We are proud to present Capsules Module 11: Acute Agitation, now published on ALiEMU. We present a summary of the module with key points from a stellar module by PharmDs Jenny Koehl, Kyle DeWitt, Gabrielle Procopio, and Zlatan Coralic. When you’re finished, head over to the Capsules page for even more practical pharmacology for the EM provider.

Course Contributors

RoleTeam MemberBackground
AuthorsJenny Koehl, PharmD, BCPS @jlkoehlEmergency Medicine Clinical Pharmacist, Massachusetts General Hospital
Kyle DeWitt, PharmD, BCPS @EmergPharmEmergency Medicine Clinical Pharmacist, University of Vermont Medical Center
Gabrielle L. Procopio, PharmD, BCPS @gppharmedEmergency Medicine Clinical Pharmacist, Hackensack University Medical Center
Zlatan Coralic, PharmD, BCPS @ZEDpharmEmergency Medicine Clinical Pharmacist, University of California-San Francisco
EditorsEmily Wiener, PharmD @PharmdEMilyEmergency Medicine Clinical Pharmacist, Baltimore Washington Medical Center
Xander Miller, PharmD @XanderBOSPGY-1 Pharmacy Resident, Massachusetts General Hospital
Lead Editor: Bryan Hayes, PharmD, FAACT, FASHP @PharmERToxGuyEmergency Medicine Clinical Pharmacist, Massachusetts General Hospital

Non-Antipsychotics for Acute Agitation

CAPSULE: Non-Antipsychotics for Acute Agitation
  • Midazolam and lorazepam are the benzodiazepines of choice due to their rapid onset and offset.
  • Diazepam enters the CNS more readily than lorazepam and its active metabolites may cause over sedation after repeat dosing.
  • In the pre-hospital setting, higher rates of intubation have been associated with high doses of ketamine (>5 mg/kg), co-administration with midazolam or haloperidol, male gender, and late night arrival.

Antipsychotics for Acute Agitation

  • In the acutely agitated patient with a known psychiatric illness, providers can use a 1st or 2nd generation antipsychotic agent as monotherapy or in combination with other agents. However, if the agitation or delirious state is due to an anticholinergic toxicity, antipsychotics should be avoided due to additive anticholinergic effects.
  • The incidence of dystonic reactions following haloperidol administration is not insignificant. Reported frequencies include 1 in 5 patients to 1 in 15 patients.
  • Second-generation antipsychotic agents are the drugs of choice for treating agitation stemming from an underlying psychiatric illness. Examples include olanzapine and ziprasidone.
  • All antipsychotics prolong the QTc interval. However, none seem to prolong the QTc to greater than 500 msec.
CAPSULE: Olanzapine
Olanzapine is available as a PO disintegrating tablet. This offers an additional administration options and benefits acutely agitated patients.

Combination Therapy

When rapid sedation is needed, a combination of a parenteral benzodiazepine and haloperidol may provide more rapid sedation than monotherapy.

CAPSULE: Syringe Compatibility
It is not recommended to mix all agents into 1 syringe. However, if used immediately, the benefit of ease of administration and prevention of needle-stick-injury may outweigh potential risks of drug incompatibility.

Special Populations

  • Geriatrics: IM dosing of haloperidol in geriatric patients may require more gradual adjustments and a lower dosage. Tardive dyskinesia occurs most frequently in elderly women and has been associated with the cumulative dose of antipsychotics.
  • Pediatrics: In general, haloperidol and 2nd generation antipsychotics are safe in children. Benzodiazepines and antihistamines may cause paradoxical disinhibition resulting in increased agitation.
  • Pregnancy: For acute agitation, Clinical Consensus Guidelines (2001) recommend haloperidol alone as first-line. Second-line options include a benzodiazepine alone, risperidone alone, or a benzodiazepine in combination with haloperidol.

What is the Capsules series?

ALiEMU Capsules is a free, online e-curriculum of high-quality, current, and practical pharmacology knowledge for the EM practitioner. The goal of Capsules is to bring EM pharmacology education to the bedside. Our expert team distills complex pharmacology principles into easy-to-apply concepts. It’s our version of what-you-need-to-know as an EM practitioner. About once a month, ALiEM will release a new course module. These modules have lessons to read (or watch) and brief quizzes to complete. With each step, your personal dashboard will keep track of your progress.

Bryan D. Hayes, PharmD, DABAT, FAACT, FASHP

Bryan D. Hayes, PharmD, DABAT, FAACT, FASHP

Leadership Team, ALiEM
Creator and Lead Editor, Capsules and EM Pharm Pearls Series
Attending Pharmacist, EM and Toxicology, MGH
Associate Professor of EM, Division of Medical Toxicology, Harvard Medical School
Bryan D. Hayes, PharmD, DABAT, FAACT, FASHP


EM Pharmacist & Toxicologist @MassGeneralEM | Asst Prof @HarvardMed/@EMRES_MGHBWH | @ALiEMteam leadership | Capsules creator, ALiEMU | President, ABAT | #FOAMed