Lesuride (Lisuride) in Parkinson's Disease
Critical Context: Lesuride is Not a Standard Treatment Option
Lesuride (lisuride) is a dopamine agonist that was studied in the 1980s-1990s for Parkinson's disease but is not included in current evidence-based guidelines and should not be considered a standard treatment option. The provided evidence contains no contemporary guidelines recommending lisuride, and all research evidence is from 1981-1996, making it outdated by modern standards 1, 2, 3, 4, 5.
Historical Context and Evidence
The available research on lisuride is limited to older studies that showed:
Efficacy as adjunct therapy: When added to levodopa/benserazide, lisuride 0.1-0.8 mg daily (mean 0.5 mg) produced 50% improvement in disability scores and allowed 38% reduction in levodopa dose in some patients 2.
Monotherapy results: As monotherapy, lisuride 3.6 mg daily showed 56-57% improvement in disability scores, with 5 out of 10 patients performing better on lisuride than levodopa alone 3.
Early combination therapy: A 4-year trial showed that early combination of lisuride with low-dose levodopa resulted in fewer end-of-dose failures and dyskinesias compared to high-dose levodopa alone, while maintaining equal therapeutic response 4.
Subcutaneous infusion: Continuous subcutaneous infusion of lisuride was effective for controlling ON-OFF fluctuations, with 6 out of 13 patients managed on lisuride alone using 12-hour infusion regimens 5.
Significant Adverse Effects
Common side effects: Dry mouth, nausea, weakness, postural hypotension, and headache were frequently reported, though these often resolved within 3-4 days with dose adjustment 2.
Serious adverse effects requiring discontinuation: Mental changes (3 patients) and persistent nausea (1 patient) led to drug discontinuation in older studies 3.
Contraindications: Caution was advised in patients with hypotension, hepatic dysfunction, cardiac arrhythmias, and dementia 1.
Loss of efficacy: Decline in effectiveness was noted after a mean of 45 months in patients who initially responded 3.
Why Modern Guidelines Do Not Recommend Lisuride
The provided guidelines from 2018 and 2025 focus on:
- Deep brain stimulation (STN DBS vs GPi DBS) for advanced Parkinson's disease 6
- Restless legs syndrome management with alpha-2-delta ligands (gabapentin, pregabalin) as first-line therapy, explicitly recommending against dopamine agonists due to augmentation risk 7, 8
Notably, the American Academy of Sleep Medicine specifically recommends against standard use of dopamine agonists like pramipexole and ropinirole due to augmentation risk 7, 8. While these guidelines address RLS rather than Parkinson's disease, the concern about long-term dopamine agonist use is relevant.
Clinical Recommendation
Do not use lisuride for Parkinson's disease in contemporary practice. Instead, follow current evidence-based guidelines that recommend:
- Modern dopamine agonists (pramipexole, ropinirole, rotigotine) with established safety profiles
- Levodopa/carbidopa as the gold standard for symptomatic treatment
- Deep brain stimulation (STN or GPi) for advanced disease with motor fluctuations 6
If a patient is currently on lisuride (unlikely in modern practice), consult with a movement disorders specialist for transition to evidence-based therapies with contemporary safety and efficacy data.