Pharmacotherapeutic strategies in the treatment of severe Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is a slowly progressive neurodegenerative disease. Patients with severe AD often require assistance with daily functioning and have a substantially higher probability of admission to nursing homes compared to the general population. AREAS COVERED: Medications approved by the US Food and Drug Administration for the treatment of severe AD include the cholinesterase inhibitors (ChEIs), donepezil (10 and 23 mg/day) and rivastigmine (transdermal patch, 13.3 mg/24 hours), and the N-methyl-D-aspartate receptor antagonist memantine (immediate- and extended-release formulations). This article will review the efficacy, safety, and tolerability data of these agents in the treatment of severe AD. Issues related to combination therapy, neuropsychiatric symptoms, and treatment discontinuation are also discussed. EXPERT OPINION: AD therapeutics provide benefits on measures of cognition, functioning, behavior, and global status even in the severe stages of AD. Combination therapy with memantine and ChEIs may provide additive benefits compared with ChEI monotherapy. Decisions regarding discontinuation of these medications should be made on a case-by-case basis, with some evidence suggesting that discontinuation may worsen cognition and functional impairment. It is recommended that patients entering the terminal stages of AD discontinue all medications not necessary for comfort.