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Namenda (Memantine, D-145)
Alzheimer's disease is a progressive type of dementia, characterized by a loss of cognitive, intellectual, and functional abilities over time. There are currently more than 4 million Americans living with Alzheimer's disease in the United States, costing the nation approximately $100 billion dollars annually.1 To date, there is no cure for this condition, and underlying causes are not entirely understood.
There is, however, increasing evidence to suggest that excess activation of the central nervous system N-methyl- D-aspartate (NMDA) receptors may play an important role in contributing to the symptoms of Alzheimer's disease. Marketed by Forest Laboratories, Namenda (memantine) is the first agent in the class of NMDA receptor antagonists, approved by the FDA for the treatment of Alzheimer's disease. Prior to the approval of Namenda, the only agents indicated for the treatment of this condition were the cholinesterase inhibitors. Unlike Namenda, which was approved for moderate-to-severe Alzheimer's disease, the cholinesterase inhibitors are recommended for mild-to-moderate forms of the disease.
Overstimulation of NMDA receptors by the excitatory neurotransmitter glutamate has been thought to be a cause of neuronal damage and the subsequent decline in functions of memory and cognition seen in Alzheimer's disease. Namenda exerts its effects by binding to NMDA receptors, resulting in the regulation of glutamate. Namenda is excreted predominantly in the urine, unchanged, and it is not significantly affected by the CYP450 enzyme system. The elimination halflife of Namenda is 60 to 80 hours.2
Two randomized, double-blind, placebo-controlled clinical studies of Namenda evaluated the cognitive and day-to-day function of patients with moderate-to-severe Alzheimer's disease. In both studies, cognitive function was measured using the Severe Impairment Battery (SIB), and day-to-day function was assessed using the modified Alzheimer's Disease Cooperative Study?Activities of Daily Living inventory (ADCS-ADL). Both studies showed that patients who were taking Namenda experienced less decline of function in both measures, compared with those taking a placebo.3,4
In the first study, 252 patients with moderate-to-severe Alzheimer's disease were randomized to receive Namenda or a placebo.
In the second study, 404 patients with moderate-to-severe Alzheimer's disease who had been treated with donepezil for the past 3 months were randomized to receive Namenda or a placebo while still receiving donepezil. At 24 weeks, the mean difference in change in the ADCS-ADL score between the groups, was 1.6 units, and the mean difference in change in the SIB score was 3.3 units.4
In clinical trials, the most common adverse events noted were constipation, headache, dizziness, and confusion. Namenda is not recommended for patients with severe renal dysfunction and should be used with caution in those with mild-to-moderate renal dysfunction.
Namenda is available as 5-mg and 10-mg tablets. The recommended starting dose is 5 mg once daily, with a target dose of 20 mg/day (10 mg twice daily). The dose should be increased in 5-mg increments at intervals of 1 week. Namenda can be taken with or without food.
Namenda offers an option for patients who have moderate-to-severe Alzheimer's disease, as well as a unique mechanism of action for treating the condition. Further studies are needed to evaluate the effects of Namenda on the prevention or slowing of neurodegeneration, as well as the potential benefits of combination therapy with cholinesterase inhibitors.