What are the best medications to give on a Pro Re Nata (PRN) basis for agitation and aggression in child and adolescent populations?

PRN Medications for Agitation and Aggression in Children and Adolescents

Critical Regulatory Warning

PRN use of chemical restraints is explicitly prohibited according to JCAHO standards and AACAP guidelines 1. The American Academy of Child and Adolescent Psychiatry states that "Pro re nata (p.r.n.) use of chemical restraints is prohibited" and that JCAHO considers such use "an inappropriate use of medication needing to be addressed as part of the facility's performance improvement process" 1.

Recommended Approach for Acute Agitation Management

Given the prohibition on PRN chemical restraints, the evidence-based approach differs significantly from traditional PRN ordering:

For Standing Treatment (Not PRN Chemical Restraint)

Risperidone is the best-evidenced medication for irritability and aggression in children and adolescents, but should be used as scheduled treatment after nonpharmacological interventions have been attempted 1. Multiple RCTs demonstrate risperidone improves irritability, aggression, and conduct problems, with effects typically starting within 2 weeks 1.

• Efficacy data: Risperidone reduces aggression scores by 6.49 points on the ABC-Irritability subscale (0-45 scale) and conduct problem scores by 8.61 points on the NCBRF-CP (0-48 scale), both clinically significant reductions 2
• Dosing: Mean effective dose is approximately 2.9 mg/day in adolescents 1, 3
• Side effects: Weight gain (mean 2.37 kg more than placebo), headache, somnolence, and asymptomatic prolactin elevation 1, 2
• Important caveat: Should only be considered after addressing potential contributors to aggression through nonpharmacological means 1

For Emergency/Stat Use Only (Not PRN Orders)

When medications must be used emergently for acute agitation, they should be administered on a stat or emergency basis with continuous monitoring, not as standing PRN orders 1:

Medication Options for Emergency Use:

High-potency neuroleptics:

• Haloperidol has been used in pediatric populations, though with risk of extrapyramidal symptoms and dystonic reactions 1
• Mean dose: 4 mg (0.07 mg/kg per dose) with 36% response rate 4
• Requires monitoring for EPS, dystonias, and neuroleptic malignant syndrome 1

Atypical antipsychotics (oral):

• Quetiapine shows promise with mean dose 32 mg (0.54 mg/kg per dose), 53% response rate, and low EPS rates 4
• Olanzapine (oral or IM) has been used for acute agitation in adolescents, though evidence is limited 5
• Note: Atypical antipsychotics have "long period before onset of antipsychotic effect" which limits their utility for immediate chemical restraint 1

Short-acting anxiolytics:

• Lorazepam has been used, though carries risk of paradoxical rage reactions that cannot be predicted unless previously documented 1
• Increased somnolence when combined with IM olanzapine 6

Antihistamines:

• Diphenhydramine or hydroxyzine may be useful for mild aggression, primarily through placebo effect 5
• Risk of paradoxical increase in rage exists 1

Critical Safety Requirements for Emergency Medication Use

When medications are given emergently (not as PRN orders), the following must occur 1:

• Continuous monitoring by trained nursing personnel until patient is awake and ambulatory
• Physician review of rationale for single versus multiple medications and drug interactions must be documented
• Parental approval should be obtained in advance when possible
• Oral route offered first before intramuscular administration
• Monitor for: allergic reactions, paradoxical reactions, dystonias, extrapyramidal side effects, neuroleptic malignant syndrome 1
• Cardiovascular monitoring is essential given potential for QTc prolongation and orthostatic hypotension 1

Agents to Avoid

• Benzodiazepines are not recommended for chronic anxiety in children with intellectual disabilities due to heightened sensitivity to behavioral side effects such as disinhibition 1
• Droperidol raises concerns due to its amnestic effect and obligatory IM administration, which may induce trauma 1
• Low-potency neuroleptics (chlorpromazine) have anticholinergic effects that may be contraindicated in patients with asthma or other conditions 1

Clinical Algorithm

1. First-line: Implement nonpharmacological interventions (de-escalation, environmental modifications, 1:1 staffing, time-out settings) 1

2. If scheduled medication needed: Consider risperidone as standing treatment after comprehensive assessment, starting conservatively given increased sensitivity to side effects in pediatric populations 1

3. If emergency medication required: Administer on stat/emergency basis only (not PRN), with preference for oral quetiapine or haloperidol depending on clinical context and prior response history 4

4. Continuous reassessment: Monitor for medication effects, side effects, and need for ongoing treatment versus environmental/behavioral interventions 1

Important Caveats

• Age restrictions: Safety and effectiveness in children under 13 years (or under 10 for combination treatments) have not been established 6
• Weight gain monitoring: Regular monitoring of weight and metabolic parameters is essential with atypical antipsychotics 1, 6, 2
• Conservative dosing: Children may be more sensitive to medication side effects, requiring lower initial doses 1
• Drug interactions: Obtain history of current medications and illicit drug use before administration (e.g., phencyclidine with haloperidol may promote hypotension) 1
• Limited evidence: Most evidence comes from studies in children with intellectual disabilities or specific diagnoses; generalizability to all pediatric populations with aggression is uncertain 1, 2