Inhaled loxapine for the urgent treatment of acute agitation associated with schizophrenia or bipolar disorder

Abstract

Background: Acute agitation is a serious complication of schizophrenia and bipolar disorder, which may escalate quickly to aggressive behavior. Rapid treatment is therefore important to calm and stabilize the patient, reducing the potential for harm to the patient and others, and allowing further assessment. Current guidelines suggest that where pharmacologic intervention is indicated, medication should preferably be non-invasive, should have a rapid onset and should control aggressive behavior in the short term without compromising the physician–patient relationship in the long term.

Objectives: This article presents an overview of a new inhaled formulation of the established antipsychotic loxapine, which aims to provide a more rapidly acting agent for the treatment of acute agitation without the disadvantages of intramuscular or intravenous injection.

Discussion: Inhaled loxapine is rapidly absorbed with intravenous-like pharmacokinetics, with a time to maximum plasma concentration of 2 minutes and a plasma half-life of approximately 6 hours. In phase III studies, loxapine reduced agitation within 10 minutes of inhalation; agitation was decreased at all subsequent assessments during a 24-hour evaluation period. Inhaled loxapine was generally well tolerated with no undue sedation. The most common adverse events were dysgeusia, mild sedation, and dizziness. Inhaled loxapine is contraindicated in patients with asthma, COPD or other pulmonary disease associated with bronchospasm.

Conclusions: Inhaled loxapine rapidly reduces acute agitation in patients with schizophrenia or bipolar disorder and is generally well tolerated. The non-invasive route of delivery respects the patient’s autonomy, reducing the perception of coercion or forced medication. Inhaled loxapine is therefore an effective and appropriate option for use in the emergency setting in patients with acute agitation.

Keywords:

• Acute agitation
• Antipsychotic
• Bipolar disorder
• Emergency treatment
• Inhaled loxapine
• Schizophrenia

Transparency

Declaration of funding

Teva Pharmaceuticals (Frazer, PA, USA) provided funding for editorial assistance. Teva provided a single medical accuracy review of the final draft but otherwise had no involvement in the content of the paper. The author was not compensated and retained full editorial control over the content of the paper.

Declaration of financial/other relationships

C.V.P. has disclosed the receipt of honoraria for consulting services provided to Teva.

CMRO peer reviewer 1 has disclosed that he has received sponsorship from Adamed and Janssen; has received grants from Lundbeck, Otsuka and Ministerio Sanidad; has been a consultant to Ferrer and Janssen and is on the Speakers’ Bureau of Janssen and Lundbeck. Peer reviewer 2 has no relevant financial or other relationships to disclose.

Acknowledgments

Editorial assistance was provided by Dr Duncan Porter of Anthemis Consulting Ltd, funded by Teva Pharmaceuticals.

Notes

*Adasuve is a registered trademark of Teva Pharmaceuticals USA Inc., Horsham, PA, USA

†Staccato is a registered trademark of Alexza Pharmaceuticals Inc., Mountain View, CA, USA