Treatment Options for Acute Agitation in Psychiatric Patients: Theoretical and Empirical Evidence

Abstract

Acute agitation is a common presenting symptom in the emergency ward and is also dealt with on a routine basis in psychiatry. Usually a symptom of an underlying mental illness, it is considered urgent and immediate treatment is indicated. The practice of treating agitation on an acute care basis is also referred to as rapid tranquilization. A variety of psychotropic drugs and combinations thereof can be used. The decision is usually made based on availability and the clinician’s experience, with the typical antipsychotic haloperidol (alone or in combination with antihistaminergic and anticholinergic drugs such as promethazine), the benzodiazepines lorazepam, diazepam and midazolam as well as a variety of atypical antipsychotics being used for this purpose. Haloperidol is associated with extrapyramidal symptoms (which can be controlled by co-administration of promethazine) and may control agitation without inducing sedation, while benzodiazepines have a more pronounced sedating activity. The atypical antipsychotics aripiprazole and ziprasidone are better tolerated, while olanzapine is also a powerful sedative. Clinical trials evaluating the efficacy of different treatment options have been conducted but they are extremely heterogenous and most have numerous methodological flaws, leading to a poor overall quality of evidence upon which guidelines for the appropriate treatment could be based. The combination of haloperidol and promethazine, which combines the sedative properties of the antihistamine with the more selective calming action of haloperidol (with a reduced risk of extrapyramidal effects compared to haloperidol alone because of the anticholinergic properties of promethazine) may be the best choice based on empirical evidence.

The Management of Psychomotor Agitation Associated with Schizophrenia or Bipolar Disorder: A Brief Review

“…Benzodiazepines (BDZs) are a class of sedative drugs that have been used extensively for rapid tranquilization [ 69 ]. All benzodiazepines share a common action mechanism and produce a similar range of effects, including anxiolytic, hypnotic, muscle relaxant, and anticonvulsant actions.…”

“…The action mechanism is related to allosteric modulation of GABA-A receptors that increases the receptor’s affinity for its cognate ligand. For this reason, the central nervous system depressant effects of BDZs are more prominent than those associated with antipsychotic agents [ 69 ].…”

Which Emergent Medication Should I Give Next? Repeated Use of Emergent Medications to Treat Acute Agitation

“…Current evidence from research examining first-line interventions should guide sequential medication selection (7,9,14,29,(32)(33)(34). Evidence-based antipsychotics for acute agitation include loxapine, haloperidol, droperidol, olanzapine, risperidone, ziprasidone, aripiprazole, and asenapine (13,(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53).…”

Characterization of Psychotropic PRN Medications in a Canadian Psychiatric Intensive Care Unit

“…Evidence-based management of agitation in psychiatric disorders is made difficult given that there is not one formally and universally accepted guideline. Moreover, available evidence comparing the efficacy and safety of psychotropic agents is dated and of poor quality (“Use of Antipsychotics,” 2015; Zareifopoulos & Panayiotakopoulos, 2019). Clinical practice is often dependent on regional policies and culture, available pharmacological formulations and therapies, utilization of nonpharmacological measures, and the patient’s psychiatric history.…”