Question. I am interested in your opinion on the use of Depakote and BuSpar, as opposed to benzodiazepines, in the treatment of agitation and aggression in dementia. What dosages would you suggest? Do you know of any articles reviewing these topics?
Answer. There are very few controlled studies bearing on your questions; most of the data are based on case reports and open trials. Typical is the study by Lott, et al., Journal of Neuropsychiatry and Clinical Neurosciences, Summer 1995, pp. 314-319. This was an open study of valproate (375-750 mg/day) in elderly patients with dementia and behavioral agitation; 8 of the 10 patients showed improvement on the valproate, which was well-tolerated. Interestingly, serum levels were in the low range, around 35-50 mcg/ml; some patients were treated with adjunctive psychotropics.
Similarly, buspirone (doses of around 30 mg/day ) has been found useful in the treatment of organic-induced aggression and dementia (Stanislav, et al., Journal of Clinical Psychopharmacology, 1994;14:126-130; Colenda, Lancet, 1988;1169). In general, I tend to discourage the use of benzodiazepines (BZDs) for agitated demented patients, since these agents are often (though not always) disinhibiting in patients with structural brain damage and dementia. Moreover, the BZDs are commonly associated with confusion, falls and hip fractures in the elderly. This is often said to be more common when long-acting BZDs are used, but more recent data suggests that the rate of dosage escalation is a more important factor.
Certainly, if benzodiazepines are used, the very lowest dose effective should be employed; e.g., 0.5 mg/day of clonazepam (Klonopin). I have also had good results using low doses of trazodone (25-50 mg, mainly at night) in agitated, aggressive, demented patients. Some anecdotal reports suggest that low-dose risperidone (0.5 mg/day) may also be useful in such populations, though this carries the risk of tardive dyskinesia.