Effectiveness and Safety of Intravenous Medications for the Management of Acute Disturbance (Agitation and Other Escalating Behaviors): A Systematic Review of Prospective Interventional Studies

Megan Castro; Matt Butler; Alysha Naomi Thompson; Siobhan Gee; Sotiris Posporelis

doi:10.1016/j.jaclp.2024.01.004

Effectiveness and Safety of Intravenous Medications for the Management of Acute Disturbance (Agitation and Other Escalating Behaviors): A Systematic Review of Prospective Interventional Studies

J Acad Consult Liaison Psychiatry. 2024 Feb 2:S2667-2960(24)00012-0. doi: 10.1016/j.jaclp.2024.01.004. Online ahead of print.

Authors

Megan Castro¹, Matt Butler², Alysha Naomi Thompson³, Siobhan Gee⁴, Sotiris Posporelis⁵

Affiliations

¹ Neuropsychiatry Research and Education Group, Institute of Psychiatry, Psychology, and Neuroscience, London, United Kingdom.
² Neuropsychiatry Research and Education Group, Institute of Psychiatry, Psychology, and Neuroscience, London, United Kingdom; South London and Maudsley NHS Foundation Trust, London, United Kingdom. Electronic address: matthew.butler@kcl.ac.uk.
³ GKT School of Medical Education, King's College London, London, United Kingdom.
⁴ Pharmacy Department, South London and Maudsley NHS Foundation Trust, London, United Kingdom; Institute of Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, KCL, London, United Kingdom.
⁵ Neuropsychiatry Research and Education Group, Institute of Psychiatry, Psychology, and Neuroscience, London, United Kingdom; South London and Maudsley NHS Foundation Trust, London, United Kingdom.

PMID: 38309683
DOI: 10.1016/j.jaclp.2024.01.004

Abstract

Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available management options include de-escalation techniques and rapid tranquilization, mostly via parenteral formulations of medication. While the intramuscular route has been extensively studied in a range of clinical settings, the same cannot be said for intravenous (IV); this is despite potential benefits, including rapid absorption and complete bioavailability. This systematic review analyzed existing evidence for effectiveness and safety of IV medication for management of acute disturbances. It followed a preregistered protocol (PROSPERO identification CRD42020216456) and is reported following the guidelines set by Preferred Reporting Items for Systematic Review and Meta-Analysis. APA PsycINFO, MEDLINE, and EMBASE databases were searched for eligible interventional studies up until May 30th, 2023. Data analysis was limited to narrative synthesis since primary outcome measures varied significantly. Results showed mixed but positive results for the effectiveness of IV dexmedetomidine, lorazepam, droperidol, and olanzapine. Evidence was more limited for IV haloperidol, ketamine, midazolam, chlorpromazine, and valproate. There was no eligible data on the use of IV clonazepam, clonidine, diazepam, diphenhydramine, propranolol, ziprasidone, fluphenazine, carbamazepine, or promethazine. Most studies reported favorable adverse event profiles, though they are unlikely to have been sufficiently powered to pick up rare serious events. In most cases, evidence was of low or mixed quality, accentuating the need for further standardized, large-scale, multi-arm randomized controlled trials with homogeneous outcome measures. Overall, this review suggests that IV medications may offer an effective alternative parenteral route of administration in acute disturbance, particularly in general hospital settings.

Keywords: acute disturbance; clonazepam; clonidine; dexmedetomidine; diazepam; droperidol; haloperidol; intravenous; ketamine; lorazepam; midazolam; olanzapine; promethazine; systematic review; valproate.

Publication types

Review