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To the Editor:
Given the ongoing controversy concerning selegiline’s toxicity, we read with interest the study by Donnan et al.1 Although we endorse their primary conclusion affirming selegiline’s safety, we were perplexed by their other finding that levodopa monotherapy increases mortality in patients with PD.1 Their caution in interpreting the data is laudable, given the limitations of their study. They concede that their number of subjects is small (total of 56 in all three groups) and clinical details concerning their patients are virtually nonexistent. Patients were not seen nor were their medical charts reviewed. Rather, the investigators assumed a diagnosis of PD if an antiparkinsonian drug prescription was identified in a regional pharmaceutical database.
The mortality findings in the study of Donnan et al. are surprising.1 The levodopa-treated patients were presumed to have recent onset parkinsonism (presumably receiving their first levodopa prescription), yet had a 2-year mortality rate of 50%. This is astoundingly high, and we are not aware of a previous levodopa trial with mortality rates even approaching this order of magnitude. Also, the majority of the levodopa monotherapy patients who died had their cause of death listed as stroke, myocardial infarction, or congestive heart failure. Are we to conclude that levodopa monotherapy accelerates atherosclerosis? Studies addressing PD and vascular disease have found just the opposite, or no causal relationship.2-4⇓⇓
The results of the Donnan et al. study1 contrast with a virtually identically designed investigation that included a vastly larger number of subjects (12,621).5 In the latter study, an opposite although not significant trend was noted, with increased mortality associated with selegiline administration, in comparison to levodopa monotherapy.5 The authors of the accompanying editorial acknowledge the methodologic shortcomings of the Donnan et al. study, yet comment that their findings are …
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