Rapid acute treatment of agitation in individuals with schizophrenia: multicentre, randomised, placebo-controlled study of inhaled loxapine

Background There is a need for a rapid-acting, non-injection, acute treatment for agitation. Aims To evaluate inhaled loxapine for acute treatment of agitation in schizophrenia. Method 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) 2h after dose one. The key secondary end-point was Clinical Global Impression-Improvement scale (CGI-I) score 2h 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 10min 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.