At the 65th Annual Scientific Convention of the Society of Biological Psychiatry in May, Amit Anand reported that the anti-Alzheimer’s drug memantine (20 mg/day) was superior to placebo in augmenting the acute antidepressant effects of lamotrigine. These data are of particular interest since one of the assumed mechanisms of action of lamotrigine is to decrease the release of glutamate.
Memantine is a drug approved for the treatment of Alzheimer’s disease and is a partial antagonist (blocker) of glutamate NMDA receptors. This suggests that the dual actions of inhibiting glutamate’s release pre-synaptically (with lamotrigine) and blocking glutamate receptor activity post-synaptically (with memantine) combine to produce a better effect than that of lamotrigine alone.
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.