Primary endpoint reached based on data projection from interim analysis.

The purpose of this study is to determine whether intramuscular olanzapine is safer (fewer adverse events) and more effective (shorter time to sedation) than conventional haloperidol or midazolam when used in the management of acute agitation in the emergency department.

To address significant knowledge gaps by several means:

1. Investigate intramuscular use of sedative drugs within a predominantly Chinese population, to address this void in international literature impacting the management of acute agitation.

   The multi-centre RCT will determine the safety and efficacy of intramuscular olanzapine, in comparison with conventional medicines (haloperidol or midazolam) in a three-arm comparison for the sedation of acutely agitated patients in emergency department. Specifically, we aim to determine if administration of intramuscular olanzapine (a)is more effective than sedation with intramuscular haloperidol or intramuscular midazolam alone; (b)is safer than sedation with comparison arms; (c)decreases the amount of subsequent redosing or alternative drugs required; (d)is more favourable than the haloperidol and midazolam arms with respect to safety, efficacy and adverse events.

2. Investigate potential variables leading to emergency attendance and/or admission requiring parenteral sedation. These may include patient demographics and regular medications and adherence.

Inclusion Criteria:

• Emergency Department patients, requiring parenteral drug sedation (as determined by an emergency clinician) will be enrolled.

Exclusion Criteria:

• Patients will be excluded if there are

  1. known hypersensitivity or contraindication to the study drugs
  2. reversible aetiology for agitation (e.g. hypotension, hypoxia, hypoglycaemia)
  3. known pregnancy
  4. acute alcohol withdrawal
  5. patients aged>75 years.