Wirksamkeit und Sicherheit von Rivastigmin bei Patienten mit Demenz unter Praxisbedingungen

W. Retz; F. Tracik; M. Rösler

doi:10.1055/s-0038-1626817

Nervenheilkunde, Table of Contents

Nervenheilkunde 2006; 25(12): 1039-1045
DOI: 10.1055/s-0038-1626817

Original- und Übersichtsarbeiten - Original and Review Articles

Schattauer GmbH

Wirksamkeit und Sicherheit von Rivastigmin bei Patienten mit Demenz unter Praxisbedingungen

Efficacy and safety of rivastigmine in patients with dementia in practice

W. Retz

¹Institut für Gerichtliche Psychologie und Psychiatrie der Universität des Saarlandes, Homburg/Saar, Nürnberg

,

F. Tracik

²Medizinische Abteilung, Novartis Pharma AG, Nürnberg

,

M. Rösler

¹Institut für Gerichtliche Psychologie und Psychiatrie der Universität des Saarlandes, Homburg/Saar, Nürnberg

› Author Affiliations

Abstract

Zusammenfassung

Das Ziel dieser offenen, prospektiven Beobachtungsstudie war es, den klinischen Verlauf von Patienten mit Demenz unter der Therapie mit Rivastigmin, einem Azetylcholinund Butyrylcholinesterasehemmstoff, unter Praxisbedingungen zu untersuchen.

867 Ärzte in Arztpraxen, Ambulanzen und Memory-Kliniken rekrutierten 1 214 Demenzpatienten, von denen 75% leicht bis mittelgradig (Mini-Mental-State-Test ≥ 10) und 25% schwergradig ausgeprägte Symptome aufwiesen. Die Patienten erhielten Rivastigminlösung peroral in einer durchschnittlichen Tagesdosierung von 6,7 mg über4 Monate.

Unter Rivastigmin besserten sich die Patienten in allen untersuchten Symptombereichen (Gedächtnis-, Sprach-, Orientierungs-, Verhaltensund Alltagskompentenzstörungen) signifikant (p < 0,05). Bei Patienten mit schwergradiger Demenz war der therapeutische Effekt von Rivastigmin am stärksten ausgeprägt. Die Verträglichkeit von Rivastigmin wurde von 93,2% der behandelnden Ärzte als gut oder sehr gut beurteilt.

Rivastigmin zeigte bei Patienten mit leicht bis schwergradiger Demenz unter Praxisbedingungen eine klinisch relevante Wirksamkeit und gute Verträglichkeit.

Summary

The aim of the present observational open study was to investigate prospectively the clinical effects of rivastigmine, an inhibitor of acetylcholinesterase as well as butyrylcholinesterase, on the course of patients with dementia under “real life” practice conditions.

867 physicians in primary care settings and memory clinics included 1 214 patients with dementia of whom 75% had mild to moderate (Mini Mental State Examination ≥ 10)

and 25% severe symptoms. Rivastigmine solution was administered orally at an average daily dose of 6.7 mg over4 months.

All investigated symptoms (disturbances of memory, speech, orientation, behaviour and capability of daily living) significantly improved during treatment with rivastigmine (p< 0.05). The therapeutic effect of rivastigmine was most pronounced in patients with severe dementia. 93.2% of the treating physicians judged the tolerability of rivastigmine to be good or very good.

Rivastigmine revealed clinical relevant efficacy and was tolerated well by patients with mild to severe dementia.

Schlüsselwörter

Rivastigmin - Demenz - Wirksamkeit - Verträglichkeit - Praxisbedingungen

Keywords

Rivastigmine - dementia - efficacy - tolerability - “real life” practice conditions

Full Text

References

Literatur
1 Anand R, Gharabawi G. Clinical development of exelon (ENA 713): the ADENA programme. J Drug Dev Clin Pract 1996; 08: 117-22.
2 Anand R, Hartman R, Sohn H, Danyluk J, Graham SM. Impact of study design and patient population on outcomes from cholinesterase inhibitor trials. Am J Geriatr Psychiatry 2003; 11: 160-8.
3 Arendt T, Bruckner MK, Lange M, Bigl V. Changes in acetylcholinesterase and butylcholinesterase in Alzheimer disease resemble embryonic development: a study of molecular froms. Neurochem Int 1992; 21: 381-96.
4 Beach TG, Honer WG, Hughes LH. Cholinergic fibre loss associated with diffuse plaques in the non-demented elderly: the preclinical stage of Alzheimer disease?. Acta Neuropathol 1997; 93: 146-53.
5 Bickel H. Demenzsyndrom und Alzheimer Krankheit: Eine Schätzung des Krankenstandes und der jährlichen Neuerkrankungen in Deutschland. Gesundheitswesen 2000; 62: 211-8.
6 Bowler J, Hachinski VC. Vascular dementia. In: Ginsberg MD, Bogousslavsky J. (Hrsg) Cerebrovascular disease Pathophysiology, diagnosis, and management. Oxford, London: Blackwell Science Malden; 1998: 1126-44.
7 Corey-Bloom J, Anand R, Veach J. A randomized trial evaluating the efficacy and safety of ENA 73 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer disease. Int J Geriatr Psychopharmacol 1998; 01: 55-65.
8 Dennler HJ, Retz W, Rösler M. Rivastigmin bei leichter bis mäßig stark ausgeprägter AlzheimerKrankheit. Ergebnisse einer offenen klinischen Prüfung. Psychopharmakotherapie 2001; 08: 111-7.
9 Desai A, Grossberg G. Review of rivastigmine in patients and its clinical applications in Alzheimer`s disease and related disorders. Expert Opin Pharmacother 2001; 02: 653-66.
10 Enz A, Amstutz R, Boddeke H, Gmelin G, Malanoski J. Brain selective inhibition of AchE: a novel approach to therapy for Alzheimer´s disease. Brain Res 1993; 98: 431-8.
11 Enz A, Boddeke H, Gray J, Spiegel R. Pharmacologic and clinicopharmacologic properties of SDZ ENA 713 a centrally selective acetylChEI. Ann NY Acad Sci 1991; 640: 272-5.
12 Farlow MR, Anand R, Messina Jr J, Hartman R, Veacii J. A 52-week study of the efficacy of rivastigmine in patients with mild-to-moderatey severe Alzheimer`s disease. Eur Neurol 2000; 44: 236-41.
13 Farlow M, Gracon SJ, Hershey CA, Lewis KW, Sadowsky CH, Dolan-Ureno J. A controlled trial of tacrine in Alzheimer`s disease. JAMA 1992; 268: 2523-9.
14 Folstein MF, Folstein SE, McHugh PR. “MiniMental-State”: A practical method for grading the cognitive state of patients for the clinician. J Psychiat Res 1975; 12: 189-98.
15 Forette F, Anand R, Gharabawi G. A phase II study in patients with Alzheimer`s disease to assess the preliminary efficacy and maximum tolerated dose of rivastigmine (exelon). Eur J Neurol 1999; 06: 423-9.
16 Imbibo BP. Pharmacodynamic-tolerability relationships of cholinesterase inhibitors in Alzheimer`s disease. CNS Drugs 2001; 15: 375-90.
17 McKeith I, Del Ser T, Spano PF, Emre M, Wesnes K, Ananand R, Cicin-Sain A, Ferrara R, Spiegel R. Efficacy of rivastigmine in dementia with Lewy bodies: a randomized, double-blind, placebo-controlled international study. Lancet 2000; 356: 2031-6.
18 Mesulam M, Guillozet A, Shaw P, Quinn B. Wideley spread butyrylcholinesterase can hydrolize acetylcholine in the normal and Alzheimer brain. Neurobiol Dis 2002; 09: 88-93.
19 Moretti R, Torre P, Antonello RM, Cazzato G, Bava A. Rivastigmine in vascular dementia. Expert Opin Pharmacother 2004; 05: 1399-410.
20 Perry EK, Gibson PH, Blessed G, Perry RH, Tomlinson BE. Neuro-transmitter enzyme abnormalities in senile dementia. Choline acetyltransferase and glutamic acid decarboxyalse activities in necropsy brain tissue. J Neurol Sci 1977; 34: 247-65.
21 Perry EK, Perry RH, Blessed G, Tomlinson BE. Changes in brain cholinesterases in senile dementia of Alzheimer type. Neuropathol Appl Neurobiol 1978; 04: 273-7.
22 Potkin SG, Anand R, Fleming K, Alva G, Keator D, Carreon D, Messina J, Wu JG, Hartman R, Fallon JH. Brain metabolic and clinical effects of rivastigmine in Alzheimer`s disease. Int J Neuropsychopharmacol 2001; 04: 223-30.
23 Raskind M, Peskind E, Wessel T, Yuan W. Galantamine in AD: a 6-month randomized placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group. Neurology 2000; 54: 2261-8.
24 Rösler M. The efficacy of cholinesterase inhibitors in treating the behavioural symptoms of dementia. Int J Clin Pract 2002; 127 Suppl 20-36.
25 Rösler M, Anand R, Cicin-Sain A, Gauthier S, Agid Y, Dal-Bianco P, Stahelin HB, Hartman R, Gharabawi M. Efficacy and safety of rivastigmine in patients with Alzheimer`s disease: international randomised controlled trial. BMJ 1999; 318: 633-40.
26 Rogers SL, Friedhoff LT. The efficacy and safety of donepezil in patients with Alzheimers`s diease: results of a US multicentre, randomized, doubleblind, placebo-controlled trial. The Donepezil Study Group. Dementia 1996; 07: 293-303.
27 Schneider A, Anand R, Farlow M. Systematic review of the efficacy of rivastigmine in patients with Alzheimers disease. Int J Geriatr Psychopharmacol 1998; 01 suppl 26-34.
28 Siek GC, Katz LS, Fishman EB, Korosi TS, Marquis JK. Molecular forms of acetylcholinesterase in subcortical areas of normal and Alzheimer disease brain. Biol Psychiatry 1990; 27: 573-80.
29 Spencer CM, Noble S. Rivastigmine: a review of its use in Alzheimer`s disease. Drugs Aging 1998; 13: 391-411.
30 Supprian T, Wobrock T, Retz W, Kessler H, Tracik F, Dennler HJ, Rösler M. Wirksamkeit von Riv-astigmin bei vaskulärer Demenz und AlzheimerDemenz mit zerebraler Mikroangiopathie. Psychopharmakotherapie 2004; 11: 50-8.
31 Williams BR, Nazarians A, Gill MA. A review of rivastigmine: a reversible cholinesterase inhibitor. Clin Ther 2003; 25: 1634-53.
32 Wrigit CI, Geula C, Mesulam MM. Neurological cholinesterases in the normal brain and in Alzheimer´s disease: relationship to plaques, tangles and patterns. Ann Neurol 1993; 34: 373-84.