Comparison of continuous versus pulsatile dopaminergic therapy in the erderly with Parkinson’s Disease

Fulvio Lauretani, Gian Paolo Ceda, Augusto Scaglioni, Anna Nardelli

Department of Clinical and Experimental Medicine, Section of Geriatrics, University of Parma, Parma, Italy;Geriatric Clinic Unit, Geriatric and Rehabilitation Department, University Hospital of Parma, Parma, Italy.
Geriatric Unit and Laboratory of Disability Prevention, Geriatric and Rehabilitation Department, University Hospital of Parma, Parma, Italy.
Neurology Unit, Ospedale di Fidenza—San Secondo, Azienda Unità Sanitaria Locale di Parma, Parma, Italy.

DOI: 10.4236/apd.2013.22008                

Abstract

Objective: Levodopa is the gold-standard of therapy in Parkinson’s disease (PD), but it is associated with motor complications that affect 50% of patients after five years of treatment. Development of delirium and psychosis is the main limitation of dopaminergic treatment in older persons. These adverse effects may result from pulsatile stimulation of the dopamine receptors. Dopamine agonists with transdermal delivery that continuously stimulate the dopamine receptors may reduce these complications. The objective of this study was to evaluate the frequencies of acute delirium and psychosis in elderly patients treated with rotigotine vs. levodopa in a newly diagnosed drugnaive Parkinson’s disease (PD). Methods: Patients admitted to the Geriatric-Rehabilitation Department of the University-Hospital of Parma were screened for the presence of Parkinsonism. All subjects admitted with diagnosis of PD according to the UK Brain Bank Criteria were randomly treated with Rotigotine or levodopa. All subjects were assessed by Movement Disorder Society (MDS)-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III. Acute delirium was asessed by CAM Diagnostic Algorithm during the first week after admission. After six months, diagnosis of psychosis was performed according to pro posed diagnostic criteria by NINDS and NIMH. Patients with cognitive impairment (MMSE < 21) and affected by any diseases potentially leading to psychosis, in cluding dementia with Lewy bodies (DLB), were excluded. Results: 60 consecutive newly diagnosed drugnaive PD patients were evaluated. No statistical significant difference between the two groups were observed in term of age, gender, MMSE score, severity of disease expressed by H&Y staging. 30 patients were treated with rotigotine (6 mg/daily) and 30 patients were treated with L-Dopa (250 mg/daily). All participants completed the study. UPDRS Part III was statistical significant lower in both groups after treatment from 26.4 to 18.3 (rotigotine group) and from 26.3 to 17.3 (levodopa group), but comparable within groups (p = 0.83). After 6-month follow-up, acute delirium and/ or psychosis were observed in two cases (6.6%) of patients treated with rotigotine and in three cases (10%) of those treated with levodopa (p = 0.54). Conclusions: Transdermal rotigotine seems comparable to levodopa in regard to motor skill efficacy and neuropsychiatric safety, because provides a more continuous delivery of drug. Dopamine agonists may represent a valid therapeutic option in newly diagnosed older PD patients.

Keywords

Parkinson’s Disease; Rotigotine; Continuous Dopaminergic Therapy; Elderly

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Murray, A.M., Bennett, D.A., Mendes de Leon, C.F., Beckett, L.A. and Evans, D.A. (2004) A longitudinal study of Parkinsonism and disability in a community population of older people. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 59, 864-870. doi:10.1093/gerona/59.8.M864
[2]	Lauretani, F., Maggio, M., Silvestrini, C., Nardelli, A., Saccavini, M. and Ceda, G.P. (2012) Parkinson’s disease (PD) in the elderly: an example of geriatric syndrome (GS)? Archives of Gerontology and Geriatrics, 54, 242-246. doi:10.1016/j.archger.2011.03.002
[3]	Jankovic, J. (2008) Parkinson’s disease: Clinical features and diagnosis. Journal of Neurology, Neurosurgery & Psychiatry, 79, 368-376. doi:10.1136/jnnp.2007.131045
[4]	Lees, A. (2010) The bare essentials: Parkinson’s disease. Practical Neurology, 10, 240-246. doi:10.1136/jnnp.2010.217836
[5]	Lauretani, F., Maggio, M., Nardelli, A. and Ceda, G.P. (2012) Parkinson’s disease: Diagnosis, treatment and prognosis. In: Yoshida, C. and Ito, A., Eds., Treatment of Parkinson’s Disease and Parkinsonism in the Elderly, Nova Science Publishers, New York, pp. 165-178.
[6]	Braak, H., Del Tredici, K., Rüb, U., de Vos, R.A., Jansen Steur, E.N. and Braak, E. (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiology of Aging, 24, 197-211. doi:10.1016/S0197-4580(02)00065-9
[7]	Ahlskog, J.E. and Muenter, M.D. (2001) Frequency of levodopa related dyskinesias and motor fluctuations as estimated from the cumulative literature. Movement Disorders, 16, 448-458. doi:10.1002/mds.1090
[8]	Horstink, M., Tolosa, E., Bonuccelli, U., Deuschl, G., Friedman, A., Kanovsky, P., et al. (2006) Review of the therapeutic management of Parkinson’s disease. Report of a joint task force of the European federation of neurological societies and the movement disorder society—European Section. Part I: Early (uncomplicated) Parkinson’s disease. European Journal of Neurology, 13, 1170-1185. doi:10.1111/j.1468-1331.2006.01547.x
[9]	Olanow, C.W., Stern, M.B. and Sethi, K. (2009) The scientific and clinical basis for the treatment of Parkinson disease. Neurology, 72, S1-136. doi:10.1212/WNL.0b013e3181a1d44c
[10]	Fasano, A., Guidubaldi, A., De Nigris, F. and Bentivoglio, A.R. (2011) Safety and efficacy of rotigotine in individuals with Parkinson’s disease aged 75 and older. Journal of the American Geriatrics Society, 59, 2386-2387. doi:10.1111/j.1532-5415.2011.03689.x
[11]	Goetz, C.G., Tilley, B.C., Shaftman, S.R., Stebbins, G.T., Fahn, S., Martinez-Martin, P., et al. (2008) Movement disorder society-sponsored revision of the unified Parkinson’s disease rating scale (MDS-UPDRS): Scale presentation and clinimetric testing results. Movement Disorders, 23, 2129-2170. doi:10.1002/mds.22340
[12]	Inouye, S.K., van Dyck, C.H., Alessi, C.A., Balkin, S., Siegal, A.P. and Horwitz, R.I. (1990) Clarifying confusion: The confusion assessment method. A new method for detection of delirium. Annals of Internal Medicine, 113, 941-948. doi:10.7326/0003-4819-113-12-941
[13]	Ravina, B., Marder, K., Fernandez, H.H., Friedman, J.H., McDonald, W., Murphy, D., Aarsland, D., et al. (2007) Diagnostic criteria for psychosis in Parkinson’s disease: Report of an NINDS/NIMH work group. Movement Disorders, 22, 1061-1068. doi:10.1002/mds.21382
[14]	Lauretani, F., Caffarra, P., Ruffini, P., Nardelli, A., Ceda, G.P., Maggio, M., et al. (2011) Brief practical clinical diagnostic criteria for the neurodegenerative diseases in the elderly. Drugs and Therapy Studies, 1, e6.
[15]	Lauretani F., Ceda, G.P., Maggio, M., Nardelli, A., Saccavini, M. and Ferrucci, L. (2010) Capturing side-effect of medication to identify persons at risk of delirium. Aging Clinical and Experimental Research, 22, 456-458.
[16]	LeWitt, P.A., Lyons, K.E. and Pahwa, R. (SP 650 Study Group) (2007) Advanced Parkinson disease treated with rotigotine transdermal system: PREFER study. Neurology, 68, 1262-1267. doi:10.1212/01.wnl.0000259516.61938.bb
[17]	Watts, R.L., Jankovic, J., Waters, C., Rajput, A., Boroojerdi, B. and Rao, J. (2007) Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson disease. Neurology, 68, 272-276. doi:10.1212/01.wnl.0000252355.79284.22
[18]	Hely, M.A., Reid, W.G., Adena, M.A., Halliday, G.M. and Morris, J.G. (2008) The Sydney multicenter study of Parkinson’s disease: The inevitability of dementia at 20 years. Movement Disorders, 23, 837-844.