F106. EFFICACY OF LURASIDONE IN ANTIPSYCHOTIC-NAïVE ADOLESCENTS WITH SCHIZOPHRENIA: POST-HOC ANALYSIS OF A 6-WEEK, RANDOMIZED, PLACEBO-CONTROLLED STUDY

Onset of schizophrenia commonly occurs during late adolescence or early adulthood. Earlier onset (before age 18) is often characterized by greater symptom severity and higher rates of chronic functional impairment. Few studies have examined treatment response in adolescents with schizophrenia who are treatment-naïve, and no placebo-controlled study in first episode treatment-naïve patients with schizophrenia exists at any age. The aim of the current post-hoc analysis was to evaluate the efficacy of lurasidone in antipsychotic-naïve adolescents with a diagnosis of schizophrenia. Patients aged 13–17 years with a DSM-IV-TR diagnosis of schizophrenia, and a Positive and Negative Symptom Scale (PANSS) total score ≥70 and <120, were randomized to 6 weeks of double-blind, fixed-dose treatment with lurasidone (40 or 80 mg/day) or placebo. In a post-hoc analysis, efficacy at week 6 endpoint was compared for lurasidone (both doses combined) vs. placebo in patient groups based on prior treatment status (treatment naïve [Tx-] vs. previously treated [Tx+]). Baseline to week 6 change in the PANSS total and Clinical Global Impression, Severity (CGI-S) scores were assessed using a mixed model for repeated measurement (MMRM) analysis. Effect size was calculated as the least squares mean difference in week 6 change score for lurasidone vs. placebo divided by the pooled standard deviation. Treatment response (criteria: ≥20% reduction from baseline in PANSS total score) was evaluated using a logistic regression model. In the primary a priori analysis, treatment with lurasidone was associated with significantly greater week 6 reduction in least-squares mean PANSS total score for lurasidone 40 mg/d (N=108; -18.6; P<0.001; effect size [ES]=0.51) and lurasidone 80 mg/d (N=106; -18.3; P<0.001; [ES]=0.48) compared with placebo (N=112; -10.5). The sample size was notably smaller for the Tx- patient group (lurasidone, N=39 vs. placebo, N=18) compared to the Tx+ group (lurasidone, N=175 vs. placebo, N=94). The most notable baseline differences in the Tx- vs. Tx+ groups were lower rates of prior psychiatric hospitalization (42.0% vs. 70.2%) and higher levels of functioning on the Children’s Global Assessment Scale (CGAS, 47.9 vs. 43.5). Greater early improvement on lurasidone vs. placebo was noted in the Tx- vs. Tx+ groups at week 1 (effect size, 0.45 vs. 0.28) and week 2 (effect size, 0.59 vs. 0.28); and this higher level of improvement was maintained through week 6 (effect size, 0.75 vs. 0.45). Similar differences in effect sizes for the Tx- vs. Tx+ groups were observed for the CGI-S scale (week 6, 0.97 vs. 0.38), and for the PANSS positive (week 6, 0.89 vs. 0.57), and negative (week 6, 0.40 vs. 0.32) subscale scores. Response rates were also higher for lurasidone vs. placebo in the Tx- group (84.6% vs. 38.9%; number needed to treat [NNT]= 3) compared with the Tx+ group (60.0% vs. 42.6%; NNT= 6). In this post-hoc analysis of a double-blind, 6-week study, adolescents experiencing an acute exacerbation of schizophrenia who had received no previous antipsychotic therapy were found to respond especially well to treatment with lurasidone at doses of 40 mg/d or 80 mg/d. Effect sizes at endpoint were notably larger for lurasidone vs. placebo (+60% for PANSS total and +255% for CGI-S endpoint scores) in the treatment-naïve group compared to patients with previous lifetime antipsychotic treatment.