What are dopamine analogs (Dopamine agonists)?

From the Guidelines

Dopamine analogs should not be used as a first-line treatment for restless legs syndrome (RLS) due to the risk of augmentation, which is a major issue that has led to their downgrading in recent clinical practice guidelines. The use of dopamine agonists, such as pramipexole and ropinirole, has been associated with augmentation, which can worsen RLS symptoms over time 1. This is a significant concern, as dopamine agonists are commonly prescribed for RLS, and their use can lead to a substantial increase in symptoms, making it challenging to manage the condition.

Some of the key points to consider when using dopamine analogs for RLS include:

• The risk of augmentation, which can occur in up to 50% of patients taking dopamine agonists for RLS 1
• The need for careful monitoring of patients taking dopamine agonists, including regular assessments of symptom severity and potential side effects 1
• The importance of considering alternative treatments, such as alpha-2-delta ligands, opioids, and iron supplementation, which may be more effective and have a lower risk of augmentation 1
• The potential for dopamine agonists to be reestablished as a recommended treatment for RLS if predictors of augmentation, such as genetic markers or iron status, can be identified 1

In terms of specific medications, pramipexole and ropinirole are commonly used dopamine agonists for RLS, but their use should be carefully considered in light of the risk of augmentation. Other medications, such as rotigotine and bromocriptine, may also be used, but their efficacy and safety profiles should be carefully evaluated in individual patients. It is essential to weigh the potential benefits of dopamine analogs against the risks and to consider alternative treatments that may be more effective and have a lower risk of adverse effects 1.

The most recent and highest quality study on this topic is the 2025 American Academy of Sleep Medicine clinical practice guideline, which downgrades the use of dopamine agonists for RLS due to the risk of augmentation 1. This guideline recommends considering alternative treatments, such as alpha-2-delta ligands, opioids, and iron supplementation, and emphasizes the importance of careful monitoring and individualized treatment plans for patients with RLS.

From the FDA Drug Label

Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking ropinirole. A symptom complex resembling the neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction of, withdrawal of, or changes in, dopaminergic therapy Symptoms including insomnia, apathy, anxiety, depression, fatigue, sweating, and pain have been reported during taper or after discontinuation of dopamine agonists, including ropinirole. Augmentation is a phenomenon in which dopaminergic medication causes a worsening of symptom severity above and beyond the level at the time the medication was started Cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, pericarditis, and cardiac valvulopathy have been reported in some patients treated with ergot-derived dopaminergic agents.

Dopamine analogs can cause various side effects and complications, including:

• Withdrawal symptoms such as insomnia, apathy, anxiety, depression, fatigue, sweating, and pain
• Augmentation of symptoms, particularly in patients with Restless Legs Syndrome
• Fibrotic complications, such as retroperitoneal fibrosis, pulmonary infiltrates, and cardiac valvulopathy, although the evidence for a causal relationship is not sufficient It is essential to monitor patients closely and adjust the dosage or discontinue treatment as needed to minimize the risk of these complications 2.

From the Research

Dopamine Analogs

• Dopamine analogs, such as pramipexole, are used to treat restless legs syndrome (RLS) and Parkinson's disease 3, 4, 5.
• Pramipexole is a non-ergoline dopamine agonist with high selectivity for D(2) and D(3) receptors, and is effective in controlling sensory symptoms and motor signs of RLS 3.
• Rotigotine is another dopamine-receptor agonist that is delivered transdermally and has been shown to be effective in the management of Parkinson's disease, with comparable efficacy to ropinirole and pramipexole 6.

Treatment of Restless Legs Syndrome

• The first line treatment for idiopathic RLS is represented by dopamine agonists, such as pramipexole and ropinirole 5.
• However, alpha-2-delta drugs, such as gabapentin, are now considered the first line of treatment in patients with troublesome RLS, due to the growing appreciation of problems associated with long-term dopamine agonist treatment 7.
• Opioids can be considered as an alternative therapy, particularly in patients with dopamine agonist-related augmentation, and intravenous iron therapy may be considered in patients with refractory RLS 7.

Dopamine Agonists

• Pramipexole has been shown to be effective as monotherapy in early Parkinson's disease and as adjunctive therapy in advanced disease, with benefits extending beyond the relief of motor symptoms to the amelioration of depressive symptoms 4.
• Rotigotine has been shown to be effective in reducing "off" hours in levodopa-treated patients with advanced Parkinson's disease, and has a favorable safety and tolerability profile 6.
• Dopamine agonists, such as pramipexole and ropinirole, have been compared in terms of efficacy and tolerability, with some studies suggesting differences favoring pramipexole 5.