What is the preferred route of administration, intramuscular (I/M) or intravenous (I/V), for haloperidol in the acute management of agitation?

From the Guidelines

Intramuscular (I/M) administration is the preferred route for haloperidol in the acute management of agitation. The typical adult dose ranges from 2-10 mg I/M, which can be repeated every 30-60 minutes as needed until agitation is controlled, with a maximum daily dose of 20 mg 1. I/M haloperidol has a more predictable absorption and onset of action (15-30 minutes) compared to oral administration, making it more suitable for emergency situations. While intravenous (I/V) haloperidol is sometimes used, it carries higher risks of QT prolongation and cardiac arrhythmias, particularly torsades de pointes 1. Additionally, I/V administration is not FDA-approved for haloperidol. The I/M route provides a good balance between rapid effect and safety profile.

When administering I/M haloperidol, the gluteal muscle is typically used, and patients should be monitored for:

• Extrapyramidal symptoms
• Hypotension
• Cardiac effects ECG monitoring is advisable, especially with repeated doses, due to the risk of QT prolongation even with I/M administration 1. It is also important to consider the potential for other adverse effects, such as weight gain, hyperglycemia, and metabolic changes 1.

In terms of precautions, it is essential to:

• Monitor patients for signs of QT prolongation and cardiac arrhythmias
• Avoid co-administration with other QT-prolonging medications
• Use the lowest effective dose and avoid high doses
• Monitor patients for extrapyramidal symptoms and adjust the dose accordingly
• Consider alternative treatments, such as benzodiazepines, in patients who are severely distressed or causing immediate danger to others 1.

From the FDA Drug Label

Parenteral medication, administered intramuscularly in doses of 2 to 5 mg, is utilized for prompt control of the acutely agitated schizophrenic patient with moderately severe to very severe symptoms HALOPERIDOL INJECTION IS NOT APPROVED FOR INTRAVENOUS ADMINISTRATION.

The preferred route of administration for haloperidol in the acute management of agitation is intramuscular (I/M).

• The dose is 2 to 5 mg, and it can be administered as often as every hour, although 4 to 8 hour intervals may be satisfactory.
• Intravenous (I/V) administration is not approved and may be associated with a higher risk of QTc interval-prolongation and Torsades de Pointes. Precautions include:
• Monitoring the ECG for QTc prolongation and arrhythmias if haloperidol injection is administered intravenously
• Caution in treating patients with other QTc-prolonging conditions
• Risk of cerebrovascular adverse reactions, tardive dyskinesia, and neuroleptic malignant syndrome 2 2

From the Research

Comparison of I/M and I/V Haloperidol for Acute Management of Agitation

• The preferred route of administration for haloperidol in the acute management of agitation is not explicitly stated in the provided studies, but the available evidence suggests that both intramuscular (I/M) and intravenous (I/V) routes can be effective 3, 4, 5.
• A study from 1995 reported the use of continuous I/V infusions of haloperidol to control severe delirium and agitation in critically ill adults, with rapid control achieved in all three patients without adverse effects attributable to therapy 4.
• Another study from 1985 demonstrated the safe and effective use of high-dose I/V haloperidol in agitated cardiac patients, with dosages exceeding 100 mg/day required for control of severe agitation in some cases 5.
• In contrast, a 2004 study compared I/M olanzapine with I/M haloperidol and found that olanzapine was associated with fewer adverse movement disorders than haloperidol 6.
• A 2018 study compared I/M midazolam, olanzapine, ziprasidone, and haloperidol for treating acute agitation in the emergency department, and found that midazolam resulted in a greater proportion of patients adequately sedated at 15 minutes compared to the other medications, including haloperidol 7.

Precautions for Haloperidol Administration

• Haloperidol can cause significant extrapyramidal symptoms, and has rarely been associated with cardiac arrhythmia and sudden death 3.
• I/V haloperidol can cause prolongation of the QT interval and multiform ventricular tachycardia, and close monitoring for these adverse effects is mandatory 4.
• High-dose I/V haloperidol may be required for control of severe agitation in some patients, but this should be done with caution and close monitoring due to the potential for adverse effects 5.
• The use of haloperidol in combination with other CNS depressants should be avoided due to the risk of additive effects and adverse events 3, 7.