Management of Undifferentiated Agitated Delirium

First-Line Pharmacologic Options

The American College of Emergency Physicians recommends benzodiazepines, such as lorazepam or midazolam, or conventional antipsychotics, such as droperidol or haloperidol, as effective monotherapy for initial treatment of undifferentiated agitated delirium in the emergency room, with midazolam showing superior sedation at 15 minutes compared to other options 1
Benzodiazepines are particularly advantageous when the etiology might involve alcohol withdrawal or seizures, and lorazepam 2-4 mg IM/IV is an appropriate first-line agent for undifferentiated agitation 2
Droperidol 5 mg IM/IV should be considered when rapid sedation is required, as it works faster than haloperidol, according to the American College of Emergency Physicians 3

For agitated but cooperative patients who can take oral medications, a combination of oral lorazepam and oral risperidone is recommended by the American College of Emergency Physicians 1
For patients requiring parenteral medication, the combination of a benzodiazepine and haloperidol may produce more rapid sedation than monotherapy, as suggested by the American College of Emergency Physicians 1

For patients with known psychiatric illness for which antipsychotics are indicated, use an antipsychotic as monotherapy for both management of agitation and initial drug therapy, according to the American College of Emergency Physicians 1
Be cautious when treating agitation due to medical illness, as some medications may exacerbate the underlying condition, and antipsychotics and medications used to manage extrapyramidal symptoms can potentially worsen agitation in patients with anticholinergic or sympathomimetic toxicity 2

While droperidol carries an FDA black box warning for QT prolongation, large patient series have demonstrated its safety in the ED setting with few adverse events, as reported by the American College of Emergency Physicians 3

For severely agitated patients, intramuscular administration is often necessary, and for cooperative but agitated patients, oral medications are preferred, according to the American College of Emergency Physicians 1
Patient and provider safety remains the priority in cases of severe agitation, and pharmacologic intervention should be used after attempting verbal de-escalation techniques when possible, as recommended by the American College of Emergency Physicians 2