Dopamine agonists such as pramipexole, ropinirole, rotigotine, and apomorphine have long been recommended as initial therapy for younger patients with Parkinson’s disease, typically those younger than 65, in an effort to postpone the need for levodopa. However, concerns about their association with impulse control disorders (ICDs) — including gambling, hypersexuality, and compulsive shopping — have prompted a reassessment of their role in first-line treatment.

At a session during the 2026 French Language Neurology Days, two neurologists outlined their perspectives on the treatment approach for these patients. Although dopamine agonists provide important advantages over levodopa, they emphasized that their use should be guided by caution and tailored more closely to the individual patient.

According to the recommendations of the French National Authority for Health on the management of Parkinson’s disease, published in 2016, dopamine agonists should be the treatment of choice for as long as possible in young patients (aged < 65 years) with Parkinson’s disease. The goal is to “delay as long as possible” the start of levodopa, which is associated with severe dyskinesia.

Benefits for Nonmotor Symptoms

“Dopamine agonists may be somewhat less effective than levodopa for controlling motor symptoms, but they offer an important advantage by helping prevent motor complications, particularly dyskinesias,” said Tatiana Witjas, MD, of the Neurology Department at Assistance Publique-Hôpitaux de Marseille, Timone University Hospital, Marseille, France. She added that these agents remain a strong first-line option for younger patients.

Extended-release agonists, administered as a single daily dose or transdermally via a patch, provide a more consistent level of dopaminergic stimulation, which may partly explain the reduced risk for motor fluctuations and dyskinesias.

By limiting the number of doses, dopamine agonists also have the advantage of improving treatment adherence, the neurologist emphasized, which is usually poor with levodopa therapy that often requires multiple daily doses.

Pramipexole Recommended for Depressive Syndromes

Another advantage highlighted is their effect on certain nonmotor symptoms of Parkinson’s disease. Agonists are effective against depression, anxiety, and apathy, which affect more than half of Parkinson’s patients. They also have an effect on sleep disorders and certain types of pain that tend to worsen as the disease progresses.

An expert consensus published in 2024 specifically highlighted the benefits of dopamine agonists for depressive symptoms associated with Parkinson’s disease. The highest level of evidence pertains to pramipexole, which was the subject of a double-blind, randomized study in the treatment of depression associated with Parkinson’s disease. In cases of apathy, experts recommend piribedil instead. Ropinirole may also be of benefit.

Regarding sleep disorders, rotigotine is particularly recommended, as its benefit in improving sleep quality in patients with Parkinson’s disease has been demonstrated.

Data on pain symptoms remain more limited, but agonists may also be of benefit, particularly in cases of painful dystonia (prolonged involuntary muscle contraction).

Better Management of the Risk for ICDs

However, due to their effect on the reward system, dopamine agonists are associated with a risk for ICDs, which can manifest as gambling addiction, eating disorders, compulsive shopping, or hypersexuality. The prevalence of ICDs among patients taking dopamine agonists ranges from 14% to 30%.

“Nevertheless, we are seeing a decrease in ICDs among patients on agonists due to lower prescribed doses,” Witjas noted. Risk factors are also being better addressed. Agonists are notably not recommended for patients with a history of substance abuse or pathological gambling.

For his part, Marc Vérin, professor and neurologist, Orléans University Hospital, Orléans, France, highlighted the increased risk for ICDs with agonists prescribed at high doses. He further noted that certain agonists carry a higher risk than others, depending on their affinity for the dopamine D3 receptor, which is implicated in the onset of these disorders.

According to a recent study, pramipexole appears to be the agonist with the highest risk for ICDs (nearly 50%), followed by ropinirole (37%), far ahead of rotigotine (8.3%) and apomorphine (5.6%).

Levodopa as the First-Line Treatment for Motor Symptoms

To improve patients’ quality of life, the neurologist emphasized the need to consider the stimulation of different subtypes of dopamine receptors. D1 and D2 receptors are involved in motor and cognitive symptoms, whereas D3 receptors play a greater role in motivational symptoms, such as apathy.

“We must balance the stimulation of the different receptors.” However, in the context of reduced agonist doses, levodopa remains, in his view, the most effective way to stimulate D1 and D2 receptors in order to control motor symptoms. “Levodopa should be prescribed as early as possible and at the dose necessary to control symptoms. In terms of quality of life, there is nothing better,” said Vérin.

In his view, levodopa should now be introduced as first-line therapy whenever motor symptoms are present, regardless of age. “There is indeed a risk of dyskinesia, but studies show that this complication does not necessarily occur earlier.” Management of dyskinesias has also improved, he added.

“We need to stop prescribing agonists as monotherapy,” said Vérin, while clarifying that these medications should not, however, be excluded from the treatment of Parkinson’s disease. In his view, they remain useful in cases of mood disorders. The addition of a low-dose agonist to levodopa therapy is then justified, with a preference for the lowest-risk compounds.

Toward a More Targeted Use of Agonists

“Dopamine agonists still have a place in the treatment of Parkinson’s disease but at low doses.” On this point, both speakers share the same view and advocate for a more personalized approach to managing Parkinson’s disease, taking into account the presence or absence of motivational disorders.

However, Fabienne Ory-Magne, MD, neurologist at Toulouse University Hospital in Toulouse, France, said following the two presentations that evidence remains insufficient to support routine early combination therapy with levodopa and a dopamine agonist, limiting its role in treatment decisions. We need personalized medicine, but in 2026, it remains clinical and phenotypic.

According to Ory-Magne, pharmacogenetics should also be incorporated to better identify patients at risk for adverse effects or those more likely to respond to specific treatments. These approaches have yet to be validated.

This story was translated from Medscape’s French edition.