Ask the Pharmacist

Q) My mom is about to undergo testing to see if she has Alzheimer’s or some other form of dementia. If the tests confirm my fears, should we put her on medication?

A) Unfortunately, this is a better question than it has any right to be. Short of a few cancers, I struggle to think of a more serious medical condition than Alzheimer’s for which we have so little in the way of treatment options.

There are the three cholinesterase inhibitors, namely Aricept (donepezil), Reminyl (galantamine) and Exelon (rivastigmine), which have been the mainstays of pharmaceutical therapy since they were first approved by the FDA in the United States way back in 1996. We also have the drug Ebixa (memantine) which was first introduced in the United States way back in 2003 and belongs to a class of drugs known as the NMDA-inhibitors (N-methyl-D-aspartate).

All four of these drugs are okay and help some people somewhat, but none of them are even close to being considered a game changer when it comes to treating Alzheimer’s. It is also more than mildly disturbing that it has been 17 years since we last had a new therapeutic option introduced, which is stunning given the prevalence of this disease and the utter destruction it is having on individuals, their families and our health-care budgets.

But rather than raise our hands in despair, let’s look at these four options and discuss both their positives and their negatives.

The cholinesterase inhibitors work by preventing the breakdown of acetylcholine in our body, thereby increasing the amount that is within our brain. They do this by blocking the effect of an enzyme known as acetylcholinesterase (hence the name chosen for this group of drugs, a much easier albeit less creative process than selecting a name for new rock band) whose purpose is to breakdown acetylcholine into its inactive component chemicals. Acetylcholine is one of the main neurotransmitters that nerve cells use in order to communicate with other cells within the brain. It is intimately involved with learning, memory and multiple other cognitive type functions as well as playing a role elsewhere in the body such as widening your blood vessels, slowing your heart down, helping your stomach move food along among a host of other benefits. Scientists have long believed that reduced levels of acetylcholine levels in the brain are responsible for at least some of the symptoms that are displayed in people diagnosed with Alzheimer’s.

Cholinesterase inhibitors help to make the cognitive functioning of people already diagnosed with dementia slightly better. They do not prevent people from developing the disease nor do they stop its progression to a significant extent. However, for some people they seem to slow the progression of dementia or improve their cognitive functioning to an extent that they may appear to be as “sharp” as they were 3 to 6 months ago. However, most do not even improve this much as it is estimated that only about 1 in 12 people who take these drugs will achieve even these modest benefits.

An equal number will have significant side effects which are usually not life altering (such as diarrhea, nausea and anorexia which can be minimized by taking them with food and slowly “ramping” up the dose over a few weeks/ months) but can rarely be serious such as bradycardia (a slowing of the heart rate) which can leave a person susceptible to falling and possibly fracturing a bone.

Despite nearly thirty years of use, we still do not have much evidence that they change the parameters that family members and health care practitioners really care about. Namely we cannot say for a fact they these drugs will allow the affected individual to remain at home for a longer period of time (although there is one open-label study that contradicts this and seems to show they can delay the need to enter assisted living type homes for several months), enjoy an improved quality of life or limit the burden on their caregivers. They also don’t seem to help in reducing agitation or aggressive behaviours.

However, like everything in life, the results noted above describe the average patient experience and there will be a select few that will exhibit remarkable improvement on these drugs. It is also important to consider the caregiver(s) since even a slight or insignificant benefit may be worthwhile trying rather than waiting for the inevitable and sad outcome.

If I were to select one of these drugs to try first it would probably be donepezil since its price is modest (although all 3 are covered by most drug plans and provincial formularies), you only need to take it once a day and it seems to be better tolerated than its two cohorts. These drugs take a number of months to work so it is usually a decent idea to reassess their use sometime in the 3 to 6 months range.

If donepezil does not appear to work or causes too many side effects, it is a common and legitimate strategy to try one of the other two options which may well yield more favourable results. The three cholinesterase inhibitors are meant to be used in people with mild to moderate cognitive impairment as their limited benefits have not been evident in people who have declined past this point.

Memantine, on the other hand, does not seem to help much until a person is at least moderately impacted by these diseases so it is naturally started later in the course of the disorder. It is a well tolerated drug by most people with the most common side effects noted being constipation, drowsiness, fatigue, headache and an upset stomach but the percentage of people who struggle with these is lower when contrasted with the cholinesterase inhibitors.

There are a few potentially serious side effects, as there are with all medications, but they occur rarely. While its benefits tend to be modest, memantine in clinical trials has seemed to reduce symptoms such as delusions, agitation, aggression and irritability while improving patient scores on measurements such as global well-being, daily function, independence and the ability to pay attention.

The 2 classes of drugs can be used together, and frequently are, and while the results of the studies are conflicting there may be at least some patients who benefit.

One challenge with all of these drugs is deciding if and when to stop therapy. It is very hard to judge just how well they are working with a disease that is relentlessly progressive. It is not uncommon for a caregiver to see little improvement in their loved one’s day-to-day behaviours and then bring them back to see their doctor and be told they scored “better” than before on a cognitive test.

There is also the challenge of wondering that, as poor as their spouse/ parent is fairing, would it be much worse if the drug was stopped? These are hard questions to answer and in truth, there is no magic equation to turn this decision into a “black and white” answer.

Fortunately, there are a few guidelines that might help. For starters, side effects need to be considered and determine whether they are affecting the quality of life of either the patient and/ or the caregiver (in the case of vomiting for instance). As noted earlier, desired effects should be exhibited within 3 to 6 months so if there appears to be no improvement or at least stabilization of behaviours, stopping the drugs is not a bad idea.

Next, if the patient is refusing or having difficulty swallowing pills, the benefits these drugs may provide are probably not worth the aggravation. In other words, the little benefit may not be worth the daily trials and tribulations to get the medicine down.

As well, for severely impaired patients (these patients may be incontinent frequently, unable to dress or groom themselves or even communicate effectively on a semi-regular basis), these drugs are generally useless and not worth the cost or potential side effects.

Lastly, when the focus of treatment shifts towards end-of-life type care such as the admission to a long-term care facility, it is often a good time to re-evaluate whether these drugs should be continued. The grim reality with Alzheimer’s is that we do not have a great treatment type answer. We are far better at preventing it but those steps are best enacted much earlier in life than at time of diagnosis.

Natural remedies such as gingko biloba, Prevagen and vitamin E are relatively unproven but can be safely tried in most, but please check with your doctor/ pharmacist for the potential for interactions with other commonly prescribed medications. For more information about this or any other health related questions, contact your pharmacist.