A double-blind, randomized comparison of the efficacy and safety of intramuscular injections of olanzapine, lorazepam, or placebo in treating acutely agitated patients diagnosed with bipolar mania

J Clin Psychopharmacol. 2001 Aug;21(4):389-97. doi: 10.1097/00004714-200108000-00006.


There are no rapid-acting intramuscular formulations of atypical antipsychotics available for quickly calming an agitated patient with bipolar disorder. In this study, 201 agitated patients with bipolar mania were randomly assigned to receive one to three injections of the atypical antipsychotic olanzapine (10 mg, first two injections; 5 mg, third injection), the benzodiazepine lorazepam (2 mg, first two injections; 1 mg, third injection), or placebo (placebo, first two injections; olanzapine, 10 mg, third injection) within a 24-hour period. Agitation was measured at baseline, every 30 minutes for the first 2 hours, and at 24 hours after the first injection using the Positive and Negative Syndrome Scale-Excited Component subscale and two additional agitation scales. At 2 hours after the first injection, patients treated with olanzapine showed a significantly greater reduction in scores on all agitation scales compared with patients treated with either placebo or lorazepam. At 24 hours after the first injection, olanzapine remained statistically superior to placebo in reducing agitation in patients with acute mania, whereas patients treated with lorazepam were not significantly different from those treated with placebo or olanzapine. Furthermore, no significant differences among the three treatment groups were observed in safety measures, including treatment-emergent extrapyramidal symptoms, the incidence of acute dystonia, or QTc interval changes. These findings suggest that intramuscular olanzapine is a safe and effective treatment for reducing acute agitation in patients with bipolar mania.

Publication types

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

MeSH terms

  • Adult
  • Affect / drug effects
  • Anti-Anxiety Agents / administration & dosage
  • Anti-Anxiety Agents / adverse effects
  • Anti-Anxiety Agents / therapeutic use*
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / psychology
  • Cholinergic Antagonists / therapeutic use
  • Double-Blind Method
  • Female
  • Heart Rate / drug effects
  • Humans
  • Injections, Intramuscular
  • Lorazepam / administration & dosage
  • Lorazepam / adverse effects
  • Lorazepam / therapeutic use*
  • Male
  • Middle Aged
  • Olanzapine
  • Pirenzepine / administration & dosage
  • Pirenzepine / adverse effects
  • Pirenzepine / analogs & derivatives*
  • Pirenzepine / therapeutic use*
  • Psychiatric Status Rating Scales
  • Psychomotor Agitation / drug therapy
  • Psychomotor Agitation / psychology
  • Treatment Outcome


  • Anti-Anxiety Agents
  • Antipsychotic Agents
  • Cholinergic Antagonists
  • Benzodiazepines
  • Pirenzepine
  • Olanzapine
  • Lorazepam