Effectiveness and safety of velnacrine for the treatment of Alzheimer's disease. A double-blind, placebo-controlled study. Mentane Study Group. Arch Intern Med 1995 Sep 11;155(16):1766-72
Date
09/11/1995Pubmed ID
7654110DOI
10.1001/archinte.1995.00430160102010Scopus ID
2-s2.0-0029143531 (requires institutional sign-in at Scopus site) 60 CitationsAbstract
BACKGROUND: Alzheimer's disease is characterized by cognitive and behavioral disturbances that are mediated in part by cholinergic brain deficits.
OBJECTIVE: To evaluate the long-term effectiveness and safety of an investigational cholinesterase inhibitor, that is, velnacrine maleate, in treating patients with clinically probable Alzheimer's disease (according to the criteria of the National Institute of Neurological Disorders and Stroke [Washington, DC]-Alzheimer Disease and Related Disorders Association [Chicago, Ill]).
METHODS: This was a double-blind, placebo-controlled study. After a single-blind washout period, patients were randomized to receive placebo (n = 152), velnacrine maleate, 150 mg/d (n = 149), or velnacrine maleate, 225 mg/d (n = 148) for 24 weeks. Primary end points were cognitive behavior and memory components of the Alzheimer's Disease Assessment Scale and the Clinical Global Impression of Change scale. Secondary end points were caregiver-rated scales.
RESULTS: The scores for the cognitive behavior and memory components of the Alzheimer's Disease Assessment Scale deteriorated in the placebo-treated group (P < .05) but not in the velnacrine-treated groups. Between-group comparisons favored velnacrine maleate, 225 mg over 150 mg (P < .05). Findings were similar for the Clinical Global Impression of Change scale and three of the four caregiver-rated scales. Treatment-related adverse clinical events occurred in 36%, 28%, and 30% of patients in the groups that received placebo, velnacrine maleate (150 mg), and velnacrine maleate (225 mg), respectively. The most common adverse clinical event was diarrhea, which rarely interrupted therapy. Treatment was stopped because of reversible abnormal liver function test results (five or more times the upper limits of normal) in 3%, 30%, and 24% of the patients who received placebo, velnacrine maleate (150 mg), and velnacrine maleate (225 mg), respectively.
CONCLUSIONS: Velnacrine produces modest but significant benefits in patients with Alzheimer's disease. Velnacrine maleate (225 mg) is more effective than 150 mg of velnacrine. Both dosages have acceptable safety profiles.
Author List
Antuono PGAuthor
Piero G. Antuono MD Professor in the Neurology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAged
Aged, 80 and over
Alzheimer Disease
Cholinesterase Inhibitors
Cognition
Double-Blind Method
Female
Humans
Male
Memory
Middle Aged
Tacrine
Treatment Outcome
