Dopamine agonists appear least likely to cause dyskinesia, off times

Analysis points to potential benefits for people in Parkinson's early stages

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Among available dopamine agonists to treat early Parkinson’s disease, ropinirole is the least likely to cause dyskinesia, the  involuntary movements that can occur from long-term use of these and other Parkinson’s medications, a meta-analysis study suggests.

Pramipexole, meanwhile, may be the least likely to cause wearing off periods and on-off fluctuations, times when disease symptoms are not adequately controlled by medications.

The study, “Dopamine agonists versus levodopa monotherapy in early Parkinson’s disease for the potential risks of motor complications: A network meta-analysis,” was published in the European Journal of Pharmacology.

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Possibility of fewer motor complications with dopamine agonists

Parkinson’s is characterized by the loss of nerve cells that produce dopamine, a vital neurotransmitter responsible for transmitting electrical signals between nerve cells. Levodopa is its main medication, used to alleviate symptoms such as muscle rigidity that limit mobility. It occurs naturally within the body and acts as a precursor to dopamine.

However, wearing off periods are known with its use, times when the effects of levodopa diminish before the next dose can be taken, leading to fluctuations in how well motor symptoms are controlled throughout the day.

When levodopa is used for too long or its level is too high, patients also can experience dyskinesia, a type of uncontrolled, involuntary movement. Those with early stage or young-onset Parkinson’s are at higher risk of this complication.

Dopamine agonists, which work by mimicking dopamine in the brain, are less potent than levodopa. Yet previous work suggests they can reduce the likelihood of dyskinesia and other levodopa-associated motor complications. Which dopamine agonist may be best at doing this, however, is unclear.

Researchers in China tried to address this gap by analyzing data from multiple randomized controlled trials testing levodopa and/or any of four dopamine agonists: Parlodel (bromocriptine), pergolide, Mirapex (pramipexole), and ropinirole in early Parkinson’s patients.

Their study included nine randomized controlled trials involving a total of 2,112 patients who were followed for an average of 33 months (almost three years). Seven compared levodopa with either of the four dopamine agonists, and two compared ropinirole with either Parlodel or Mirapex.

As expected, levodopa was most likely to cause dyskinesia, followed by pergolide, Mirapex, ropinirole, and Parlodel. All dopamine agonists were associated with significantly lower rates of dyskinesia and wearing-off periods when compared with levodopa.

While Parlodel appeared to be the least likely to cause dyskinesia, use of this type of dopamine agonist is no longer recommended as a first-line treatment due to the risk of serious side effects, such as heart problems.

For this reason, ropinirole, originally sold as Requip (now discontinued in the U.S.) and available as a generic medication “may be a better choice for early [Parkinson’s] patients [to reduce] the risk of dyskinesia,” the researchers wrote.

Mirapex was found to be the least likely to cause both wearing off and on-off fluctuations.

Levodopa better at supporting patients’ motor function over time

Levodopa resulted in better improvements in motor function, as assessed using the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts 2 and 3, than any of the four dopamine agonists.

Among the different dopamine agonists, patients on Mirapex performed better in terms of motor function while those on Parlodel ranked last. Parlodel also resulted in more total trial withdrawals and withdrawals due to side effects.

These findings continued to hold true when the researchers looked at data from patients not yet using Parkinson’s medications or those on treatment for no longer than three months.

“Ropinirole as monotherapy [treatment with a single medication] is associated with a lower risk of dyskinesia while pramipexole is associated with lower risks of wearing-off and on-off fluctuations in early [Parkinson’s disease],” the researchers concluded.

Researchers noted that additional clinical trials in larger patient groups and with longer follow-up periods would be needed to validate these findings.

“To our knowledge, the available evidence is insufficient to make conclusions regarding the risk of motor complications between different [dopamine agonists] in long-term treatment of early [Parkinson’s disease], especially the risk of dyskinesia,” they wrote.