Pharmacological Management of Acute Behavioural Agitation

Primer

Acute agitation (a “Code White”) in the medical setting can present as a challenge for both patients and health care providers. When using medications to manage acute agitation, there are several key concepts to consider, including the route of administration, onset of action, absorption, half-life, and the risk of adverse events.

What to Give?

Current practices for acutely agitated patients includes the combined use of an antipsychotic and a benzodiazepine. The reason for this combination is because it results in a rapid onset of action, with a short total duration of action and high sedation. Certain types of antipsychotics are also chosen to lower the risk of extrapyramidal symptoms (EPS). Anticholinergics may be given in combination as well to reduce the risk of extrapyramidal symptoms.

Don't Forget About Verbal De-escalation!

Before doing any kind of pharmacological intervention for agitation, always think about non-pharmacological ways to de-escalate the situation. In any Code White situation, understand that a patient is usually feeling threatened or scared, often due to their psychiatric symptoms or the stressful environment that they are in. In these cases, it is helpful to consider triggers that may be leading to these behaviours. For example, is there some way to bring the patient to a calmer environment and avoid the need for medications?

If security or additional staff are called to a Code White, it is important to outline to an agitated patient why there are additional people. If the patient doesn't understand why so many people are near them, this may worsen agitation or cause fear! Reassure the patient. For example, it can be helpful to tell the patient: “You may be wondering why there are security guards here. We work as a team and the staff are here for everyone's safety, including yours.”

Choosing an Antipsychotic

Haloperidol or loxapine are the most commonly used medications in management of acute agitation.

Haloperidol versus Loxapine

Adapted from Procyshyn, Ric M., Kalyna Z. Bezchlibnyk-Butler, and J. Joel Jeffries. Clinical Handbook of Psychotropic Drugs. Hogrefe, 2017.
Description Haloperidol Loxapine
Potency The amount of medication that needs to be given High Intermediate
D2 Antagonism Amount of antipsychotic effect, and EPS risk +++++ ++++
H1 Antagonism Amount of sedation, drowsiness, postural hypertension + +++
5-HT2 Antagonism Amount of anxiolytic effect/sedation +/+++ +++/++++
ACh M1 Antagonism Mitigation of EPS, sedation + ++

Typical and High Potency Antipsychotics are CONTRAINDICATED in Lewy Body Dementia!

A severe sensitivity reaction occurs in an estimated 25-50% of Dementia with Lewy Bodies (DLB) patients administered typical antipsychotic drugs (especially haloperidol). This results in cognitive impairment, sedation, increased/irreversible acute onset of parkinsonism, or symptoms resembling neuroleptic malignant syndrome. If an antipsychotic must be used, then low potency atypical antipsychotics like clozapine or quetiapine should be used.[1]

Zuclopenthixol

Choosing a Benzodiazepine

Emergency Benzodiazepine Use

Benzodiazepine Onset of Action Half-life
Lorazepam Rapid 12 hours
Clonazepam Rapid 12-48 hours
Diazepam Rapid 24-100 hours
Midazolam Intermediate 2-3 hours
Alprazolam Intermediate 12 hours

Common Orders

Antipsychotics

Loxapine 25 PO/IM q1h PRN for agitation (max 100mg/24hrs)
Haldol 2.5-5mg PO/IM q1h PRN for agitation (max 20mg/24hrs)
Olanzapine 5-10mg PO q2h PRN for agitation (max 20mg/24hrs)

Benzodiazepines

Lorazepam 1-2mg PO/SL/IM q1h PRN for agitation (max 8mg/24hrs)

EPS Prevention

Benztropine 2mg PO q4h PRN for symptoms of EPS (max 6mg/24hrs)
Pearls

IM Tip

Lorazepam and haloperidol can be delivered in the same syringe, whereas lorazepam and loxapine will require 2 separate injections.
  • When agitation presents as an acute risk, these medications can be given as an intramuscular (IM) dose for even more rapid onset of action, and when time is of essence. One should wait at least 20 – 30 minutes before repeating IM meds.
  • The maximum doses of medications given depends on the comfort of MD, the patient's vital signs, and the level of agitation. There needs to be a balance of obtaining the desired effect while minimizing risk of side effects.
  • Whenever giving medications for agitation, you should consider patient factors such as if they have: allergies, a past history of agitation, patient size, patient age, co-morbid conditions, antipsychotic use history, co-morbid substance use, patient preference
  • Remember to decrease dose/frequency in the medication-naïve, the young, or the elderly
  • Keep peak onset in mind when choosing a frequency of dosing (olanzapine peaks at ~4 hours for example)

Side Effects

Extrapyramidal Symptoms

Guidelines

Agitation Guidelines

Guideline Location Year PDF Website
National Institute for Health and Care Excellence (NICE) UK 2015 - Link
American Association for Emergency Psychiatry (AAEP) USA 2012, 2019 - • 2012 Guidelines
• 2019 Guidelines
• 2020 Review

Resources

For Providers

References

1) Lewy Body Dementia Association: Emergency Room Treatment of Psychosis