = 0.0002; SMD -2.52, 95 % CI -3.52 to -1.53, P < 0.00001, respectively). We conclude that nicotine appears to have efficacy in animal models of LID. Large randomized clinical trials testing the effect of nicotine in PD patients with LID are warranted.
Topics: Animals; Antiparkinson Agents; Dyskinesia, Drug-Induced; Ganglionic Stimulants; Levodopa; Nicotine; Parkinsonian Disorders
PubMed: 24510151
DOI: 10.1007/s10072-014-1652-5 -
Archives of Gerontology and Geriatrics 2021To identify drug interactions of potentially inappropriate medications and mental and behavioral disorders, according to explicit potentially inappropriate medications... (Review)
Review
OBJECTIVES
To identify drug interactions of potentially inappropriate medications and mental and behavioral disorders, according to explicit potentially inappropriate medications criteria-based tools.
METHODOLOGY
A systematic scoping review was conducted in February 2020. Study characteristics, potentially inappropriate medications, drug interactions, rationale, and therapeutic management proposed were extracted. The commercialization and potentially inappropriate medications standard as essential in Brazil and in the world were identified. Therapeutic management was proposed for the most cited potentially inappropriate medications.
RESULTS
36 tools including 151 drug interactions, in addition to 132 potentially inappropriate medications with concerns related to six mental and behavioral disorders were identified. Cognitive impairment and dementia were the most frequently disorders reported and antipsychotics, anticholinergics, and benzodiazepines were the pharmacological classes more involved in the drug interactions. Despite the tools recommended risperidone and quetiapine when the use of antipsychotics were inevitable; levodopa + carbidopa for Parkinson's disease; and short and intermediate half-life benzodiazepines; the quality of the evidence needs to be assessed. In this review, sleep hygiene; deprescription; medication review; and clinical monitoring of adverse drug reactions are strongly recommended. In addition, to consider agomelatine, bupropion, moclobemide and melatonin as potential safer options for benzodiazepines.
CONCLUSION
Knowing the clinical conditions or risk morbidities associated with the use of potentially inappropriate medications and management of these medications for safer therapeutic equivalents or non-pharmacotherapeutic alternatives are relevant for patient safety.
Topics: Aged; Brazil; Drug Interactions; Humans; Inappropriate Prescribing; Mental Disorders; Potentially Inappropriate Medication List
PubMed: 33227533
DOI: 10.1016/j.archger.2020.104283 -
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 -
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 -
General Hospital Psychiatry 2022The present study aimed to systematically analyze the risk factors for RBD. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The present study aimed to systematically analyze the risk factors for RBD.
METHODS
A systematic review and meta-analysis of case-control studies, cohort studies, and cross-sectional studies derived from the articles published in eight electronic databases before December 1, 2021. The primary outcome was the odds ratio (OR) and 95% confidence interval (95% CI), and heterogeneity was quantified using I. Subgroup analyses and meta-regression were used to explore sources of heterogeneity. Egger's test and sensitivity analysis were performed. The PROSPERO ID number of the present study is CRD42021293942.
RESULTS
We identified 26 studies (44,230 subjects) among 2022 citations, and 13 factors were considered. Male sex (OR = 1.36, 95% CI = 1.13-1.64), smoking (OR = 1.37, 95% CI: 1.26-1.50), depression (OR = 2.06, 95% CI = 1.66-2.56), antidepressant use (OR = 2.36, 95% CI = 1.98-2.82), duration of neuropsychiatric disorders(OR = 1.43, 95% CI = 1.13-1.73), levodopa equivalent daily dose (LEDD, OR = 60.15, 95% CI = 23.95-96.35) and observable motor dysfunction (OR = 2.43, 95% CI = 0.65-4.22) were associated with a higher risk of RBD. Tertiary education and above (OR = 0.58, 95% CI = 0.35-0.96) was associated with a lower RBD risk. Men (OR = 1.40, 95% CI: 1.10-1.78, I = 0%, P = 0.005) and older individual (OR = 2.73, 95% CI: 1.03-4.43, I = 60%, P = 0.002) were more likely to have iRBD.
CONCLUSION
Six modifiable risk factors and one protective factor were associated with RBD. Further research is required to understand the mechanisms and to develop preventative strategies.
Topics: Male; Humans; Cross-Sectional Studies; REM Sleep Behavior Disorder; Levodopa; Risk Factors; Sleep
PubMed: 36375340
DOI: 10.1016/j.genhosppsych.2022.10.009 -
Sleep Medicine Reviews Apr 2016Patients with primary dystonia, the third most prevalent movement disorder, suffer from a markedly reduced quality of life. This might, at least in part, be mediated by... (Review)
Review
Patients with primary dystonia, the third most prevalent movement disorder, suffer from a markedly reduced quality of life. This might, at least in part, be mediated by non-motor symptoms, including sleep disturbances. Characterising and treating sleep disturbances might provide new inroads to improve relevant patient-centred outcomes. This review evaluates the state of research on sleep in patients with dystonia and outlines an agenda for future research. A literature search was performed in July 2014 using PubMed, Medline via Ovid, PsycInfo, PsycArticles via Proquest and Embase via Ovid. Search results were screened for eligibility by two independent raters. Peer-reviewed publications reporting on sleep in patients with primary dystonia were included. Of 1445 studies identified through the search strategy, 18 met the inclusion criteria. In total, the included studies reported on 708 patients diagnosed with focal dystonia (cervical dystonia or blepharospasm), torsion dystonia, and dopa-responsive dystonia. The results indicate that at least half of the patients with focal cranial dystonia suffer from sleep disturbances, but excessive daytime sleepiness is uncommon. Sleep disturbance is associated with depressive symptoms. The frequency and duration of dystonic movements is markedly reduced during sleep. Reduced sleep quality appears to persist after treatment with botulinum toxin that successfully reduces motor symptoms. The findings are limited by a high clinical and methodological heterogeneity. Future research is needed to i) further characterize subjective and PSG sleep in patients with different types of dystonia, ii) determine the aetiology of sleep disturbances (e.g., abnormal brain function associated with dystonia, side effects of medication, psychological reasons), and iii) test whether targeted sleep interventions improve sleep and quality of life in patients with primary dystonia.
Topics: Depression; Dystonic Disorders; Humans; Polysomnography; Quality of Life; Sleep Wake Disorders
PubMed: 26164369
DOI: 10.1016/j.smrv.2015.04.004 -
Frontiers in Neuroscience 2021Movement fluctuations are the main complication of Parkinson's disease (PD) patients receiving long-term levodopa (L-dopa) treatment. We compared and ranked the...
Comparative Efficacy and Safety of Dopamine Agonists in Advanced Parkinson's Disease With Motor Fluctuations: A Systematic Review and Network Meta-Analysis of Double-Blind Randomized Controlled Trials.
Movement fluctuations are the main complication of Parkinson's disease (PD) patients receiving long-term levodopa (L-dopa) treatment. We compared and ranked the efficacy and safety of dopamine agonists (DAs) with regard to motor fluctuations by using a Bayesian network meta-analysis (NMA) to quantify information from randomized controlled trials (RCTs). We carried out a systematic review and meta-analysis, and only RCTs comparing DAs for advanced PD were included. Electronic databases (PubMed, Embase, and Cochrane Library) were systematically searched for relevant studies published until January 2021. Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Network meta-analyses using a Bayesian framework were used to calculate the related parameters. The pre-specified primary and secondary outcomes were efficacy ("ON" time without troublesome dyskinesia, "OFF" time, "ON" time, "UPDRS-III," and "UPDRS-II") and safety [treatment-emergent adverse events (TEAE) and other adverse events] of DAs. The results are presented as the surface under the cumulative ranking (SUCRA) curve. A total of 20 RCTs assessing 6,560 patients were included. The general DA effects were ranked from high to low with respect to the amount of "ON" time without troublesome dyskinesia as follows: apomorphine (SUCRA = 97.08%), pramipexole_IR (probability = 79.00%), and ropinirole_PR (SUCRA = 63.92%). The general safety of DAs was ranked from high to low with respect to TEAE as follows: placebo (SUCRA = 74.49%), pramipexole_ER (SUCRA = 63.6%), sumanirole (SUCRA = 54.07%), and rotigotine (SUCRA = 53.84%). This network meta-analysis shows that apomorphine increased "ON" time without troublesome dyskinesia and decreased "OF" time for advanced PD patients. The addition of pramipexole, ropinirole, or rotigotine to levodopa treatment in advanced PD patients with motor fluctuations increased "ON" time without troublesome dyskinesia, improved the UPDRS III scores, and ultimately ameliorated the UPDRS II scores, thereby maximizing its benefit. This NMA of pramipexole, ropinirole, and rotigotine represents an effective treatment option and has an acceptable safety profile in patients with advanced PD.
PubMed: 34776841
DOI: 10.3389/fnins.2021.728083 -
Maturitas Sep 2022The aim of the present systematic review was to assess the efficacy of ketogenic therapy in Parkinson's disease (PD), using all available data from randomized controlled...
OBJECTIVE
The aim of the present systematic review was to assess the efficacy of ketogenic therapy in Parkinson's disease (PD), using all available data from randomized controlled trials (RCTs) on humans and animal studies with PD models.
DESIGN
Systematic review of in vivo studies.
METHODS
Studies related to the research question were identified through searches in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, clinicaltrials.gov and the gray literature, from inception until November 2021. Rayyan was employed to screen and identify all studies fulfilling the inclusion criteria. Cochrane's revised Risk of Bias 2.0 and SYRCLE tools evaluated bias in RCTs and animal studies, respectively. An effect direction plot was developed to synthesize the evidence of the RCTs.
RESULTS
Twelve studies were identified and included in the qualitative synthesis (4 RCTs and 8 animal trials). Interventions included ketogenic diets (KDs), supplementation with medium-chain triglyceride (MCT) oil, caprylic acid administration and ketone ester drinks. The animal research used zebrafish and rodents, and PD was toxin-induced. Based on the available RCTs, ketogenic therapy does not improve motor coordination and functioning, cognitive impairment, anthropometrics, blood lipids and glycemic control, exercise performance or voice disorders in patients with PD. The evidence is scattered and heterogenous, with single trials assessing different outcomes; thus, a synthesis of the evidence cannot be conclusive regarding the efficacy of ketogenic therapy. On the other hand, animal studies tend to demonstrate more promising results, with marked improvements in locomotor activity, dopaminergic activity, redox status, and inflammatory markers.
CONCLUSIONS
Although animal studies indicate promising results, research on the effect of ketogenic therapy in PD is still in its infancy, with RCTs conducted on humans being heterogeneous and lacking PD-specific outcomes. More studies are required to recommend or refute the use of ketogenic therapy in PD.
Topics: Animals; Cognitive Dysfunction; Humans; Parkinson Disease
PubMed: 35714419
DOI: 10.1016/j.maturitas.2022.06.001