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<p>Negative symptoms (avolition, anhedonia, asociality, blunted affect, and alogia) are among the most disabling features of schizophrenia spectrum disorders. In the absence of treatment consensus guidelines, this PRISMA-compliant meta-analysis (PROSPERO: CRD42024613967) evaluated efficacy and clinical significance of interventions targeting this dimension. Web of Science/PsycInfo databases were searched from inception to December 2024. Five categories (antipsychotics, other pharmacological agents, brain stimulation, psychosocial, and lifestyle interventions) were analyzed across short/middle/long follow-up times. Categories were divided into 27 subcategories (e.g., ‘other pharmacological agents’ divided in 14 subcategories including antidepressants, antibiotics, immunomodulators) regardless of follow-up, assessing evidence with GRADE criteria. The primary outcome was the change in negative symptom severity, measured with validated scales (PANSS/SANS/BPRS/CAINS/BNSS) as standardized mean differences (SMD). A clinically meaningful SMD threshold was estimated from the regression between SMD and one-point reductions on the Clinical Global Impression-Severity (CGI-S) scale. This study meta-analyzed 451 trials (n = 42566). The clinically meaningful threshold, obtained from 122 trials reporting CGI-S, was SMD ≥ 0.457. In 214 high-quality studies (n = 19746), 2 category-by-follow-up combinations and 16 subcategories showed significant improvements. Clinically meaningful SMDs for subcategories were antibiotics (0.95; CI: 0.18–1.71; moderate-GRADE), integrated psychosocial interventions (0.93; CI: 0.53–1.33; very-low-GRADE), antidepressants (0.76; CI: 0.33–1.19; moderate-GRADE), physical activity (0.68; CI: 0.39–0.96; very-low-GRADE), transcranial current stimulation (0.52; CI: 0.17–0.86; low-GRADE), and immunomodulators (0.47; CI: 0.26–0.67; high-GRADE), typically as adjuncts to antipsychotics. Heterogeneity was the main limitation. While selected interventions may yield meaningful improvements, more rigorous designs are needed to identify reliable, personalized and scalable treatment options.</p>

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Interventions for negative symptoms in schizophrenia: efficacy and clinical interpretability in a meta-analysis of 451 randomized controlled trials

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月23日

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  • Stefano Damiani,
  • Riccardo Stefanelli,
  • Lydia Fortea,
  • Aldo D’Imperio,
  • Matteo Calò,
  • Francesco Casarini,
  • Andrea Crippa,
  • Cecilia Maria Esposito,
  • Roberto Leggi,
  • Marika Orlandi,
  • Sara Patron,
  • Alessandro Peviani,
  • Alessandro Piccolo,
  • Umberto Provenzani,
  • Fabrizio Santilli,
  • Cecilia Spallarossa,
  • Evangelos Papanastasiou,
  • Matteo Cella,
  • Rashmi Patel,
  • Marco Solmi,
  • Silvana Galderisi,
  • Stefan Leucht,
  • Daniel Stahl,
  • Joaquim Radua,
  • Paolo Fusar-Poli

摘要

Negative symptoms (avolition, anhedonia, asociality, blunted affect, and alogia) are among the most disabling features of schizophrenia spectrum disorders. In the absence of treatment consensus guidelines, this PRISMA-compliant meta-analysis (PROSPERO: CRD42024613967) evaluated efficacy and clinical significance of interventions targeting this dimension. Web of Science/PsycInfo databases were searched from inception to December 2024. Five categories (antipsychotics, other pharmacological agents, brain stimulation, psychosocial, and lifestyle interventions) were analyzed across short/middle/long follow-up times. Categories were divided into 27 subcategories (e.g., ‘other pharmacological agents’ divided in 14 subcategories including antidepressants, antibiotics, immunomodulators) regardless of follow-up, assessing evidence with GRADE criteria. The primary outcome was the change in negative symptom severity, measured with validated scales (PANSS/SANS/BPRS/CAINS/BNSS) as standardized mean differences (SMD). A clinically meaningful SMD threshold was estimated from the regression between SMD and one-point reductions on the Clinical Global Impression-Severity (CGI-S) scale. This study meta-analyzed 451 trials (n = 42566). The clinically meaningful threshold, obtained from 122 trials reporting CGI-S, was SMD ≥ 0.457. In 214 high-quality studies (n = 19746), 2 category-by-follow-up combinations and 16 subcategories showed significant improvements. Clinically meaningful SMDs for subcategories were antibiotics (0.95; CI: 0.18–1.71; moderate-GRADE), integrated psychosocial interventions (0.93; CI: 0.53–1.33; very-low-GRADE), antidepressants (0.76; CI: 0.33–1.19; moderate-GRADE), physical activity (0.68; CI: 0.39–0.96; very-low-GRADE), transcranial current stimulation (0.52; CI: 0.17–0.86; low-GRADE), and immunomodulators (0.47; CI: 0.26–0.67; high-GRADE), typically as adjuncts to antipsychotics. Heterogeneity was the main limitation. While selected interventions may yield meaningful improvements, more rigorous designs are needed to identify reliable, personalized and scalable treatment options.