Examining the safety, efficacy, and patient acceptability of inhaled loxapine for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults

Abstract

Agitation is a common and serious symptom of bipolar mania and schizophrenia, and can be defined as excessive motor and verbal activity. If left unrecognized and untreated, agitation can evolve into aggression, resulting in potential patient and staff injury. An ideal treatment for agitation would have a rapid onset, cause calmness without sedation, and be tolerable, efficacious, and non-coercive, while managing the underlying condition. A novel approach for the treatment of agitation is inhaled loxapine. Inhaled loxapine is rapidly absorbed into the systemic circulation through the alveoli, resulting in a near immediate onset of action. The efficacy of inhaled loxapine was established in an extensive clinical development program that included persons with schizophrenia and bipolar mania. Additionally, inhaled loxapine has comparable efficacy to intramuscular ziprasidone, olanzapine, haloperidol, aripiprazole, and lorazepam, with the added benefit of being non-painful and non-traumatizing. Inhaled loxapine carries a bolded black box warning for bronchospasm, and as a result, in the US, requires enrollment in a Risk Evaluation and Mitigation Strategy program, and is contraindicated in those with pulmonary disease. Additionally, the use of inhaled loxapine can be associated with dysgeusia and throat irritation. Inhaled loxapine requires some degree of patient cooperation, and therefore may not be appropriate for all agitated patients.

Keywords:

• inhaled loxapine
• agitation
• schizophrenia
• bipolar disorder
• mania
• antipsychotic

Disclosure

Leslie Citrome was a consultant for and received personal fees from: Acadia, Alkermes, Allergan, Indivior, Intra-Cellular Therapeutics, Janssen, Lundbeck, Merck, Neurocrine, Noven, Osmotica, Otsuka, Pfizer, Shire, Sunovion, Takeda, Teva, and Vanda in the past 12 months. He was also a speaker for and received personal fees from: Acadia, Alkermes, Allergan, Janssen, Lundbeck, Merck, Neurocrine, Otsuka, Pfizer, Shire, Sunovion, Takeda, and Teva. He owns small number of shares of common stock from Bristol-Myers Squibb, Eli Lilly, J & J, Merck, Pfizer and received royalties from Wiley as the Editor-in-Chief, International Journal of Clinical Practice, UpToDate as the reviewer, and Springer Healthcare (published a book), outside the submitted work. The authors report no other conflicts of interest in this work.