Practical Pharmacology of Memantine

Abstract

When thinking of treating any patient, we have to be mindful not only of the clinical pharmacology of the treatments used and the clinical trial data but also of the clinical outcomes and adverse events seen when the treatment is widely used in clinical practice. In this chapter on the use of memantine in AD, I will attempt a brief review of the these three aspects: the clinical relevance of glutamate and the NMDA receptor with which memantine interacts, the clinical benefits seen including the effect on clinical progression, and the effect seen in the clinic of combining memantine with cholinesterase inhibitors. Memantine, importantly, has been shown to be extremely safe and well tolerated. The trial evidence showed modest levels of improvement in the core symptoms of AD, but increasing experience has shown it has a role in slowing down the progression of these core symptoms and the emergence of new unwanted behavior. The effect of memantine on agitation and disturbed nighttime behaviors emerged as a key role in AD management and the additive benefits on symptom relief and clinical progression in combination with cholinesterase inhibitors has led many to see this as the optimum treatment for AD. However, neither this stance nor the effect on agitation has been proved in prospective randomized clinical trials, partly because it has become so widely accepted since both treatments are now generically available and safe and partly as this kind of comparative trial is not seen as attractive to trial sponsors and patients.