Clinical Twisters: Treating AD-related behavior

October 25, 2004

A 72-year-old man, L.Z., has been admitted to your hospital via the ER. On admission, he was combative and agitated, and he was treated with intramuscular lorazepam. According to his wife, he has Alzheimer's disease and has become increasingly verbally and physically abusive. His medications include atorvastatin (Lipitor, Pfizer) 10 mg q.d., glipizide XL 5 mg before meals, and rivastigmine (Exelon, Novartis) 6 mg b.i.d. with meals. Oral lorazepam was initiated at a dose of 1 mg b.i.d. L.Z.'s physician asks you which antipsychotic drug you would suggest adding to this regimen. How do you respond?

A 72-year-old man, L.Z., has been admitted to your hospital via the ER. On admission, he was combative and agitated, and he was treated with intramuscular lorazepam. According to his wife, he has Alzheimer's disease and has become increasingly verbally and physically abusive. His medications include atorvastatin (Lipitor, Pfizer) 10 mg q.d., glipizide XL 5 mg before meals, and rivastigmine (Exelon, Novartis) 6 mg b.i.d. with meals. Oral lorazepam was initiated at a dose of 1 mg b.i.d. L.Z.'s physician asks you which antipsychotic drug you would suggest adding to this regimen. How do you respond?

Aggression and agitation occur in up to 80% of patients with Alzheimer's disease and are often precipitating factors in nursing home placement. Antipsychotics should be used only after the risks and benefits have been weighed. Initially, L.Z. should be assessed for underlying causes of combativeness and agitation, including infection, pain, constipation, hypoglycemia, and dehydration. In addition, he should be evaluated for psychosis, depression, and anxiety. Antipsychotic treatment would be warranted if psychotic features are present or if behavioral symptoms persist after underlying factors are treated or ruled out.

The use of lorazepam in older adults with dementia can lead to excessive sedation, increased risk of falls, and cognitive impairment associated with worsening dementia. For these reasons, discontinuation of lorazepam is advised.

Susan L. Lakey, Pharm.D.

Pharmacy Fellow

Gero-Psychiatry

University of Washington School of Pharmacy

Seattle

I'd recommend risperidone or quetiapine (Seroquel, AstraZeneca). Low-dose risperidone has the most available data for treating behavioral disturbances in patients like L.Z. Doses should start very low, 0.25-0.5 mg at bedtime, and be increased as needed. Dosages of 0.5-1.0 mg/day are generally sufficient to alleviate behavioral symptoms. Doses above that increase risk for EPS. Although risperidone carries a warning about the risk of cerebrovascular events in elderly patients with dementia-related psychosis, much of the data are conflicting; many clinicians don't perceive increased risk.

Some clinicians prefer quetiapine to risperidone because it is less likely to cause EPS, which may allow more dosing flexibility. Doses are generally started at 12.5-25 mg at bedtime and titrated as needed or tolerated. Dosages of 100-200 mg/ day are generally sufficient. Patients taking quetiapine should be monitored for orthostasis and anticholinergic side effects. The patient's weight, fasting glucose and cholesterol, and blood pressure should be monitored closely when initiating either risperidone or quetiapine.

Tawny L. Bettinger, Pharm.D., BCPP

Assistant Professor

University of Texas at Austin

College of Pharmacy

Austin, Texas

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