Motor complications arising after long-term treatment with
levodopa remain one of the main challenges in the treatment of patients with
Parkinson's disease (PD). Monotherapy with
dopamine agonists may delay the onset of motor complications or reduce their severity when added to
levodopa treatment. Here, we retrospectively analyzed data from 62 patients with advanced PD who presented with moderate to severe response fluctuations in whom we increased the dose of oral treatment with
pergolide beyond 4.5mg daily. Patients had been treated with
levodopa for 10.7+/-4.8 years.
Pergolide was increased to 8.2+/-4.3 mg per day over a median titration period of 13.5 weeks. Mean daily dose of
levodopa prior to
pergolide high-dose treatment was 733+/-468 mg and decreased to 348+/-186 mg after
pergolide titration. The duration of OFF times decreased from 7.3+/-3.8 to 1.7+/-0.9 h per day (p < 0.001) measured by patients' diaries.
Dyskinesias, present for 5.0+/-3.3 h per day at baseline, were reduced to 1.4+/-0.8 h per day (p < 0.001) and the total daily duration of motor fluctuations (off-time duration plus
dyskinesia duration) decreased from 10.5+/-7.0 to 2.8+/-2.2 h (p < 0.001). There was a significant improvement in parkinsonian symptoms (baseline to endpoint reduction of UPDRS III from a median of 36 to 8; p < 0.001). To reduce gastrointestinal side effects 23 patients required concomitant treatment with
domperidone. Seven patients developed
hallucinations during the titration period, six patients required treatment with
clozapine. Our data indicate that increasing the dose of
pergolide above 5mg per day can dramatically reduce the need for
levodopa, motor fluctuations and severity of clinical symptoms. Controlled trials are needed to further substantiate the efficacy and safety of this treatment strategy.