Cholinesterase Inhibitors: A New Class of Psychotropic Compounds

OBJECTIVE: This article reviews evidence indicating that acetylcholinesterase inhibitors have psychotropic properties. METHOD: The author reviewed the English-language literature pertinent to the response of neuropsychiatric symptoms in Alzheimer’s disease and related conditions to cholinergic agents. RESULTS: The cholinergic system originates in the basal forebrain and projects diffusely to the cerebral cortex; the limbic and paralimbic regions receive the most abundant cholinergic projections. The basal forebrain nuclei are positioned at the interface of the limbic system and cerebral cortex, where they play a role in mediating emotional responses. The basal forebrain nuclei are atrophic in Alzheimer’s disease, leading to a widespread cholinergic deficit. The cholinergic disturbance may contribute to neuropsychiatric manifestations of the disease. The treatment of patients with Alzheimer’s disease with acetylcholinesterase inhibitors reduces neuropsychiatric symptoms, particularly apathy and visual hallucinations. In some studies, a variety of other neuropsychiatric symptoms have been reported to respond to treatment with acetylcholinesterase inhibitors. Response profiles vary among acetylcholinesterase inhibitors. CONCLUSIONS: Acetylcholinesterase inhibitors have psychotropic effects and may play an important role in controlling neuropsychiatric and behavioral disturbances in patients with Alzheimer’s disease. These agents also may contribute to the management of other disorders with cholinergic system abnormalities and neuropsychiatric symptoms. The beneficial response is most likely mediated through limbic cholinergic structures.