ArticleCommunications medicine2026
Antagonizing NRG1-ERBB4 signaling pathway with spironolactone for the treatment of schizophrenia: results of a randomized controlled drug repositioning clinical trial.
Article in Communications medicine, 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.
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Who cites it
2 citing papers in PubMed.
- Model Systems infrastructure of the German Center for Mental Health (DZPG): toward an integrated, mechanism-based framework for mental health research.European archives of psychiatry and clinical neuroscience · 2026Review
- Review
Corrections and comments
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Authors and funding
29 authors.
Funding
Abstract
backgroundThe (NRG1)-ERBB4 signaling pathway has been identified to be pathophysiologically meaningful for cognitive impairments in schizophrenia. The in the 1960s approved mineralocorticoid antagonist spironolactone has been shown to be effective to modulate (NRG1)-ERBB4 signaling in preclinical and animal models. Thus, a proof-of-concept drug repurposing trial in patients with schizophrenia was justified.
methodsWe conducted a multi-site proof-of-concept randomized controlled trial. 90 patients with schizophrenia were randomized to a three-week trial of two different spironolactone dosages (100 mg or 200 mg) or placebo. The primary endpoint was predefined as change in working memory performance after three weeks of treatment. A naturalistic follow-up was performed nine weeks after the end of intervention. The trial was registered at the WHO International Clinical Trials Registry platform ( http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2014-001968-35-DE ).
resultsDespite large numerical improvements in working memory functions, particularly in the spironolactone 200 mg group, the pre-specified analyses do not demonstrate significant superiority of either intervention over placebo. However, post-hoc sensitivity analyses suggest a significant advantage of spironolactone for the primary endpoint. Safety measures show that both interventions are well tolerated.
conclusionsThis finding suggests a potential positive effect of spironolactone on working memory in people with schizophrenia and the good safety outcomes may justify further trials with longer intervention periods or higher spironolactone dosages.
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Registered trials
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