title: Efficacy and safety of loxapine for inhalation in the treatment of agitation in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  The objective of this study was to assess the efficacy and safety of inhaled loxapine in the treatment of agitation in patients with psychotic disorders.
  
  
  METHODS
  In this randomized, double-blind, placebo-controlled study, 129 agitated patients with schizophrenia or schizoaffective disorder (DSM-IV criteria) were randomized to receive in a clinical or hospital setting a single inhalation of 5 or 10 mg of loxapine or placebo administered using the Staccato loxapine for inhalation device. The inhalation device delivered thermally generated drug aerosol to the deep lung for rapid absorption. The primary efficacy measure was change on the Positive and Negative Syndrome Scale-excited component (PANSS-EC) 2 hours following treatment. Secondary outcomes included the Clinical Global Impressions-Improvement scale (CGI-I), Behavioral Activity Rating Scale (BARS), and time to first rescue medication. The study was conducted between September 2006 and January 2007.
  
  
  RESULTS
  Differences were statistically significant (P < .05) between placebo and both 5-mg and 10-mg doses on the CGI-I and the CGI-I responder analyses at 2 hours and in time to first rescue medication, and they were statistically significant (P < .05) between placebo and 10-mg loxapine on the PANSS-EC 20 minutes after administration continuing through 2 hours and in change from baseline BARS. Three serious adverse events occurred at least 6 days after treatment, but none were judged related to study treatment. The most common adverse events were sedation and dysgeusia (22% and 17%, respectively, in the 10-mg group, and 14% and 9%, respectively, in the placebo group).
  
  
  CONCLUSIONS
  Inhaled loxapine was generally safe and well tolerated and produced rapid improvement in agitated patients with psychotic disorders. Statistically significant differences in efficacy were found for the 10-mg dose compared with placebo, with results suggesting 5 mg may be effective. The delivery of loxapine by inhalation may provide a rapid, well-tolerated option for treating acute psychotic agitation that allows patients to avoid the aversive effects and loss of autonomy often associated with use of intramuscular medications. Further investigation of this new loxapine formulation is warranted.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00369577.
authors.affiliation: University of Colorado Depression Center, Aurora, CO 80045, USA. michael.allen@ucdenver.edu
authors.forename: Michael H
authors.initials: MH
authors.lastname: Allen
authors.forename: David
authors.initials: D
authors.lastname: Feifel
authors.forename: Michael D
authors.initials: MD
authors.lastname: Lesem
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Zimbroff
authors.forename: Ruth
authors.initials: R
authors.lastname: Ross
authors.forename: Patrik
authors.initials: P
authors.lastname: Munzar
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Spyker
authors.forename: James V
authors.initials: JV
authors.lastname: Cassella
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008152:Loxapine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011595:Psychomotor Agitation / Q000188:drug therapy*; D011618:Psychotic Disorders / Q000188:drug therapy; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000336:Aerosols; D014150:Antipsychotic Agents; D008152:Loxapine