New Cholinergic Therapies: Treatment Tools for the Psychiatrist

This article reviews the current status of therapy with acetylcholine-enhancing compounds in themanagement of patients with Alzheimer’s disease. The focus is on pivotal articles investigating therole of cholinergic augmentation strategies, including precursor loading and acetylcholinesterase(AChE) inhibitors, in the management of cognitive and noncognitive symptoms of Alzheimer’s disease.Precursor loading strategies have been for the most part unimpressive. By contrast, studies withAChE inhibitors—tacrine and donepezil—have been promising. For patients in whom hepatotoxicityand gastrointestinal side effects were not problematic, tacrine improves cognitive performance andselected secondary psychiatric symptoms and significantly delays nursing home placement. Donepezil,recently approved for use in mild to moderate Alzheimer’s disease, appears to be less toxic andbetter tolerated than tacrine. It improves performance on cognitive testing and, in one preliminary investigation,demonstrated a sustained drug effect over several years. Therapy with AChE inhibitorsprovides modest significant symptomatic improvement in patients with mild to moderate Alzheimer’s disease.