title: Combination drug therapy for Alzheimer's disease: what is evidence-based, and what is not?
abstract: Although FDA-approved Alzheimer's disease (AD) treatment strategies (cholinesterase inhibitors and memantine) offer proven benefits, providers recognize unmet needs beyond what is currently available. Consequently there is a significant use of anecdotal yet unproven combinations for treating AD in practice. Based on the best evidence, combination drug therapy is the standard of care for treating other medical conditions such as malignancies, human immunodeficiency virus (HIV), and hypertension. We review recent combination drug therapy studies in AD. To date, the best evidence-based combination strategy is for moderate-to-severe AD, in which the addition of memantine to stable donepezil therapy was found to benefit cognition, behavior, and function. In milder stages of AD, the benefit of combination drug therapy has not been demonstrated. This review highlights the urgent need to systematically test additional rational drug combinations and the need for future trials to enroll adequate sample sizes and utilize relevant and sensitive outcome measures.
authors.affiliation: Duke University Medical Center, Durham, NC, USA.
authors.forename: Glen
authors.initials: G
authors.lastname: Xiong
authors.forename: P Murali
authors.initials: PM
authors.lastname: Doraiswamy
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004967:Estrogens / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008559:Memantine / Q000627:therapeutic use; D019338:Polypharmacy
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D004967:Estrogens; D018691:Excitatory Amino Acid Antagonists; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008559:Memantine