Effectiveness and Safety of Velnacrine for the Treatment of Alzheimer's Disease: A Double-blind, Placebo-Controlled Study

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 P 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. (Arch Intern Med. 1995;155:1766-1772)