There is a need for a rapid-acting, non-injection, acute treatment for agitation in people with schizophrenia. This randomised (double-blind, placebo-controlled, parallel-group) controlled trial set out to evaluate the effectiveness and safety of inhaled loxapine for acute treatment of agitation in schizophrenia.
The researchers recruited 344 adults with DSM-IV schizophrenia who were in good general health and were agitated (Positive and Negative Syndrome Scale Excited Component (PANSS-EC) total score of ≥14 out of 35 and a score of ≥4 out of 7 on at least one of the five items). Participants were recruited from people admitted to hospital or a research unit, people already hospitalised for treatment of schizophrenia and individuals who were treated at a psychiatric emergency department.
Patients 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.
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.
These results are promising but the researchers admitted the limitations of the study, noting that the controlled inpatient setting and informed consent required for the RCT were not representative of a real world situation.
The researchers concluded:
Inhaled loxapine is a well-tolerated and effective novel treatment of agitation in schizophrenia and potentially other disorders.
Lesem MD, Tran-Johnson TK, Riesenberg RA, Feifel D, Allen MH, Fishman R, Spyker DA, Kehne JH, Cassella JV. Rapid acute treatment of agitation in individuals with schizophrenia: multicentre, randomised, placebo-controlled study of inhaled loxapine. Br J Psychiatry. 2011 Jan;198(1):51-8.