title: 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.
authors.affiliation: The National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", ASL 4, 64100 Teramo, Italy. domenico.deberardis@aslteramo.it.|Department of Neurosciences and Imaging, Chair of Psychiatry, University "G. D'Annunzio", 66013 Chieti, Italy. domenico.deberardis@aslteramo.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: de Berardis
authors.affiliation: New York Psychiatric Institute, Columbia University, New York, NY 10032, USA. dott.fornaro@gmail.com.|Polyedra Research Group Association, 64100 Teramo, Italy. dott.fornaro@gmail.com.
authors.forename: Michele
authors.initials: M
authors.lastname: Fornaro
authors.affiliation: Polyedra Research Group Association, 64100 Teramo, Italy. laura.orsolini@hotmail.it.|School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Herts AL10 9AB, UK. laura.orsolini@hotmail.it.|Villa S. Giuseppe Hospital, HermanasHospitalarias, 63100 Ascoli Piceno, Italy. laura.orsolini@hotmail.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Orsolini
authors.affiliation: Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of Medicine "Federico II", 80133 Naples, Italy. felix_ias@hotmail.com.
authors.forename: Felice
authors.initials: F
authors.lastname: Iasevoli
authors.affiliation: Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of Medicine "Federico II", 80133 Naples, Italy. carmine.tomasetti@aslteramo.it.
authors.forename: Carmine
authors.initials: C
authors.lastname: Tomasetti
authors.affiliation: Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of Medicine "Federico II", 80133 Naples, Italy. adebarto@unina.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: de Bartolomeis
authors.affiliation: Department of Neurosciences and Imaging, Chair of Psychiatry, University "G. D'Annunzio", 66013 Chieti, Italy. nicola.serroni@aslteramo.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Serroni
authors.affiliation: Polyedra Research Group Association, 64100 Teramo, Italy. a.valchera@ospedaliere.it.|Villa S. Giuseppe Hospital, HermanasHospitalarias, 63100 Ascoli Piceno, Italy. a.valchera@ospedaliere.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Valchera
authors.affiliation: The National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "Madonna Del Soccorso", 63074 San Benedetto del Tronto, Italy. alessandro.carano@gmail.com.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Carano
authors.affiliation: Department of Neurosciences and Imaging, Chair of Psychiatry, University "G. D'Annunzio", 66013 Chieti, Italy. federica.vellante@gmail.com.|Polyedra Research Group Association, 64100 Teramo, Italy. federica.vellante@gmail.com.
authors.forename: Federica
authors.initials: F
authors.lastname: Vellante
authors.affiliation: Department of Neurosciences and Imaging, Chair of Psychiatry, University "G. D'Annunzio", 66013 Chieti, Italy. sfnmarini@gmail.com.|Polyedra Research Group Association, 64100 Teramo, Italy. sfnmarini@gmail.com.
authors.forename: Stefano
authors.initials: S
authors.lastname: Marini
authors.affiliation: Hospital Pharmacy, Hospital "G. Mazzini", ASL 4, 64100 Teramo, Italy. monica.piersanti@aslteramo.it.
authors.forename: Monica
authors.initials: M
authors.lastname: Piersanti
authors.affiliation: Hermanas Hospitalarias, FoRiPsi, Department of Clinical Neurosciences, Villa San Benedetto Menni, Albese con Cassano, 22032 Como, Italy. pernagp@gmail.com.|Department of Psychiatry and Neuropsychology, University of Maastricht, 6200 MD Maastricht, The Netherlands. pernagp@gmail.com.|Department of Psychiatry and Behavioral Sciences, Leonard Miller School of Medicine, University of Miami, Coral Gables, FL 33124, USA. pernagp@gmail.com.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Perna
authors.affiliation: Department of Neurosciences and Imaging, Chair of Psychiatry, University "G. D'Annunzio", 66013 Chieti, Italy. giovanni.martinotti@gmail.com.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinotti
authors.affiliation: Department of Neurosciences and Imaging, Chair of Psychiatry, University "G. D'Annunzio", 66013 Chieti, Italy. digiannantonio@unich.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Giannantonio
mesh_terms: D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002986:Clinical Trials as Topic; D006801:Humans; D001239:Inhalation; D008152:Loxapine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001523:Mental Disorders / Q000150:complications* / Q000175:diagnosis; D011595:Psychomotor Agitation / Q000188:drug therapy* / Q000209:etiology*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D008152:Loxapine
keywords: agitation; antipsychotics; bipolar disorder; efficacy; inhaled; loxapine; schizophrenia; tolerability