New cholinergic therapies: treatment tools for the psychiatrist.
This article reviews the current status of therapy with acetylcholine-enhancing compounds in the management of patients with Alzheimer's disease. The focus is on pivotal articles investigating the role 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 with AChE inhibitors--tacrine and donepezil--have been promising. For patients in whom hepatotoxicity and gastrointestinal side effects were not problematic, tacrine improves cognitive performance and selected 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 and better 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 inhibitors provides modest significant symptomatic improvement in patients with mild to moderate Alzheimer's disease.
Department of Psychiatry and Behavioral Sciences, Wesley Woods Center on Aging at Emory University, Emory University School of Medicine, Atlanta, GA 30329, USA.
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D000544:Alzheimer Disease / Q000188:drug therapy*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D018678:Cholinergic Agents / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D000077265:Donepezil; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D008297:Male; D010880:Piperidines / Q000627:therapeutic use; D012642:Selegiline / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D013619:Tacrine / Q000627:therapeutic use; D014810:Vitamin E / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D018678:Cholinergic Agents; D002800:Cholinesterase Inhibitors; D000077265:Donepezil; D004967:Estrogens; D007189:Indans; D010880:Piperidines; D012642:Selegiline; D017367:Selective Serotonin Reuptake Inhibitors; D013619:Tacrine; D014810:Vitamin E