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Doubt Cast on Initial Dopamine Agonists for Parkinson Disease

Initiating Parkinson disease treatment with the dopamine agonist bromocriptine conferred no long-term advantages over initial levodopa therapy.

Should levodopa be the initial therapy for a patient with Parkinson disease (PD)? Or should therapy begin with a dopamine agonist, as is sometimes advocated to reduce later motor complications of levodopa (fluctuations and dyskinesias)? The PD Research Group of the U.K. reports the final, 14-year findings in a large PD cohort initially randomized to levodopa or a dopamine agonist (bromocriptine), allowing for later addition of the other drug or additional therapies. Of 782 patients recruited, three quarters died during follow-up and 166 completed the final assessment.

Initial agonist therapy conferred no long-term advantage in motor-complication rates or mortality. Moreover, final PD motor scores were modestly but significantly better in the initial-levodopa group. The investigators and an editorialist also argue that evidence is lacking that other, newer dopamine agonists work better than bromocriptine.

Comment: These findings add to growing evidence that early agonist treatment of PD does not provide long-term advantages over starting treatment with levodopa. Moreover, although all shorter-term trials (2–5 years) have consistently revealed lower motor-complication frequencies with agonists, this finding has been offset by less-satisfactory control of PD symptoms compared with levodopa. In addition, early motor complications of levodopa therapy often are either clinically unimportant or easily controlled with medication adjustments. Later in the disease course, motor complications of levodopa therapy contribute less to disability than do levodopa-refractory motor symptoms, dysautonomia, and dementia. Finally, there is no intuitive reason to use an agonist as the initial drug in order to limit later motor complications of levodopa; such complications should respond similarly if the agonist is added after they develop.

— J. Eric Ahlskog, MD, PhD

Dr. Ahlskog is a Consultant in Neurology, Mayo Clinic, Rochester, MN.

Published in Journal Watch Neurology September 30, 2008

Citation(s):

Katzenschlager R et al. Fourteen-year final report of the randomized PDRG-UK trial comparing three initial treatments in PD. Neurology 2008 Aug 12; 71:474.

• Original article (Subscription may be required)
• Medline abstract (Free)

Weiner WJ and Reich SG. Agonist or levodopa for Parkinson disease?: Ultimately, it doesn’t matter; neither is good enough. Neurology 2008 Aug 12; 71:470.

• Original article (Subscription may be required)
• Medline abstract (Free)