PM384. The effect of brexpiprazole (OPC-34712) versus aripiprazole in adult patients with acute schizophrenia: an exploratory study

Objectives: Identification of early clinical markers that predict later treatment outcomes in first-episode psychosis is highly valuable. The present study was conducted to determine the best time at which to predict the late treatment response in firstepisode psychosis patients treated with paliperidone ER, factors predicting early treatment responses (at weeks 2 and 3) and the relationships between paliperidone ER plasma concentrations at weeks 2 and 3, and treatment responses at weeks 2, 3, and 8. Methods: Various criteria for treatment response were employed. Plasma paliperidone concentrations at week 2 and 3 were determined using validated high-performance liquid chromatography/tandem mass spectrometry (LC-MS/MS). Treatment response at week 3 optimally predicted the later (week 8) response in terms of negative predictive value (NPV). Independent predictors for good treatment responses at weeks 2 and 3 were female gender, a higher educational level, a higher PANSS-excited score, and/or a shorter DUP. Results: The plasma paliperidone concentration at week 3, but not week 2, was a significant predictor of the late treatment response (week 8). Conclusion: These results may help appropriate clinical decision-making for early non-responders in first-episode psychosis. PM384 The effect of brexpiprazole (OPC-34712) versus aripiprazole in adult patients with acute schizophrenia: an exploratory study Leslie Citrome MD, MPH1, Ai Ota BSc2, Kazuhiro Nagamizu BSc2, Pamela Perry MSc3, Emmanuelle Weiller PsyD4, Ross Baker PhD MBA3 1New York Medical College, Valhalla, NY, USA 2Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan 3Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA 4H. Lundbeck A/S, Valby, Denmark Abstract Background: Brexpiprazole is a serotonin-dopamine activity modulator that acts as a partial agonist at 5-HT1A and dopamine D2 receptors, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors, all at similar potencies. BrexpiprazoleBackground: Brexpiprazole is a serotonin-dopamine activity modulator that acts as a partial agonist at 5-HT1A and dopamine D2 receptors, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors, all at similar potencies. Brexpiprazole has lower intrinsic activity at the D2 receptor than aripiprazole, suggesting a lower potential to induce D2 agonist-mediated adverse events such as akathisia, insomnia, restlessness, and nausea. In this open-label study the effects of 6-week treatment with brexpiprazole or aripiprazole in patients with schizophrenia were explored (NCT02054702). Methods: Patients with an acute relapse of schizophrenia were randomized to receive brexpiprazole 1 to 4mg/day (3mg/day target dose) or aripiprazole 10 to 20 mg/day (15 mg/day target dose) for 6 weeks. The mean change in Positive and Negative Syndrome Scale (PANSS) total score from baseline to Week 6 was analysed. Results: A total of 97 patients were treated with brexpiprazole (N=64) or aripiprazole (N=33). A reduction in the symptoms of schizophrenia assessed by the PANSS total score were observed in both treatment groups (LS mean change at week 6: -22.9 and -19.4 for brexpiprazole and aripiprazole, respectively). Brexpiprazole was well tolerated and the incidence of EPS-related adverse events including akathisia was lower in the patients treated with brexpiprazole (14.1%) compared with the patients treated with aripiprazole (30.3%).