Effects of Brexpiprazole Across Symptom Domains in Patients With Schizophrenia: Post Hoc Analysis of Short- and Long-Term Studies

Stephen R Marder, Stine R Meehan, Catherine Weiss, Dalei Chen, Mary Hobart, Nanco Hefting, Stephen R Marder, Stine R Meehan, Catherine Weiss, Dalei Chen, Mary Hobart, Nanco Hefting

Abstract

The successful treatment of schizophrenia entails improvement across a spectrum of symptoms. The aim of this post hoc analysis was to characterize the short- and long-term effects of brexpiprazole on Positive and Negative Syndrome Scale (PANSS) 'Marder factors.' Data were included from three 6-week, randomized, double-blind, placebo-controlled studies; a 52-week, randomized, double-blind, placebo-controlled maintenance treatment study; and two 52-week open-label extension (OLEx) studies-all in schizophrenia (DSM-IV-TR criteria). Patients receiving oral brexpiprazole were dosed at 2-4 mg/day (short-term studies) or 1-4 mg/day (long-term studies). At Week 6, least squares mean differences (LSMDs, with 95% confidence limits [CLs]) for brexpiprazole (n = 868) vs placebo (n = 517) were: Positive symptoms: -1.55 (-2.30, -0.80), P < .0001, Cohen's d effect size (ES) = 0.27; Negative symptoms: -1.12 (-1.63, -0.61), P < .0001, ES = 0.29; Disorganized thought: -1.26 (-1.78, -0.74), P < .0001, ES = 0.32; Uncontrolled hostility/excitement: -0.76 (-1.15, -0.37), P = .0002, ES = 0.26; Anxiety/ depression: -0.56 (-0.91, -0.22), P = .0014, ES = 0.22. At last visit of the maintenance study, LSMDs (95% CLs) for brexpiprazole (n = 96) vs placebo (n = 104) were: Positive symptoms: -3.44 (-4.99, -1.89), P < .0001, ES = 0.62; Negative symptoms: -1.23 (-2.52, 0.07), P = .063, ES = 0.27; Disorganized thought: -1.69 (-2.81, -0.56), P = .0035, ES = 0.42; Uncontrolled hostility/excitement: -1.26 (-2.12, -0.39), P = .0046, ES = 0.41; Anxiety/depression: -0.72 (-1.47, 0.03), P = .061, ES = 0.27. In the OLEx studies, improvements were maintained over 58 (6 + 52) weeks of brexpiprazole treatment. In conclusion, these data suggest that brexpiprazole treats the continuum of schizophrenia symptoms, in the short- and long-term. Trial Registration: Data used in this post hoc analysis came from ClinicalTrials.gov identifiers: NCT01396421, NCT01393613, NCT01810380, NCT01668797, NCT01397786, NCT01810783.

Keywords: Marder factors; Positive and Negative Syndrome Scale; antipsychotic; clinical trial.

© The Author(s) 2021. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.

Figures

Fig. 1.
Fig. 1.
Patient disposition. aSponsor terminated trial early due to interim analysis. Note: Efficacy sample, patients who received at least one dose of study medication and had a baseline and at least one post-baseline PANSS Total score assessment.
Fig. 2.
Fig. 2.
Short-term and OLEx studies: mean change in PANSS Marder Factor scores from baseline over 6 weeks and over 58 weeks (efficacy sample). *P < .05, **P < .01, ***P < .001 vs placebo, MMRM (short-term); observed cases (long-term). Note: LS, least squares; MMRM, mixed model for repeated measures; OL, open-label; OLEx, open-label extension; PANSS, Positive and Negative Syndrome Scale; SD, standard deviation; SE, standard error.
Fig. 3.
Fig. 3.
Short-term studies: mean change in PANSS item scores from baseline to week 6, organized by Marder Factor (efficacy sample). *P < .05, **P < .01, ***P < .001 vs placebo, MMRM. Note: LS, least squares; MMRM, mixed model for repeated measures; PANSS, Positive and Negative Syndrome Scale; SE, standard error.
Fig. 4.
Fig. 4.
Maintenance study: mean change in PANSS Marder Factor scores from baseline over 36 weeks in the single-blind stabilization phase and from randomization over 52 weeks in the double-blind maintenance phase (efficacy sample). Observed cases (stabilization phase); *P < .05, **P < .01, ***P < .001 vs placebo, ANCOVA, LOCF (maintenance phase). Note: ANCOVA, analysis of covariance; LOCF, last observation carried forward; LS, least squares; PANSS, Positive and Negative Syndrome Scale; SD, standard deviation; SE, standard error.

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