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.
Highlights
Being faced with an agitated or violent patient is a challenge for every psychiatrist and associated health care professional, working in the everyday “real world” clinical practice [1]
The results showed that, in subjects with asthma and Chronic Obstructive Pulmonary Disease (COPD), inhaled loxapine may cause an airway effect (FEV1 decline and bronchospasm) that is commonly reversible with a short-acting β-agonist bronchodilator
Even if the delivery system is innovative for an antipsychotic drug, it presumes that some kind of patient collaboration is undoubtedly required
Summary
Being faced with an agitated or violent patient is a challenge for every psychiatrist and associated health care professional, working in the everyday “real world” clinical practice [1]. Agitation and violence may be mediated by some clinical characteristics associated with schizophrenia or bipolar disorder (rather than schizophrenia or bipolar disorder per se), such as a heightened sensitivity to a perceived threat [9]. When considering the relationships between psychosis and agitation/violence, a pattern of personality traits related to psychosis (the so-called “threat/control-override”, TCO) [10,11], has received practical support as a likely explanatory variable for the psychosis-aggression association. As noted by Link and Stueve [10], only psychotic-like experiences that lead someone to fear a heightened perceived threat of harm (such as commanding auditory hallucinations, persecutory delusions, hypervigilance), while blocking internal constraints against violence (the “control-override” system), may precipitate agitation, aggression, and violent behaviours
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