Management of Acute Agitation and Psychosis

First-Line Options

The American College of Emergency Physicians recommends using either a benzodiazepine (lorazepam 1-2 mg) or an antipsychotic (haloperidol 0.5-5 mg IM, or olanzapine 2.5-10 mg) as monotherapy for acute agitation and psychosis, with lorazepam being the preferred first-line agent for undifferentiated agitation due to its rapid onset and favorable safety profile 1, 2
Lorazepam is the most appropriate PRN medication for acute agitation in patients with bipolar disorder and schizophrenia, demonstrating efficacy in reducing agitation scores at 30, 60, and 120 minutes after administration 2
The dosing of lorazepam starts with 1 mg PO/IM/IV/SC PRN, can repeat every 1 hour if needed, with a maximum dose of up to 2 mg per dose 1, 3, 4

For patients with known psychiatric illness requiring antipsychotics, use an antipsychotic as effective monotherapy for both agitation management and initial drug therapy, with haloperidol being a typical antipsychotic option 1
Haloperidol dosing is 0.5-1 mg PO/SC/IM PRN every 1 hour as needed, with a dose reduction to 0.25-0.5 mg in elderly or frail patients 5, 6
Olanzapine dosing is 2.5-5 mg PO/SC/IM PRN, with a scheduled dosing of 2.5-5 mg daily, and a dose reduction in elderly patients and those with hepatic impairment 4, 7, 8

For cooperative patients, oral lorazepam (2 mg) combined with oral risperidone (2 mg) is effective for agitated patients who can take oral medications 1
The combination of parenteral benzodiazepine and haloperidol may produce more rapid sedation than monotherapy for severe agitation 1

Assess patient cooperation and severity, and consider underlying diagnosis, with cooperative patients with mild-moderate agitation receiving oral lorazepam 1 mg or oral antipsychotic, and uncooperative or severe agitation receiving IM/IV lorazepam 1-2 mg or IM haloperidol 2-5 mg 1, 2

Avoid combining high-dose olanzapine with benzodiazepines due to risk of oversedation and respiratory depression, with fatalities reported with this combination 3, 4, 7, 8, 9
Monitor for paradoxical agitation with benzodiazepines, which occurs in approximately 10% of patients 2
Increased fall risk with both benzodiazepines and antipsychotics, especially in elderly or frail patients, with the recommendation to use lowest effective doses 3, 4, 2

The American Society of Clinical Oncology recommends quetiapine as a second-generation antipsychotic option for PRN use specifically in delirium management in cancer patients, but not as the primary choice 10

The recommended starting dose of quetiapine for PRN use is 25 mg orally as needed, with scheduled dosing of 25 mg every 12 hours if required 10
The dose should be reduced in older patients and those with hepatic impairment 10
Quetiapine should only be administered orally, as it cannot be given intramuscularly or intravenously 10

Quetiapine has sedating properties, making it useful for agitation with insomnia 10
It has a lower risk of extrapyramidal symptoms (EPS) compared to typical antipsychotics and some other atypical agents 10

Quetiapine's oral-only administration is a major limitation for PRN use in severely agitated or uncooperative patients who cannot safely take oral medications 10
Adverse effects to monitor include sedation, orthostatic hypotension, and dizziness 10
Elderly patients should be started with lower doses and monitored closely for falls and orthostatic hypotension 10