For patients with dementia and their caregivers, agitation, aggression, delusions, hallucinations, and wandering often cause greater distress than the condition's hallmark cognitive impairment. Consequences frequently include losses of caregivers' income and employment and lengthened hospital stays and nursing home placement for patients. Researchers conducted a literature review to determine the most effective drug therapies and came up with . . . not much.

Searching English-language, medical-study databases, they identified studies of drug therapy for neuropsychiatric symptoms in patients with Alzheimer disease, vascular dementia, or Lewy body disease. Of 66 studies selected for full review, and 12 others identified from reference lists, a total of 29 randomized controlled trials and metaanalyses were deemed worthy of analysis.

Atypical antipsychotics.

Olanzapine and risperidone "appear[ed] to be at least modestly effective" in patients with Alzheimer disease or vascular dementia. The authors pointed out a paucity of research on other atypical antipsychotics, such as clozapine, quetiapine, ziprasidone, and aripiprazole.

Cholinesterase inhibitors.

According to the authors, "Although some trials of cholinesterase inhibitors have shown statistically significant differences, the magnitude of effect has been small and of questionable clinical significance."

Typical antipsychotics were not found to be useful in treating neuropsychiatric symptoms of dementia. Haloperidol might be helpful in treating aggression, but "it is unclear if this benefit outweighs the adverse effects."

Antidepressants.

Of the serotonergic antidepressant medications studied, only citalopram showed some benefit, and improvement was seen only in two neuropsychiatric symptoms, lability and agitation.

Mood stabilizers.

The authors concluded that the use of neither valproate nor carbamazepine is recommended. Lithium appears not to have been studied in this context.

Other drugs.

There doesn't appear to be a clinically significant benefit to using memantine in the treatment of neuropsychiatric symptoms, and so far, no benefits from benzodiazepines or buspirone use have been found. The authors specifically recommend avoiding benzodiazepine use in this population.

They also say that because so few trials have examined patients with Lewy body disease, "no conclusions can be drawn" as to drug treatment for neuropsychiatric symptoms in them. For all patients with dementia, they recommend first ruling out medical causes of neuropsychiatric symptoms such as pain or delirium, then trying nonpharmacologic remedies. Drug therapies should be used with caution and targeted to specific symptoms.

In addition, although atypical antipsychotics have been found somewhat effective in treating neuropsychiatric symptoms in dementia, the risks of cerebrovascular complications associated with these drugs make using them risky. And another recent study, published in the British Medical Journal, found a further risk of using quetiapine, an atypical antipsychotic, in patients with Alzheimer disease: the drug produced a "significantly greater cognitive decline" than placebo and was ineffective in treating agitation. -Doug Brandt and Joy Jacobson, managing editor

Sink KM, et al. JAMA 2005;293(5):596-608; Ballard C, et al. BMJ 2005 Feb 18; [Epub ahead of print].