What is the best initial treatment for undifferentiated agitated delirium in the Emergency Room (ER)?

Best Treatment for Undifferentiated Agitated Delirium in the Emergency Room

For undifferentiated agitated delirium in the emergency room, a benzodiazepine (lorazepam or midazolam) or a conventional antipsychotic (droperidol or haloperidol) is recommended as effective monotherapy for initial treatment, with midazolam showing superior sedation at 15 minutes compared to other options. 1, 2

First-Line Pharmacologic Options

Benzodiazepines

• Midazolam 5 mg IM is the most effective agent for rapid sedation, achieving adequate sedation in more patients at 15 minutes compared to haloperidol, ziprasidone, and olanzapine 2
• Lorazepam 2-4 mg IM/IV is an appropriate first-line agent for undifferentiated agitation and can be used alone or in combination with antipsychotics 1, 3
• Benzodiazepines are particularly advantageous when the etiology might involve alcohol withdrawal or seizures 1

Antipsychotics

• Haloperidol 5 mg IM is effective for controlling agitation, with dosing as often as every hour if needed (though 4-8 hour intervals are often sufficient) 4
• Droperidol 5 mg IM/IV should be considered when rapid sedation is required, as it works faster than haloperidol 1
• Olanzapine 10 mg IM provides more effective sedation than haloperidol and may have fewer extrapyramidal side effects 2

Combination Therapy

• For agitated but cooperative patients who can take oral medications, a combination of oral lorazepam and oral risperidone is recommended 1
• For patients requiring parenteral medication, the combination of a benzodiazepine and haloperidol may produce more rapid sedation than monotherapy 1
• Droperidol 5 mg/midazolam 5 mg IM combination achieves adequate sedation faster (51.2% at 10 minutes) compared to haloperidol 5 mg/lorazepam 2 mg IM (7% at 10 minutes) 5

Special Considerations

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

Monitoring and Safety

• Monitor for adverse events including extrapyramidal symptoms (0.3%), hypotension (0.5%), hypoxemia (1%), and need for intubation (0.5%) 2
• Patients receiving droperidol/midazolam combination may be more likely to require oxygen supplementation (25.6%) compared to haloperidol/lorazepam (9.3%) 5
• 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 1

Route of Administration

• For severely agitated patients, intramuscular administration is often necessary 1
• Switch to oral medications as soon as the patient is cooperative enough to take them 4
• For cooperative but agitated patients, oral medications are preferred 1

Remember that pharmacologic intervention should be used after attempting verbal de-escalation techniques when possible, but patient and provider safety remains the priority in cases of severe agitation 1, 5.