Randomized placebo-controlled trial of donepezil in patients with progressive supranuclear palsy

被引:103
作者
Litvan, I
Phipps, M
Pharr, VL
Hallett, M
Grafman, J
Salazar, A
机构
[1] Henry M Jackson Fdn, Cognit Neuropharmacol Unit, Bethesda, MD 20817 USA
[2] Henry M Jackson Fdn, Def & Vet Head Injury Program, Bethesda, MD 20817 USA
[3] NINDS, Med Neurol Branch, NIH, Bethesda, MD 20892 USA
[4] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1212/WNL.57.3.467
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: There is no effective treatment for progressive supranuclear palsy (PSP). Because results of immunochemical and pharmacologic studies suggest that the cholinergic system may play a role in the cognitive and motor features of PSP, the authors investigated the effects of donepezil (10 mg/day), an acetylcholinesterase inhibitor, in 21 patients with PSP (mean age SD; 65.7 +/- 4.7 years) by a randomized, double-blind, placebo-controlled crossover trial. Methods: Donepezil and placebo were administered for 6 weeks each with a 1-month washout period. Patients were evaluated before and at the end of each treatment phase. Outcome measures evaluated neuropsychiatric, global cognitive, frontal, memory, motor, and activities of daily living (ADL) status. Results: Two patients withdrew during the washout phase because of unrelated medical problems. Donepezil-induced systemic side effects were transient and generally mild. Because of worsening of motor function, three patients received 5 mg/day of donepezil. All patients achieved blood and CSF therapeutic levels of donepezil. While the patients were taking donepezil, their Double Memory Test scores improved, whereas their ADL/mobility scores significantly worsened. Conclusion: The findings suggest that acetylcholinesterase inhibitors such as donepezil have at best selective, modest effects on cognition in patients with PSP. In light of its deleterious effects on ADL/mobility, donepezil is not recommended for this patient population.
引用
收藏
页码:467 / 473
页数:7
相关论文
共 48 条
[1]  
Agid Y, 1987, Adv Neurol, V45, P191
[2]  
Agid Y., 1992, PROGRESSIVE SUPRANUC, P254
[3]   THE FUNCTIONAL-ANATOMY OF BASAL GANGLIA DISORDERS [J].
ALBIN, RL ;
YOUNG, AB ;
PENNEY, JB .
TRENDS IN NEUROSCIENCES, 1989, 12 (10) :366-375
[4]  
BARON JC, 1985, LANCET, V1, P1163
[5]   DIFFERENTIAL VULNERABILITY OF CHOLINERGIC PROJECTIONS TO THE MEDIODORSAL NUCLEUS OF THE THALAMUS IN SENILE DEMENTIA OF ALZHEIMER TYPE AND PROGRESSIVE SUPRANUCLEAR PALSY [J].
BRANDEL, JP ;
HIRSCH, EC ;
MALESSA, S ;
DUYCKAERTS, C ;
CERVERA, P ;
AGID, Y .
NEUROSCIENCE, 1991, 41 (01) :25-31
[6]   EVALUATING STORAGE, RETENTION, AND RETRIEVAL IN DISORDERED MEMORY AND LEARNING [J].
BUSCHKE, H ;
FULD, PA .
NEUROLOGY, 1974, 24 (11) :1019-1025
[7]  
Buschke H, 1995, J Int Neuropsychol Soc, V1, P483
[9]   SEROTONINERGIC TERMINAL TRANSPORTERS ARE DIFFERENTIALLY AFFECTED IN PARKINSONS-DISEASE AND PROGRESSIVE SUPRANUCLEAR PALSY - AN AUTORADIOGRAPHIC STUDY WITH [H-3] CITALOPRAM [J].
CHINAGLIA, G ;
LANDWEHRMEYER, B ;
PROBST, A ;
PALACIOS, JM .
NEUROSCIENCE, 1993, 54 (03) :691-699
[10]   A SIMPLE METHOD FOR THE ESTIMATION OF INTERACTION BIAS IN CROSSOVER STUDIES [J].
CLEOPHAS, TJM .
JOURNAL OF CLINICAL PHARMACOLOGY, 1990, 30 (11) :1036-1040