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

Abstract

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.

The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Update 2009 on the Treatment of Acute Mania

“…It is of clinical importance that the improvement, as measured by the drop in the Young Mania Rating Scale (YMRS) scores, did not differ between psychotic and nonpsychotic manic patients. In addition, a randomized, controlled trial of injectable olanzapine in agitated mania has demonstrated significant superiority for olanzapine against placebo and lorazepam after 2 h (Meehan et al 2001).…”

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

“…Because of the strength of evidence for efficacy in alleviating agitation in this population, aripiprazole IM (level 2),125, 126 lorazepam IM (level 2),125, 127 loxapine inhaled (Level 1)128, 129 and olanzapine IM (level 2)127, 130, 131, 132, 133 are recommended as the first‐line option. Sublingual asenapine (level 3),134 haloperidol IM (level 3),131, 135, 136 haloperidol IM + midazolam IM (level 3),131, 137 haloperidol IM + promethazine IM (level 3),131, 137, 138 risperidone ODT (level 3),136 and ziprasidone IM (level 3)131, 137, 139 are recommended as a second‐line treatment.…”

Management of acute agitation in psychosis: an evidence-based approach in the USA

“…In a trial involving patients with schizophrenia, the NNT for 10 mg olanzapine was 3 (95% CI 2-3). In bipolar I mania, 10 mg olanzapine also yielded an NNT of 3 (95% CI 2-5) (Meehan 2001). Intramuscular olanzapine is as efficacious as haloperidol and has significant advantages in terms of extrapyramidal symptoms: Parkinsonism was avoided in 1 in 7 patients, acute dystonia in 1 in 14, and anticholinergic prescrip tions were avoided in 1 in 7 patients (Tulloch 2004;Citrome 2007).…”

“…The consensus guidelines mentioned above (Expert Consensus Panel for Behavioral Emergencies 2005) currently recommend atypical antipsychotics as first-line agents for acute agitation in schizophrenia, although evidence of atypical antipsychotic efficacy in managing agitation in bipolar I disorder has also been established (Meehan 2001;. Olanzapine and risperidone are both available in disintegrating oral tablets and are therefore optimal as first-line interventions for patients who will take them.…”