High-dose treatment with pergolide in Parkinson's disease patients with motor fluctuations and dyskinesias.
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.
Department of Neurology, University of Ulm, Ulm, Germany. Alexander.Storch@neuro.med.tu-dresden.de
Alexander
A
Storch
Claudia
C
Trenkwalder
Christian
C
Oehlwein
Juliane
J
Winkelmann
Ulrich
U
Polzer
Hans-Peter
HP
Hundemer
Johannes
J
Schwarz
D000328:Adult; D000368:Aged; D000547:Amantadine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003024:Clozapine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D020820:Dyskinesias / Q000188:drug therapy* / Q000503:physiopathology; D023381:Endpoint Determination; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000188:drug therapy* / Q000503:physiopathology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D010479:Pergolide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011618:Psychotic Disorders / Q000150:complications; D012189:Retrospective Studies
D000978:Antiparkinson Agents; D014150:Antipsychotic Agents; D010479:Pergolide; D000547:Amantadine; D003024:Clozapine