What is the evidence that ‘pro re nata’ (PRN) medication is effective for ending agitated outbursts in children and adolescents in psychiatric emergency rooms or inpatient units? Literature search was performed for studies of PRN medication use in children and adolescents that included an outcome measure. One randomised controlled trial, three prospective studies and six retrospective studies that included some outcome measure were identified. Outcome measures were heterogeneous, and frequently did not use standardised metrics assessing agitation level to measure effectiveness. The single small Randomized Controlled Trial (RTC) does not find a difference between placebo and medication, and outcomes of other studies do not control for potential placebo effect of the intervention itself as opposed to the medication. There is insufficient evidence to support the common practice of PRN medications for the management of acute agitation, and no data with which to inform clinical practice, such as which medicines and doses are helpful for specific populations or situations. Psychiatrists have no evidence-based medication interventions for acutely managing agitated outbursts in children and adolescents.