There are four FDA approved medications available for treatment of Alzheimer’s disease: Aricept, Exelon, Razadyne, and Namenda.  The first three are in a class of medications known as cholinesterase inhibitors and the other, Namenda, is an NMDA receptor antagonist.  In simple terms, the cholinesterase inhibitors increase the amount of a neurotransmitter called acetylcholine whereas Namenda decreases the amount of a different neurotransmitter, glutamate.  Often Namenda is used together with one of the cholinesterase inhibitors as the combination appears to be more effective to boost cognition in moderate to severe Alzheimer’s disease than either medication used alone.

The news of the week is that the FDA has approved the use of a higher dose of Aricept for those with moderate to severe Alzheimer’s disease as indicated by a score of 20 or fewer of 30 possible points on the Mini-Mental State Exam.  Until now the standard for use of Aricept was to take 5 mg for the first month to build tolerance and then 10 mg thereafter, if tolerated.  Starting in August 2010, Aricept will also be available in a new 23 mg dose.  The approval of the higher dose is based on a study indicating that there are cognitive benefits of the 23 mg dose of Aricept when compared the standard 10 mg dose.  Participants in the study had been taking 10 mg of Aricept for a minimum of three months before taking the higher dose.

As with any medication, there are trade-offs for use of a higher dose.  First, there are more frequent side effects.   The 23 mg dose induces a greater frequency of nausea, vomiting, diarrhea, and loss of appetite than does the 10 mg dose.  Other common side effects to be aware of are dizziness, weight loss, muscle cramps, urinary incontinence, fatigue, difficulty sleeping, and headache among others.  Second, there are several at risk groups that need greater caution and closer monitoring if taking the higher dose.  For example, those at risk of stomach ulcers (Aricept may increase bleeding) or heart disease (Aricept may cause slowed heart rate and fainting), lung disease, bladder problems, or seizures should also be screened and monitored more carefully if given the higher dose.

Finally, there were improvements on a very specific cognitive test called the Severe Impairment Battery.  This test is not often used outside of research settings.  Screening tests like the Mini-Mental State Exam cannot be relied on to measure outcome.  Furthermore, those caring for persons using the 23 mg dose may not see any obvious effects of the higher dose.  Despite cognitive improvement on the Severe Impairment Battery there were no reliable improvements in either clinician or caregiver ratings of those on the 23 mg dose when compared to the 10 mg dose. The clinical benefits of the higher dose remain to be determined