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) 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.