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Reference: Bourke EM, et al. PEAChY-O: Pharmacological Emergency Management of Agitation in Children and Young People: A Randomized Controlled Trial of Oral Medication. Annals of Emergency Medicine. Feb 2025
Date: April 29, 2025
Guest Skeptic: Dr. Brad Sobolewski, is a pediatric emergency medicine physician at Cincinnati Children’s Hospital and Professor of Pediatrics at the University of Cincinnati College of
Dr. Brad Sobolewski
Medicine. He is the creator of the PEMBlog and host of PEM Currents: The Pediatric Emergency Medicine Podcast. Brad is passionate about using digital media to translate complex clinical concepts into engaging, accessible educational content. His work centers on advancing knowledge sharing through innovative, tech-forward approaches to medical education.
Case: A 14-year-old girl with no known medical or psychiatric history presents to the emergency department (ED) with her family for aggression. Her parents tell you that they have been getting into arguments a lot recently. Today, she became so angry that she started punching and kicking the walls at home. You interview the girl and perform your physical examination, and determine that there are likely no medical diagnoses contributing to her aggression, nor that she has sustained any injuries requiring immediate management. After you leave the room and her parents enter, you hear them get into another argument, and she gets more agitated. The staff try a combination of de-escalation techniques, but she continues to be aggressive and starts threatening the staff. A nurse working with you asks, “I don’t think our de-escalation techniques are working. Do you want to give her something to help calm her down? We have olanzapine or diazepam here. Which one do you want to give?”
Background: Pediatric agitation can be defined as a clinical state characterized by heightened motor activity, emotional arousal, and often aggressive or disruptive behavior outside of expected developmental norms. It can be triggered by many things like underlying psychiatric disorders, medical conditions (like delirium, hypoxia, or metabolic disturbances), substance intoxication or withdrawal, and situational stressors, such as hospitalization or separation from caregivers. In the ED setting, pediatric agitation presents unique challenges. Not only can it compromise the safety of the child, caregivers, and medical staff, but it can also delay care and exacerbate underlying conditions.
When a child presents with extreme agitation or aggression, the first step is to take a broad, thoughtful approach. We can’t just assume it’s a psychiatric issue. Medical causes like hypoglycemia, intoxication, or even something like new-onset diabetic ketoacidosis can present this way. Missing these diagnoses could be dangerous.
Once we’ve ruled out organic causes, the focus shifts to early recognition and de-escalation. We try to identify the signs that a child is becoming more agitated before they escalate further. The goal is to intervene early and often with non-pharmacologic strategies. This can mean adjusting the environment: dimming the lights, reducing noise, giving the child space, or removing extra staff from the room. Sometimes something as simple as offering a snack, a drink, or a comfort item can make a big difference. Re-direction, distraction, and using calm, supportive language can also go a long way.
Of course, there are times when those strategies aren’t enough, and we may need to use physical restraints or medications. But that should never be our starting point. The overarching goal is to approach these situations with empathy and respect. Support the child and their family while protecting everyone’s safety, including our own.
There’s no perfect medication for agitation so it really depends on the situation. If the child is cooperative, start with an oral option. It gives the child a bit of control and helps avoid the trauma of restraint or an IM injection. When oral meds aren’t possible and the child poses a risk to themselves or others, IM options may be necessary. In those cases, it’s important to know what medications (dosing, onset, and potential side effects) are available and what local protocols recommend. The choice also depends on why the child is agitated. Antipsychotics, benzodiazepines, antihistamines, or even ketamine all have a role, but each comes with considerations based on the child’s history and the clinical scenario. Whatever we use, the goal is to reduce distress safely and respectfully, while keeping everyone protected.
Brad I have actually done a whole podcast series in collaboration with the EMSC innovation and Improvement Center and emDocs on agitation.
Clinical Question: Is oral olanzapine or oral diazepam more effective in achieving successful sedation in pediatric patients with acute severe behavioral disturbances?
Reference: Bourke EM, et al. PEAChY-O: Pharmacological Emergency Management of Agitation in Children and Young People: A Randomized Controlled Trial of Oral Medication. Annals of Emergency Medicine. Feb 2025
- Population: Children ages 9 to 17 years presenting to the ED with acute severe behavioral disturbances (Sedation Assessment Tool score of +1 to +3) that persisted despite nonpharmacological management that the clinician deemed to require oral medication
- Excluded: Known allergy or contraindication to the study medication, pregnant patients, history of known long QT syndrome, reversible organic cause contributing to agitation, parent/guardian request/refuse study drugs, treating clinicians decided alternative route, drug, or therapy was more appropriate
- Intervention: Oral dose of olanzapine.
- Comparison: Oral diazepam.
- Outcome:
- Primary: Successful sedation (Sedation Assessment Tool (SAT) score ≤ 0 without need for additional sedation one-hour post-randomization).
- Secondary: Parent/guardian and medical staff satisfaction, medication-related adverse events, length of stay, disposition, and whether the participant ingested medication.
- Trial: Open-label, multicenter, randomized controlled trial.
Authors’ Conclusions: “There was no evidence that oral olanzapine resulted in a greater proportion of participants with acute severe behavioral disturbance achieving successful sedation at one hour post randomization than oral diazepam. Neither medication resulted in any serious adverse events; however, approximately 40% of participants in each group did not achieve successful sedation.”
Quality Checklist for Randomized Clinical Trials: 
- The study population included or focused on those in the emergency department. Yes
- The patients were adequately randomized. Yes
- The randomization process was concealed. Yes
- The patients were analyzed in the groups to which they were randomized. Yes
- The study patients were recruited consecutively (i.e. no selection bias). Unsure
- The patients in both groups were similar with respect to prognostic factors. Yes
- All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No
- All groups were treated equally except for the intervention. Unsure
- Follow-up was complete (i.e. at least 80% for both groups). Yes
- All patient-important outcomes were considered. Yes
- The treatment effect was large enough and precise enough to be clinically significant. No
- Financial conflicts of interest. No financial conflicts of interest
Results: They enrolled 348 patients across nine sites. 176 were in the olanzapine group and 172 were in the diazepam group. Median age was around 15 years, with slightly more female patients.
Key Results: Oral olanzapine and diazepam had similar efficacy in achieving successful sedation in children with acute severe behavioral disturbance. However, 40% of participants in each group were not successfully sedated.
Primary Outcome: In the olanzapine group, 61% of participants were successfully sedated compared to 57% from the diazepam group. (aRD 3.6%, 95% CI -6.7 to 14, p=0.49).
10% of patients in both groups received additional sedation medication prior to measurement of the primary outcome.
Secondary Outcomes: There was not much difference between the two groups in many of these outcomes.
2% in each group had a study-related adverse event (aRD 0.5%, 95% CI -4.2 to 5.3) by first hour post randomization. There were a few more adverse events up until time of discharge or 48 hours after discharge, 3% in the olanzapine group compared to 4% in the diazepam group. This difference was not clinically significant (aRD -3.6%, 95% CI -7.9 to 0.6).
Further episodes of behavioral disturbance (23% olanzapine vs 26% diazepam) and requirement for mechanical restraints were also similar between the two groups.
Selection Bias
During the study, 491 patients were eligible but not enrolled. We are not certain why these patients were missed. Additionally, one of the inclusion criteria was that the patient had a behavioral disturbance that persisted despite nonpharmacological management, and the clinician determined required oral medications. We must acknowledge that while this is pragmatic, there is a great degree of subjectivity in that decision. There is a related trial including patients who received IM medications.
Caution with Disparities
We are glad that the authors included ethnicity in the patient demographics. We must acknowledge that despite our best efforts, we are not perfect, and disparities are present in the care we provide [1]. In the United States, studies demonstrate children of color are less likely to get pain medications for fractures or appendicitis and more likely to get mistriaged in the emergency department.
These disparities exist in mental health and management of behavioral crises as well. One retrospective cohort study on children hospitalized with mental health crises with data from 41 US hospitals demonstrated that non-Hispanic Black children were more likely to receive pharmacologic restraint [2]. Another cross-sectional study of pediatric visits across 11 EDs demonstrated that Black children were more likely to be physically restrained compared to White children [3].
As this research moves forward, we should remain cautious and cognizant of our own biases as we make decisions about which patients presenting with behavioral disturbances require pharmacological and physical restraint.
Primary Outcome “Successful Sedation”
There is some subjectivity to the SAT score, and it may vary based on rater perception, potentially biased by knowing treatment assignment.
The primary outcome was successful sedation, which the authors defined as a sedation assessment tool score of ≤0. Is it reasonable to expect someone highly agitated with SAT score of 3 compared to someone with a SAT score of 1 to come down to 0? Based on this definition, only around 60% of participants in each arm met the definition for successful sedation.
They also asked clinicians whether they felt the participants were successfully sedated. It turns out that clinicians felt like the participants were successfully sedated almost three-quarters of the time in both groups (75% olanzapine vs 74% diazepam, aRD 2.3% 95% CI -7.0% to 11.5%).
This is where we think the clinicians’ perception of successful sedation may be more important clinically than the SAT score. If the patient is calm enough to have an interaction, so that care can progress, that’s good enough. They don’t have to be fully back to a SAT score of 0. This is also reflected in Table S4 where 64% of the patients who were deemed not successfully sedated at 1 hour post-randomization based on the SAT score of +1 did not receive any additional medication based on the discretion of the treating clinician.
Patient and Caregiver Perspectives
We applaud the authors for including a group of four parent advisors in the development of the study. Although the authors tried to get data on patient and guardian satisfaction, there were a lot of missing responses (up to 78%). It is unclear why this happened. Was the experience too distressing or did they have other priorities at the time that they didn’t want to fill out the survey.
Among those who responded, 17% of patients and 14% of parents reported being not at all satisfied with how well the treatment helped the patient feel calm. Future research should further explore the perspectives of both patients and caregivers who experience episodes of severe agitation, with the goal of identifying opportunities for improvement and advocacy.
Medication Administration
In the study, 90% of participants in the olanzapine group ingested their medication, while only 85% of participants in the diazepam group ingested their medication.
The medications they used were in different forms. Olanzapine was a dissolving wafer, while diazepam was a pill. This is an important consideration in what medication you choose to give as well. It may be harder to spit out a dissolving wafer than a pill. Also, some children are unable to take pills.
Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusion. Finding the perfect oral medication to achieve adequate sedation in agitated pediatric patients is tricky!
SGEM Bottom Line: Both oral olanzapine and oral diazepam are similarly effective (or ineffective) for achieving sedation in agitated pediatric patients.
Case Resolution: You speak with the patient and ask if she’d be open to taking a medication to help her feel calmer. She agrees. When you ask if she’s able to take pills, she shakes her head no. You offer her an orally dissolving dose of olanzapine while continuing to use verbal de-escalation techniques. Over time, she becomes calmer and more open, eventually willing to talk about what’s been going on.
Taking medication for agitation is a lot like taking something for pain. It’s about treating something that’s bothering you, not about “drugging” or tricking anyone. Framing it this way gives the patient a sense of choice and control in a moment when so much feels out of their hands.
Clinical Application: Many medications can be considered for managing agitation in pediatric patients. It’s important to first identify and address any underlying factors contributing to the agitation, and to start with nonpharmacologic strategies and de-escalation techniques. When medication is necessary, involve the child’s parent or guardian in the decision-making process
Interventions that are carefully chosen, compassionately delivered, and well-documented might still fall short for some families. Remain thoughtful about the risks and benefits of each medication we use, and open to learning from the experiences of our patients, even when the outcomes challenge our expectations.
What Do I Tell the Nurse? There’s no evidence that olanzapine or diazepam works better than the other. Let’s first see whether the patient is willing to take an oral medication. If she agrees, we can see whether it’s preferable to give a medication that is dissolvable or must be swallowed.
Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.
References:
- Slopen N, Chang AR, Johnson TJ, et al. Racial and ethnic inequities in the quality of paediatric care in the USA: a review of quantitative evidence. Lancet Child Adolesc Health. 2024;8(2):147-158.
- Wolf RM, Hall M, Williams DJ, et al. Disparities in pharmacologic restraint for children hospitalized in mental health crisis. Pediatrics. 2024;153(1):e2023061353.
- Nash KA, Tolliver DG, Taylor RA, et al. Racial and ethnic disparities in physical restraint use for pediatric patients in the emergency department. JAMA Pediatr. 2021;175(12):1283-1285.
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