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Systematic review

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Comparison of the Efficacy of Different Drugs on Non-Motor Symptoms of Parkinson's Disease: a Network Meta-Analysis.

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Authors Li BD , Cui JJ , Song J , Qi C , Ma PF , Wang YR , Bai J
Journal Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
Year 2018
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This article includes 21 Primary studies 21 Primary studies (21 references)

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BACKGROUND/AIMS: A network meta-analysis is used to compare the efficacy of ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control, for non-motor symptoms in Parkinson's disease (PD). METHODS: PubMed, Embase and the Cochrane Library were searched from their establishment dates up to January 2017 for randomized controlled trials (RCTs) investigating the efficacy of the above ten drugs on the non-motor symptoms of PD. A network meta-analysis combined the evidence from direct comparisons and indirect comparisons and evaluated the pooled weighted mean difference (WMD) values and surfaces under the cumulative ranking curves (SUCRA). The network meta-analysis included 21 RCTs. RESULTS: The analysis results indicated that, using the United Parkinson's Disease Rating Scale (UPDRS) III, the efficacies of placebo, ropinirole, rasagiline, rotigotine, entacapone, pramipexole, sumanirole and levodopa in treating PD were lower than that of apomorphine (WMD = -10.90, 95% CI = -16.12∼-5.48; WMD = -11.85, 95% CI = -17.31∼-6.16; WMD = -11.15, 95% CI = -16.64∼-5.04; WMD = -11.70, 95% CI = -16.98∼-5.60; WMD = -11.04, 95% CI = -16.97∼-5.34; WMD = -13.27, 95% CI = -19.22∼-7.40; WMD = -10.25, 95% CI = -15.66∼-4.32; and WMD = -11.60, 95% CI = -17.89∼-5.57, respectively). Treatment with ropinirole, rasagiline, rotigotine, entacapone, pramipexole, sumanirole, bromocriptine, piribedil or levodopa, with placebo as a control, on PD exhibited no significant differences on PD symptoms when the UPDRS II was used for evaluation. Moreover, using the UPDRS III, the SUCRA values indicated that a pomorphine had the best efficacy on the non-motor symptoms of PD (99.0%). Using the UPDRS II, the SUCRA values for ropinirole, rasagiline, rotigotine, entacapone, pramipexole, sumanirole, bromocriptine, piribedil and levodopa treatments, with placebo as a control, indicated that bromocriptine showed the best efficacy on the non-motor symptoms of PD (75.6%). CONCLUSION: Among ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control, apomorphine may be the most efficacious drug for therapy in treating the non-motor symptoms of PD.

Systematic review

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Efficacy and Safety of Adjuvant Treatment with Entacapone in Advanced Parkinson's Disease with Motor Fluctuation: A Systematic Meta-Analysis.

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Authors Li J , Lou Z , Liu X , Sun Y , Chen J
Journal European neurology
Year 2017
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This article includes 14 Primary studies 14 Primary studies (14 references)

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AIMS: To assess the efficacy and safety of adjuvant treatment with entacapone in the treatment of later Parkinson's disease (PD) patients with motor fluctuation. METHODS: We conducted a systematic review of relevant studies from 8 databases to June 23, 2016. RESULTS: Fourteen studies were included in this review (n = 2,804). The results showed that compared with placebo, adjuvant therapy with entacapone significantly increased on time (p < 0.01) and reduced off time (p < 0.01), the required levodopa (LD) dose (p < 0.01) and improved Parkinson's Disease Rating Scale (UPDRS) scores (activities of daily living score: p < 0.01; motor score: p < 0.01; UPDRS I-III score: p > 0.05). However, the withdrawal (OR 1.44, 95% CI 1.10-1.89, p < 0.01) due to adverse events and adverse events rates including nausea (OR 2.23, 95% CI 1.56-3.20, p < 0.01), urine discoloration (OR 14.99, 95% CI 7.63-29.44, p < 0.01), gastrointestinal disorder (OR 2.6, 95% CI 1.89-3.57, p < 0.01) and dyskinesia (OR 2.00, 95% CI 1.56-2.58, p < 0.01) increased in patients with entacapone compared with those given a placebo . CONCLUSIONS: This meta-analysis suggests that the entacapone used as adjuvant therapy to LD is effective in the management of later PD with fluctuation. However, patients on entacapone had a higher frequency of adverse events than those on placebo but no occurrence of severe adverse reactions.

Systematic review

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Efficacy of antidepressive medication for depression in Parkinson disease: a network meta-analysis.

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Authors Zhuo C , Xue R , Luo L , Ji F , Tian H , Qu H , Lin X , Jiang R , Tao R
Journal Medicine
Year 2017
Links Pubmed DOI PubMed Central

This article includes 45 Primary studies 45 Primary studies (45 references)

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BACKGROUND: Parkinson disease (PD) was considered as the 2nd most prevalent neurodegenerative disorder after Alzheimer disease, while depression is a prevailing nonmotor symptom of PD. Typically used antidepression medication includes tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), monoamine-oxidase inhibitors (MAOI), and dopamine agonists (DA). Our study aimed at evaluating the efficacy of antidepressive medications for depression of PD. METHODS: Web of Science, PubMed, Embase, and the Cochrane library were searched for related articles. Traditional meta-analysis and network meta-analysis (NMA) were performed with outcomes including depression score, UPDRS-II, UPDRS-III, and adverse effects. Surface under the cumulative ranking curve (SUCRA) was also performed to illustrate the rank probabilities of different medications on various outcomes. The consistency of direct and indirect evidence was also assessed by node-splitting method. RESULTS: Results of traditional pairwise meta-analysis were performed. Concerning depression score, significant improvement was observed in AD, MAOI, SSRI, and SNRI compared with placebo. NMA was performed and more information could be obtained. DA was illustrated to be effective over placebo concerning UPDRS-III, MAOI, and SNRI. DA demonstrated a better prognosis in UPDRS-II scores compared with placebo and MAOI. However, DA and SSRI demonstrated a significant increase in adverse effects compared with placebo. The SUCRA value was calculated to evaluate the ranking probabilities of all medications on investigated outcomes, and the consistency between direct and indirect evidences was assessed by node-splitting method. CONCLUSION: SSRI had a satisfying efficacy for the depression of PD patients and could improve activities of daily living and motor function of patient but the adverse effects are unneglectable. SNRI are the safest medication with high efficacy for depression as well while other outcomes are relatively poor.

Systematic review

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Safety and Efficacy of Rotigotine for Treating Parkinson's Disease: A Meta-Analysis of Randomised Controlled Trials.

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Authors Chen F , Jin L , Nie Z
Journal Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
Year 2017
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This article includes 12 Primary studies 12 Primary studies (12 references)

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We aimed to comprehensively analyse the safety and efficiency of rotigotine for treating Parkinson's disease (PD). We conducted systematic literature searches of Cochrane library, PubMed and Embase databases up to April 2016, with 'Rotigotine', 'Parkinson Disease ' and 'Parkinson's disease' as key searching terms. Outcomes, including Unified Parkinson's Disease Rating Scale (UPDRS) Part III and Part II scores, 'off' time, adverse events (AEs), serious AEs and discontinuation because of AEs, were compared between rotigotine and placebo groups under a fixed or random effect model. For dichotomous and continuous data, risk ratio (RR) and weighted mean difference with their corresponding 95% confidence intervals (95% CIs) were taken as the effect sizes to calculate merged results. Twelve eligible studies were included. For patients with early or advanced PD, rotigotine could significantly improve UPDRS Part III and Part II scores (p < 0.001) and it had significantly higher incidence of AEs than the placebo (p < 0.001). Regarding discontinuation because of AEs, rotigotine showed a significant advantage over placebo in patients with early PD, whereas the overall result demonstrated no statistically significant difference between the groups. Rotigotine can improve daily living and motor ability of patients with PD, although it has higher incidence of AEs. Rotigotine might be more appropriate for patients with advanced PD than for those with early PD. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Systematic review

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Efficacy of rasagiline for the treatment of Parkinson's disease: an updated meta-analysis.

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Authors Chang Y , Wang LB , Li D , Lei K , Liu SY
Journal Annals of medicine
Year 2017
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This article includes 9 Primary studies 9 Primary studies (9 references)

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OBJECTIVE: Rasagiline is a second-generation potent selective inhibitor of monoamine oxidase-B. The aim of the study was to analyze the effectiveness of rasagiline in treatment of Parkinson's disease (PD), both as monotherapy and combination therapy. METHODS: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until 9 March 2016 using the keywords: Rasagiline, Azilect, Parkinson's disease. Randomized controlled trials of patients with PD who were randomized to treatment with rasagiline or placebo were included. Outcomes were unified Parkinson's disease rating scale (UPDRS) and the three subscales. RESULTS: Ten studies fulfilled the inclusion criteria and 2709 patients were evaluated. The overall analysis revealed a significant improvement in change of total UPDRS scores in 1 mg/day and 2 mg/day rasagiline groups compared to placebo. Significant improvement in Part I (Mentation) of UPDRS scores was observed in 1 mg/day, but not in 2 mg/day rasagiline treatment group. Part II (ADL) and Part III (Motor) subscales significantly improved with both doses of rasagiline. Both monotherapy and combination therapy significantly improved total UPDRS scores. CONCLUSIONS: Our results confirm the efficacy of rasagiline in PD. Further studies are required to establish the optimal dose of rasagiline, as well as to determine its effectiveness in different combination therapy protocols. KEY MESSAGES Rasagiline treatment was associated with significant improvement of UPDRS scores and the scores of the subscales. Both monotherapy and combination therapy significantly improved total UPDRS scores. Effect of rasagiline on total UPDRS scores was not dose-dependent.

Systematic review

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Comparison for Efficacy and Tolerability among Ten Drugs for Treatment of Parkinson's Disease: A Network Meta-Analysis.

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Authors Zhuo C , Zhu X , Jiang R , Ji F , Su Z , Xue R , Zhou Y
Journal Scientific reports
Year 2017
Links Pubmed DOI PubMed Central

This article includes 109 Primary studies 100 Primary studies (109 references)

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Parkinson's disease (PD) is a long term disorder affects the central nervous system and we aim to determine the relative efficacy of the current available drugs used in PD. Firstly, we performed a systematic review in current literature and eligible studies were retrieved from online databases, relevant data were extracted. Efficacy of these medications was assessed by different Unified Parkinson's Disease Rating Scales (UPDRS). Mean difference (MD) and odds ratio (OR) were produced by pairwise or network meta-analysis (NMA). Finally, we performed a cluster analysis for the included medications with respect to their surface under the cumulative ranking curve (SUCRA). Pairwise meta-analysis suggests that selegiline had a higher ranking in UPDRS II, UPDRS III and UPDRS total than bromocriptine and levodopa. Selegiline was more tolerable than bromocriptine (OR = 0.62, CI: 0.39 to 0.98) and pramipexole was less tolerable than levodopa (OR = 1.43, CI = 1.00 to 2.04). Results of NMA indicate that patients with levodopa, pramipexole, ropinirole and selegiline exhibited a significantly improved UPDRS III than those with lazabemide. To sum up, levodopa, selegiline, ropinirole and rotigotine were recommended for PD patients as they appeared relatively high efficacy and tolerability.

Systematic review

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Non-Ergot Dopamine Agonists Do Not Increase the Risk of Heart Failure in Parkinson's Disease Patients: A Meta-Analysis of Randomized Controlled Trials.

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Journal Journal of clinical medicine research
Year 2016
Links Pubmed DOI PubMed Central

This article includes 27 Primary studies 27 Primary studies (27 references)

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BACKGROUND: In recent years, some observational studies suggested that pramipexole, a non-ergot dopamine agonist (DA) used for the treatment of Parkinson's disease (PD), may increase the risk of heart failure (HF). However, the limitations inherent in observational studies made it difficult to determine whether the excess of incident HF was related to the drug or to other determinants. Thus, some concerns remained regarding the increased putative HF risk associated with non-ergot DAs as a class or individually. METHODS: In our meta-analysis, primary endpoint was the risk of incident HF in patients with PD treated with non-ergot DAs compared to those treated with monotherapy with levodopa. Secondary outcome measures were all-cause mortality and cardiovascular events. For these purposes, only randomized controlled trials (RCTs) were considered, provided that they offered complete outcome data pertaining to the incident HF, all-cause mortality and risk of cardiovascular events. Systematic searches were performed in the databases of PubMed, Embase and ClinicalTrial.gov up to May 2015. The effect size was estimated using the pooled relative risk (RR) of non-ergot DAs versus placebo on incident HF as well as on all-cause mortality or cardiovascular events. RESULTS: Six out of 27 RCTs reported at least one case of incident HF; therefore, we included them in the RR estimate, whereas 13 RCTs were included in the meta-analysis for mortality rates and 22 RCTs were included to evaluate cardiovascular events. Treatment with non-ergot DAs did not reveal an increase in the risk of incident HF as compared with the placebo group (pooled RR: 0.95; 95% CI: 0.30 - 2.90; P = 0.893). Similarly, patients treated with non-ergot DAs did not show any significant differences compared to controls with regard to all-cause mortality (pooled RR: 0.617; 95% CI: 0.330 - 1.153; P = 0.13) as well as with regard to cardiovascular events (pooled RR: 1.067; 95% CI: 0.663 - 1.717; P = 0.789). CONCLUSIONS: The use of non-ergot DAs in PD patients was not associated with an increased risk of incident HF, nor was it shown to increase the overall mortality or the risk of cardiovascular events compared to the PD patients taking monotherapy with levodopa alone. However, larger studies are warranted to confirm the cardiovascular safety of non-ergot DAs for PD management.

Systematic review

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Working capacity of patients with Parkinson's disease - A systematic review.

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Authors Koerts J , König M , Tucha L , Tucha O
Journal Parkinsonism & related disorders
Year 2016
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This article includes 13 Primary studies 13 Primary studies (13 references)

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INTRODUCTION: Parkinson's disease (PD) is characterized by motor and non-motor symptoms and has a median age-of-onset around 55 years. Many PD patients are thus diagnosed before reaching retirement age and it is likely that they are confronted with a reduced working capacity or loss of employment. This systematic literature review gives an overview of the research conducted on work capacity in PD. METHODS: A systematic literature search was performed in PsycINFO and PubMed (Keywords: "Parkinson" or "Parkinson's disease" combined with "employment", "work", "working", "retire" or "retirement"). RESULTS: Thirteen studies were identified and showed that PD patients retired 4-7 years earlier than the general population. Furthermore, 23%-75% of patients report that they retired early because of PD and slowness and fatigue were reported as the most debilitating symptoms in relation to working capacity. Early retirement of PD patients is associated with high societal costs and a high loss of individual lifetime earnings. Although many employed PD patients asked for adjustments at their workplace, their employers did not always support these. CONCLUSIONS: PD has a detrimental effect on working capacity and is associated with high costs. Employed PD patients do not, however, always receive the support they need. It is therefore very relevant that employers and patients are informed about strategies and techniques developed for counteracting symptoms of PD which might support patients to stay in the workforce for a longer period of time.

Systematic review

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Safety and efficacy of rasagiline in addition to levodopa for the treatment of idiopathic Parkinson's disease: A meta-analysis of randomised controlled trials.

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Authors Cai JP , Chen WJ , Lin Y , Cai B , Wang N
Journal European Neurology
Year 2015
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This article includes 3 Primary studies 3 Primary studies (3 references)

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BACKGROUND: To assess the safety and efficacy of rasagiline for the treatment of Parkinson’s disease (PD) among individuals currently receiving levodopa. METHODS: A systematic literature search was conducted to identify randomised controlled trials (RCT) comparing rasagiline with placebo/no treatment in individuals with PD currently receiving levodopa. Outcome measures included improvement in motor functions; symptomatic improvement; improvement in quality of life; adverse effects. Random-effect meta-analytical techniques were conducted for the outcome measure and subgroup analyses. RESULTS: Three RCTs were included (n = 1002). The results showed significantly greater improvements in daily ‘on’ time without dyskinesia in levodopa-treated participants with idiopathic PD receiving 1 mg/day rasagiline compared to placebo (n = 712, 2 RCTs, MD 0.80, CI 0.45 to 1.15; p &lt; 0.00001), and significantly greater improvements in Unified Parkinson’s Disease Rating Scale motor performance scores during ‘on’ time in participants receiving 0.5– 1 mg/day rasagiline (0.5 mg/day: n = 282, MD –2.91, CI –4.59 to –1.23; p = 0.0007; 1 mg/day: n = 712, 2 RCTs, MD –2.91, CI –4.02 to –1.80; p &lt; 0.00001). There were no significant differences in adverse effects. CONCLUSION: 0.5 to 1 mg/day rasagiline in addition to levodopa is a safe and well-tolerated combination therapy for individuals with Parkinson’s disease. (PsycInfo Database Record (c) 2024 APA, all rights reserved)

Systematic review

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Rasagiline for Parkinson's disease: A meta-analysis

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Authors , YANG Xin-ling
Journal 中国循证医学杂志 (Chinese Journal of Evidence-Based Medicine)
Year 2014
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This article includes 6 Primary studies 6 Primary studies (6 references)

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Objective: To systematically review the effectiveness and safety of rasagiline for Parkinson's disease. Methods: Databases including The Cochrane Library (Issue 3, 2013), Web of Science, MEDLINE (Ovid), PubMed, CBM, CNKI, WanFang Data and VIP were electronically searched from inception to March 2013 for randomized controlled trials (RCTs) on rasagiline for Parkinson's disease. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted the data, and assessed the methodological quality of included studies. Meta-analysis was performed using RevMan 5.1 software. Results: In total, 6 studies involving 2 865 patients were included. The results of meta-analyses indicated that, compared with placebo, rasagiline 2 mg/d and 1 mg/d was significantly effective (MD= -3.16, 95%CI -3.21 to -3.11, P<0.000 01; MD= -3.01, 95%CI -3.06 to -2.96, P<0.000 01). Rasagiline 1 mg/d was more effective than rasagiline 2 mg/d in the treatment of early PD (MD= -0.65, 95%CI -0.73 to -0.57, P<0.000 01). There was no significant difference between rasagiline and placebo in the incidences of nausea, headache, and dizziness (nausea: OR=0.72, 95%CI 0.49 to 1.07, P=0.60; headache: OR=1.02, 95%CI 0.70 to 1.49, P=0.91; dizziness: OR=0.87, 95%CI 0.49 to 1.55, P=0.35). Conclusion: Rasagiline is effective for early Parkinson's disease, and the dosage 1 mg/d is better than 2 mg/d based on current limited evidence. Rasagiline has a good tolerance and safety. Due to the limited quantity of the included studies and the evidence with limited strength, further high-quality RCTs are needed to verify the aforementioned conclusion. © 2014 Editorial Board of Chin J Evid-based Med.