Baseline severity of positive and negative symptoms predicts relapse in opposing directions among placebo-treated schizophrenia patients: analysis of five placebo-controlled, antipsychotic withdrawal, relapse-prevention trials
- 1Bar-Ilan University
Abstract
Background and HypothesisIdentifying which patients with schizophrenia will remain stable and which will relapse is relevant to both trial design and clinical practice. We hypothesized that higher negative and lower positive symptoms at baseline would predict longer time to relapse.
Study DesignThis analysis pooled individual participant data on 557 patients with schizophrenia randomized to placebo from five placebo-controlled antipsychotic withdrawal relapse-prevention studies, each with a double-blind phase of at least 6 months. Relapse was defined as a [≥]12-point increase in Positive and Negative Syndrome Scale (PANSS) total score from double-blind baseline at any time during the double-blind phase. Cox regression analyses modeled time to relapse with the three PANSS subscales, age and sex.
Study ResultsPANSS Negative and Positive symptom subscales predicted relapse in opposite directions and at almost equal magnitude in the pooled model. Higher negative symptoms predicted lower relapse risk (hazard ratio (HR)=0.94 per point, 95% confidence interval (CI)=0.90-0.99) and higher positive symptoms predicted higher relapse risk (HR=1.06, 95% CI=1.00-1.13). PANSS General Psychopathology did not predict relapse (HR=0.98, 95% CI=0.95-1.02). Based on the pooled estimates, a 4-point higher baseline PANSS Positive score corresponded to a 27% higher relapse risk, while a 4-point higher baseline PANSS Negative score corresponded to a 21% lower risk.
ConclusionsThese results may help predict relapse risk in clinical care and in clinical trial samples but require prospective validation.
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BibTeX
@misc{rabinowitz2026baseline,
title = {{Baseline severity of positive and negative symptoms predicts relapse in opposing directions among placebo-treated schizophrenia patients: analysis of five placebo-controlled, antipsychotic withdrawal, relapse-prevention trials}},
author = {J. Rabinowitz and M. Davidson and C. U. Correll and H. Speyer and M. S. Ben-Shachar and A. Noy and A. Ciubara and R. Luthringer},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.28.26363883},
url = {https://www.medrxiv.org/content/10.64898/2026.09.28.26363883v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Baseline severity of positive and negative symptoms predicts relapse in opposing directions among placebo-treated schizophrenia patients: analysis of five placebo-controlled, antipsychotic withdrawal, relapse-prevention trials
AU - J. Rabinowitz
AU - M. Davidson
AU - C. U. Correll
AU - H. Speyer
AU - M. S. Ben-Shachar
AU - A. Noy
AU - A. Ciubara
AU - R. Luthringer
PY - 2026
DA - 2026/09/28
PB - medRxiv
DO - 10.64898/2026.09.28.26363883
UR - https://www.medrxiv.org/content/10.64898/2026.09.28.26363883v1
AB - Background and HypothesisIdentifying which patients with schizophrenia will remain stable and which will relapse is relevant to both trial design and clinical practice. We hypothesized that higher negative and lower positive symptoms at baseline would predict longer time to relapse. Study DesignThis analysis pooled individual participant data on 557 patients with schizophrenia randomized to placebo from five placebo-controlled antipsychotic withdrawal relapse-prevention studies, each with a double-blind phase of at least 6 months. Relapse was defined as a [≥]12-point increase in Positive and Negative Syndrome Scale (PANSS) total score from double-blind baseline at any time during the double-blind phase. Cox regression analyses modeled time to relapse with the three PANSS subscales, age and sex. Study ResultsPANSS Negative and Positive symptom subscales predicted relapse in opposite directions and at almost equal magnitude in the pooled model. Higher negative symptoms predicted lower relapse risk (hazard ratio (HR)=0.94 per point, 95% confidence interval (CI)=0.90-0.99) and higher positive symptoms predicted higher relapse risk (HR=1.06, 95% CI=1.00-1.13). PANSS General Psychopathology did not predict relapse (HR=0.98, 95% CI=0.95-1.02). Based on the pooled estimates, a 4-point higher baseline PANSS Positive score corresponded to a 27% higher relapse risk, while a 4-point higher baseline PANSS Negative score corresponded to a 21% lower risk. ConclusionsThese results may help predict relapse risk in clinical care and in clinical trial samples but require prospective validation.
ER -