Complexities of AD Require Extensive Counseling

Dr. Knudsen is a clinical pharmacistat Arizona Medical Clinic Ltd inPeoria, Ariz.

Alzheimer's disease (AD) is aprogressive and degenerativeneurologic disorder that ischaracterized by a slow but suredecline in cognition and behavior. AD isthe most common cause of dementiaamong people aged 65 and older, andscientists estimate that 4.5 millionpeople in the United States currentlyhave the disease.¹ This disease not onlyaffects the individual suffering from itsmind-altering effects, but also affectsthe family, friends, and caregivers ofthe patient.

The disease is a mystery to the medicalcommunity; diagnosis is by exclusionand is not confirmed until deathwith an autopsy. Just as the disease isan enigma for health care providers, itcan be frustrating to family members,friends, and caregivers of the patient.For that reason, it is important to providecounseling to the patient, the family,and caregivers. As the medicationexperts in the community, pharmacistsmust educate patients and caregiversto ensure that they have realisticexpectations and understand the limitationsof AD medications.

Table 1

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

Pharmacists need to emphasize thatAD medications slow the progressionof the disease, but patients should notbe expected to return to baseline functioning.A change in medicationsshould take place only if the decline inthe MMSE score is equal to or greaterthan normal disease progression afterthe patient has used a specific treatmentfor 1 year.²

Pharmacotherapy

For a disease that affects so manypeople and has no cure, only 4 medicationsin 2 drug classes are available toslow the progression (Table 2). Acetylcholinesterase(AChE) inhibitors arethe mainstay of AD therapy. There are 4agents in the class, but only 3 are commonlyprescribed: donepezil (Aricept),galantamine (Razadyne, Razadyne ER),and rivastigmine (Exelon). Tacrine(Cognex) was approved in 1993 but israrely used because of its severe sideeffects and the risk of hepatotoxicity.

Table 2

Donepezil has an easy titrationschedule and can be increased from 5mg to 10 mg once daily (maximumdose) in 4 to 6 weeks.⁴ Unlike the otheragents in this class, the side effects areusually mild and include headache,nausea, diarrhea, anorexia, and fatigue.⁴Donepezil also comes in an orally disintegratingtablet for easier administration.

Rivastigmine has a time-consumingtitration schedule and is dosed twiceper day. The capsules should not beopened and mixed with food or a beverage. If administration is a problem, anoral solution and a patch are available.Patients and caregivers should be educatedon the proper administration anddisposal of the Exelon Patch. WhenExelon Oral Solution is combined withcold fruit juice or soda, the mixture isstable at room temperature for up to 4hours.⁵ If the patient stops the medicationfor more than several days, treatmentshould be reinitiated with thelowest daily dose and titrated back upto the previous dose.⁵ It is important tolet the caregiver know about the titrationrequirements to avoid intolerablegastrointestinal (GI) adverse effects.

Galantamine has a complicated titrationschedule and must be given withmeals. Tablets are dosed at 4 mg twicedaily, titrated monthly to 12 mg twicedaily. Extended-release tablets are availablefor once-daily dosing, and an oralsolution is available if administration is aproblem. Caregivers should be instructedin the correct procedure for administeringthe Razadyne Oral Solution andshould be shown the instruction sheetthat comes with the product. If therapyhas been interrupted for several days orlonger, the medicine should be restartedat the lowest dose and escalated tothe current dose.⁶

Memantine is the only agent availablein the N-methyl-D-aspartate antagonistclass. It is approved for moderate-to-severe disease. It can be used asmonotherapy or combination therapywith an AChE inhibitor. It can be titratedfrom 5 mg daily every 7 days untilthe goal dose of 10 mg twice daily isreached.⁷

Alternative/Complementary Therapies

As with any disease for which themedical community cannot provide acure, people often go beyond allopathictreatment options (Table 3). Herbaland dietary supplements such as ginkgobiloba, coenzyme Q₁₀, orvitamin E are used as alternativesor adjuncts topharmacotherapy. Ginkgobiloba may have a bleedingrisk if used concomitantlywith other bleeding-riskmedications (eg, nonsteroidalanti-inflammatorydrugs [NSAIDs], warfarin)and may increase theadverse effects of AChEinhibitors.⁸ Coenzyme Q₁₀ may increasebleeding risk and should be used withcaution with antidiabetic, psychiatric,and cardiovascular drugs. CoenzymeQ₁₀ has potential adverse effects similarto those with the AChE inhibitors.⁹

Table 3

Vitamin E at more than 400 IU/dayhas been studied, and, although it hasnot shown clinically significant resultsin large studies for AD, it was associatedwith an increase in all-cause mortalityin a large meta-analysis and thusshould be avoided.² Epidemiologicstudies have suggested that NSAIDsmay have a benefit, but the risks ofbleeding events and GI adverse effectsoutweigh the possible benefit.²

Patients wanting more informationregarding these products can reviewthe ongoing clinical trials at theNational Institutes of Health ClinicalTrials Web site, www.clinicaltrials.gov,but this information is not targeted tothe lay public. If a pharmacist directssomeone to this site, it is important tostress that the patient should discussthe findings with a pharmacist oranother qualified health care providerbefore making any changes to his orher therapy.

Pharmacists are in a great positionto discuss these products with patients.Many of the electronic resourcesavailable to pharmacists—such as Lexi-Comp, Micromedex, andClinical Pharmacology—have scientificinformation available regarding dietarysupplements or natural products.Pharmacists need to educate patientsthat, with any product that falls underthe FDA's definition of dietary supplement(vitamin, mineral, herb, botanical,amino acid, enzyme, organtissue, metabolite, etc),there is a lack of standardizationand a lack of safetyinformation about the potentialfor adverse effectsand medication interactions.

Also, pharmacists are inan excellent place to helpthe caregivers of ADpatients. This disease isoften difficult for the caregiver,especially when the patient hasepisodes of depression, paranoia,sleep disturbances, and aggression.Spousal or caregiver abuse can occur.Being aware of these types of issuescan allow the pharmacist to providesupport and encouragement. Lettingthe caregiver know about supportgroups and the availability of treatmentfor these additional conditions thatoften accompany AD can increase thequality of life for the caregiver and inturn the quality of life for the patient.

References

• 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.
• DiPiro JT, Talbert RL, Yee GC, Matzke GR. Pharmacotherapy. 6th ed. New York, NY: McGraw-Hill; 2005: 1163-1167.
• 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.
• Aricept prescribing information. Available at: www.aricept.com. Accessed August 30, 2007.
• Exelon prescribing information. Available at: www.pharma.us.novartis.com/product/pi/pdf/exelon.pdf. Accessed August 30, 2007.
• Razadyne ER prescribing information. Available at: https://www.ortho-mcneilneurologics.com. Accessed August 30, 2007.
• Namenda prescribing information. Available at: www.frx.com/products/namenda.aspx. Accessed August 30, 2007.
• Lexi-Comp online. Ginkgo biloba. Available at: online.lexi.com/crlsql/servlet/crlonline. Accessed August 29, 2007.
• Lexi-Comp online. Coenzyme Q10. Available at: online.lexi.com/crlsql/servlet/crlonline. Accessed August 29, 2007.