Acute treatment of psychotic agitation: a randomized comparison of oral treatment with risperidone and lorazepam versus intramuscular treatment with haloperidol and lorazepam

J Clin Psychiatry. 2004 Mar;65(3):386-94.


Background: Standard treatment for acute psychotic agitation often involves intramuscular administration of the benzodiazepine lorazepam and the antipsychotic haloperidol. This study compared the efficacy and safety of oral treatment with the atypical antipsychotic risperidone plus lorazepam with those of standard intramuscular treatment. We hypothesized that the efficacy and speed of action of both treatments would be similar.

Method: In a prospective, parallel-group, randomized, rater-blinded noninferiority study conducted at 24 sites in the United States, 162 patients exhibiting agitation associated with active psychosis were randomly assigned to receive either oral treatment with 2 mg of risperidone plus 2 mg of lorazepam (N = 83) or intramuscular treatment with 5 mg of haloperidol plus 2 mg of lorazepam (N = 79). The change scores on a 5-item acute-agitation cluster from the Positive and Negative Syndrome Scale (hallucinatory behavior, excitement, hostility, uncooperativeness, and poor impulse control) were the main outcome measure. The study was conducted from January 8 to August 8, 2001.

Results: Mean acute-agitation cluster scores were similar in the 2 groups at baseline. Mean score improvements at 30, 60, and 120 minutes after dosing were significant at each timepoint in both groups (p <.0001) and were similar in both groups (p >.05). Both treatments were well tolerated.

Conclusion: A single oral dose of risperidone plus lorazepam was as effective as parenterally administered haloperidol plus lorazepam for the rapid control of agitation and psychosis. These findings suggest that this oral regimen is an acceptable alternative to the current intramuscular treatment for acute psychotic agitation.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / therapeutic use*
  • Cluster Analysis
  • Drug Therapy, Combination
  • Female
  • Haloperidol / administration & dosage
  • Haloperidol / therapeutic use*
  • Humans
  • Injections, Intramuscular
  • Lorazepam / administration & dosage
  • Lorazepam / therapeutic use*
  • Male
  • Middle Aged
  • Prospective Studies
  • Psychomotor Agitation / diagnosis
  • Psychomotor Agitation / drug therapy*
  • Risperidone / administration & dosage
  • Risperidone / therapeutic use*
  • Severity of Illness Index
  • Single-Blind Method


  • Antipsychotic Agents
  • Haloperidol
  • Risperidone
  • Lorazepam