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Dr. Fernandez

Post of the Week: Dopamine Agonists

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What are dopamine agonists?

 

Dopamine agonists are a class of drug that exert their clinical benefits through the direct stimulation of dopamine receptors in the brain. Dopamine agonists are generally grouped into two: the ergot derivatives (bromocriptine and pergolide) and those that have a nonergot structure (pramipexole, ropinirole, and rotigotine). The ergot-derived dopamine agonists are rarely used nowadays. Bromocriptine has been consistently found to be inferior in efficacy when compared head-to-head with the newer dopamine agonists. Pergolide has been pulled out of the market because of its risk in developing potentially irreversible valvular defects.

 

Several trials have explored the clinical benefits of dopamine agonists in patients with early Parkinson’s disease. Pramipexole was evaluated in a head-to-head trial with levodopa that assessed changes in the parkinson motor scores as well as occurrences of dopaminergic complications (wearing off, dyskinesias, and on-off fluctuations) (Parkinson Study Group 2000). This study found that while pramipexole treatment resulted in significantly less wearing off, dyskinesias, and “on-off” motor fluctuations (28%) compared with levodopa (51%), pramipexole was not as powerful in relieving Parkinson’s disease symptoms as measured by change in the Parkinson motor scores. This is true of every dopamine agonist that compared itself to levodopa: they each had lesser incidence of motor fluctuations and dyskinsias, but had inferior Parkinson motor scores compared to levodopa. Thus we know that while levodopa use may result in earlier onset of motor fluctuations, it is still the most efficacious (and one of the cheapest) drug we have to date. In terms of safety and tolerability, significantly more patients taking pramipexole experienced somnolence, hallucinations, and generalized and peripheral edema compared with those in the levodopa group (Parkinson Study Group 2000). Again, this is a common theme noticed with each dopamine agonist pitted against levodopa: the patients on dopamine agonists experienced more cognitive and behavioral side effects (such as hallucinations), more nausea, lightheadedness and more sleepiness.

 

Similarly, a 5-year study of the incidence of dyskinesias in 268 PD patients treated with ropinirole found that early use of ropinirole significantly reduced the risk of dyskinesia (by a factor of almost 3) compared to the patients treated with levodopa, but there was a significant difference in Parkinson motor scores favoring levodopa treatment (Rascol et al 2000). Likewise, adverse events were greater among the ropinirole patients than the levodoa patients, with significantly more individuals experiencing hallucinations (17.3% vs 5.6%).

 

In summary, our trial results and clinical experience suggest that, compared to the efficacy observed with levodopa, the use of dopamine agonists results in less effective relief of motor symptoms and often is associated with more treatment-related side effects, especially in the elderly (nausea, hallucinations, postural hypotension, and drowsiness) (Guttman 2003). However, this should be balanced against data suggesting their use may reduce the risk of motor complications associated with disease progression compared to initial use with levodopa therapy.

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An excellent recap ... seems to come down to picking which of the downsides of levadopa vs. the DA one wants to deal with. Right now I am only on Azilect but will soon start with the next level of medication. My doctor recommends the levadopa path primarily because of the drowsiness impact if the DA.

 

As I don't want to fall asleep behind the wheel or have strange behavioral implications, I agree with the doctor.

 

Rich

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