The Role of Inhaled Loxapine in the Treatment of Acute Agitation in Patients with Psychiatric Disorders: A Clinical Review

Abstract

Loxapine is a first generation antipsychotic, belonging to the dibenzoxazepine class. Recently, loxapine has been reformulated at a lower dose, producing an inhaled powder that can be directly administered to the lungs to treat the agitation associated with psychiatric disorders, such as schizophrenia and bipolar disorder. Thus, the aim of this narrative and clinical mini-review was to evaluate the efficacy and tolerability of inhaled loxapine in the treatment of acute agitation in patients with psychiatric disorders. The efficacy of inhaled loxapine has been evaluated in one Phase II trial on patients with schizophrenia, and in two Phase III trials in patients with schizophrenia and bipolar disorder. Moreover, there are two published case series on patients with borderline personality disorder and dual diagnosis patients. Inhaled loxapine has proven to be effective and generally well tolerated when administered to agitated patients with schizophrenia and bipolar disorder. Two case series have suggested that inhaled loxapine may also be useful to treat agitation in patients with borderline personality disorder and with dual diagnosis, but further studies are needed to clarify this point. However, the administration of inhaled loxapine requires at least some kind of patient collaboration, and is not recommended in the treatment of severe agitation in totally uncooperative patients. Moreover, the drug-related risk of bronchospasm must always be kept in mind when planning to use inhaled loxapine, leading to a careful patient assessment prior to, and after, administration. Also, the higher costs of inhaled loxapine, when compared to oral and intramuscular medications, should be taken into account when selecting it for the treatment of agitation.

Experience coercion, post‐traumatic stress, and satisfaction with treatment associated with different coercive measures during psychiatric hospitalization

“…) and physical (de Berardis et al . ; Zacher & Roche‐Desilets ) side effects in patients, including the risk of death (Rakhmatullina et al . ).…”

“…Their use is controversial as it involves an ethical conflict; in theory, it is used to guarantee the safety of patients and those around them, but the implementation of these measures implies conflicting with a patient's will and restricting their freedom. Moreover, these measures have psychological (Fugger et al 2016) and physical (de Berardis et al 2017;Zacher & Roche-Desilets 2005) side effects in patients, including the risk of death (Rakhmatullina et al 2013). In recent years, several interventions have been developed to reduce the use of coercive measures, and there is evidence to support their effectiveness (Bowers et al 2015;Guzman-Parra et al 2015, 2016aLeBel et al 2014).…”

The Use of Rapid Tranquilization in Aggressive Behavior

“…Other publications retrieved by the literature search for the recently issued German clinical practice guideline on the prevention of coercive measures in psychiatry (7) were considered as well. Since the publication of that guideline, the evidence base has expanded to included data on loxapine, an inhaled antipsychotic drug (8,9), and on ketamine, a narcotic (10).…”

Current Understanding of the Neurobiology of Agitation

“…An inhaled formulation of loxapine, a mid-potency typical antipsychotic, was approved in 2012 by the FDA for control of agitation associated with schizophrenia and bipolar disorder. While showing effectiveness in management of agitation, 45 providing this medication effectively requires a considerable degree of patient cooperation, which may not always be feasible. In addition, the recommended dosing is limited to a one-time 10-milligram (mg) administration per 24-hour period, with patients requiring monitoring for bronchospasm for one hour after use.…”