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To the Editor:
The well-considered editorial1 and two reviews2,3⇓ on therapeutic decisions in Parkinson’s disease (PD) missed several points and some rationales are suspect.
Trials of pramipexole4 and ropinirole5 versus levodopa were discounted. The greater dyskinesias with levodopa were attributed to more aggressive treatment interpreted from differences on the Unified Parkinson Disease Rating Scale (UPDRS) motor scores. However, physicians were blinded and could not have utilized different criteria for adequate control. This is supported by the lack of significant difference in the UPDRS activities of daily living (ADL) scores. It is possible that the differences in the UPDRS motor scores were an artifact. Factor analysis demonstrated that certain symptom domains may have a disparate effect on the scores of the UPDRS motor scores.6 Thus, a slight and perhaps clinically insignificant advantage of levodopa among these symptoms could skew the motor score.
Were differences in UPDRS motor scores sufficient to explain the differences in dyskinesia? From the published data,5 174 patients would have to be treated have a 90% chance of detecting a significant difference at the p < 0.05 level (Stata, Stata Corporation, College Station, TX). Conversely, only 80 patients would have to be treated to see a significant difference in the prevalence of dyskinesias. Before the introduction of levodopa, only 49 patients would have to be treated.
The higher risks of short-term and lower efficacy of dopamine agonists were used as straw-man arguments. The reversible acute side effects are qualitatively different than potentially irreversible dyskinesias. For patients achieving adequate control on either medication, the dopamine agonists are just as efficacious as levodopa. Also, discounting the consequences of dyskinesia skews risk/benefit considerations.
Although not intentional, the lack of smoking gun evidence may give some the impression of immunity for any position. Alternative explanations …
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