Inhaled Loxapine for the Management of Acute Agitation in Bipolar Disorder and Schizophrenia: Expert Review and Commentary in an Era of Change

Abstract

Agitation is a common and costly phenomenon associated with a number of psychiatric conditions including schizophrenia and bipolar disorder. Early identification and prompt intervention to relieve the symptoms of agitation are essential to avoid symptomatic escalation and emergence of aggressive behaviour. Recent consensus guidelines emphasise the need for non-coercive management strategies to protect the therapeutic alliance between patients and their healthcare providers—an alliance that is critical for the effective management of chronic psychiatric conditions. Rapid symptom relief and de-escalation of agitation are necessary to avoid the costly and traumatic use of coercive techniques of physical restraint and seclusion, which require admission and prolonged hospitalisation. Inhaled loxapine is approved for the treatment of acute agitation in patients with schizophrenia or bipolar disorder. Clinical studies have confirmed the efficacy, rapid onset of action, and safety and tolerability of this agent in the psychiatric emergency and hospital settings. Emerging data have indicated the potential for inhaled loxapine as a self-administered agent for use in the community setting without the direct supervision of a healthcare professional. We discuss the evolving treatment paradigm and the place of inhaled medications for acutely agitated patients both within and outside the emergency and hospital setting.

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

“…This technology quickly vaporizes an excipient-free drug formulation to yield an aerosol that is ideal for inhalation and produces peak plasma levels of loxapine within 2 min. Moreover, administration via inhalation of the Staccato ® loxapine aerosol is associated with a lower risk of adverse effects (extrapyramidal symptoms, sedative effects) than other systemically administered antipsychotics [ 47 , 48 ]. The pharmacokinetic profile of inhaled loxapine is similar to that of the intravenous formulation [ 49 , 50 , 51 ].…”

“…The pharmacokinetic profile of inhaled loxapine is similar to that of the intravenous formulation [ 49 , 50 , 51 ]. In a clinical study of patients with schizophrenia or BD, inhaled loxapine (5 mg or 10 mg) exhibited efficacy for mild-to-moderate agitation with a rapid onset of action as determined using PANSS-EC scores [ 47 ]. In the PLACID study [ 52 ], inhaled loxapine attenuated agitation was measured with the CGI scale faster than IM aripiprazole in patients with schizophrenia or BD in both hospital and emergency settings.…”

“…The most commonly reported adverse effects were mild to moderate and included dysgeusia, throat soreness, and sedation [ 50 , 51 , 52 , 56 ]. Severe adverse events were rare and included excessive sedation, akathisia [ 51 ], asthenia [ 52 ], neck dystonia and oculogyric crisis [ 50 ], and dystonia in a patient with a history of jaw clenching secondary to antipsychotic treatment [ 47 ]. Inhaled loxapine is not associated with cardiovascular toxicity; however, a primary safety issue is the potential for pulmonary adverse events.…”

“…It is reasonable to recommend a brief pulmonary assessment (e.g., medical history and physical examination) before treatment with inhaled loxapine [ 60 ]. A short-acting β-agonist bronchodilator should always be readily available in psychiatric emergency settings when choosing this drug to treat PMA [ 47 ].…”

Aggression in Psychiatry: prevention, epidemiology & treatment

“…For the short-term treatment of aggression in emergency situations, loxapine can now be administered through inhalation. There is evidence that inhaled loxapine is efficient for the treatment of agitation and can be used when fast administration is needed (McDowell et al, 2019;Pacciardi, Calcedo, & Messer, 2019). Inhalation could be less traumatic and painful for patients and a safer alternative for needles.…”