The goal of this research investigation is to conduct a prospective observational study of the comparative efficacy of haloperidol versus olanzapine versus midazolam versus ziprasidone for the treatment of acute undifferentiated agitation in the emergency department.

The ED will implement a treatment protocol as a quality improvement initiative. All patients requiring chemical sedation for will receive haloperidol as the initial treatment for agitation for 21 days, followed by ziprasidone as the initial treatment for agitation for 21 days, followed by olanzapine as the initial treatment for agitation for 21 days, and finally midazolam as the initial treatment for agitation for 21 days.

This is a clinical care quality improvement protocol. The research component is the observation of this clinical care protocol.

Patients who receive medications in the ED will be observed by research staff, evaluating efficacy and safety of the administered medication. The decision to administer the medication is at the discretion of the physician. Research protocols are only such that we are observing the efficacy and safety, which coincides the quality improvement purposes of this clinical protocol.

Trained Research Associates will collect all data on patients who receive a protocol medication. This will include baseline demographic data including age, gender, etiology of agitation (according to the treating physician, presumed at the time of medication administration), initial vital signs, breath alcohol level, drug screen results, pre-hospital medications administered, and any other laboratory data available at the time (e.g. glucose).

Research associates will record the patient's level of agitation using a validated agitation scale, the Altered Mental Status (AMS scale). The AMS scale is an ordinal scale ranging from -4 (profoundly somnolent) to +4 (profoundly agitated), with agitation generally defined as an AMS scale of 2 or greater. This scale is a modified version of the Observer's Assessment of Alertness Scale and the Behavioral Activity Rating Scale.

AMS scores will be recorded at the time of medication administration and at every subsequent 15-minute interval until 120 minutes. Research associates will also carry stopwatches and record the time elapsed until adequate sedation (defined as an AMS ≤ 0), as well as whether other medications (defined as "rescue medications") were administrated for any reason and at what time this occurred.

Research associates will prospectively monitor each patient for all adverse side effects of the medications, including hypoxia, need for airway intervention (nasal cannula, facemask, non-invasive positive pressure ventilation, endotracheal intubation), hypotension, cardiac dysrhythmias, extrapyramidal side effects, and other complications.

Inclusion Criteria:

• Emergency Department patients (18+) with acute undifferentiated agitation requiring chemical sedation at the discretion of the attending emergency physician

Exclusion Criteria:

• Known pregnancy
• Allergy to the medication during the block
• Prisoner/under arrest

Emergency Department patients with acute undifferentiated agitation requiring chemical sedation at the discretion of the attending emergency physician. Patients studied are from a population where agitation is predominantly due to alcohol, illicit substances, or psychiatric agitation.