MEDICATION USE IN THE TREATMENT OF ALZHEIMER’S DISEASE
By Carrie Williams, PharmD
Symptoms of Alzheimer’s disease are divided into two categories: cognitive and behavioral. Cognitive symptoms include impairment of memory, language, judgment, planning, ability to pay attention and other thought processes. Behavioral symptoms do not affect every AD patient but may develop. Examples of behavioral disturbances are agitation, wandering, and hallucinations.
COGNITIVE SYMPTOMS
Below is a short list of factors that may be taken into account when cognitive-enhancing medications are being considered:
§ Stage of Alzheimer’s disease (mild, moderate, severe)
§ Other medical conditions
§ Ease of use - It is essential that these medications are taken as prescribed (daily, twice a day). It takes several weeks for these medications to reach a constant level in the body and if doses are missed the level drops and the medication may not be effective.
§ Tolerability/ Adverse effect profile of the medication
§ Cost
There are currently five medications approved by the U.S. Food and Drug Administration (FDA) that may slow the worsening of cognitive symptoms of Alzheimer’s disease (AD). Some research has also shown improvement of behavioral symptoms. These medications are divided into two classes that target different chemicals involved in carrying messages between brain cells.
The first group of medications target an enzyme called cholinesterase. By inhibiting cholinesterase, they increase the amount of acetylcholine available in the brain. Acetylcholine is a naturally occurring chemical in the body and plays an important role in learning and memory. As an individual ages acetylcholine levels decline, a process that is believed to occur more rapidly with the progression of AD. This class of drugs includes Aricept® (donepazil), Razadyne® (ER) (galantamine), Exelon® (rivastigmine), and Cognex® (tacrine). All are approved for the treatment of mild to moderate dementia. Aricept is also approved for use in severe stages of AD. These medications may delay worsening of symptoms for 6-12 months in about half the people who take them. Patients should be evaluated for effectiveness of a cholinesterase inhibitor after at least 6 months of therapy.
Namenda® (memantime) is currently in a class of its own called NMDA – receptor blockers. It works on a nerve-stimulating chemical called glutamate, when not regulated, excess glutamate may lead to brain cell death. Namenda® blocks NMDA-receptors on nerve cells to prevent overstimulation by glutamate. It may be prescribed alone or in combination with a cholinesterase inhibitor. Other NMDA receptor blockers are currently in development.
Both groups of medications have side-effects that sometimes occur during the initiation of therapy. Side-effects that may occur with cholinesterase-inhibitors include nausea, vomiting, loss of appetite, or increased frequency of bowel movement. Cognex® is rarely prescribed in the United States because of a significant risk of liver toxicity. Headache, constipation, confusion, and dizziness are side effects that have been experienced with Namenda®. With the exception of Cognex®, the symptoms listed above are relatively minor and usually go away with time. Rare, but more concerning side effects, may include slow heartbeat, persistent dizziness, sudden weight loss, stomach pain, or yellowing of the skin. If you experience any of these symptoms you should report them to your doctor immediately. When starting any of these medications, a schedule will be determined to increase the dose slowly. This titration usually occurs over a few weeks and will vary depending on the patient and medication selected. If you experience any disturbing side effect, notify the prescriber to discuss your options. Adjustments to consider before stopping treatment may include: slower titration, timing change, or possibly trying another medication.
Finally, the goals of drug therapy include temporary improvement, stabilization, or slowing decline. No medications are available to stop the deterioration of brain cells, therefore drastic changes should not be expected. As discussed, not all patients will respond to medication treatment.
BEHAVIORAL SYMPTOMS
In different stages of AD patients may experience aggression, emotional distress, hallucinations (seeing, hearing, or feeling things that are not there). These feelings can cause severe agitation or even combativeness. All patients who develop these symptoms should receive a thorough medical exam, especially if symptoms appear suddenly. Pain, infection, problems with vision or hearing, or medication side-effects could cause an acute change in behavior unrelated to AD. Other situational or environmental changes could also contribute to fear or increased confusion.
§ Monitor personal comfort. Check for pain, hunger, thirst, constipation, full bladder, fatigue, infections and skin irritation. Maintain a comfortable room temperature.
§ Avoid being confrontational or arguing about facts.
§ Redirect the person's attention. Try to remain flexible, patient and supportive.
§ Create a calm environment. Avoid noise, glare, insecure space, and too much background distraction, including television.
§ Simplify the environment, tasks and solutions.
§ Allow adequate rest between stimulating events.
§ Provide a security object or privacy.
If symptoms are thought to be associated with AD, first-line treatment should include environmental modification, task simplification, clear communication and other non-pharmacologic options. If these methods are unsuccessful, then medications targeted to specific behaviors can be explored. In patients with significant behavioral disturbances the risks of not treating these complications must be weighed against the risks associated with treatment. There are no medications approved by the FDA specifically for the treatment of behavioral symptoms associated with Alzheimer’s disease. This means that medications that are FDA-approved to treat other conditions may be prescribed “off-label” to treat similar symptoms in AD patients. “Off-label” use is a medical practice in which a physician may prescribe a drug for a different purpose than the ones for which it is approved. The “off-label” use of any drug should be done with caution and by physicians experienced with their use. Side effects can be serious and patients must be closely monitored. The minimum effective dose should be used and if the symptom has improved, periodic trials of medication withdrawal should be attempted. Examples of medications used off-label for behavioral symptoms include anti-anxiety, antipsychotics, and mood stabilizers.
Antipsychotics: Riperidone(Risperdal®),Quetiapine (Seroquel®), and Olanzapine (Zyprexa®)
If treatment is started with one of these medications be sure to discuss the side-effect profile and when/what specific improvements can be expected. Changes may not be significant for months depending on the treatment. To decrease the risk of complications, it is absolutely necessary to start with low doses and increase slowly if required.
All AD patients should be followed closely by a physician to monitor and adjust their personal treatment plan, including management of other medical conditions. The plan should be flexible and reevaluated on a regular basis. A personal journal that describes specific times and events is helpful to identify triggers and make changes. Take an accurate and up-to-date medication list to all appointments.
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