SynthesisMolecular psychiatry2026
Interventions for negative symptoms in schizophrenia: efficacy and clinical interpretability in a meta-analysis of 451 randomized controlled trials.
Synthesis in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Reconsidering the Term "Treatment Resistant Schizophrenia".Schizophrenia bulletin · 2026Article
- Digital psychoeducational rehabilitation supported by serious games for psychiatric inpatients: a protocol study.Frontiers in psychology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.