Antagonizing NRG1-ERBB4 signaling pathway with spironolactone for the treatment of schizophrenia: results of a randomized controlled drug repositioning clinical trial
Abstract
The (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. We 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). Despite 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. This finding suggests a potential positive effect of spironolactone on working memory in people with schizophrenia and the good…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 90 participants or records.
Read the paper
Related studies
- Improving sleep quality leads to better mental health: A meta-analysis of randomised controlled trials
- Tocilizumab in patients with severe COVID-19: a retrospective cohort study
- A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study
- Fruit, vegetable, and legume intake, and cardiovascular disease and deaths in 18 countries (PURE): a prospective cohort study
- Are noise and air pollution related to the incidence of dementia? A cohort study in London, England
- Long COVID symptoms and duration in SARS-CoV-2 positive children — a nationwide cohort study
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.