Effects of acute paliperidone palmitate treatment in subjects with schizophrenia recently treated with oral risperidone

Objective: To examine efficacy and safety of acute treatment with paliperidone palmitate in subjects with schizophrenia whose disease remained symptomatic despite recent treatment with oral risperidone. Methods: Post hoc analysis of a 13-week, double-blind, placebo-controlled study of subjects with symptomatic schizophrenia randomized to paliperidone palmitate 39, 156, or 234 mg (25, 100, or 150 mg equivalents of paliperidone) or placebo. Paliperidone palmitate subjects received a 234-mg day 1 dose, followed by their assigned dose on day 8 and monthly thereafter. Subjects treated with oral risperidone within 2 weeks before randomization regardless of duration were included. Assessments: PANSS, CGI-S, PSP scores; AEs. ANCOVA models with LOCF methodology evaluated treatment group differences. Results: 216 subjects received prior oral risperidone (paliperidone palmitate 39 mg, n = 53; 156 mg, n = 58; 234 mg, n = 48; placebo, n = 57). Median prior risperidone use was 22 days. Significant improvement was observed with paliperidone palmitate 156-mg or 234-mg versus placebo in least-squares mean (SE) score change at end point in PANSS total (156 mg, -15.8 [3.0], p = 0.0001; 234 mg, -17.6 [3.2], p = 0.0001), CGI-S (156 mg, -0.9 [0.2], p = 0.0068; 234 mg, -1.1 [0.2], p = 0.0003), and PSP (156 mg, 10.7 [2.3], p = 0.0061; 234 mg, 12.9 [2.4], p = 0.0009). Most common AEs (>= 10%) in any paliperidone palmitate group were insomnia, anxiety, and headache. Conclusions: In subjects with schizophrenia who recently received oral risperidone but who remained symptomatic, acute treatment with monthly doses of 156-mg and 234-mg paliperidone palmitate significantly improved clinical symptoms, global illness ratings, and functioning compared with placebo, with no unexpected safety findings. (C) 2011 Elsevier B.V. All rights reserved.