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Medications Currently Available for Alzheimer’s Disease: Are Modest Benefits Better than No Benefits?
By Dr. Joseph Quinn
There are two main classes of medications that have been FDA (Federal Drug Administration) approved and are available for people with Alzheimer’s disease and other forms of dementia.
Cholinesterase Inhibitors
Cholinesterase inhibitors make up one class of medications. The most common cholinesterase inhibitors are Aricept, Razadyne (formerly marketed as Reminyl), and Exelon. These drugs work by boosting the chemical in the brain called acetylcholine, which we believe helps with memory and alertness, as well as thought process. Individuals with Alzheimer’s disease show a decrease in their levels of acetylcholine, and these drugs work to raise that level and/or increase the brain’s response to acetylcholine.
There hasn’t been sound evidence that one works better than the other, so we tend to think of these drugs as interchangeable.
Side Effects
The most common side effect is stomach upset. Acetylcholine, the chemical these drugs boost in the brain, also works in the gastrointestinal tract, so sometimes patients will experience some discomfort – although the severity and prevalence is much lower than you would expect. In order to prevent stomach problems, we usually start a patient on a very low dose and increase it over the next several months. Taking the medication with food can also help.
Namenda—In a Class by Itself
Memantine, or Namenda, works in a completely different way than the other three drugs. It affects glutamate, another chemical involved in the function of the brain that plays a role in learning and memory. Namenda has been approved for people with moderate to severe Alzheimer’s disease. Some patients experience improved results without further side effects when Namenda is combined with a cholinesterase inhibitor.
Side Effects
There is no stomach upset with Namenda, but some patients do experience dizziness. Starting with a lower dose and gradually increasing it seems to help combat this side effect.
How Do We Know These Medications Work?
All four of these medications have been studied in double-blind placebo-controlled trial studies, the gold standard of drug development. Patients take a study drug and neither the patient nor the treating physician knows whether it’s an active drug or a placebo. All of the assessments are made in this blinded state in order to try to remove any wishful thinking.
In these studies, these drugs have shown treatment effects. At the end of six or 12 months, when the patients on treatment are compared to the patients on placebo, the former fared better than the latter.
This positive result has been consistent across the drugs and across the trials, and I don’t think anyone would argue that point. The data was strong enough to lead the FDA to approve these drugs.
The Argument for and Against
What people do argue about – and they argue about it a lot – is whether the magnitude of the effect is worth the cost of the drug. The effect is very small in general. It’s usually three to four points on a 70 point scale. A minority of treated patients (10% – 20%) do have a more visible effect. They are robust responders who are obviously benefiting from the treatment. The family can see an improvement; some of the tests scores vastly improve. But most patients don’t experience those kinds of benefits.
In the controversy around the drugs, there are two ends of the spectrum of opinion. The pharmaceutical companies say these are valuable drugs with dramatic results and everyone with a memory problem should be on them. And those that are trying to control costs say these drugs are not so effective and they’re not worth the retail cost of them.
Working With What We Have Until We Have Something Better
This controversy is not a matter of science, but a value judgment. My feelings, and those of many of the physicians working with Alzheimer’s patients, fall somewhere in between. We think these drugs are definitely worth trying. At the very least, we need to determine if the patient turns out to be one of the robust responders, and we don’t know who those people are in advance. And for those who experience mild results? If we are able to make a sick brain even just a little better, we believe there is value in that.
We all look forward to a time when we can offer all our patients newer drugs with substantial benefits in fighting and even preventing Alzheimer’s disease.
Dr. Quinn specializes in general neurology and dementia. The assistant professor of Neurology received his medical degree from the University of Southern California, Los Angeles, in 1990. He completed his residency training at OHSU, and his fellowship in Geriatric Neurology at the Portland Veterans Affairs Medical Center. Dr. Quinn received his board certification in Neurology in 1997.
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