Sublingual Dexmedetomidine as a Potential New Treatment for Agitation

Abstract

cal setting is a crisis demanding swift and safe resolution. Traditionally, behavioral agitation, often due to psychosis, was managed by psychiatry, particularly when physical restraints were the primary options. 1 After chlorpromazine's calming, neuroleptic properties were recognized in the 1950s, 2 pharmacological management became possible. Additional first-generation neuroleptic antipsychotics were introduced through the 1960s. In subsequent decades, the pharmaceutical industry developed the second-generation antipsychotics and benzodiazepines now used to treat agitation.Today, emergency departments now rival and perhaps surpass psychiatric units as settings where out-of-control, agitated patients must be managed. Both settings share basic approaches: ensuring patient and staff safety, deescalation as the preferred intervention, and avoidance of physical restraint. Intramuscular antipsychotic agents (olanzapine, ziprasidone, haloperidol) and benzodiazepines (midazolam, lorazepam) are the initial choice for chemical management. 3 However, psychiatrists and emergency physicians diverge somewhat in their ultimate objective managing agitation.In the emergency department, the target outcome is control of aggression and rapid sedation. If antipsychotics (such as haloperidol) and benzodiazepines are insufficient, some emergency medicine clinicians may use parenteral ketamine, a dissociative anesthetic. In a study of acute agitation in an emergency department, 66% (27 of 41) of patients who received ketamine were sedated within 15 minutes, compared with 7% (3 of 45) of patients who received haloperidol and lorazepam. 4 In contrast, in psychiatry, consensus recommendations for managing agitation emphasize that "the 'ideal' medication should calm without over-sedate." 5 A sleeping patient is difficult to engage, but psychiatry's aversion to excessive sedation may also reflect a salutary reaction to its earlier enthusiasm for rapid tranquilization with megadose, parenteral antipsychotics; an approach that is now thoroughly discredited. 6 Critical care is another setting where agitation is common and must be quickly controlled. Untreated agitated delirium could be catastrophic for a critically ill patient in the intensive care unit (ICU) connected to multiple monitors, intravenous (IV) and intra-arterial lines, and receiving mechanical ventilation. Parenteral haloperidol had been the choice for managing agitated delirium of adults in the ICU. 7 However, guidelines from 2018 recommend that dexmedetomidine be used to manage agitated delirium rather than haloperidol or other antipsychotics and recommend dexmedetomidine or propofol rather than benzodiazepines for sedation for adults receiving mechanical ventilation. 7

Dexmedetomidine as an Emerging Treatment of Agitation in Psychiatric Patients: A Narrative Review

“…10 In the following decades, the pharmaceutical industry developed second -generation antipsychotics and benzodiazepines, which added to the professional's toolbox for managing the agitated or violent patient. 11 Currently, the standards for the acute treatment of agitation recommend patient -centered approaches, in which verbal and non -verbal de -escalation techniques are used, giving preference to less invasive treatments when possible. 12 When these methods are not effective, the use of psychotropic drugs such as antipsychotics (typical or atypical) and/or benzodiazepines is a frequent option utilized.…”

Sublingual Dexmedetomidine for the Treatment of Agitation in Patients with Schizophrenia and Bipolar Disorder

“…Third, medications delivered sublingu-ally limit their use in patients who are severely agitated requiring involuntary medication. Indeed, one criticism of the available data on sublingual dexmedetomidine is that participants may not represent the full spectrum and severity of patients presenting with acute agitation since participants were able to consent to and self-administer treatment [ 29 ]. The wholesaler acquisition cost (WAC) in the United States is $105 per dose.…”

“…The wholesaler acquisition cost (WAC) in the United States is $105 per dose. The WAC price represents a published list price, but may not represent an actual transactional price for this medication [ 30 ].…”

Could dexmedetomidine be repurposed as a glymphatic enhancer?

“…of uncooperative patients [59]. Particularly the subcutaneous route displays a favorable pharmacokinetic profile due to its long duration of action [58].…”