Cholinesterase-Inhibitoren und Alzheimer-Demenz: Metaanalyse zu Wirksamkeitsnachweis, Ursprung und Ergebnisverzerrung in publizierten Studien

Zusammenfassung

Hintergrund und Fragestellung: Die Cholinesterase-Inhibitoren (ChE-I) Donepezil, Galantamin und Rivastigmin werden zur symptomatischen Behandlung des cholinergen Defizits bei der Alzheimer Demenz (AD) und anderen Demenzformen eingesetzt. Untersucht wurden (I) die klinische Wirksamkeit der ChE-I bei der AD; (II) Unterschiede zwischen US-amerikanischen und internationalen Studien; sowie (III) Hinweise auf einen Publikationsbias.

Methodik: Ausgewertet wurden die publizierten, doppelblind durchgeführten, randomisierten, Plazebo-kontrollierten Parallelgruppen-Studien mit einer Fallzahl von n ≥100 Patienten und einer Studientherapiedauer von ≥12 Wochen. Eingeschlossene Krankheitsbilder waren AD, vaskuläre Demenzen (VD), Demenz mit Lewy Bodies, Demenz bei Morbus Parkinson und bei leichten kognitiven Störungen.

Ergebnisse: In den großen publizierten Untersuchungen wird übereinstimmend eine signifikante Wirksamkeit der ChE-I hinsichtlich Kognition und klinischem Gesamteindruck belegt. Die US-amerikanischen Untersuchungen zeigten im Durchschnitt deutlichere Effekte der Cholinesterase-Hemmer auf die kognitive Leistung der Patienten. Hinweise auf eine Ergebnisverzerrung (Publikationsbias) waren nicht zu eruieren.

Folgerungen: Die publizierten Daten zur Therapie der leichten und mittelschweren AD mit Donepezil, Galantamin oder Rivastigmin demonstrieren deren klinische Wirksamkeit. Relevante Hinweise auf eine wesentliche Beeinflussung der Ergebnisse durch Studienort oder selektive Publikation ergaben sich nicht.

Summary

Background and objective: The cholinesterase-inhibitors (AChE-I) donepezil, galantamine and rivastigmine are currently used in the symptomatic treatment of patients with Alzheimer’s dementia (AD) and the associated cholinergic deficits as well as those with other forms of dementia. Threee aspects were analysed: (1) data on their clinical efficacy, (2) differences between North-American and international studies, and (3) potential publication biases.

Methods: Included were data from randomized, placebo-controlled, double-blind parallel group trials on more than 100 patients who had been treated for ≥12 weeks for AD, VaD, dementia with Lewy bodies, dementia with Parkinson’s disease or with mild cognitive impairment.

Results: These large published trials support the clinical efficacy of AChE-I in patients with mild to moderate AD and other forms of dementia with regard to cognition and global impression. there was a trend towards greater beneficial cognitive effects in North-American studies, but this was non-significant. There was no evidence of a publication bias.

Conclusions: Published data provide evidence for the clinical efficacy of donepezil, galantamine and rivastigmine in patients with mild to moderate AD. There is no indication that these results are critically influenced by the origin or a bias of the publication.

Schlüsselwörter

Alzheimer-Demenz - Acetylcholinesterase-Hemmer - Donepezil - Galantamin - Rivastigmin - Wirksamkeitsnachweis - Publikationsbias - Evidenz - Forest Plot - Funnel Plot

Key words

Alzheimer’s disease - dementia - acetylcholinesterase inhibitors - donepezil - galantamine - rivastigmine - clinical evidence - publication bias - forest plot - funnel plot

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