Clinically Meaningful Improvement in the treatment of Negative Symptoms of Schizophrenia: The Case of Roluperidone
- 1Bar-Ilan University
Abstract
BackgroundClinical meaningfulness in schizophrenia trials requires evidence that symptom change is recognizable in clinical practice. Established anchors include a [≥]1-point improvement on the CGI-S and a [≥]7-to 10-point improvement on the Personal and Social Performance scale (PSP), alongside the [≥]20% improvement on the PANSS negative symptom factor score (NSFS) conventionally applied in negative-symptom trials.
MethodsThese clinically meaningful anchors were applied as benchmarks to pooled 12-week completer data from two randomized, placebo-controlled trials of roluperidone in adults with schizophrenia and moderate to severe negative symptoms.
ResultsRoluperidone was associated with higher responder rates than placebo on all three endpoints: [≥]20% NSFS improvement (66/176 [38%] vs 39/182 [21%]; RR=1.75, 95% CI: 1.25- 2.45; p=0.0008), [≥]1-point CGI-S improvement (68/167 [41%] vs 48/177 [27%]; RR=1.50, 95% CI: 1.11-2.03; p=0.0077), and [≥]10-point PSP improvement (63/176 [36%] vs 44/181 [24%]; RR=1.47, 95% CI: 1.06-2.04; p=0.018). Effects were consistent across symptoms, global-severity, and functional outcomes, with no evidence of heterogeneity between studies.
ConclusionsAcross all three anchor criteria, roughly 1.5 to 1.75 times as many patients treated with roluperidone as with placebo reached thresholds of improvement that clinicians and patients would recognize as clinically meaningful, supporting its relevance for persistent negative symptoms in schizophrenia.
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BibTeX
@misc{rabinowitz2026clinically,
title = {{Clinically Meaningful Improvement in the treatment of Negative Symptoms of Schizophrenia: The Case of Roluperidone}},
author = {J. Rabinowitz and S. Leucht and M. Davidson and R. Luthringer},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.07.26362403},
url = {https://www.medrxiv.org/content/10.64898/2026.09.07.26362403v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Clinically Meaningful Improvement in the treatment of Negative Symptoms of Schizophrenia: The Case of Roluperidone
AU - J. Rabinowitz
AU - S. Leucht
AU - M. Davidson
AU - R. Luthringer
PY - 2026
DA - 2026/09/07
PB - medRxiv
DO - 10.64898/2026.09.07.26362403
UR - https://www.medrxiv.org/content/10.64898/2026.09.07.26362403v1
AB - BackgroundClinical meaningfulness in schizophrenia trials requires evidence that symptom change is recognizable in clinical practice. Established anchors include a [≥]1-point improvement on the CGI-S and a [≥]7-to 10-point improvement on the Personal and Social Performance scale (PSP), alongside the [≥]20% improvement on the PANSS negative symptom factor score (NSFS) conventionally applied in negative-symptom trials. MethodsThese clinically meaningful anchors were applied as benchmarks to pooled 12-week completer data from two randomized, placebo-controlled trials of roluperidone in adults with schizophrenia and moderate to severe negative symptoms. ResultsRoluperidone was associated with higher responder rates than placebo on all three endpoints: [≥]20% NSFS improvement (66/176 [38%] vs 39/182 [21%]; RR=1.75, 95% CI: 1.25- 2.45; p=0.0008), [≥]1-point CGI-S improvement (68/167 [41%] vs 48/177 [27%]; RR=1.50, 95% CI: 1.11-2.03; p=0.0077), and [≥]10-point PSP improvement (63/176 [36%] vs 44/181 [24%]; RR=1.47, 95% CI: 1.06-2.04; p=0.018). Effects were consistent across symptoms, global-severity, and functional outcomes, with no evidence of heterogeneity between studies. ConclusionsAcross all three anchor criteria, roughly 1.5 to 1.75 times as many patients treated with roluperidone as with placebo reached thresholds of improvement that clinicians and patients would recognize as clinically meaningful, supporting its relevance for persistent negative symptoms in schizophrenia.
ER -