Combined administration of physostigmine and clonidine to patients with dementia of the Alzheimer type: a pilot safety study.

Reports of cholinergic and noradrenergic deficits in brain specimens from Alzheimer patients have suggested that concomitant augmentation of cholinergic and noradrenergic neurotransmission can benefit some dementia of the Alzheimer type (DAT) patients. However, pharmacological agents that enhance central cholinergic and noradrenergic neurotransmission, like physostigmine and clonidine, might have serious adverse effects. Therefore, prior to the commitment of major resources in efficacy studies, feasibility pilot studies are necessary to ensure that physostigmine and clonidine, combined, can be safely administered to DAT patients. Physostigmine, 2 mg every 2 h, and clonidine, up to 0.3 mg/day, were tolerated by the nine DAT patients without clinically meaningful adverse effects.