Effect of selegiline on mortality in patients with Parkinson's disease

Olanow, C. Warren; Myllylä, Vilho V.; Sotaniemi, K. A.; Larsen, Jan Petter; Pålhagen, Sven; Przuntek, H.; Heinonen, Esa; Kilkku, Olavi; Lammintausta, Risto; Mäki-Ikola, O; Rinne, U. K.

doi:10.1212/wnl.51.3.825

Cited by 89 publications

(36 citation statements)

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“…The effect of selegiline, under the intention to treat assumption, was not statistically significant. A meta-analysis of five randomized trials (not including DATATOP) of selegiline or levodopa/placebo in patients with early Parkinson's disease with a mean follow-up of 4 years also did not find an increase in mortality in the selegiline treated group [5]. However, it is difficult to draw meaningful conclusions from this study because of the low overall death rate over 4 years (4%).…”

Section: Figurementioning

confidence: 55%

Disease progress and response to treatment as predictors of survival, disability, cognitive impairment and depression in Parkinson's disease

Nutt

Holford

2012

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The marked between variability in the rate of progression of Parkinson's disease severity assessed with a global functional score (Unified Parkinson' Disease Rating Scale, UPDRS) is recognized but its origin is uncertain and variously attributed to different subtypes of Parkinson's disease, life style, genetic variability and treatment. An increased risk of death in patients treated with selegiline has been reported but this is controversial. WHAT THIS STUDY ADDS• We used a hazard model approach to describe the time to clinical events (death, disability, depression and dementia). The time course of disease status changes was shown to be a key predictor of the risk of these events. Baseline motor subtype was not a predictor of outcome events. Selegiline was associated with an increased risk of death that was independent of its effect on disease status. AIMTo describe the time to clinical events (death, disability, cognitive impairment and depression) in Parkinson's disease using the time course of disease status and treatment as explanatory variables. METHODSDisease status based on the Unified Parkinson's Disease Rating Scale (UPDRS) and the time to clinical outcome events were obtained from 800 patients who initially had early Parkinson's disease. Parametric hazard models were used to describe the time to the events of interest. RESULTSTime course of disease status (severity) was an important predictor of clinical outcome events. There was an increased hazard ratio for death 1.4 (95% CI 1.31, 149), disability 2.75 (95% CI 2.30, 3.28), cognitive impairment 4.35 (95% CI 1.94, 9.74), and depressive state 1.43 (95% CI 1.26, 1.63) with each 10 unit increase of UPDRS. Age at study entry increased the hazard with hazard ratios of 49.1 (95% CI 8.7, 278) for death, 4.76 (95% CI 1.10, 20.6) for disability and 90.0 (95% CI 63.3-128) for cognitive impairment at age 60 years. Selegiline treatment had independent effects as a predictor of death at 8 year follow-up with a hazard ratio of 2.54 (95% CI 1.51, 4.25) but had beneficial effects on disability with a hazard ratio of 0.363 (95% CI 0.132, 0.533) and depression with a hazard ratio of 0.372 (95% CI 0.12, 0.552). CONCLUSIONSOur findings show that the time course of disease status based on UPDRS is a much better predictor of future clinical events than any baseline disease characteristic. Continued selegiline treatment appears to increase the hazard of death.

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Section: Figurementioning

confidence: 55%

Disease progress and response to treatment as predictors of survival, disability, cognitive impairment and depression in Parkinson's disease

Nutt

Holford

2012

Brit J Clinical Pharma

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“…A meta-analysis of prospective trials with longterm follow-up including patients with similar exposure to selegiline as in the UK Parkinson Disease Research Group study was performed. 26 There was no difference in mortality between selegiline and nonselegiline treatment groups. Analysis of levodopa plus selegiline versus levodopa alone did not reveal a difference in mortality rates.…”

Section: Selegilinementioning

confidence: 88%

Practice parameter: Initiation of treatment for Parkinson’s disease: An evidence-based review [RETIRED]

Miyasaki¹,

Martin²,

Suchowersky³

et al. 2002

Neurology

346

185

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Abstract-In 1993, the last AAN Practice Parameter on medical treatment of Parkinson's disease (PD) concluded that levodopa was the most effective drug for management of this disorder. Since then, a number of new compounds including non-ergot dopamine agonists (DA) and sustained-release levodopa have been released and studied. Thus, the issue of treatment in de novo PD patients warrants reexamination. Specific questions include: 1) does selegiline offer neuroprotection; 2) what is the best agent with which to initiate symptomatic treatment in de novo PD; and 3) is there a benefit of sustained release levodopa over immediate-release levodopa? Using evidence-based principles, a literature review using MEDLINE, EMBASE, and the Cochrane Library was performed to identify all human trials in de novo PD between 1966 and 1999. Only articles that fulfilled class I or class II evidence were included. Based on this review, the authors conclude: 1) Selegiline has very mild symptomatic benefit (level A, class II evidence) with no evidence for neuroprotective benefit (level U, class II evidence). 2) For PD patients requiring initiation of symptomatic therapy, either levodopa or a DA can be used (level A, class I and class II evidence). Levodopa provides superior motor benefit but is associated with a higher risk of dyskinesia. 3) No evidence was found that initiating treatment with sustained-release levodopa provides an advantage over immediate-release levodopa (level B, class II evidence).

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“…436 However, this study had methodological flaws, 437 and increased mortality in selegiline-treated patients was not observed in a meta-analysis of other trials. 438 A follow-up study of the DATATOP cohort similarly showed that cumulative exposure to deprenyl was not associated with increased mortality. 439 Rasagiline.…”

Section: Bbbmentioning

confidence: 99%

“…Levodopa, dopamine agonists and MAO-B inhibitors may all cause or exacerbate orthostatic hypotension, especially during the first weeks of treatment. 797 Indeed, it has been proposed that orthostatic hypotension induced by selegiline might lead to increased mortality, 798 but increased mortality with selegiline has not been confirmed in other studies 437,438 and all dopaminergic agents have the potential to aggravate hypotension. 797 Gradual dosage increases when initiating therapy or dose reductions in established patients can minimize the risk of orthostatic hypotension.…”

Section: Impulse Dyscontrol and Dopamine Dysregulation Disordersmentioning

confidence: 99%

The scientific and clinical basis for the treatment of Parkinson disease (2009)

Olanow¹,

Stern²,

Sethi³

2009

Neurology

Self Cite

760

658

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Parkinson disease (PD) is an age-related neurodegenerative disorder that affects as many as 1-2% of persons aged 60 years and older. With the aging of the population, the frequency of PD is expected to increase dramatically in the coming decades. Current therapy is largely based on a dopamine replacement strategy, primarily using the dopamine precursor levodopa. However, chronic treatment is associated with the development of motor complications, and the disease is inexorably progressive. Further, advancing disease is associated with the emergence of features such as freezing, falling, and dementia which are not adequately controlled with dopaminergic therapies. Indeed, it is now appreciated that these nondopaminergic features are common and the major source of disability for patients with advanced disease. Many different therapeutic agents and treatment strategies have been evaluated over the past several years to try and address these unmet medical needs, and many promising approaches are currently being tested in the laboratory and in the clinic. As a result, there are now many new therapies and strategic approaches available for the treatment of the different stages of PD, with which the treating physician must be familiar in order to provide patients with optimal care. This monograph provides an overview of the management of PD patients, with an emphasis on pathophysiology, and the results of recent clinical trials. It is intended to provide physicians with an understanding of the different treatment options that are available for managing the different stages of the disease and the scientific rationale of the different approaches. 1 PD is the second most common neurodegenerative disorder, with an average age at onset of about 60 years. An estimated 5 million people throughout the world have PD, with 1 million individuals each in the United States and in Europe with the disorder. PD affects approximately 0.3% of the population and 1% to 2% of those older than 60 years.2 With the aging of the population and the substantial increase in the number of at-risk individuals older than 60 years, it is anticipated that the prevalence of PD will increase dramatically in the coming decades.

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Effect of selegiline on mortality in patients with Parkinson's disease

Abstract: These results contrast with those of the PDRG-UK study and demonstrate no increase in mortality associated with selegiline treatment whether or not patients also received levodopa.

Cited by 89 publications

References 16 publications

Disease progress and response to treatment as predictors of survival, disability, cognitive impairment and depression in Parkinson's disease

Disease progress and response to treatment as predictors of survival, disability, cognitive impairment and depression in Parkinson's disease

Practice parameter: Initiation of treatment for Parkinson’s disease: An evidence-based review [RETIRED]

The scientific and clinical basis for the treatment of Parkinson disease (2009)

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