Safety and efficacy of tolcapone in Parkinson's disease: systematic review.
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ABSTRACT: Purpose
Tolcapone is an efficacious catechol-O-methyltransferase inhibitor for Parkinson's disease (PD). However, safety issues hampered its use in clinical practice. We aimed to provide evidence of safety and efficacy of tolcapone by a systematic literature review to support clinicians' choices in the use of an enlarging PD therapeutic armamentarium.Methods
We searched PubMed for studies on PD patients treated with tolcapone, documenting the following outcomes: liver enzyme, adverse events (AEs), daily Off-time, levodopa daily dose, unified Parkinson's disease rating scale (UPDRS) part-III, quality of life (QoL), and non-motor symptoms. FAERS and EudraVigilance databases for suspected AEs were interrogated for potential additional cases of hepatotoxicity.Results
Thirty-two studies were included, for a total of 4780 patients treated with tolcapone. Pertaining safety, 0.9% of patients showed liver enzyme elevation > 2. Over 23 years, we found 7 cases of severe liver injury related to tolcapone, 3 of which were fatal. All fatal cases did not follow the guidelines for liver function monitoring. FAERS and EudraVigilance database search yielded 61 reports of suspected liver AEs possibly related to tolcapone. Pertaining efficacy, the median reduction of hours/day spent in Off was 2.1 (range 1-3.2), of levodopa was 108.9 mg (1-251.5), of "On" UPDRS-III was 3.6 points (1.1-6.5). Most studies reported a significant improvement of QoL and non-motor symptoms.Conclusion
Literature data showed the absence of relevant safety concerns of tolcapone when strict adherence to hepatic function monitoring is respected. Given its high efficacy on motor fluctuations, tolcapone is probably an underutilized tool in the therapeutic PD armamentarium.
SUBMITTER: Artusi CA
PROVIDER: S-EPMC8128808 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND AND OBJECTIVE: Safinamide is a novel anti-parkinsonian drug with possible anti-dyskinetic properties. Parkinson's disease (PD) is a complex disease. The objective of this systematic review and meta-analysis is to evaluate the efficacy and safety of safinamide administration compared to placebo in PD patients on multiple outcomes.MethodsPubMed, EMBASE, Cochrane CENTRAL, LILACS, and trial databases were searched up to 23 December 2020 for randomized controlled studies (RCTs) comparing safinamide to placebo, alone or as add-on therapy in PD. Data were extracted from literature and regulatory agencies. Primary outcomes were ON-time without troublesome dyskinesia, OFF-time, and Unified Parkinson's Disease Rating Scale (UPDRS) section III (UPDRS-III). Secondary outcomes included any dyskinesia rating scale (DRS), ON-time with troublesome dyskinesia, UPDRS-II, and Parkinson's Disease Questionnaire 39 (PDQ-39). In order to estimate mean difference (MD) and odds ratios with 95% confidence intervals (CI), generic inverse variance and Mantel-Haenszel methods were used for continuous and dichotomous variables, respectively. Analyses were performed grouping by PD with (PDwMF) or without (PDwoMF) motor fluctuations, safinamide dose, and concomitant dopaminergic treatment. Summary of findings with GRADE were performed.ResultsSix studies with a total of 2792 participants were identified. In PDwMF patients, safinamide 100 mg as add-on to levodopa (L-dopa) significantly increased ON-time without troublesome dyskinesia (MD = 0.95 h; 95% CI from 0.41 to 1.49), reduced OFF-time (MD = - 1.06 h; 95% CI from - 1.60 to - 0.51), and improved UPDRS-III (MD = - 2.77; 95% CI from - 4.27 to - 1.28) with moderate quality of evidence. Similar results were observed for the 50 mg dose. However, the quality of evidence was moderate only for ON-time without troublesome dyskinesia, whereas for OFF-time and UPDRS-III was low. In PDwoMF patients taking a single dopamine agonist, safinamide 100 mg resulted in little to no clinically significant improvement in UPDRS-III (MD = - 1.84; 95% CI from - 3.19 to - 0.49), with moderate quality of evidence. Conversely, in PDwoMF patients, the 200 mg and 50 mg doses showed nonsignificant improvement in UPDRS-III, with very low and moderate quality of evidence, respectively. In PDwMF patients taking safinamide 100 mg or 50 mg, nonsignificant differences were observed for ON-time with troublesome dyskinesia and DRS, with high and low quality of evidence, respectively. In the same patients, UPDRS-II was significantly improved at the 100 mg and 50 mg dose, with high and moderate quality of evidence. In PDwoMF, UPDRS-II showed a little yet significant difference only at 100 mg, with low quality of evidence. PDQ-39 resulted significantly improved only with the 100 mg dose in PDwMF, with low quality of evidence.ConclusionOverall, safinamide is effective in PDwMF patients taking L-dopa both at 100 and 50 mg daily. Evidence for efficacy in early PD is limited. Further trials are needed to better evaluate the anti-dyskinetic properties of safinamide.
| S-EPMC8004480 | biostudies-literature
Project description:ObjectiveClinical data has recently shown an association between Parkinson's disease (PD), Dementia with Lewy bodies (DLB), and zonisamide. The purpose of this study was to thoroughly evaluate the efficacy and safety of zonisamide in PD and DLB.MethodsPubmed, the Cochrane Library, Web of Science, and Embase databases were searched for all randomized clinical trials (RCTS) on the role of zonisamide in PD and DLB that were completed by April 18, 2022. UPDRS II (off) total score, UPDRS III total score, Daily "off" time, and UPDRS Part IV, Nos. 32, 33, and 34 were used as clinical efficacy endpoints. Adverse events reported in the RCTs will be considered in the final safety analysis. To better understand the effect of zonisamide on the efficacy and safety of PD and DLB, the UPDRS III total score and the six overlapping adverse events were examined in subgroups. Either a fixed effects model analysis (OR) or a random effects model analysis (MD) is used to figure out the mean difference (MD) and the relative risk.ResultsSeven articles involving 1749 patients (916 PD and 833 DLB) were included in this study. Compared to the control group, zonisamide could significantly reduce the UPDRS III total score in patients with PD and DLB (WMD-2.27 [95% CI: -3.06, -1.48], p < 0.0001). For patients with PD, compared to the control group, zonisamide could significantly reduce the UPDRS II (off) total score (WMD-0.81 [95% CI: -1.36, -0.26], p = 0.004), daily "off" time (WMD-0.67 [95% CI: -1.10, 0.24], p = 0.002), and UPDRS part IV, No. 32 worsen (OR-3.48 [95% CI: 1.20, 10.10], p = 0.02). In terms of safety, compared with the control group, for patients with DLB, zonisamide could significantly increase the incidence of contusion (OR-0.60 [95% CI: 0.38, 0.96], p = 0.03) and may increase the probability of reduced appetite (OR-3.13 [95% CI: 1.61, 6.08], p = 0.0008). And for patients with PD, zonisamide may increase the probability of somnolence (OR-2.17 [95% CI: 1.25, 3.76], p = 0.006).ConclusionsFor the analysis of the current study results, our results show that zonisamide could improve the motor function in patients with PD and DLB and improve the activities of daily living (off) and wearing off and decrease the duration of dyskinesia in patients with PD. In terms of safety, the use of zonisamide significantly increases the probability of contusion in patients with DLB and may increase the probability of reduced appetite in patients with DLB and somnolence in patients with PD. Zonisamide appears to be a new treatment option for patients with PD and DLB. However, the effectiveness and safety of zonisamide in the treatment of PD and DLB need to be further investigated.
| S-EPMC9484885 | biostudies-literature
Project description:Background and objectiveIn Parkinson's disease (PD), wearing off and side effects of long-term medication and complications pose challenges for neurologists. Although Tai Chi is beneficial for many illnesses, its efficacy for PD remains uncertain. The purpose of this review was to evaluate the efficacy and safety of Tai Chi for PD.MethodsRandomized controlled trials (RCTs) of Tai Chi for PD were electronically searched by the end of December 2013 and identified by two independent reviewers. The tool from the Cochrane Handbook 5.1 was used to assess the risk of bias. A standard meta-analysis was performed using RevMan 5.2 software.ResultsTen trials with PD of mild-to-moderate severity were included in the review, and nine trials (n = 409) were included in the meta-analysis. The risk of bias was generally high in the blinding of participants and personnel. Improvements in the Unified Parkinson's Disease Rating Scale Part III (mean difference (MD) -4.34, 95% confidence interval (CI) -6.67--2.01), Berg Balance Scale (MD: 4.25, 95% CI: 2.83-5.66), functional reach test (MD: 3.89, 95% CI: 1.73-6.04), Timed Up and Go test (MD: -0.75, 95% CI: -1.30--0.21), stride length (standardized MD: 0.56, 95% CI: 0.03-1.09), health-related quality of life (standardized MD: -1.10, 95% CI: -1.81--0.39) and reduction of falls were greater after interventions with Tai Chi plus medication. Satisfaction and safety were high. Intervention with Tai Chi alone was more effective for only a few balance and mobility outcomes.ConclusionsTai Chi performed with medication resulted in promising gains in mobility and balance, and it was safe and popular among PD patients at an early stage of the disease. This provides a new evidence for PD management. More RCTs with larger sample size that carefully address blinding and prudently select outcomes are needed. PROSPERO registration number CRD42013004989.
| S-EPMC4057148 | biostudies-literature
Project description:Background: Safinamide, a recently developed drug with several mechanisms of action has been investigated as an add-on therapy for Parkinson's disease patients suffering from motor complications due to the usage of anti-Parkinson's medications such as levodopa and dopaminergic drugs. The aim of the study is to investigate the efficacy and safety of Safinamide as add-on therapy for Parkinson's disease patients. Methods: A computerized literature search was conducted of PubMed, EMBASE, ClinicalTrial.gov and Cochrane Library until August 2019. We selected relevant randomized controlled trials comparing safinamide groups to placebo groups. Relevant outcomes were pooled as mean difference (MD) and risk ratio (RR) using Review Manager 5.3. Results: We found that the overall MD of changes in "off-time" and "on time without troublesome dyskinesia" favored the safinamide group over the placebo group (MD -0.72 h, 95% CI -0.89 to -0.56 and MD 0.71 h, 95% CI 0.52 to 0.90, respectively). Additionally, the overall MD of change in Unified Parkinson's Disease Rating Scale part three (UPDRS III) favored the safinamide group (MD -1.83, 95% CI -2.43 to -1.23). In case of adverse events, the pooled meta-analysis did not favor the safinamide group over the placebo group. Conclusions: In this study, we provide class I evidence about the potential role of safinamide as an add-on therapy for Parkinson's disease patients suffering from motor fluctuations. However, a few included studies did not mention the data of important outcomes. Also, we report high risk of bias in individual studies. Future randomized controlled trials with different doses are recommended to provide more evidence for the efficacy and safety of safinamide as a treatment for motor complications of anti-Parkinson's medications.
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Project description:Objective: The effects of rotigotine transdermal patch (RTG) on the neuropsychiatric symptoms of Parkinson's disease (PD) outcomes remain controversial. The aim of this review was to determine the efficacy and safety of RTG on the neuropsychiatric symptoms of PD. Methods: In this systematic review and meta-analysis, PubMed, Cochrane Library, EMBASE, and Web of Science were searched for randomized controlled trials comparing RTG and placebo in PD up to May 10, 2021. We analyzed the data using Review Manager 5.2 software. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation Approach. In order to avoid false-positive results caused by random error, we use TSA software for trial sequential analysis (TSA). Results: We included 10 studies (1,844 patients). The meta-analysis showed that, compared with placebo, RTG can significantly improve the scores for Apathy Scale (MD = -1.68, 95% confidence interval, CI: -2.74 to -0.62, P = 0.002; moderate certainty), Beck Depression Inventory-II (MD = -1.19, 95% CI: -2.26 to -0.11, P = 0.03; moderate certainty), the Non-Motor Symptoms Scale (MD = -3. 66, 95% CI: -4. 30 to -3.01, P < 0.00001; moderate certainty), the sleep/fatigue domains of the Parkinson's Disease Non-motor Symptom Assessment Scale (MD = -2.03, 95% CI: -3.08 to -0.98, P = 0.0001; moderate certainty), the mood/apathy domains of the Non-motor Symptom Scale (MD = -2.48, 95% CI: -4.07 to -0.89, P = 0.002; high certainty), the eight-item Parkinson's Disease Questionnaire (MD = -4. 93, 95% CI: -6.79 to -3.07, P < 0.00001; moderate certainty), and the 39-item Parkinson's Disease Questionnaire (MD = -3.52, 95% CI: -5.25 to -1.79, P < 0.0001; high certainty). However, there was no statistically significant difference on the Snaith-Hamilton Pleasure Scale (MD = -0.12, 95% CI: -0.58 to 0.34, P = 0.61). Our results showed that RTG exerts a positive effect on sleep. According to the TSA, the results implied that, except for the Beck Depression Inventory-II, conclusive evidence have been obtained in the RTG group. It has been proven in our meta-analysis that rotigotine has good safety and tolerability. Conclusions: RTG can effectively improve the neuropsychiatric symptoms, sleep quality, and quality of life in patients with PD.
| S-EPMC8567083 | biostudies-literature
Project description:ObjectiveTo systematically evaluate the efficacy and safety of acupuncture therapy for neuropsychiatric symptoms in patients with Parkinson's disease.MethodsWe searched eight databases from their inception until 14 April 2024, including PubMed, Cochrane Library, Embase, Web of Science, SinoMed, China National Knowledge Infrastructure, China Science and Technology Periodical Database, and Wanfang Database. The search aimed to find randomized controlled trials assessing the effectiveness of acupuncture for neuropsychiatric symptoms in patients with Parkinson's disease. Literature screening and data extraction were performed independently by the authors. Meta-analysis was conducted using RevMan V.5.3 software, and Stata 17.0 software was used for detecting publication bias and performing sensitivity analysis.ResultsTwenty-eight studies, involving 2148 participants, met the inclusion criteria. The meta-analysis revealed that acupuncture therapy improved depression-related scale scores (standardized mean difference (SMD) = -0.70, 95%CI [-0.98, -0.42], p < 0.00001), anxiety-related scale scores (SMD = -0.78, 95% CI [-1.43, -0.14], p = 0.02), Montreal Cognitive Assessment scores (weighted mean difference (WMD) = 2.74, 95% CI [2.43, 3.05], p < 0.00001), Mini Mental State Examination scores (WMD = 2.36, 95% CI [0.78, 3.94], p = 0.003), Yale-Brown Obsessive Compulsive Scale scores, and Parkinson's Disease Questionnaire-39 scores (WMD = -2.66, 95% CI [-4.83, -0.49], p = 0.02) compared to controls.ConclusionThis review supports the application of acupuncture to reduce the severity of neuropsychiatric symptoms including depression, anxiety, and impulse control disorders, and to improve cognition and quality of life in patients with Parkinson's disease. The adverse effects associated with acupuncture, either alone or as adjunctive therapy, were relatively minor.
| S-EPMC11348633 | biostudies-literature
Project description:ObjectiveTo evaluate the efficacy and safety of botulinum toxin (BTX) for motor dysfunction in Parkinson's disease (PD).DesignSystematic review and meta-analysis.Data sourcesSearches of PubMed, EMBASE and the Cochrane Library, from database inception to 20 October 2022.Eligibility criteriaStudies reported in English with adult PD patients treated with BTX.Data extraction and synthesisPrimary outcomes were United Parkinson's Disease Rate Scale Section (UPDRS) III (or its items) and Visual Analogue Scale (VAS). Secondary outcomes were UPDRS-II (or its items), Freezing of Gait Questionnaire (FOG-Q), Timed Up and Go test (TUG) and treatment-related adverse events (TRAEs). Mean difference (MD) or standardised MD (SMD) before and after treatment with 95% CIs were used for continuous variables and risk ratios (RRs) with 95% CIs was used for TRAEs.ResultsSix randomised controlled trials (RCTs) and six non-RCTs (case series) were included (ntotal=224 participants, nRCT=165). No significant difference was found in pooled results of UPDRS-III (available in four RCTs and two non-RCTs, SMD=-0.19, 95% CI -0.98 to 0.60), UPDRS-II (four RCTs and one non-RCT, SMD=-0.55, 95% CI -1.22 to 0.13), FOG-Q (one RCT and one non-RCT, SMD=0.53, 95% CI -1.93 to 2.98) or the risk of TRAEs (five RCTs, RR 0.87, 95% CI 0.37 to 2.01). Significant decreases were found in pooled VAS score (three RCTs and five non-RCTs, MD=-2.14, 95% CI -3.05 to -1.23) and TUG (MD=-2.06, 95% CI -2.91 to -1.20) after BTX treatment.ConclusionsBTX may not be associated with motor symptoms alleviation, although it benefits pain alleviation and functional mobility improvement.
| S-EPMC10277107 | biostudies-literature
Project description:BackgroundNo curative therapy for mitochondrial disease (MD) exists, prioritizing supportive treatment for symptom relief. In animal and cell models ketones decrease oxidative stress, increase antioxidants and scavenge free radicals, putting ketogenic diets (KDs) on the list of management options for MD. Furthermore, KDs are well-known, safe and effective treatments for epilepsy, a frequent symptom of MD. This systematic review evaluates efficacy and safety of KD for MD.MethodsWe searched Pubmed, Cochrane, Embase and Cinahl (November 2020) with search terms linked to MD and KD. From the identified records, we excluded studies on Pyruvate Dehydrogenase Complex deficiency. From these eligible reports, cases without a genetically confirmed diagnosis and cases without sufficient data on KD and clinical course were excluded. The remaining studies were included in the qualitative analysis.ResultsOnly 20 cases (14 pediatric) from the 694 papers identified met the inclusion criteria (one controlled trial (n = 5), 15 case reports). KD led to seizure control in 7 out of 8 cases and improved muscular symptoms in 3 of 10 individuals. In 4 of 20 cases KD reversed the clinical phenotype (e.g. cardiomyopathy, movement disorder). In 5 adults with mitochondrial DNA deletion(s) related myopathy rhabdomyolysis led to cessation of KD. Three individuals with POLG mutations died while being on KD, however, their survival was not different compared to individuals with POLG mutations without KD.ConclusionData on efficacy and safety of KD for MD is too scarce for general recommendations. KD should be considered in individuals with MD and therapy refractory epilepsy, while KD is contraindicated in mitochondrial DNA deletion(s) related myopathy. When considering KD for MD the high rate of adverse effects should be taken into account, but also spectacular improvements in individual cases. KD is a highly individual management option in this fragile patient group and requires an experienced team. To increase knowledge on this-individually-promising management option more (prospective) studies using adequate outcome measures are crucial.
| S-EPMC8254320 | biostudies-literature
Project description:IntroductionSleep disorders are the main non-motor characteristics of Parkinson's disease (PD). The quality of life is significantly impacted by rapid eye movement sleep behaviour disorder (RBD). It is not clearly evidenced in the literature that some medications can reduce the dream activities of patients with PD and RBD and improve sleep quality. And, they have side effects that may increase the severity of this disease. To further understand which medication has better efficacy and fewer adverse effects for patients with PD and RBD, it is necessary to perform a network meta-analysis.Methods and analysisThis protocol is performed accordingly to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols and the Cochrane Collaboration Handbook.A thorough literature selection will be conducted up to September 2021 using PubMed, Cochrane Library (The Cochrane Database of Systematic Reviews) and Embase. We will not only include randomised controlled trials, but prospective, retrospective cohort, case-control, nested case-control, case-cohort, cross-sectional and case series. We will use the Cochrane Collaboration tool to assess the risk of bias. Pairwise and network meta-analyses will be conducted using the R netmeta package and Stata V.14.0. The relative ranking probability of the best intervention will be estimated using the surface under the cumulative ranking curve. Additionally, sensitivity analysis, subgroup analysis, quality assessment and publication bias analysis will be performed.Ethics and disseminationNo research ethics approval is required for this systematic review, as no confidential patient data will be used. We will disseminate our findings through publication in a peer-reviewed journal and conference presentations, and our review will support development of a BMJ Rapid Recommendations providing contextualised clinical guidance based on this body of evidence.Prospero registration numberCRD42020206958.
| S-EPMC8685944 | biostudies-literature
Project description:BackgroundNon-ergot dopamine agonists (NEDAs) have been used as monotherapy or as an adjunctive therapy to levodopa for many years. Novel long-acting formulations of NEDAs including pramipexole extended-release (ER), ropinirole prolonged-release (PR), and rotigotine transdermal patch have been developed. However, there is no strong evidence that a given NEDA is more potent than another. We performed a systematic review and network meta-analysis to evaluate the efficacy, tolerability and safety of six commonly used NEDAs in early Parkinson's disease (PD).MethodsSix NEDAs including piribedil, rotigotine transdermal patch, pramipexole immediate-release (IR)/ER, and ropinirole IR/PR were investigated. The efficacy outcomes including Unified Parkinson's Disease Rating Scale activities in daily life (UPDRS-II), motor function (UPDRS-III), and their subtotal (UPDRS-II + III), tolerability and safety outcomes were analyzed.ResultsA total of 20 RCTs (5,355 patients) were included in the current study. The result indicated that compared with placebo, all six investigated drugs had statistically significant differences in the improvement of UPDRS-II, UPDRS-III, and UPDRS-II + III (except ropinirole PR in UPDRS-II). There were no statistically significant differences between six NEDAs for the UPDRS-II and UPDRS-III. For UPDRS-II + III, the improvement of ropinirole IR/PR and piribedil were higher than that of rotigotine transdermal patch, and piribedil was higher than that of pramipexole IR. The surface under the cumulative ranking curve (SUCRA) indicated that piribedil resulted in best improvement in UPDRS-II and UPDRS-III (0.717 and 0.861, respectively). For UPDRS-II + III, piribedil and ropinirole PR exhibited similar improvement and both had high rates (0.858 and 0.878, respectively). Furthermore, piribedil performed better as monotherapy, ranking first in the improvement of UPDRS-II, III, and II + III (0.922, 0.960, and 0.941, separately). With regard to tolerability, there was a significant increase in overall withdrawals with pramipexole ER (0.937). In addition, the incidence of adverse reaction of ropinirole IR was relatively high (nausea: 0.678; somnolence: 0.752; dizziness: 0.758; fatigue: 0.890).ConclusionsIn this systematic review and network meta-analysis of six NEDAs, piribedil exhibited better efficacy, especially as monotherapy, and ropinirole IR was associated with a higher incidence of adverse events in patients with early PD.
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