Brexpiprazole improves PANSS scores by 0.19 Cohen's d in early-episode schizophrenia versus placebo

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Psychiatry research Published June 1, 2026 Medically reviewed June 1, 2026 Study authors: Correll Christoph U, Yildirim Murat, Zhang Zhen, Palma Anton M, Pham Tim, Pflug Brian PubMed ↗ NCT01396421 ↗ DOI ↗ By Dr. Ji-eun Park, MD · Brain, Mind & Pain

Key Takeaway

Consider brexpiprazole for early-episode schizophrenia; post hoc analysis shows efficacy versus placebo.

This post hoc analysis examined data from Phase 3 clinical trials involving 476 participants aged 13-35 years with early-episode schizophrenia, defined as illness duration of 5 years or less. The study population included 289 participants receiving brexpiprazole and 187 receiving placebo. The setting was not reported in the source data.

The primary outcome measured change from baseline to Week 6 on the PANSS total score. Results indicated that the change was greater with brexpiprazole versus placebo, with a Cohen's d of 0.19. The 95% confidence interval for this effect was -7.0, -0.1, and the p-value was 0.04. A secondary outcome assessed change from baseline to Week 6 on the combined PSP/CGAS functioning score. This score also showed greater improvement with brexpiprazole versus placebo, sharing the same Cohen's d of 0.19, a 95% CI of 0.1, 4.5, and a p-value of 0.04.

Regarding safety, the incidence of treatment-emergent adverse events was 50.7% with brexpiprazole and 46.3% with placebo. The most common adverse events with brexpiprazole were insomnia at 9.2% and akathisia at 6.5%. Serious adverse events were not reported, and discontinuations were not reported. The tolerability profile was consistent with previous clinical trials.

Key limitations include that this is a post hoc analysis. The study expands the evidence base for brexpiprazole in schizophrenia by demonstrating efficacy in patients who are early in their disease course.

Study Details

Study typeRct

Sample sizen = 289

EvidenceLevel 2

Follow-up1.4 mo

PublishedJun 2026

PMID41849920

TrialNCT01396421

View Original Abstract ↓

OBJECTIVE: To evaluate the efficacy and safety of brexpiprazole in patients with early-episode schizophrenia. METHODS: Data were pooled from four 6-week, randomized, double-blind, placebo-controlled trials in schizophrenia. Three trials (ClinicalTrials.gov identifiers: NCT01396421, NCT01393613, NCT01810380) enrolled adults aged 18-65 years; one trial (NCT03198078) enrolled adolescents aged 13-17 years. Data from participants meeting early-episode criteria (age 13-35 years, ≤5 years illness duration) were pooled for participants randomized to brexpiprazole 2-4 mg or placebo. Efficacy on schizophrenia symptoms was primarily evaluated using the Positive and Negative Syndrome Scale (PANSS; primary endpoint in all trials). Change in functioning was measured using the Personal and Social Performance (PSP) scale in adults and Children's Global Assessment Scale (CGAS) in adolescents. Safety was also assessed. RESULTS: Across 476 participants (brexpiprazole 2-4 mg/day, n = 289; placebo, n = 187), change from baseline to Week 6 was greater with brexpiprazole versus placebo on PANSS total score (least squares [LS] mean difference -3.6; 95% confidence interval [CI] -7.0, -0.1; p = 0.04; Cohen's d 0.19), and a combined PSP/CGAS functioning score (LS mean difference 2.3; 95% CI: 0.1, 4.5; p = 0.04; Cohen's d 0.19). The incidence of treatment-emergent adverse events (TEAEs) was 50.7% with brexpiprazole and 46.3% with placebo. The most common TEAEs with brexpiprazole were insomnia (brexpiprazole, 9.2%; placebo, 9.5%) and akathisia (brexpiprazole, 6.5%; placebo, 2.1%). CONCLUSION: This analysis expands the evidence base for brexpiprazole in schizophrenia by demonstrating efficacy in patients who are early in their disease course. The safety profile of brexpiprazole was consistent with previous clinical trials.