Treatment Strategies for the Behavioral Symptoms of Alzheimer's Disease: Focus on Early Pharmacologic Intervention

Manju T. Beier, Pharm.D., FASCP


Pharmacotherapy. 2007;27(3):399-411. 

In This Article


The behavioral symptoms of Alzheimer's disease tend to increase in prevalence and severity as the disease progresses and frequently precipitate nursing home placement. Recognizing and treating behavioral symptoms early with nonpharmacologic and/or pharmacologic treatments can slow symptom progression. Appropriate treatment of Alzheimer's disease can also reduce the distress to patients and caregivers and may delay placement of a patient in a residential care facility or nursing home.[97,98]

Prospective, randomized, placebo-controlled trials have shown that the cholinesterase inhibitors, donepezil and galantamine, can provide behavioral benefits for patients with mild-to-moderate Alzheimer's disease. In addition, donepezil treatment has been shown to improve behavioral symptoms in patients with moderate-to-severe Alzheimer's disease. Memantine treatment as an add-on to long-term donepezil therapy has also been shown to benefit patients with moderate-to-severe Alzheimer's disease, and memantine monotherapy has provided behavioral benefits in patients with mild-to-moderate Alzheimer's disease. In contrast, results from randomized, placebo-controlled studies of cholinesterase inhibitors in nursing home patients are less convincing, mainly due to the robust placebo response and the uncertain sensitivity of the Neuropsychiatric Inventory as a measure of behavioral problems in these patients.

When considering the effects of cholinesterase inhibitors and memantine on behavior, the benefits, although significant, are often high-lighted as generally being small.[56,64] As shown in Table 2, this is often the case. However, even when the reported changes in Neuropsychiatric Inventory scores seem numerically low in relation to the overall scale range, the percentage change from baseline score can occasionally show more promise. For example, in one study, among patients with mild-to-moderate Alzheimer's disease, those treated with donepezil showed a 2.9-point reduction in Neuropsychiatric Inventory score, which seems negligible in relation to the overall scale range of 0–120.[49] Nevertheless, when considered in relation to the change from baseline scores, the donepezil-treated patients showed a 20% improvement in behavioral symptoms, whereas placebo-treated patients showed a 22% worsening of behavioral symptoms over the same time period. When viewed in this manner, the possible benefits of these agents are somewhat clearer.

In addition to cholinesterase inhibitors and memantine, other pharmacologic agents, such as antipsychotics, antidepressants, mood-stabilizing agents, and benzodiazepines, can assist with problem behaviors. Indeed, many of these agents are effectively used to treat the behavioral symptoms of Alzheimer's disease, particularly in patients with severe behavioral problems. However, none of these agents is approved by the FDA for the specific treatment of the behavioral symptoms of Alzheimer's disease. Moreover, use of these agents may be limited by uncertain efficacy, poor safety profiles, and/or potential anticholinergic effects, and many are not recommended for long-term management of behavioral problems.


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