Monday, October 16, 2006
The New England Journal of Medicine has published a trial of atypical antipsychotics for agitation/other behaviors with dementia. The multicenter trial randomized ~420 patients with dementia and behaviors (agitation, aggression, psychosis) to risperidone, quetiapine, olanzapine, or placebo; patients were followed for 36 weeks. The starting doses were fixed, but clinicians could titrate the drugs as they saw fit. The major outcome was time to discontinuation (due to lack of efficacy or side effects). Overall the results weren't very encouraging. Risperidone and olanzapine seemed to be more effective than quetiapine or placebo (time to discontinuation due to lack of efficacy 22-27 weeks); this was outweighed by their increased rates of discontinuation due to adverse effects such that overall the time to discontiuation was similar between all agents and placebo (5-8 weeks). These findings, along with the (likely) increased mortality from these agents, argue against their routine use in dementia. As with many similar interventions, a major problem is selecting patients likely to benefit without limiting side effects. How to do this--no one knows as of now.
A couple palliative care focused follow-up points. 1) This issue is entirely separate from the acute management of delirium/similar symptoms in the medically & terminally ill. 2) Looking at the side effect findings, this study supports the concept that quetiapine causes fewer extrapyramidal side effects than other antipsychotics.