Trial reportPsychopharmacology2020
S-Adenosylmethionine (SAMe) monotherapy for depression: an 8-week double-blind, randomised, controlled trial.
Trial report in Psychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.
- Efficacy of Pharmacological Interventions in Milder Depression: A Systematic Review and Meta-Analysis.Neuropsychopharmacology reports · 2025Pooled it
- Pooled it
- Personalised Nutraceutical Treatment Guided byNutrients · 2026Article
- Targeting epigenetic remodeling of the blood-brain barrier: current knowledge for drug therapy.Epigenomics · 2026Review
- Biomarker-Guided Dietary Supplementation: A Narrative Review of Precision in Personalized Nutrition.Nutrients · 2024Review
- F. prausnitzii potentially modulates the association between citrus intake and depression.Microbiome · 2024Article
- Recent advances in the synthesis of antidepressant derivatives: pharmacologic insights for mood disorders.3 Biotech · 2024Review
- Review
- A Near-Infrared Fluorescent and Photoacoustic Probe for Visualizing Biothiols Dynamics in Tumor and Liver.Molecules (Basel, Switzerland) · 2023Article
- BDNF as a Mediator of Antidepressant Response: Recent Advances and Lifestyle Interactions.International journal of molecular sciences · 2022Review
- The Efficacy of S-Adenosyl Methionine and Probiotic Supplementation on Depression: A Synergistic Approach.Nutrients · 2022Review
- SAMe, Choline, and Valproic Acid as Possible Epigenetic Drugs: Their Effects in Pregnancy with a Special Emphasis on Animal Studies.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Exploring the Role of Nutraceuticals in Major Depressive Disorder (MDD): Rationale, State of the Art and Future Prospects.Pharmaceuticals (Basel, Switzerland) · 2021Review
- New agents and perspectives in the pharmacological treatment of major depressive disorder.Progress in neuro-psychopharmacology & biological psychiatry · 2021Review
- The Role of Mitochondria in Mood Disorders: From Physiology to Pathophysiology and to Treatment.Frontiers in psychiatry · 2021Review
- Prenatal S-Adenosine Methionine (SAMe) Induces Changes in Gene Expression in the Brain of Newborn Mice That Are Prevented by Co-Administration of Valproic Acid (VPA).International journal of molecular sciences · 2020Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
rationaleDysregulation of the one carbon cycle is documented in depression. Thereby, S-adenosylmethionine (SAMe), a one-carbon cycle nutraceutical compound with a favourable side effect profile, has a theoretical rationale for efficacy. However, further controlled studies are required to confirm SAMe's efficacy.
objectivesTo test the efficacy of SAMe versus placebo in unmedicated DSM-5 diagnosed (major depressive disorder) (MDD) patients with mild-to-moderate levels of depressive symptoms.
methodsWe conducted an 8-week, double-blind, randomised controlled trial testing 800 mg/day of SAMe monotherapy versus placebo in 49 patients with MDD (Montgomery-Åsberg Depression Rating Scale [MADRS] score 14-25) who were not currently taking antidepressants. One-carbon cycle biomarkers, brain-derived neurotropic factor (BDNF), and relevant single nucleotide polymorphisms (SNPs) were analysed as potential treatment moderators.
resultsA clinically relevant differential reduction from baseline to week 8 of 3.76 points occurred on the primary outcome (MADRS) in favour of SAMe. This however was not significant (p = 0.13) on an adjusted linear mixed model, notwithstanding a medium to large effect size of 0.72. A high placebo response rate of 53% occurred (> 50% reduction on MADRS). Exploratory analyses showed that SAMe was however effective in reducing depression amongst participants with milder depression severity (MADRS ≤ 22, p = 0.045). Response was not moderated by BDNF, SNPs, or one-carbon cycle biomarkers, although increased folate concentrations were correlated with improved symptoms in the SAMe group (r = - 0.57, p = 0.026). The treatment was safe and well tolerated.
conclusionsAlthough a differential reduction in depression symptoms between groups was observed in favour of SAMe, the results of this pilot study were not statistically significant.
trial registrationANZCTR-Australian New Zealand Clinical Trials Registry; No.: ACTRN12613001299796; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364900.
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