Cholinesterase inhibitors in Alzheimer's disease: a consensus view on managing treatment failure

Initial treatment of Alzheimer's disease (AD) with a cholinesterase (ChE) inhibitor may fail to provide benefits due to lack/loss of efficacy or poor tolerability. Since the available ChE inhibitors differ in their pharmacological profiles, switching is an option which should be considered when initial treatment is unsuccessful. Preliminary evidence from open studies and case series suggest that patents who fail to draw benefit from an initial drug may still improve when a second ChE inhibitor is administered. Switching should only be considered when a patient does not respond to the first drug, when initial efficacy is lost or when the drug is poorly tolerated. A proper trial of the first agent should be given, with appropriate doses for a sufficient length of time before concluding a therapeutic failure. Switching can be undertaken without a wash out period if the issue is lack/loss of efficacy, but a wash out period of 1-2 weeks should be allowed if a patient is switched for poor tolerability.