Dopamine agonists are used as initial treatment in patients with Parkinson's disease (PD) to reduce incidence and severity of motor complications. This paradigm is based on long-term studies, allowing "rescue" therapy with levodopa. The present strict monotherapy study (PELMOPET, the acronym for the pergolide-versus-L-dopa-monotherapy-and-positron-emission-tomography trial) evaluated the efficacy and safety of pergolide versus levodopa without levodopa "rescue" medication. This multicenter, double-blind, randomized, 3-year trial compared pergolide monotherapy (n=148) with levodopa monotherapy (n=146) in dopamine-naive patients with early PD (Hoehn and Yahr stage 1-2.5). Primary efficacy measures were clinical efficacy, severity and time to onset of motor complications, and disease progression. During the 3 years, severity of motor complications was significantly lower and time to onset of dyskinesia was significantly delayed in the group receiving pergolide (3.23 mg/day) compared with those receiving levodopa (504 mg/day). However, time to onset of motor complications was not longer in patients receiving pergolide after 3 years. Symptomatic relief (assessed by Unified Parkinson's Disease Rating Scale [UPDRS], UPDRS II, and III, Clinical Global Impressions [CGI] severity, and CGI and Patient Global Impressions [PGI] improvement) was significantly greater in patients receiving levodopa. Adverse events led to discontinuation of therapy in 17.6% of pergolide patients and 9.6% of levodopa patients. This is the first study comparing strict monotherapy with a dopamine agonist versus levodopa in previously untreated early PD. In principle, both levodopa and a dopamine agonist such as pergolide seem to be suitable options as initial PD therapy. The choice remains with the treating physician based on the different efficacy and adverse event profiles.

The proportion of patients who met combined remission or recovery criteria is low. Early treatment adaptations in case of early non-remission are mandatory.

An open follow-up of a controlled study in patients with restless legs syndrome (RLS) shows that the beneficial effect of pergolide on RLS symptoms persists throughout at least 1 year. Twenty-two patients of 28 (78.6%) continued to take pergolide. Polysomnographic measurements showed a persistent improvement of PLM index, PLMS arousal index, total sleep time, and sleep efficiency (p = 0.0001). Side effects, in particular nausea, were common but were well controlled by domperidone in most patients.

Our findings suggest that dopamine agonists modulate two EC tasks differently. Furthermore, there seems to be a selective modulation of different aspects of the Stroop task.

Pergolide substantially improves periodic limb movement measures and subjective sleep disturbance associated with restless legs syndrome. Low-dose pergolide was well tolerated and maintained its efficacy in the long term.