Donepezil +/- Memantine: Does It Matter?

Donepezil has been around for a while.  It wasn't the first acetylcholinesterase inhibitor (rather the second), but it's the one by which all others are judged, since it's a simple once daily medication w/o any hepatoxicity.  In fact, it's been for such a long time that a generic version is now available.  In essence, it's the go to drug for which most family physicians will reach when they diagnose someone with Alzheimer's disease (AD), as it's indicated for a stages, mild, moderate & severe.

Memantine is the first & thus far only NMDA receptor antagonist on the market.  It's indicated for moderate to severe stages of AD, although I recall back in the day that there was some push to use it off-label in the earliest, mild stage rather than to wait for disease progression.  If you'll remember back almost a year ago, a meta-analysis of 3 studies demonstrated no benefit to use of memantine in mild stage AD.

But the debate rages on.  Do these drugs really make a difference?  Not just numerically on some paper test, but clinically speaking.  To answer this question, the authors published in today's New England Journal of Medicine a randomized double blind, placebo controlled trial for which they found 295 community-dwelling patients average 77+yo with moderate-to-severe AD who had taken donepezil for at least 3 months.  The participants were randomized to one of four groups:  1) continue donepezil 2) discontinue donepezil 3) switch from donepezil to memantine or 4) add memantine to donepezil, and then followed for 52 weeks.

Using standard cognitive function scores as well as functional measurements, specifically Activities of Daily Living (ADLs), continuation of donepezil demonstrated statistically significant higher cognitive function compared to discontinuation.  However, use of memantine in isolation did not lead to any difference in cognitive function compared to use of donepezil in isolation, although memantine in isolation was better than placebo.  Furthermore, the combination of donepezil + memantine did not lead to any improvement over use of donepezil alone.  Which then raises the question, why use memantine?  But if you're tempted to discontinue donepezil, think twice and don't, at least not without substituting memantine.

Follow @alvinblin
Tweet