Response to inhaled loxapine in patients with schizophrenia or bipolar I disorder: PANSS-EC responder analyses

Abstract

Background: Efficacy of inhaled loxapine 5 or 10 mg in treating agitation was shown using the Positive and Negative Syndrome Scale - Excited Component (PANSS-EC) in two Phase III randomised, double-blind, placebo-controlled trials in 344 agitated patients with schizophrenia and 314 patients with bipolar I disorder (Clinicaltrials.gov: NCT00628589, NCT00721955).

Aims: To examine the five individual items comprising the PANSS-EC and the percentage of patients achieving a clinical response (reduction of ≥40%) in PANSS-EC (Response-40) for these two studies.

Method: Response-40 was examined at the primary end-point (2 h) and over time.

Results: Response-40 and each PANSS-EC item score were statistically significant v. placebo at 2 h and at each assessment time point for both doses.

Conclusions: Inhaled loxapine produced rapid improvement in agitated patients with schizophrenia or bipolar I disorder, achieving Response-40 at the first assessment (10 min post dose). These results highlight the effectiveness of loxapine across all components of agitation as measured by the PANSS-EC.

Declaration of interest: S.Z. is a member of the speakers bureau for Grupo Ferrer. L.Z. has been a speaker and grant recipient for Teva Pharmaceuticals. J.V.C. and D.A.S. were employees of Alexza Pharmaceuticals during execution of the studies, and are currently paid consultants for and have received stock and/or stock options from Alexza Pharmaceuticals. P.P.Y. is a full-time employee and receives stock options from Teva Pharmaceuticals.

Copyright and usage: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Fig. 1. PANSS-EC response over time: patients with ≥40% PANSS-EC score reduction. PANSS-EC, Positive and Negative Syndrome Scale – Excited Component.

Fig. 2. Odds ratio (OR) forest plot for responders at 2 h: CGI responders, total PANSS-EC scores and individual PANSS-EC subscale scores. BD, bipolar I disorder; CI, confidence interval; CGI, Clinical Global Impression scale; OR, odds ratio; SC, schizophrenia; PANSS-EC, Positive and Negative Syndrome Scale – Excited Component. All ORs are statistically significant (95% CI excludes 1.0).

Fig. 3. Changes from baseline in individual PANSS-EC item scores at 2 h post dose (bar graph) and changes in individual PANSS-EC item scores over time (line graphs). PANSS-EC, Positive and Negative Syndrome Scale – Excited Component. In the individual PANSS-EC item analyses, all time points from 10 min to 2 h for both doses were statistically significant (P<0.05), except for the uncooperative item (P=0.0853 for the 5 mg dose at 10 min in the schizophrenia study).