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UAMS MRC
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THE NEW ISSUE IS IN!!!
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Topic of the Month Memantine Therapy for Moderate to Severe Alzheimer’s Disease Lisa C Hutchison, PharmD, MPH Associate Professor, UAMS College of Pharmacy
The newest addition to the list of medications available for patients with dementia is memantine. Marketed under the trade name Namenda® and made available in the US in January 2004, memantine is in a class of drugs known as N-methyl-D-aspartate (NMDA) antagonists.
This drug appears to regulate the activity of glutamate, a chemical in the brain that is involved in learning and memory processes. Although a necessary chemical for learning to occur, glutamate when excessively released as it is in dementia overstimulates NMDA receptors allowing surplus calcium into nerve cells, which causes cell disruption and death. Memantine blocks NMDA receptors, thereby protecting cells against excess release of glutamate.
Symptoms in individuals with moderate to severe Alzheimer’s Disease have improved in memantine studies. In one study, subjects on memantine scored an average of 6.3% higher on the ability to eat, dress or bathe compared to those on placebo. Memantine-treated subjects also ranked 5.7% higher on a scale that measures thinking ability, memory, and language. In two studies, the combined use of memantine and donepezil produced a slight improvement or a smaller decline compared to donepezil alone. Overall, the drug appears to cause modest improvement or temporary stabilization in daily function and behavior. Caregivers for individuals on memantine spent 45.8 hours less per month providing care than caregivers of those not on this drug in one study.
Investigators have also tested memantine in people with mild to moderate vascular dementia in two studies with similar results although the US Food and Drug Administration has not yet approved this agent for vascular dementia.
Memantine is available in 5mg and 10mg tablets. The recommended starting dose is 5mg once a day. The dose should be increased by 5mg increments up to the target dose of 10mg two times a day or 20mg once a day. In the studies noted above, a large number of subjects had difficulty completing the study both in the treatment and placebo groups. This does not indicate that memantine causes a large number of side effects, but rather that individuals with progressive dementia have difficulty taking any new medication. The most common side effects and their estimated occurrence include agitation (18%), urinary incontinence (11%), insomnia (10%), diarrhea (10%), dizziness (7%), confusion (6%), headache (6%), urinary tract infection (6%), and constipation (5%).
Research in the
treatment of Alzheimer’s Disease has progressed steadily over the past
25 years. The first drug approved for use in the disease, tacrine (Cognex®),
has been replaced with the safer agents of donepezil (Aricept),
rivastigmine (Exelon) and galantamine
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