Dual Drug Treatment for Alzheimer’s

June 17, 2010 · Posted in Current Treatments 

The two main classes of drugs for the treatment of Alzheimer’s disease currently include cholinesterase inhibitors, which increase brain acetylcholine levels, and memantine (Namenda), which is a partial blocker of glutamate receptors. Treating patients with both types of drugs in combination may help their cognitive functioning.

The brains of patients with Alzheimer’s are deficient in acetylcholine. Acetylcholinesterase breaks down acetylcholine, so the first class of Alzheimer’s drugs inhibits these esterases and makes more acetylcholine available.

Memantine works a different way. Glutamate is the major excitatory neurotransmitter in the brain. Excesses of glutamate may be toxic to cells, so memantine’s ability to partially block glutamate receptors may explain the drug’s effectiveness in Alzheimer’s.

An extended release formulation of memantine (28mg once daily) has now been shown to improve behavior in patients with moderate to severe Alzheimer’s disease (in a poster by George Grossberg et al. at the American Psychiatric Association meeting in San Francisco in May 2009). In another poster, the same investigators reported that extended release memantine (28mg once daily) also improved attention and verbal fluency in patients with moderate to severe Alzheimer’s disease.

Previous work had indicated that the combination of an anticholinergic such as donepezil (Aricept) with regular release memantine gave an additive improvement in cognitive function when both drugs were given from the outset of the treatment of Alzheimer’s disease. With this additive improvement, the time it took a patient to fall below their baseline level of cognitive dysfunction was also extended for several years’ greater duration than with either drug alone. These data would suggest that in contemplating pharmacotherapy for Alzheimer’s disease, combination approaches should be carefully investigated and considered, rather than starting with either a cholinesterase inhibitor or memantine alone.

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