To evaluate the efficacy of lurasidone for schizophrenia using an established five-factor model of the Positive and Negative Syndrome Scale (PANSS).

Patient-level data were pooled from five randomized, double-blind, placebo-controlled, 6-week studies of lurasidone (fixed doses, 40–160 mg/d) for patients with an acute exacerbation of schizophrenia. Changes in five established PANSS factors were assessed using mixed-model repeated measures analysis.

Compared with placebo (n = 496), lurasidone (n = 1029, dose groups pooled) significantly improved the PANSS total score at Week 6 (−22.6 vs. −12.8; P < 0.001; effect size, 0.45), as well as all factor scores (P < 0.001 for each): positive symptoms (−8.4 vs. −6.0; effect size, 0.43), negative symptoms (−5.2 vs. −3.3; effect size, 0.33), disorganized thought (−4.9 vs. −2.8; effect size, 0.42), hostility/excitement (−2.7 vs. −1.6; effect size, 0.31), and depression/anxiety (−3.2 vs. −2.3; effect size, 0.31). Separation from placebo occurred at Week 1 for the positive symptoms, disorganized thought, and hostility/excitement factors and at Week 2 for the other factors.

In this pooled analysis of short-term studies in patients with acute schizophrenia, lurasidone demonstrated significant improvement for each of the five PANSS factor scores, indicating effectiveness across the spectrum of schizophrenia symptoms.

Brexpiprazole is a serotonin-dopamine activity modulator that is a partial agonist at 5-HT1A and dopamine D2 receptors at similar potency, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors.

Evaluating the efficacy, safety, and tolerability of flexible doses of brexpiprazole compared with placebo in patients with acute schizophrenia.

Primary endpoint was change from baseline to week 6 in PANSS total score and key secondary endpoint was change from baseline to week 6 in CGI-S score.

Phase 3, multi-center, randomized, double-blind, placebo-controlled, active reference, trial (NCT01810380). Hospitalized patients were randomized to brexpiprazole (2 to 4 mg/day), placebo, or quetiapine extended release (400 to 800 mg/day) for 6 weeks. Quetiapine was included as an active reference. Changes from baseline were analyzed using an MMRM approach.

Mean change in PANSS total score was −20.0 and −15.9 in the brexpiprazole (n = 150) and placebo (n = 159) groups, respectively (P = 0.056). Sensitivity analyses suggested treatment effect (e.g., ANCOVA, LOCF: P = 0.025; ANCOVA, OC: P = 0.026). Mean change in PANSS total score (−24.0) with quetiapine (n = 150) was significantly greater than that with placebo (P < 0.001), demonstrating sensitivity of the assay. Brexpiprazole separated from placebo on the mean change in CGI-S score (−1.2 vs. −0.9, P = 0.014). The proportion of patients reporting TEAEs were similar between the brexpiprazole and placebo treatment groups (54% versus 54.7%).

Treatment with brexpiprazole showed a clinically meaningful improvement in patients with acute schizophrenia. While the difference between brexpiprazole and placebo only approached statistical significance, sensitivity analyses and secondary endpoints supported a treatment effect of brexpiprazole.

The authors have not supplied their declaration of competing interest.