Comparisons Between Dopamine Agonists

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Tan and Jankovic (6) summarized 15 comparative trials between dopamine agonists, and reported conversion factors of 10:1 for bromocriptine to pergolide, 1:1 for pergolide to pramipexole, 1:6 for pergolide to ropinirole, and 10:6 for bromocriptine to ropinirole. Hanna et al. (56) followed 21 stable subjects on pergolide and switched them to pramipexole in a 1:1 ratio. Although not significant, levodopa dosages were reduced by 16.5%, and 13 of the 21 (62%) subjects reported improvement with the change in regimen. Hauser et al. reported the conversion of stable subjects on levodopa and pramipexole to levodopa and ropinirole in a 1:3 mg ratio. A gradual transition was better tolerated than a rapid change (57). However, in retrospect, the difficulties reported by subjects may have been improved with a higher conversion factor for ropinirole.

Although there are obvious difficulties when making direct comparisons in studies to determine dosage equivalence, a reasonable equation of relative dopamine agonist potency would suggest bromocriptine x 10 = pergolide = pramipexole = ropinirole x 6 on a mg:mg basis. Perhaps a better measure of treatment response is to review similar trials of dopamine agonist therapy. In the early PD population, UPDRS data are similar. Placebo-controlled studies of pramipexole and ropinirole found remarkably similar benefit. Another potential comparison is to evaluate trials comparing two active interventions, such as a dopamine agonist and levodopa. In the imaging trials of pergolide, pramipexole, and ropinirole, subjects treated with an agonist demonstrated similar benefit, which was less than that with levodopa.

The PELMOPET, CALM-PD, ropinirole 056, and REAL-PET trials may represent the most rigorous and careful information gathered about these compounds, and it is therefore useful to compare them (2-4). Subjects treated with pergolide at an average dosage of 3.23 mg/d demonstrated a UPDRS motor scale worsening of 3 points over 36 months, whereas subjects randomized to levodopa demonstrated an improvement of 2.5 points in the same time interval. Although the dopamine ago-nist/levodopa trials using pramipexole and ropinirole allowed for levodopa supplementation and had different durations, like the 5.5 point difference seen between pergolide and levodopa in the PELMOPET trial, the differences between pramipexole (- 3.4) and levodopa (-7.3) at 23.5 months (difference = 3.9 points) and ropinirole (-0.8) and levodopa (-4.8) at 60 months (difference=4 points) are similar. The neu-roimaging data from these investigations are also similar for dosages of pergolide 3.23 mg/d, pramipexole 2.78 mg/d, and ropinirole 16.5 mg/d. Modifications of these data to reflect a ratio of dopamine agonist to levodopa striatal decline produce percentages ranging from 52.6% to 65%. F-dopa PET demonstrates ropinirole striatal decline 65% of levodopa at 24 months and pergolide striatal decline 54.5% of levodopa at 36 months. SPECT imaging with p-CIT demonstrates 52.6%, 55.6%, and 62.7% pramipexole to levodopa decline at 22, 34, and 46 months of treatment, respectively. The imaging impact of added levodopa in the pramipexole and ropinirole groups is unknown.

In summary, similar designs between pergolide, pramipexole, and ropinirole demonstrate similar benefits in terms of levodopa dosage reduction, levodopa percent reduction, treatment responders, and decrease in off time in adjunctive therapy trials. In these studies, subject selection, methodological design, and data collected differed to the point that trends are less reliable than in the early patient studies, but, in general, similar improvements in all variables are seen.

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