PLACID study: A randomized trial comparing the efficacy and safety of inhaled loxapine versus intramuscular aripiprazole in acutely agitated patients with schizophrenia or bipolar disorder

Abstract

The aim of the study was to investigate the efficacy and safety of inhaled loxapine compared with the intramuscular (IM) antipsychotic aripiprazole in acutely agitated patients with schizophrenia or bipolar I disorder. PLACID was an assessor-blind, parallel-group trial conducted in 23 centres in the Czech Republic, Germany, Spain, and Russia. Patients (aged 18–65 years) diagnosed with schizophrenia or bipolar I disorder experiencing acute agitation (Clinical Global Impression [CGI]-Severity score ≥ 4) while hospitalized or attending an emergency room were randomized to receive up to two doses of inhaled loxapine 9.1 mg or IM aripiprazole 9.75 mg (≥ 2 h between doses) during the 24-h study period. The primary efficacy endpoint was time to response (CGI-Improvement score 1 [very much improved] or 2 [much improved]). The primary analysis included randomized patients who provided informed consent (full analysis set [FAS]); the safety analysis included all patients who received study medication. The FAS comprised 357 patients (enrolled December 2, 2014 – October 31, 2016). The between-treatment difference in median time to CGI-Improvement response was 10 min (95% CI 0.0–30.0); p = 0.0005) in favour of inhaled loxapine (median [95% CI]: 50 min [30.0–50.0] vs 60 min [50.0–90.0] with IM aripiprazole); the difference was significant at 10 min (responders: 14% [loxapine] vs 4% [aripiprazole]; p = 0.001). There were no safety issues. Inhaled loxapine reduced agitation faster than IM aripiprazole, supporting its use as a first-line option for managing acute agitation in patients with schizophrenia or bipolar disorder.