Raloxifene as an Adjuvant Therapy for Patients With Schizophrenia: An Up‐To‐Date Systematic Review and Meta‐Analysis

Abstract Background and Hypothesis Raloxifene may be useful as an adjunctive treatment for schizophrenia, particularly in addressing psychotic symptoms. This meta‐analysis aimed to evaluate the effectiveness and safety of adjunctive raloxifene in improving positive, negative, and general psychopatho...

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Main Authors: Tzu‐Rong Peng, Hung‐Hong Lin, Jian‐Ying Wang, Ming‐Chia Lee, Shih‐Ming Chen
Format: Article
Language:English
Published: Wiley 2025-07-01
Series:Brain and Behavior
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Online Access:https://doi.org/10.1002/brb3.70649
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author Tzu‐Rong Peng
Hung‐Hong Lin
Jian‐Ying Wang
Ming‐Chia Lee
Shih‐Ming Chen
author_facet Tzu‐Rong Peng
Hung‐Hong Lin
Jian‐Ying Wang
Ming‐Chia Lee
Shih‐Ming Chen
author_sort Tzu‐Rong Peng
collection DOAJ
description Abstract Background and Hypothesis Raloxifene may be useful as an adjunctive treatment for schizophrenia, particularly in addressing psychotic symptoms. This meta‐analysis aimed to evaluate the effectiveness and safety of adjunctive raloxifene in improving positive, negative, and general psychopathology symptoms, as measured by the Positive and Negative Syndrome Scale (PANSS). Study Design A systematic search was performed using PubMed, Embase, and the Cochrane Library databases for articles published until May 2024. Randomized controlled trials investigating the effectiveness and safety of adjunctive raloxifene for treating schizophrenia were included. The primary outcome was psychotic symptom severity using PANSS subscales. Mean differences (MDs) and their 95% confidence intervals (CIs) were calculated using random effects models. Study Results Ten studies were included in the final analysis. Compared with the placebo group, raloxifene as an adjunctive therapy significantly improved the positive, negative, general, and total PANSS scores, MD = −1.00 (95% CI = −2.00 to −0.20; I2 = 48%; p = 0.02; τ2 = 0.87), MD = −1.35 (95% CI = −2.74 to 0.04; I2 = 71%; p = 0.06; τ2 = 3.27), MD = −3.29 (95% CI = −5.74 to −0.83; I2 = 74%; p = 0.009; τ2 = 9.59), and MD = −7.12 (95% CI = −11.89 to −2.36; I2 = 74%; p = 0.003; τ2 = 41.86), respectively. Conclusions Adjunctive raloxifene appears to be a safe and effective treatment for improving positive, general, and total symptoms in patients with schizophrenia, particularly in those with mild‐to‐moderate illness and postmenopausal women. The 60 mg daily dose over at least 12 weeks yielded the most consistent benefits. Further high‐quality trials are needed to confirm its efficacy across diverse populations and guide personalized treatment strategies.
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spelling doaj-art-e996dc39dbbe4e46ae8328962f8ebfb62025-08-20T03:09:00ZengWileyBrain and Behavior2162-32792025-07-01157n/an/a10.1002/brb3.70649Raloxifene as an Adjuvant Therapy for Patients With Schizophrenia: An Up‐To‐Date Systematic Review and Meta‐AnalysisTzu‐Rong Peng0Hung‐Hong Lin1Jian‐Ying Wang2Ming‐Chia Lee3Shih‐Ming Chen4Department of Pharmacy, Taipei Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation New Taipei City TaiwanDepartment of Pharmacy Chia‐Nan University of Pharmacy and Science Tainan TaiwanDepartment of Pharmacy New Taipei City Hospital New Taipei City TaiwanSchool of Pharmacy, College of Pharmacy Taipei Medical University Taipei TaiwanSchool of Pharmacy, College of Pharmacy Taipei Medical University Taipei TaiwanAbstract Background and Hypothesis Raloxifene may be useful as an adjunctive treatment for schizophrenia, particularly in addressing psychotic symptoms. This meta‐analysis aimed to evaluate the effectiveness and safety of adjunctive raloxifene in improving positive, negative, and general psychopathology symptoms, as measured by the Positive and Negative Syndrome Scale (PANSS). Study Design A systematic search was performed using PubMed, Embase, and the Cochrane Library databases for articles published until May 2024. Randomized controlled trials investigating the effectiveness and safety of adjunctive raloxifene for treating schizophrenia were included. The primary outcome was psychotic symptom severity using PANSS subscales. Mean differences (MDs) and their 95% confidence intervals (CIs) were calculated using random effects models. Study Results Ten studies were included in the final analysis. Compared with the placebo group, raloxifene as an adjunctive therapy significantly improved the positive, negative, general, and total PANSS scores, MD = −1.00 (95% CI = −2.00 to −0.20; I2 = 48%; p = 0.02; τ2 = 0.87), MD = −1.35 (95% CI = −2.74 to 0.04; I2 = 71%; p = 0.06; τ2 = 3.27), MD = −3.29 (95% CI = −5.74 to −0.83; I2 = 74%; p = 0.009; τ2 = 9.59), and MD = −7.12 (95% CI = −11.89 to −2.36; I2 = 74%; p = 0.003; τ2 = 41.86), respectively. Conclusions Adjunctive raloxifene appears to be a safe and effective treatment for improving positive, general, and total symptoms in patients with schizophrenia, particularly in those with mild‐to‐moderate illness and postmenopausal women. The 60 mg daily dose over at least 12 weeks yielded the most consistent benefits. Further high‐quality trials are needed to confirm its efficacy across diverse populations and guide personalized treatment strategies.https://doi.org/10.1002/brb3.70649meta‐analysispsychosisraloxifeneschizophrenia
spellingShingle Tzu‐Rong Peng
Hung‐Hong Lin
Jian‐Ying Wang
Ming‐Chia Lee
Shih‐Ming Chen
Raloxifene as an Adjuvant Therapy for Patients With Schizophrenia: An Up‐To‐Date Systematic Review and Meta‐Analysis
Brain and Behavior
meta‐analysis
psychosis
raloxifene
schizophrenia
title Raloxifene as an Adjuvant Therapy for Patients With Schizophrenia: An Up‐To‐Date Systematic Review and Meta‐Analysis
title_full Raloxifene as an Adjuvant Therapy for Patients With Schizophrenia: An Up‐To‐Date Systematic Review and Meta‐Analysis
title_fullStr Raloxifene as an Adjuvant Therapy for Patients With Schizophrenia: An Up‐To‐Date Systematic Review and Meta‐Analysis
title_full_unstemmed Raloxifene as an Adjuvant Therapy for Patients With Schizophrenia: An Up‐To‐Date Systematic Review and Meta‐Analysis
title_short Raloxifene as an Adjuvant Therapy for Patients With Schizophrenia: An Up‐To‐Date Systematic Review and Meta‐Analysis
title_sort raloxifene as an adjuvant therapy for patients with schizophrenia an up to date systematic review and meta analysis
topic meta‐analysis
psychosis
raloxifene
schizophrenia
url https://doi.org/10.1002/brb3.70649
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