Cases That Test Your Skills

After 62 years, her husband is a ‘stranger’

Current Psychiatry. 2004 June;3(6):88-95

References

1. Askin-Edgar S, White KE, Cummings JL. Neuropsychiatric aspects of Alzheimer’s disease and other dementing illnesses. In: Textbook of neuropsychiatry and clinical neurosciences (4th ed). Washington, DC: American Psychiatric Publishing, 2002.

2. Tariot PN, Erb R, Podgorski CA, et al. Efficacy and tolerability of carbamazepine for agitation and aggression in dementia. Am J Psychiatry 1998;155:54-61.

3. Loy R, Tariot PN. Neuroprotective properties of valproate: potential benefit for AD and tauopathies. J Mol Neurosci 2002;19:303-7.

4. Roane DM, Feinberg TE, Meckler L, et al. Treatment of dementiaassociated agitation with gabapentin. J Neuropsychiatry Clin Neurosci 2000;12:40-3.

5. Tekin S, Aykut-Bingol C, Tanridag T, Aktan S. Antiglutamatergic therapy in Alzheimer’s disease—effects of lamotrigine. J Neural Transm 1998;105:295-303.

6. Street JS, Clark WS, Kadam DL, et al. Long-term efficacy of olanzapine in the control of psychotic and behavioral symptoms in nursing home patients with Alzheimer’s dementia. Int J Geriatr Psychiatry 2001;16(suppl 1):S62-S70.

7. Tariot PN, Ismail MS. Use of quetiapine in elderly patients. J Clin Psychiatry 2002;63(suppl 13):21-6.

8. DeVane CL, Mintzer J. Risperidone in the management of psychiatric and neurodegenerative disease in the elderly: an update. Psychopharmacol Bull 2003;37:116-32.

9. Pollock BG, Mulsant BH, Rosen J, et al. Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients. Am J Psychiatry 2002;159:460-5.

10. Lyketsos CG, DelCampo L, Steinberg M, et al. Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS. Arch Gen Psychiatry 2003;60:737-46.

11. Swann AC. Neuroreceptor mechanisms of aggression and its treatment. J Clin Psychiatry 2003;64(suppl 4):26-35.

12. Olin JT, Schneider LS, Katz IR, et al. Provisional diagnostic criteria for depression of Alzheimer disease. Am J Geriatr Psychiatry 2002;10:125-8.

13. Physician’sdesk reference(58thed). Montvale, NJ:Thomson PDR,2004.

14. Porsteinsson AP, Tariot PN, Erb R, Gaile S. An open trial of valproate for agitation in geriatric neuropsychiatric disorders. Am J Geriatr Psychiatry 1997;5:344-51.

15. Assal F, Cummings JL. Neuropsychiatric symptoms in the dementias. Curr Opin Neurol 2002;15:445-50.

16. Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. N Engl J Med 1997;336:1216-22.

17. Kittur S, Hauser P. Improvement of sleep and behavior by methylphenidate in Alzheimer’s disease. Am J Psychiatry 1999;156:1116-7.

18. Salzman C. Treatment of the agitation of late-life psychosis and Alzheimer’s disease. Eur Psychiatry 2001;16(suppl 1):25s-28s.

19. Ginsburg ML. Clonazepam for agitated patients with Alzheimer’s disease. Can J Psychiatry 1991;36:237-8.

20. Jackson CW, Pitner JK, Mintzer JE. Zolpidem for the treatment of agitation in elderly demented patients. J Clin Psychiatry 1996;57:372-3.

21. Reisberg B, Doody R, Stoffler A, et al. Memantine Study Group. Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med 2003;348:1333-41.

Treating agitation and delaying nursing home placement for patients with AD is challenging. When faced with inadequate or no response, consider less-conventional alternatives.

Vitamin E and selegiline were found separately to postpone functional decline in ambulatory patients with moderately severe AD, but the agents given together were less effective than either agent alone.¹⁶

Use of methylphenidate,¹⁷ buspirone,¹⁸ clonazepam,¹⁹ zolpidem,²⁰ and—most recently— memantine²¹ for AD-related agitation also has been described.

Continued treatment: Medication changes

Quetiapine was increased to 350 mg nightly across 4 weeks, resulting in mild to moderate improvement. The higher dosage did not significantly worsen rigidity or motor function, and Ms. A tolerated the increased dosage without clinical orthostasis.

Memantine was added to address Ms. A’s agitation and preserve function. The agent was started at 5 mg/d and titrated across 4 weeks to 10 mg bid.

On clinical exam, Ms. A was more calm and directable and required less intervention. Her paranoia also decreased, allowing improved interaction with family, caregivers, and others. Ms. A remains stable on memantine, 10 mg bid; galantamine, 8 mg; quetiapine, 350 mg nightly; and vitamin E, 400 IU bid. Her cognitive ability has gradually declined over the past 18 months, as evidenced by her most recent MMSE score of 16/30.

Related resources

Cummings JL. Use of cholinesterase inhibitors in clinical practice: evidence-based recommendations. Am J Geriatr Psychiatry 2003; 11:131-45.
Alzheimer’s Disease Education and Referral Center, a service of the National Institute on Aging. http://www.alzheimers.org.
Paleacu D, Mazeh D, Mirecki I, et al. Donepezil for the treatment of behavioral symptoms in patients with Alzheimer’s disease. Clin Neuropharmacol 2002;25:313-7.
Tariot PN, Loy R, Ryan JM, et al. Mood stabilizers in Alzheimer’s disease: symptomatic and neuroprotective rationales. Adv Drug Deliv Rev 2002;54:1567-77.

Drug brand names

Buspirone • BuSpar
Carbamazepine • Tegretol
Citalopram • Celexa
Clonazepam • Klonopin
Clozapine • Clozaril
Divalproex • Depakote, DepakoteER
Fluoxetine • Prozac
Gabapentin • Neurontin
Galantamine • Reminyl
Lamotrigine • Lamictal
Memantine • Namenda
Methylphenidate • Concerta, Ritalin
Olanzapine • Zyprexa
Oxcarbazepine • Trileptal
Paroxetine • Paxil
Quetiapine • Seroquel
Risperidone wafers • RisperdalM-Tabs
Rivastigmine • Exelon
Selegiline • Eldepryl
Sertraline • Zoloft
Ziprasidone • Geodon
Zolpidem • Ambien

Disclosure

Dr. Goforth is a speaker for Pfizer Inc., Forest Pharmaceuticals, and BristolMyers Squibb Co., and has received grant support from Pfizer Inc. He has also received support from the Bristol-Myers Squibb Fellowship in Geriatric Psychiatry through the American Association of Geriatric Psychiatry.

Dr. Rao is a speaker for Pfizer Inc.

Drs. Raval and Ruth report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.