Trial reportSchizophrenia bulletin2021
Simvastatin Augmentation for Patients With Early-Phase Schizophrenia-Spectrum Disorders: A Double-Blind, Randomized Placebo-Controlled Trial.
Trial report in Schizophrenia bulletin, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Systematic Review and Meta-Analysis of Randomized Clinical Trials of Anti-Inflammatory Agents in Early-Stage Psychotic Disorders.Schizophrenia bulletin · 2026Pooled it
- Beneficial adjunctive effects of the 5HT3 receptor antagonist ondansetron on symptoms, function and cognition in early phase schizophrenia in a double-blind, 2 × 2 factorial design, randomised controlled comparison with simvastatin.Journal of psychopharmacology (Oxford, England) · 2024Trial
- Natural products as HMG-CoA reductase inhibitors (statins) for the management of non-communicable diseases.Inflammopharmacology · 2026Review
- Neuroinflammation and insulin resistance in major depression and bipolar disorder: Implications for clinical trials evaluating immunometabolic targeted therapies.Brain, behavior, & immunity - health · 2026Review
- Functional implications of polygenic risk for schizophrenia in human neurons.Nature communications · 2026Article
- Do the pharmacokinetics of statins explain psychiatric symptom improvement from adjunctive statin prescribing in severe mental illness? Three target trial emulation studies.BMJ mental health · 2025Article
- HMG-CoA reductase inhibitors (statins) versus placebo for people with schizophrenia.The Cochrane database of systematic reviews · 2025Article
- Addressing the Evidence to Practice Gap: What to Expect From International Antipsychotic Dose Reduction Studies in the Tapering Anti-Psychotics and Evaluating Recovery Consortium.Schizophrenia bulletin · 2024Article
- Lack of Efficacy of Simvastatin Adjunctive Therapy for Patients with Schizophrenia: A Meta-Analysis of Randomized Controlled Trials.Neuropsychiatric disease and treatment · 2024Article
- Statins-From Fungi to Pharmacy.International journal of molecular sciences · 2023Review
- The association of childhood trauma with depressive and negative symptoms in recent onset psychosis: a sex-specific analysis.Psychological medicine · 2023Article
- Study protocol for a randomized controlled trial with rituximab for psychotic disorder in adults (RCT-Rits).BMC psychiatry · 2023Article
- Is It Time for a Paradigm Shift in the Treatment of Schizophrenia? The Use of Inflammation-Reducing and Neuroprotective Drugs-A Review.Brain sciences · 2023Review
- Augmentation Therapies as Treatments for Coexisting Somatic Problems in Schizophrenia-A Systematic Review.Journal of clinical medicine · 2023Review
- Review
- Anti-inflammatory medications for the treatment of mental disorders: A scoping review.Brain, behavior, & immunity - health · 2022Article
- Inflammatory monocyte gene signature predicts beneficial within group effect of simvastatin in patients with schizophrenia spectrum disorders in a secondary analysis of a randomized controlled trial.Brain, behavior, & immunity - health · 2022Article
- Diagnostic model development for schizophrenia based on peripheral blood mononuclear cell subtype-specific expression of metabolic markers.Translational psychiatry · 2022Article
- Transcriptional Regulation ofBiomolecules · 2021Article
- Brain Lipids and Lipid Droplet Dysregulation in Alzheimer's Disease and Neuropsychiatric Disorders.Complex psychiatryReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Schizophrenia-spectrum disorders (SSD) are associated with increased inflammatory markers, both in brain and periphery. Augmentation with drugs that lower this pro-inflammatory status may improve clinical presentation. Simvastatin crosses the blood-brain barrier, has anti- inflammatory and neuroprotective effects and reduces metabolic syndrome. In this study, we investigated if 12 months of simvastatin augmentation can improve symptoms and cognition in patients with early SSD. This double-blind placebo-controlled trial included 127 SSD patients across the Netherlands, <3 years after their diagnosis. From these, 119 were randomly assigned 1:1 to simvastatin 40 mg (n = 61) or placebo (n = 58), stratified for sex and study site. Primary outcomes were symptom severity and cognition after 12 months of treatment. Depression, symptom subscores, general functioning, metabolic syndrome, movement disorders, and safety were secondary outcomes. Intention to treat analyses were performed using linear mixed models and ANCOVA. No main effect of simvastatin treatment was found on total symptom severity after 12 months of treatment as compared to placebo (X2(1) = 0.01, P = .90). Group differences varied over time (treatment*time X2(4) = 11.2; P = .025), with significantly lower symptom severity in the simvastatin group after 6 months (mean difference = -4.8; P = .021; 95% CI: -8.8 to -0.7) and at 24 months follow-up (mean difference = -4.7; P = .040; 95% CI: -9.3 to -0.2). No main treatment effect was found for cognition (F(1,0.1) = 0.37, P = .55) or secondary outcomes. SAEs occurred more frequently with placebo (19%) than with simvastatin (6.6%). This negative finding corroborates other large scale studies on aspirin, minocycline, and celecoxib that could not replicate positive findings of smaller studies, and suggests that anti-inflammatory augmentation does not improve the clinical presentation of SSD.
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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.