title: Rapid acute treatment of agitation in individuals with schizophrenia: multicentre, randomised, placebo-controlled study of inhaled loxapine.
abstract: BACKGROUND
  There is a need for a rapid-acting, non-injection, acute treatment for agitation.
  
  
  OBJECTIVE
  To evaluate inhaled loxapine for acute treatment of agitation in schizophrenia.
  
  
  METHODS
  This phase III, randomised, double-blind, placebo-controlled, parallel-group study (ClinicalTrials.gov number NCT00628589) enrolled 344 individuals who received one, two or three doses of inhaled loxapine (5 or 10 mg) or a placebo. Lorazepam rescue was permitted after dose two. The primary efficacy end-point was change from baseline in Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) 2 h after dose one. The key secondary end-point was Clinical Global Impression-Improvement scale (CGI-I) score 2 h after dose one.
  
  
  RESULTS
  Inhaled loxapine (5 and 10 mg) significantly reduced agitation compared with placebo as assessed by primary and key secondary end-points. Reduced PANSS-EC score was evident 10 min after dose one with both 5 and 10 mg doses. Inhaled loxapine was well tolerated, and the most common adverse events were known effects of loxapine or minor oral effects common with inhaled medications.
  
  
  CONCLUSIONS
  Inhaled loxapine provided a rapid, well-tolerated acute treatment for agitation in people with schizophrenia.
authors.affiliation: Claghorn-Lesem Research Clinic Ltd, 1010 Waverly Street, Houston, Texas 77008, USA. mlesem@claghorn-lesem.com
authors.forename: Michael D
authors.initials: MD
authors.lastname: Lesem
authors.forename: Tram K
authors.initials: TK
authors.lastname: Tran-Johnson
authors.forename: Robert A
authors.initials: RA
authors.lastname: Riesenberg
authors.forename: David
authors.initials: D
authors.lastname: Feifel
authors.forename: Michael H
authors.initials: MH
authors.lastname: Allen
authors.forename: Robert
authors.initials: R
authors.lastname: Fishman
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Spyker
authors.forename: John H
authors.initials: JH
authors.lastname: Kehne
authors.forename: James V
authors.initials: JV
authors.lastname: Cassella
mesh_terms: D000208:Acute Disease; D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008152:Loxapine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D011595:Psychomotor Agitation / Q000188:drug therapy*; D012559:Schizophrenia / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D010919:Placebos; D008152:Loxapine