Evidence-Based Review of Pharmacotherapy for Acute Agitation. Part 1: Onset of Efficacy

The main goal of antipsychotic medication in the management of acute agitation in the emergency department is to rapidly induce calm without oversedation, enabling patients to participate in their own care. However, there is a paucity of comparative studies, particularly with newer fast-acting second-generation antipsychotic agents.

This structured evidence-based review compared the onset of efficacy of antipsychotic treatments for acute agitation using data from randomized controlled trials identified by a literature search of the PubMed database.

Based on findings from 28 blinded randomized controlled trials, onset of efficacy was rapid and generally observed at the first time point after intramuscular administration of ziprasidone (15-30 min) or olanzapine (15-30 min), but was more likely to be delayed with intramuscular haloperidol, even when combined with lorazepam (30-60 min), and intramuscular aripiprazole (45-90 min). When administered orally, rapid onset of efficacy was also consistently observed at the first assessment time point with olanzapine (15-120 min), risperidone (30-120 min), and sublingual asenapine (15 min). Significant effects were apparent for inhaled loxapine within 10-20 min. Effects were apparent within approximately 5-10 min with i.v. droperidol. Onset of efficacy was typically more rapid with second-generation antipsychotic agents than benzodiazepines, but data are limited.

Although the patient populations of trials included in this review do not truly reflect that of the emergency department, the results provide useful information to emergency physicians on the rapid efficacy of certain newer-generation antipsychotic agents for the treatment of acutely agitated patients.