Abstract
Objective: To compare the tremorlytic properties of pramipexole, a non-ergoline dopamine agonist to those of placebo as add on medication in patients with Parkinson's disease.
Methods: Eighty four patients with early or advanced Parkinson's disease and marked, drug resistant tremor under a stable and optimised antiparkinsonian medication were included in a double blind, randomised, placebo controlled, multicentre study and assigned to add on treatment (7 week dose titration interval, 4 week maintenance period) with either pramipexole (n=44) or placebo (n=40) as adjunct. The primary end point was the absolute change in tremor score, defined as the sum of tremor related items (16, 20, 21) of the unified Parkinson's disease rating scale (UPDRS) in "on" periods. Secondary end points included the percentage change in tremor score, the absolute and percentage changes in long term EMG tremor registration, and the change in tremor self rating scales. Safety and tolerability were assessed on the basis of adverse events, laboratory tests, ECG, and vital signs.
Results: Pramipexole was significantly superior to placebo with a difference between treatment groups in the mean absolute change in tremor score of -4.4 (95% confidence interval (95% CI) -6.2 to -2.5) (p<0.0001), corresponding to a difference in the mean percentage change of -34.7% in favour of pramipexole. The secondary end points were consistent with the significant change in tremor score and provided further evidence for the benefit of pramipexole compared with placebo. Long term EMG registration as an objective measure showed a difference in mean absolute change in tremor occurrence of -15.2% (95%CI -21.4 to -9.0) (p<0.0001), and a difference in the mean percentage change of -45.7% in favour of pramipexole. The treatment effects increased during dose titration and remained stable during the 4 week maintenance dose period until the end of the study. The average daily pramipexole dose during maintenance was 4.1 (SD 0.9) mg. Safety analysis showed an increased rate of fatigue, insomnia, nausea, abdominal pain, and headache under pramipexole, comparable with previous studies.
Conclusion: Pramipexole proved to be an effective agent for patients with Parkinson's disease and drug resistant tremor.
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Selected References
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- Benabid A. L., Pollak P., Gao D., Hoffmann D., Limousin P., Gay E., Payen I., Benazzouz A. Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders. J Neurosurg. 1996 Feb;84(2):203–214. doi: 10.3171/jns.1996.84.2.0203. [DOI] [PubMed] [Google Scholar]
- Boose A., Spieker S., Jentgens C., Klockgether T., Scholz E., Dichgans J. Assessing tremor severity with long-term tremor recordings. J Neurol Neurosurg Psychiatry. 1994 Mar;57(3):397–397. doi: 10.1136/jnnp.57.3.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Factor S. A., Sanchez-Ramos J. R., Weiner W. J. Parkinson's disease: an open label trial of pergolide in patients failing bromocriptine therapy. J Neurol Neurosurg Psychiatry. 1988 Apr;51(4):529–533. doi: 10.1136/jnnp.51.4.529. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frucht S., Rogers J. D., Greene P. E., Gordon M. F., Fahn S. Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole. Neurology. 1999 Jun 10;52(9):1908–1910. doi: 10.1212/wnl.52.9.1908. [DOI] [PubMed] [Google Scholar]
- Gibb W. R., Lees A. J. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. J Neurol Neurosurg Psychiatry. 1988 Jun;51(6):745–752. doi: 10.1136/jnnp.51.6.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guttman M. Double-blind comparison of pramipexole and bromocriptine treatment with placebo in advanced Parkinson's disease. International Pramipexole-Bromocriptine Study Group. Neurology. 1997 Oct;49(4):1060–1065. doi: 10.1212/wnl.49.4.1060. [DOI] [PubMed] [Google Scholar]
- Koller W., Pahwa R., Busenbark K., Hubble J., Wilkinson S., Lang A., Tuite P., Sime E., Lazano A., Hauser R. High-frequency unilateral thalamic stimulation in the treatment of essential and parkinsonian tremor. Ann Neurol. 1997 Sep;42(3):292–299. doi: 10.1002/ana.410420304. [DOI] [PubMed] [Google Scholar]
- Krack P., Benazzouz A., Pollak P., Limousin P., Piallat B., Hoffmann D., Xie J., Benabid A. L. Treatment of tremor in Parkinson's disease by subthalamic nucleus stimulation. Mov Disord. 1998 Nov;13(6):907–914. doi: 10.1002/mds.870130608. [DOI] [PubMed] [Google Scholar]
- Künig G., Pogarell O., Möller J. C., Delf M., Oertel W. H. Pramipexole, a nonergot dopamine agonist, is effective against rest tremor in intermediate to advanced Parkinson's disease. Clin Neuropharmacol. 1999 Sep-Oct;22(5):301–305. [PubMed] [Google Scholar]
- Laihinen A., Rinne U. K., Suchy I. Comparison of lisuride and bromocriptine in the treatment of advanced Parkinson's disease. Acta Neurol Scand. 1992 Dec;86(6):593–595. doi: 10.1111/j.1600-0404.1992.tb05493.x. [DOI] [PubMed] [Google Scholar]
- Lieberman A., Ranhosky A., Korts D. Clinical evaluation of pramipexole in advanced Parkinson's disease: results of a double-blind, placebo-controlled, parallel-group study. Neurology. 1997 Jul;49(1):162–168. doi: 10.1212/wnl.49.1.162. [DOI] [PubMed] [Google Scholar]
- Limousin P., Krack P., Pollak P., Benazzouz A., Ardouin C., Hoffmann D., Benabid A. L. Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease. N Engl J Med. 1998 Oct 15;339(16):1105–1111. doi: 10.1056/NEJM199810153391603. [DOI] [PubMed] [Google Scholar]
- Mierau J., Schingnitz G. Biochemical and pharmacological studies on pramipexole, a potent and selective dopamine D2 receptor agonist. Eur J Pharmacol. 1992 May 14;215(2-3):161–170. doi: 10.1016/0014-2999(92)90024-x. [DOI] [PubMed] [Google Scholar]
- Mierau J., Schneider F. J., Ensinger H. A., Chio C. L., Lajiness M. E., Huff R. M. Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors. Eur J Pharmacol. 1995 Jun 23;290(1):29–36. doi: 10.1016/0922-4106(95)90013-6. [DOI] [PubMed] [Google Scholar]
- Olanow C. W., Fahn S., Muenter M., Klawans H., Hurtig H., Stern M., Shoulson I., Kurlan R., Grimes J. D., Jankovic J. A multicenter double-blind placebo-controlled trial of pergolide as an adjunct to Sinemet in Parkinson's disease. Mov Disord. 1994 Jan;9(1):40–47. doi: 10.1002/mds.870090107. [DOI] [PubMed] [Google Scholar]
- Piercey M. F. Pharmacology of pramipexole, a dopamine D3-preferring agonist useful in treating Parkinson's disease. Clin Neuropharmacol. 1998 May-Jun;21(3):141–151. [PubMed] [Google Scholar]
- Pinter M. M., Pogarell O., Oertel W. H. Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson's disease: a double blind, placebo controlled, randomised, multicentre study. J Neurol Neurosurg Psychiatry. 1999 Apr;66(4):436–441. doi: 10.1136/jnnp.66.4.436. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shannon K. M., Bennett J. P., Jr, Friedman J. H. Efficacy of pramipexole, a novel dopamine agonist, as monotherapy in mild to moderate Parkinson's disease. The Pramipexole Study Group. Neurology. 1997 Sep;49(3):724–728. doi: 10.1212/wnl.49.3.724. [DOI] [PubMed] [Google Scholar]
- Spieker S., Eisebitt R., Breit S., Przuntek H., Müller D., Klockgether T., Dichgans J. Tremorlytic activity of budipine in Parkinson's disease. Clin Neuropharmacol. 1999 Mar-Apr;22(2):115–119. doi: 10.1097/00002826-199903000-00010. [DOI] [PubMed] [Google Scholar]
- Spieker S., Jentgens C., Boose A., Dichgans J. Reliability, specificity and sensitivity of long-term tremor recordings. Electroencephalogr Clin Neurophysiol. 1995 Dec;97(6):326–331. doi: 10.1016/0924-980x(95)00208-3. [DOI] [PubMed] [Google Scholar]
- Spieker S., Löschmann P., Jentgens C., Boose A., Klockgether T., Dichgans J. Tremorlytic activity of budipine: a quantitative study with long-term tremor recordings. Clin Neuropharmacol. 1995 Jun;18(3):266–272. [PubMed] [Google Scholar]
- Zimmermann R., Deuschl G., Hornig A., Schulte-Mönting J., Fuchs G., Lücking C. H. Tremors in Parkinson's disease: symptom analysis and rating. Clin Neuropharmacol. 1994 Aug;17(4):303–314. [PubMed] [Google Scholar]