Clinically Meaningful Improvement in the treatment of Negative Symptoms of Schizophrenia: The Case of Roluperidone
Year: 2026
Type: preprint
Abstract: Background Clinical 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. Methods These 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. Results Roluperidone 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. Conclusions Across 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.
Source: medRxiv
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7212026831