A Drug Combination Used for Alzheimer’s Disease

The current drugs used routinely in treating mild to moderate Alzheimer’s are cholinesterase inhibitors – tacrine (Cognex®), donepezil (Aricept®), rivastigmine (Excelon®), and galantamine (Razadyne® or Remenyl®). These have been shown to delay nursing home admission in patients compared to those not taking them; they delay worsening of symptoms for 6 to 12 months for about half the people who take them.

Memantine (Namenda®) blocks the NMDA receptor, regulating the activity of glutamate, which is involved in memory and learning. It’s approved for moderate to severe Alzheimer’s disease; it also delays worsening of symptoms.

A study has now been done of combination treatment of a cholinesterase inhibitor with memantine, measuring time to death and time to nursing home admission. It’s the first of its type with duration of more than a year, and it’s reported in the Journal of Neurology, Neurosurgery, and Psychiatry.

Almost 1,000 Alzheimer patients who had at least one year follow-up evaluation were included in analysis. Of these, 15% used both a cholinesterase inhibitor and memantine, 45% used only cholinesterase inhibitors, and 40% used neither. The average follow-up period was just over 5 years.

An analysis of the results showed that the patients taking a cholinesterase inhibitor had a significant delay in nursing home admissions compared with those taking no medication. Addition of memantine led to a significant further decrease in the time to admission over those taking the cholinesterase inhibitors alone. Cholinesterase inhibitors alone, or in combination with memantine, had no significant effect on the mortality.

These medications (both types) seem to help with the symptomatology of Alzheimer’s – or at least help postpone the need for nursing home admission. Their absence of an effect on mortality can be seen from two viewpoints: first, they don’t prolong life of a fatal condition; but second, they don’t have the ‘toxic’ effect of shortening lifespan. For now, a memantine-plus-cholinesterase inhibitor probably represents the best approach we’ve got.