Atypical antipsychotic efficacy and safety in managing delirium: A systematic review and critical analysis

Delirium is a common syndrome in hospitalised patients, particularly in the elderly. While haloperidol has long been the preferred treatment, atypical antipsychotics are now often used, even though their efficacy and safety remain unclear. The review was intended to identify published studies on use of olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole in managing delirium; to assess their methodological quality; and to formulate clinical recommendations. From Medline and Embase databases (1996-2008), we included all retrospective and prospective group studies that made use of standardised symptom rating scales. We classified studies according to research design quality and extracted information on efficacy and safety. Overall, we found methodological quality to be low-to-moderate although it does seem to be improving. While two randomised olanzapine trials and one risperidone trial found these molecules to be as effective as haloperidol, results are contaminated by various biases. The only available randomised quetiapine trial used amisulpride as the control. These agents appear reasonably safe and induce fewer extrapyramidal side effects than haloperidol does. Occasional hypotension has been reported with risperidone and quetiapine, and occasional worsening of delirium with olanzapine. Data are scarce on their potential for relieving acute agitation in delirium. Haloperidol remains a time-tested treatment, particularly in critical care; safe, it is available in oral, IM and IV forms. Newer agents may be preferable when looking to avoid neurological side effects. Data on ziprasidone and aripiprazole are sparse; these molecules most likely are unsafe given their arrhythmia-inducing potential.