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Systematic review

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Indirect meta-analysis of randomised placebo-controlled clinical trials on rasagiline and selegiline in the symptomatic treatment of Parkinson's disease

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Journal Basal Ganglia
Year 2012
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This article is included in 1 Structured summary of systematic reviews 21 Structured summaries of systematic reviews (1 reference)

This article includes 21 Primary studies 21 Primary studies (21 references)

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Introduction: Selegiline and rasagiline are established in the treatment of Parkinson's disease. As no direct comparative randomised controlled trials on these drugs are available, an indirect meta-analysis was conducted. Objective: Goal of the meta-analysis was to examine the clinical differentiation between rasagiline and selegiline based on efficacy and safety in Parkinson's disease. Methods: Literature databases, study registries and references of relevant publications were the basis of our literature search. Studies were selected according to Jadad and Delphi criteria. The analysis used a fixed effects model based on standardised mean differences for efficacy criteria and risk differences of safety outcomes. As outcomes, UPDRS (primary) and UPDRS motor functions, mental and ADL, the Schwab and England scale, the off-time as well as safety as secondary outcomes were used. Results: Rasagiline showed a statistically significant advantage in the primary endpoint UPDRS total scores (monotherapy: p=. 0.048, sensitivity analysis: p=. 0.023; pooled analyses: p=. 0.043, sensitivity analysis p=. 0.014) and the secondary endpoint UPDRS motor functions (monotherapy: p=. 0.049, sensitivity analysis p=. 0.031; pooled analyses: not significant, sensitivity analysis: p=. 0.046). For the other secondary outcome parameters, a numerical advantage for rasagiline was found. Discontinuation rates due to adverse effects showed a tendency in favour of rasagiline. Risk for adverse events such as dizziness, hallucinations, diarrhoea and syncope were lower with rasagiline than selegiline (each p<. 0.15). Conclusion: This meta-analysis showed a statistically significant and clinically relevant advantage for rasagiline over selegiline in the primary endpoint. The superiority of rasagiline was further substantiated with advantages in tolerability and safety. © 2012 Elsevier GmbH.

Systematic review

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The effects of antidepressants in Parkinson's disease: A meta-analysis.

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Journal The International journal of neuroscience
Year 2008
Links Pubmed DOI

This article includes 24 Primary studies 21 Primary studies (24 references)

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This study explored the therapeutic effect of antidepressants in Parkinson's disease (PD) using a meta-analysis. Altogether, 24 placebo-controlled trials qualified for inclusion and revealed that tricyclic antidepressants (TCAs) had a greater antidepressant effect relative to selective serotonin reuptake inhibitors (SSRIs), <i>Qb</i>(1) = 8.87, p &lt; .01, and the mono-amine-oxidase inhibitor, selegiline, <i>Qb</i>(1) = 7.90, p &lt; .01. Whereas TCAs produced a significant side effect profile (odds ratio = 3.07), adverse events were negligible with SSRIs (odds ratio = 1.83) and selegeline (odds ratio = 1.63). Antidepressants can be beneficial for patients with PD. However, the choice of antidepressants needs to take depressive symptomatologies into account while monitoring side effects. (PsycINFO Database Record (c) 2016 APA, all rights reserved)

Systematic review

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The effects of antidepressants on the health outcomes of Parkinson's disease patients: A meta-analysis.

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Authors Frisina, Pasquale
Journal Dissertation Abstracts International: Section B: The Sciences and Engineering
Year 2006

This article includes 45 Primary studies 41 Primary studies (45 references)

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A meta-analysis of 44 placebo-controlled trials was conducted to examine three issues pertaining to the safety and efficacy of antidepressants in Parkinson's disease (PD). The first examined the magnitude and significance of the effects of antidepressants on depression. The second assessed whether or not antidepressants can provide salutary benefits to PD patients. Finally, the third issue was concerned with the side effect profile of antidepressants. To examine these three issues, a meta-analysis was conducted using Cohen's d as the effect size. The results show that TCAs produced a moderate antidepressant effect (d = .55, p = .01). TCAs also provided salutary benefits on motor outcomes (d = .30, p = .07), headache pain (d = 1.79, p = .00), and global psychological function (d = .81, p = .00). Although a significant effect size result was observed on adverse events (d = -.27, p = .02), they were deemed tolerable because PD patients subjectively evaluated their TCA medication positively (d = 1.02, p = .01). SSRIs produced a robust antidepressant effect on moderately depressed PD patients (d = .44, p &lt; .05). A modestly positive and significant effect size result was observed with SSRIs on motor function (d = .34, p &lt; .05), and there were no significant side effects (d = -.002, p = .50). These results provide evidence that SSRIs can be used to treat depression without the fear of worsening PD. Finally, selegeline did not improve depression when given at a dose where it was influencing dopamine metabolism (i.e., 10 mg daily). However, the MAO-B inhibitor did improve motor function (d = .36, p &lt; .00), global psychological functioning (d = .21, p &lt; .00), and health-related quality of life (d = .23, p &lt; .00). Few effects were observed with selegeline (d = -.07, ns), especially with mortality (d = -.06, p = .10) and depression (d = .15, p = .06). All things considered, the decision to choose between antidepressant classes should be carefully considered and monitored on an individual basis, weighing (and/or ranking) the benefits of improving depressive symptomatology together with the risk of creating and tolerating side effects. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Systematic review

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Monoamine oxidase B inhibitors for early Parkinson's disease

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Journal Cochrane Database of Systematic Reviews
Year 2005
Links Pubmed DOI PubMed Central

This article includes 52 Primary studies 45 Primary studies (52 references)

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BACKGROUND: Monoamine oxidase B (MAO-B) inhibitors slow disease progression in Parkinson's disease (PD) but clinical trials have produced conflicting results. OBJECTIVES: To assess the evidence from randomised controlled trials for the effectiveness and safety of long-term use of MAO-B inhibitors in early PD. SEARCH METHODS: We searched the following electronic databases: Cochrane Central Register of Controlled trials (CENTRAL) (The Cochrane Library Issue 11, 2011), MEDLINE (last searched 8th November 2011) and EMBASE (last searched 8th November 2011); and handsearched neurology and movement disorders conference proceedings, checked reference lists of relevant studies and contacted other researchers. SELECTION CRITERIA: We included all unconfounded randomised controlled trials that compared a MAO-B inhibitor with control, in the presence or absence of levodopa or dopamine agonists, in patients with early PD where treatment and follow up lasted at least one year. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed the methodological quality, and extracted the data. Some additional data were provided by the original authors. Random-effects models were used to analyse results, where appropriate. MAIN RESULTS: Twelve trials were included (2514 patients, average follow-up six years), 11 using selegiline. The methodological quality was reasonable although concealment of allocation was definitely adequate in only five trials. MAO-B inhibitors were not associated with a significant increase in deaths (odds ratio (OR) 1.12; 95% confidence interval (CI) 0.90 to 1.41). They provided small benefits over control in impairment (weighted mean difference (WMD) for change in motor UPDRS score 3.79 points less with MAO-B inhibitors; 95% CI 2.27 to 5.30) and disability (WMD for change in UPDRS ADL score 1.49 less; 95% CI 0.49 to 2.49) at one year which may not be clinically significant. There was a levodopa-sparing effect with MAO-B inhibitors, which was associated with a significant reduction in motor fluctuations (OR 0.73; 95% CI 0.58 to 0.91) but not dyskinesia (OR 0.96; 95% CI 0.76 to 1.22). The reduction in motor fluctuations was, however, not robust in sensitivity analyses. There was a trend to more withdrawals due to adverse events with MAO-B inhibitors (OR 1.72; 95% CI 0.98 to 3.01). AUTHORS' CONCLUSIONS: MAO-B inhibitors (more specifically selegiline which contributes most of the data) do not appear to delay disease progression in terms of improved survival but may reduce later motor fluctuations. At present, we do not feel these drugs can be recommended for routine use in the treatment of early Parkinson's disease.

Systematic review

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Monoamine oxidase type B inhibitors in early Parkinson's disease: Meta-analysis of 17 randomised trials involving 3525 patients.

Journal BMJ (Clinical research ed.)
Year 2004
Links Pubmed DOI PubMed Central

This article is included in 1 Structured summary of systematic reviews 17 Structured summaries of systematic reviews (1 reference)

This article includes 23 Primary studies 17 Primary studies (23 references)

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OBJECTIVE: To quantify more reliably the benefits and risks of monoamine oxidase type B inhibitors (MAOBIs) in early Parkinson's disease. Data sources: Searches of the Cochrane Library, Medline, Embase, PubMed, and Web of Science for years 1966-2003, plus major journals in the field, abstract books, and proceedings of meetings, for randomized trials comparing MAOBIs with placebo or levodopa. Data extraction: Available data on mortality, motor complications, side effects, treatment compliance, and clinician rated disability (for example, unified Parkinson's disease rating scale) were extracted from 17 trials and combined using standard meta-analytic methods. RESULTS: No significant difference in mortality existed between patients on MAOBIs and control patients (odds ratio 1.13,95% confidence interval 0.94 to 1.34; P=0.2). Patients randomised to MAOBIs had significantly better total scores, motor scores, and activities of daily living scores on the unified Parkinson's disease rating scale at three months compared with patients taking placebo; they were also less likely to need additional levodopa (0.57,0.48 to 0.67; P&lt;0.00001) or to develop motor fluctuations (0.75,0.59 to 0.95; P=0.02). No difference existed between the two groups in the incidence of side effects or withdrawal of patients. CONCLUSIONS: MAOBIs reduce disability, the need for levodopa, and the incidence of motor fluctuations, without substantial side effects or increased mortality. However, because few trials have compared MAOBIs with other antiparkinsonian drugs, uncertainty remains about the relative benefits and risks of MAOBIs. Further large, long term comparative trials that include patient rated quality of life measures are needed. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Systematic review

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Diagnosis and treatment of Parkinson's disease: a systematic review of the literature.

Journal Evidence report/technology assessment (Summary)
Year 2003
Links Pubmed PubMed Central

This article is included in 2 Structured summaries of systematic reviews 180 Structured summaries of systematic reviews (2 references)

This article includes 180 Primary studies 180 Primary studies (180 references)

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