/publications/issue/2007/2007-11/2007-11-8249

Complexities of AD Require Extensive Counseling

Author: Dawn S. Knudsen, PharmD


Dr. Knudsen is a clinical pharmacist at Arizona Medical Clinic Ltd in Peoria, Ariz.


Alzheimer's disease (AD) is a progressive and degenerative neurologic disorder that is characterized by a slow but sure decline in cognition and behavior. AD is the most common cause of dementia among people aged 65 and older, and scientists estimate that 4.5 million people in the United States currently have the disease.1 This disease not only affects the individual suffering from its mind-altering effects, but also affects the family, friends, and caregivers of the patient.

The disease is a mystery to the medical community; diagnosis is by exclusion and is not confirmed until death with an autopsy. Just as the disease is an enigma for health care providers, it can be frustrating to family members, friends, and caregivers of the patient. For that reason, it is important to provide counseling to the patient, the family, and caregivers. As the medication experts in the community, pharmacists must educate patients and caregivers to ensure that they have realistic expectations and understand the limitations of AD medications.

Table 1

The Alzheimer's Disease Assessment Scale-Cognition (ADAS-cog) and the Mini-Mental State Examination (MMSE) are 2 tools to evaluate the status and progression of AD. The ADAS-cog is time-consuming, whereas the MMSE is easier to administer in clinical practice.2 MMSE scores range from 0 to 30 (from severe to mild disease; Table 1).3 MMSE scores naturally decrease 2 to 4 points per year if AD is untreated.2

Pharmacists need to emphasize that AD medications slow the progression of the disease, but patients should not be expected to return to baseline functioning. A change in medications should take place only if the decline in the MMSE score is equal to or greater than normal disease progression after the patient has used a specific treatment for 1 year.2

Pharmacotherapy

For a disease that affects so many people and has no cure, only 4 medications in 2 drug classes are available to slow the progression (Table 2). Acetylcholinesterase (AChE) inhibitors are the mainstay of AD therapy. There are 4 agents in the class, but only 3 are commonly prescribed: donepezil (Aricept), galantamine (Razadyne, Razadyne ER), and rivastigmine (Exelon). Tacrine (Cognex) was approved in 1993 but is rarely used because of its severe side effects and the risk of hepatotoxicity.

Table 2


Donepezil has an easy titration schedule and can be increased from 5 mg to 10 mg once daily (maximum dose) in 4 to 6 weeks.4 Unlike the other agents in this class, the side effects are usually mild and include headache, nausea, diarrhea, anorexia, and fatigue.4 Donepezil also comes in an orally disintegrating tablet for easier administration.

Rivastigmine has a time-consuming titration schedule and is dosed twice per day. The capsules should not be opened and mixed with food or a beverage. If administration is a problem, an oral solution and a patch are available. Patients and caregivers should be educated on the proper administration and disposal of the Exelon Patch. When Exelon Oral Solution is combined with cold fruit juice or soda, the mixture is stable at room temperature for up to 4 hours.5 If the patient stops the medication for more than several days, treatment should be reinitiated with the lowest daily dose and titrated back up to the previous dose.5 It is important to let the caregiver know about the titration requirements to avoid intolerable gastrointestinal (GI) adverse effects.

Galantamine has a complicated titration schedule and must be given with meals. Tablets are dosed at 4 mg twice daily, titrated monthly to 12 mg twice daily. Extended-release tablets are available for once-daily dosing, and an oral solution is available if administration is a problem. Caregivers should be instructed in the correct procedure for administering the Razadyne Oral Solution and should be shown the instruction sheet that comes with the product. If therapy has been interrupted for several days or longer, the medicine should be restarted at the lowest dose and escalated to the current dose.6

Memantine is the only agent available in the N-methyl-D-aspartate antagonist class. It is approved for moderate- to-severe disease. It can be used as monotherapy or combination therapy with an AChE inhibitor. It can be titrated from 5 mg daily every 7 days until the goal dose of 10 mg twice daily is reached.7

Alternative/Complementary Therapies

As with any disease for which the medical community cannot provide a cure, people often go beyond allopathic treatment options (Table 3). Herbal and dietary supplements such as ginkgo biloba, coenzyme Q10, or vitamin E are used as alternatives or adjuncts to pharmacotherapy. Ginkgo biloba may have a bleeding risk if used concomitantly with other bleeding-risk medications (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], warfarin) and may increase the adverse effects of AChE inhibitors.8 Coenzyme Q10 may increase bleeding risk and should be used with caution with antidiabetic, psychiatric, and cardiovascular drugs. Coenzyme Q10 has potential adverse effects similar to those with the AChE inhibitors.9

Table 3


Vitamin E at more than 400 IU/day has been studied, and, although it has not shown clinically significant results in large studies for AD, it was associated with an increase in all-cause mortality in a large meta-analysis and thus should be avoided.2 Epidemiologic studies have suggested that NSAIDs may have a benefit, but the risks of bleeding events and GI adverse effects outweigh the possible benefit.2

Patients wanting more information regarding these products can review the ongoing clinical trials at the National Institutes of Health Clinical Trials Web site, www.clinicaltrials.gov, but this information is not targeted to the lay public. If a pharmacist directs someone to this site, it is important to stress that the patient should discuss the findings with a pharmacist or another qualified health care provider before making any changes to his or her therapy.

Pharmacists are in a great position to discuss these products with patients. Many of the electronic resources available to pharmacists— such as Lexi-Comp, Micromedex, and Clinical Pharmacology—have scientific information available regarding dietary supplements or natural products. Pharmacists need to educate patients that, with any product that falls under the FDA's definition of dietary supplement (vitamin, mineral, herb, botanical, amino acid, enzyme, organ tissue, metabolite, etc), there is a lack of standardization and a lack of safety information about the potential for adverse effects and medication interactions.

Also, pharmacists are in an excellent place to help the caregivers of AD patients. This disease is often difficult for the caregiver, especially when the patient has episodes of depression, paranoia, sleep disturbances, and aggression. Spousal or caregiver abuse can occur. Being aware of these types of issues can allow the pharmacist to provide support and encouragement. Letting the caregiver know about support groups and the availability of treatment for these additional conditions that often accompany AD can increase the quality of life for the caregiver and in turn the quality of life for the patient.

References

  1. Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol. 2003;60:1119-1122.
  2. DiPiro JT, Talbert RL, Yee GC, Matzke GR. Pharmacotherapy. 6th ed. New York, NY: McGraw-Hill; 2005: 1163-1167.
  3. Galasko D. An integrated approach to the management of Alzheimer's disease: assessing cognition function and behavior. Eur J Neurol. 1998;5(suppl 4):S9-S17.
  4. Aricept prescribing information. Available at: www.aricept.com. Accessed August 30, 2007.
  5. Exelon prescribing information. Available at: www.pharma.us.novartis.com/product/pi/pdf/exelon.pdf. Accessed August 30, 2007.
  6. Razadyne ER prescribing information. Available at: https://www.ortho-mcneilneurologics.com. Accessed August 30, 2007.
  7. Namenda prescribing information. Available at: www.frx.com/products/namenda.aspx. Accessed August 30, 2007.
  8. Lexi-Comp online. Ginkgo biloba. Available at: online.lexi.com/crlsql/servlet/crlonline. Accessed August 29, 2007.
  9. Lexi-Comp online. Coenzyme Q10. Available at: online.lexi.com/crlsql/servlet/crlonline. Accessed August 29, 2007.