Research

SAMe (S-Adenosyl Methionine)

53 peer-reviewed studies curated from PubMed and Semantic Scholar.

5
Meta-analyses
3
Systematic reviews
40
RCTs
5
Other studies
Meta-analyses (9%)
Systematic reviews (6%)
RCTs (75%)
Observational (2%)

Studies

Sorted by quality and recency

2024·Progress in neuro-psychopharmacology & biological psychiatry·Nahathai Limveeraprajak, Sirapop Nakhawatchana, Apidsada Visukamol, et al

Efficacy and acceptability of S-adenosyl-L-methionine (SAMe) for depressed patients: A systematic review and meta- analysis.

Meta-analysisn = 2,183Mood

This systematic review and meta-analysis assessed the efficacy and acceptability of S-adenosyl-L-methionine (SAMe) in treating depression, including 23 trials with 2183 participants. SAMe showed significantly superior efficacy compared to placebo in reducing depressive symptoms, but no significant difference when used with or compared to antidepressants. No significant differences in dropout rates were observed.

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2024·General hospital psychiatry·Tzu-Rong Peng, Han-Yu Cheng, Ta-Wei Wu

S-Adenosylmethionine (SAMe) as an adjuvant therapy for patients with depression: An updated systematic review and meta-analysis.

Meta-analysisn = 1,522Mood -

Systematic review and meta-analysis of 14 trials with 1522 subjects examining the efficacy of SAMe as a monotherapy or in combination with antidepressants for major depressive disorder. SAMe showed no significant difference in depression symptoms compared to placebo, imipramine, or escitalopram.

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2015·PloS one·Tao Guo, Lei Chang, Yusha Xiao, et al

S-adenosyl-L-methionine for the treatment of chronic liver disease: a systematic review and meta-analysis.

Meta-analysisn = 705

Systematic review and meta-analysis of 12 RCTs involving 705 patients with chronic liver disease, examining the effects of SAMe supplementation. Results showed significant differences in total bilirubin and aspartate transaminase levels, but not in alanine transaminase levels. SAMe was found to be safe but demonstrated limited clinical value compared to other treatments like UDCA and SNMC.

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2006·The Cochrane database of systematic reviews·A Rambaldi, C Gluud

S-adenosyl-L-methionine for alcoholic liver diseases.

Meta-analysisn = 434

Meta-analysis of nine randomised clinical trials with 434 patients with alcoholic liver diseases, evaluating the effects of S-adenosyl-L-methionine (SAMe). The analysis found no significant effects of SAMe on all-cause mortality, liver-related mortality, or complications. The authors concluded that more high-quality trials are needed to determine the efficacy of SAMe for alcoholic liver diseases.

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2001·The Cochrane database of systematic reviews·A Rambaldi, C Gluud

S-adenosyl-L-methionine for alcoholic liver diseases.

Systematic reviewn = 330

Systematic review of eight placebo-controlled RCTs with 330 patients with alcoholic liver disease assessing the efficacy of SAMe. The review found no significant effects of SAMe on mortality, liver-related mortality, or liver complications. SAMe was not significantly associated with adverse events.

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2026·Alzheimer's & dementia : the journal of the Alzheimer's Association·Sarah Holper, Kevin J Barnham, Leonid Churilov, et al

A phase 2, randomized, multicenter, double-blind, placebo-controlled trial of S-adenosyl methionine in participants with mild cognitive impairment or dementia due to Alzheimer's disease.

RCTn = 63Brain Health -

Phase 2 RCT of S-adenosyl methionine (SAMe) in 63 participants with Alzheimer's disease. SAMe did not demonstrate disease-modifying efficacy on plasma phosphorylated tau levels but was safe and well tolerated.

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2023·Wiadomosci lekarskie (Warsaw, Poland : 1960)·Оleg S Chaban, Olena O Khaustova, Dmytro O Assonov, et al

SAFETY AND EFFICACY OF THE COMPLEX DEPRILIUM® IN REDUCING SUBCLINICAL SYMPTOMS OF DEPRESSION IN PATIENTS WITH CHRONIC NON-COMMUNICABLE DISEASES: DOUBLE-BLIND RANDOMIZED CONTROLLED STUDY.

RCTn = 140Mood

Double-blind RCT of 140 patients with chronic non-communicable diseases assessing the Deprilium® complex, containing SAMe, L-methylfolate, and methylcobalamin, for reducing subclinical symptoms of depression. The intervention group showed significant improvement in depression scores compared to placebo after 60 days.

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2022·Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie·Hammad Ullah, Alessandro Di Minno, Cristina Esposito, et al

Efficacy of a food supplement based on S-adenosyl methionine and probiotic strains in subjects with subthreshold depression and mild-to-moderate depression: A monocentric, randomized, cross-over, double-blind, placebo-controlled clinical trial.

RCTn = 80Mood

A monocentric, randomized, double-blind, placebo-controlled, cross-over clinical trial with 80 subjects evaluated the efficacy of a food supplement containing S-adenosyl methionine and probiotics in reducing symptoms of subthreshold and mild-to-moderate depression. The supplement significantly decreased PHQ-9 and HAM-D scores, indicating improved mood compared to placebo.

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2021·Journal of the College of Physicians and Surgeons--Pakistan : JCPSP·Lingmei Zeng, Mao Li, Yuting Cen, et al

Effects of S-adenosyl-L-Methionine Combined with Ursodesoxycholic Acid on Serum Endotoxin, MMP-9 and IL-18 in Neonates with Cholestasis.

RCTn = 102

RCT comparing the effects of ursodesoxycholic acid (UDCA) alone versus S-adenosyl-L-methionine (SAMe) plus UDCA in neonates with cholestasis. The SAMe plus UDCA group showed a higher total effective treatment rate and lower levels of serum endotoxin, MMP-9, and IL-18 compared to the UDCA alone group.

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2020·The primary care companion for CNS disorders·Alberto Saccarello, Paolo Montarsolo, Ivano Massardo, et al

Oral Administration of S-Adenosylmethionine (SAMe) and Lactobacillus Plantarum HEAL9 Improves the Mild-To-Moderate Symptoms of Depression: A Randomized, Double-Blind, Placebo-Controlled Study.

RCTn = 90Mood Mental Clarity

This 6-week randomized, double-blind, placebo-controlled study assessed the effects of SAMe and Lactobacillus plantarum HEAL9 on mild-to-moderate depression. The combination significantly improved depression, anxiety, and cognitive symptoms compared to placebo, with no treatment-related adverse events.

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2019·European child & adolescent psychiatry·Mariela Mosheva, Liran Korotkin, Raquel E Gur, et al

Effectiveness and side effects of psychopharmacotherapy in individuals with 22q11.2 deletion syndrome with comorbid psychiatric disorders: a systematic review.

Systematic reviewn = 182

Systematic review of pharmacological treatments for psychiatric disorders in individuals with 22q11.2 deletion syndrome. The review included studies on antipsychotics, stimulants, SSRIs, S-adenosyl-L-methionine (SAMe), and metyrosine, highlighting the need for syndrome-specific pharmacological agents.

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2017·The Journal of clinical psychiatry·Anup Sharma, Patricia Gerbarg, Teodoro Bottiglieri, et al

S-Adenosylmethionine (SAMe) for Neuropsychiatric Disorders: A Clinician-Oriented Review of Research.

Systematic reviewMood Brain Health

Systematic review of S-adenosylmethionine (SAMe) for neuropsychiatric conditions, including major depressive disorder. The review found promising but limited evidence for SAMe's efficacy and safety as a monotherapy and augmentation for antidepressants, with potential benefits for neurocognitive, substance use, and psychotic disorders.

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2013·Journal of psychopharmacology (Oxford, England)·Pauline Turner, Rakesh Kantaria, Allan H Young

A systematic review and meta-analysis of the evidence base for add-on treatment for patients with major depressive disorder who have not responded to antidepressant treatment: a European perspective.

Meta-analysisMood

This meta-analysis reviewed the efficacy of EU-licensed add-on therapies for patients with major depressive disorder (MDD) who did not respond to antidepressants. It included seven RCTs and found that SAMe and quetiapine XR had a significantly greater likelihood of response compared to placebo. Most interventions showed similar efficacy.

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2002·The American journal of clinical nutrition·Roberto Delle Chiaie, Paolo Pancheri, Pierluigi Scapicchio

Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies.

RCTn = 576Mood

Two multicenter RCTs compared the efficacy and tolerability of SAMe (1600 mg orally and 400 mg intramuscularly) to imipramine in patients with major depression. SAMe showed comparable antidepressant efficacy to imipramine but was significantly better tolerated.

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2019·Journal of affective disorders·J. Sarris, G. Byrne, C. Stough, et al

Nutraceuticals for major depressive disorder- more is not merrier: An 8-week double-blind, randomised, controlled trial.

RCTn = 158Mood

An 8-week, double-blind RCT involving 158 outpatients with MDD compared a nutraceutical combination (S-adenosyl methionine, folinic acid, omega-3 fatty acids, 5-HTP, zinc picolinate) to placebo. The placebo was superior in reducing MADRS scores, with no significant differences in secondary outcomes. High placebo response rates were noted.

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2019·Journal of affective disorders·Hitoshi Sakurai, Linda L Carpenter, Audrey R Tyrka, et al

Dose increase of S-Adenosyl-Methionine and escitalopram in a randomized clinical trial for major depressive disorder.

RCTn = 65Mood

RCT involving 65 patients with major depressive disorder who did not respond to initial doses of SAMe, escitalopram, or placebo. The study examined the effects of doubling the doses for an additional 6 weeks. Depression severity scores decreased significantly across all treatment arms, but no significant differences were found between the groups. Higher doses of SAMe were associated with increased abdominal discomfort.

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2019·Journal of psychiatric research·Steven D Targum, Beth R Cameron, Ludvina Ferreira, et al

Early score fluctuation and placebo response in a study of major depressive disorder.

RCTMood

Phase II double-blind, placebo-controlled trial of adjunctive s-adenosyl methionine (MSI-195) in MDD subjects with inadequate response to antidepressants. The study failed to meet specified endpoints, but post-hoc analysis excluding subjects with early score fluctuations showed statistical significance for MSI-195 over placebo in the MADRS sub-group.

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2015·Pharmacopsychiatry·J Sarris, L H Price, L L Carpenter, et al

Is S-Adenosyl Methionine (SAMe) for Depression Only Effective in Males? A Re-Analysis of Data from a Randomized Clinical Trial.

RCTn = 189Mood

Post-hoc analysis of a 12-week double-blind RCT with 189 adults assessing the efficacy of SAMe vs. placebo and escitalopram for major depressive disorder. SAMe was found to be superior to placebo among males but not females, suggesting gender differences in antidepressant efficacy.

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2014·The Journal of clinical psychiatry·David Mischoulon, Lawrence H Price, Linda L Carpenter, et al

A double-blind, randomized, placebo-controlled clinical trial of S-adenosyl-L-methionine (SAMe) versus escitalopram in major depressive disorder.

RCTn = 189Mood -

A double-blind, randomized, placebo-controlled clinical trial comparing S-adenosyl-L-methionine (SAMe) and escitalopram in 189 outpatients with major depressive disorder. Both SAMe and escitalopram showed significant improvement in depression scores, but no significant differences were found between the treatment arms or compared to placebo. Tolerability was good, with gastrointestinal side effects being the most common in the SAMe arm.

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2014·Journal of affective disorders·Jerome Sarris, George I Papakostas, Ottavio Vitolo, et al

S-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression RCT: efficacy and effects of histamine and carnitine as moderators of response.

RCTn = 144Mood

RCT comparing the antidepressant efficacy of S-adenosyl methionine (SAMe) to escitalopram and placebo in adults with Major Depressive Disorder. SAMe showed significant improvement in depression scores compared to placebo and escitalopram, with higher response and remission rates. Serum histamine and carnitine levels did not moderate treatment response.

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2013·Hepato-gastroenterology·Zhao-Ran Su, Zhong-Lu Cui, Jin-Liang Ma, et al

Beneficial effects of S-adenosyl-L-methionine on post-hepatectomy residual liver function: a prospective, randomized, controlled clinical trial.

RCTn = 79

Prospective RCT of 79 hepatitis-related chronic patients undergoing hepatectomy, comparing postoperative intravenous SAMe treatment to control. SAMe group showed reduced frequency of postoperative liver insufficiency and lower serum total bilirubin levels, indicating benefits to residual liver function.

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2012·Journal of alternative and complementary medicine (New York, N.Y.)·Amit Sood, Kavita Prasad, Ivana T Croghan, et al

S-adenosyl-L-methionine (SAMe) for smoking abstinence: a randomized clinical trial.

RCTn = 120

A randomized, blinded, placebo-controlled, three-arm, dose-ranging clinical trial investigated the efficacy of SAMe for increasing tobacco abstinence among cigarette smokers. The study found no significant differences in abstinence rates between SAMe dose groups and placebo, and SAMe did not attenuate withdrawal symptoms. Higher rates of gastrointestinal side-effects were observed with SAMe 1600 mg/d compared to placebo.

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2011·European psychiatry : the journal of the Association of European Psychiatrists·C M Dording, D Mischoulon, I Shyu, et al

SAMe and sexual functioning.

RCTSexual Health

RCT examining adjunctive S-adenosyl-l-methionine (SAMe) for sexual functioning in SSRI/SNRI nonresponders. Men treated with SAMe showed significantly lower arousal and erectile dysfunction compared to placebo, independent of depressive symptom improvement.

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2002·The international journal of neuropsychopharmacology·Paolo Pancheri, Pierluigi Scapicchio, Roberto Delle Chiaie

A double-blind, randomized parallel-group, efficacy and safety study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAMe) versus imipramine in patients with major depressive disorder.

RCTn = 146Mood

This multicentre, double-blind RCT compared the efficacy and safety of intramuscular SAMe (400 mg/d) to oral Imipramine (150 mg/d) in patients with major depressive disorder. SAMe was found to be comparable to Imipramine in terms of antidepressive efficacy but was significantly better tolerated.

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2002·Methods and findings in experimental and clinical pharmacology·P Anderer, B Saletu, H V Semlitsch, et al

Structural and energetic processes related to P300: LORETA findings in depression and effects of antidepressant drugs.

RCT

The study used electrophysiological neuroimaging to assess cognitive components of ERPs in depressed patients and healthy subjects. It found that 2 mg of citalopram and 800 mg of SAMe increased P300 source strength in specific brain regions, indicating changes in energetic sources related to depression and antidepressant action.

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2015·Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer·Kunal C Kadakia, Charles L Loprinzi, Pamela J Atherton, et al

Phase II evaluation of S-adenosyl-L-methionine (SAMe) for the treatment of hot flashes.

RCTn = 43Womens Health -

Phase II single-arm trial evaluating the efficacy of S-adenosyl-L-methionine (SAMe) for treating hot flashes in 43 women. The decrease in hot flash score and frequency was not statistically significant compared to historical placebo response. Treatment was well tolerated with mild gastrointestinal toxicity.

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2013·TheScientificWorldJournal·Domenico De Berardis, Stefano Marini, Nicola Serroni, et al

S-Adenosyl-L-Methionine augmentation in patients with stage II treatment-resistant major depressive disorder: an open label, fixed dose, single-blind study.

RCTn = 33Mood

Open-label, fixed-dose, single-blind study of S-Adenosyl-L-Methionine (SAMe) augmentation in 33 patients with treatment-resistant major depressive disorder. Significant decrease in HAM-D score observed, with 60% response rate and 36% remission rate after 8 weeks. SAMe was effective and well tolerated, though further placebo-controlled trials are needed.

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2012·Journal of neural transmission (Vienna, Austria : 1996)·Tamar Green, Lital Steingart, Amos Frisch, et al

The feasibility and safety of S-adenosyl-L-methionine (SAMe) for the treatment of neuropsychiatric symptoms in 22q11.2 deletion syndrome: a double-blind placebo-controlled trial.

RCTn = 12Mood -Focus -Mental Clarity -

This double-blind placebo-controlled trial assessed the feasibility and safety of S-adenosyl-L-methionine (SAMe) for treating depressive disorder, ADHD, and cognitive deficits in individuals with 22q11.2 deletion syndrome. SAMe treatment up to 1,600 mg/day for 6 weeks was found to be safe and well tolerated, with no significant benefit in depressive or ADHD symptoms detected compared to placebo.

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2011·Journal of affective disorders·Yechiel Levkovitz, Jonathan E Alpert, Carrie E Brintz, et al

Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder.

RCTn = 46Mental Clarity

Secondary analysis of a clinical trial involving 46 SRI non-responders with MDD in a 6-week, double-blind, randomized trial of adjunctive oral SAMe. SAMe showed greater improvement in memory-related cognitive symptoms compared to placebo.

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2011·Veterinary surgery : VS·Darren J Imhoff, Wanda J Gordon-Evans, Richard B Evans, et al

Evaluation of S-adenosyl l-methionine in a double-blinded, randomized, placebo-controlled, clinical trial for treatment of presumptive osteoarthritis in the dog.

RCTn = 33Joint Bone Health -

Double-blinded, placebo-controlled clinical trial evaluating the efficacy of S-adenosyl l-methionine (SAMe) in 33 dogs with osteoarthritis. No significant difference was found between the SAMe and placebo groups in reducing clinical signs of osteoarthritis over 6 weeks.

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2010·PloS one·Magdalena Filipowicz, Christine Bernsmeier, Luigi Terracciano, et al

S-adenosyl-methionine and betaine improve early virological response in chronic hepatitis C patients with previous nonresponse.

RCTn = 29

Open-label pilot study of 29 chronic hepatitis C patients who failed previous therapy, treated with SAMe, betaine, pegIFNα2b, and ribavirin. 59% showed an early virological response, and 10% achieved a sustained virological response. SAMe and betaine were safe when used with pegIFNα/ribavirin.

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2010·Gastroenterology·Jordan J Feld, Apurva A Modi, Ramy El-Diwany, et al

S-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonresponders.

RCTn = 24

RCT assessing the effect of S-adenosyl methionine (SAMe) on early antiviral response and interferon signaling in hepatitis C nonresponders. SAMe improved the second phase slope of viral decline and increased induction of interferon-stimulated genes, suggesting it may enhance peginterferon-based therapies.

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2008·European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology·Rael D Strous, Michael S Ritsner, Shmuel Adler, et al

Improvement of aggressive behavior and quality of life impairment following S-adenosyl-methionine (SAM-e) augmentation in schizophrenia.

RCTn = 18Mood Mental Clarity

RCT of 18 patients with chronic schizophrenia receiving SAM-e (800 mg) or placebo for 8 weeks. SAM-e administration resulted in some reduction in aggressive behavior and improved quality of life, with female patients showing improvement in depressive symptoms. Two patients experienced increased irritability.

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2005·European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology·O Arnold, B Saletu, P Anderer, et al

Double-blind, placebo-controlled pharmacodynamic studies with a nutraceutical and a pharmaceutical dose of ademetionine (SAMe) in elderly subjects, utilizing EEG mapping and psychometry.

RCTn = 12

Double-blind, placebo-controlled crossover study investigating the effects of S-adenosyl-l-methionine (SAMe) on brain function in 12 elderly volunteers using EEG mapping and psychometry. Both nutraceutical (400 mg) and pharmaceutical (1600 mg) doses of SAMe showed significant central effects compared to placebo, with EEG changes typical of activating antidepressants. Psychometric tests showed no significant differences between SAMe and placebo, indicating good tolerability.

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2002·The American journal of clinical nutrition·Bernd Saletu, Peter Anderer, Carlo Di Padova, et al

Electrophysiological neuroimaging of the central effects of S-adenosyl-L-methionine by mapping of electroencephalograms and event-related potentials and low-resolution brain electromagnetic tomography.

RCTn = 20Mood Brain Health

Double-blind, placebo-controlled, crossover study in 20 healthy volunteers investigating the central effects of S-adenosyl-L-methionine (SAMe) using EEG and ERP mapping. SAMe showed significant acute and subacute encephalotropic effects, with changes typical of antidepressants and cognition enhancers.

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2002·Journal of neural transmission (Vienna, Austria : 1996)·B Saletu, P Anderer, L Linzmayer, et al

Pharmacodynamic studies on the central mode of action of S-adenosyl-L-methionine (SAMe) infusions in elderly subjects, utilizing EEG mapping and psychometry.

RCTn = 10Brain Health

Double-blind, placebo-controlled cross-over study on the effects of S-adenosyl-L-methionine (SAMe) infusions on brain function and behavior in 10 elderly volunteers. EEG mapping showed significant central effects of SAMe, with changes typical of antidepressants and nootropic effects after one week. Psychometric tests showed no significant differences between SAMe and placebo, indicating good tolerability.

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2002·The international journal of neuropsychopharmacology·Gerda M Saletu-Zyhlarz, Peter Anderer, Leopold Linzmayer, et al

Visualizing central effects of S-adenosyl-L-methionine (SAMe), a natural molecule with antidepressant properties, by pharmaco-EEG mapping.

RCTn = 10Mood

Double-blind, placebo-controlled, cross-over study investigating the central effects of S-adenosyl-L-methionine (SAMe) using EEG mapping and psychometry in 10 healthy volunteers. Significant encephalotropic effects were observed, with changes in EEG power spectra typical of classical antidepressants, suggesting both inhibitory and excitatory effects at the neurophysiological level.

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1993·Psychotherapy and psychosomatics·P Salmaggi, G M Bressa, G Nicchia, et al

Double-blind, placebo-controlled study of S-adenosyl-L-methionine in depressed postmenopausal women.

RCTn = 80Mood

Double-blind, placebo-controlled randomized trial assessing the efficacy of oral SAMe in treating depression in 80 postmenopausal women. The SAMe group showed significantly greater improvement in depressive symptoms compared to placebo from day 10 of the study.

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1986·Psychiatry research·M A Sherer, G L Cantoni, R N Golden, et al

Effects of S-adenosyl-methionine on plasma norepinephrine, blood pressure, and heart rate in healthy volunteers.

RCTHeart Health

RCT studying the effects of S-adenosyl-methionine (SAMe) on plasma norepinephrine, heart rate, and blood pressure in healthy volunteers. Chronic SAMe administration reduced standing heart rate and plasma norepinephrine, similar to effects seen with monoamine oxidase inhibitors, but without changes in plasma MHPG.

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1986·Clinical neuropharmacology·M W Carney, J Edeh, T Bottiglieri, et al

Affective illness and S-adenosyl methionine: a preliminary report.

RCTMood

Preliminary report suggests S-adenosyl methionine (SAM) may have an antidepressant action beyond placebo, particularly in endogenous depression. SAM affects folate, dopamine, and serotonin metabolism, indicating potential for further study.

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1975·Minerva medica·E Polli, M Cortellaro, L Parrini, et al

[Pharmacological and clinical aspects of S-adenosylmethionine (SAMe) in primary degenerative arthropathy (osteoarthrosis)].

RCTn = 90Inflammation Joint Bone Health

An open trial on 90 patients with severe degenerative arthropathies showed that 30 mg SAMe intravenously twice a day for 14 days had a marked anti-inflammatory effect with no side-effects. In a double-crossover investigation, SAMe was compared to indomethacin in 15 arthropathic patients, showing similar therapeutic responses but without the side-effects of indomethacin. In 9 patients with rheumatoid arthritis, SAMe was less effective, though some clinical parameters improved.

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1997·Scandinavian journal of rheumatology·H Volkmann, J Nørregaard, S Jacobsen, et al

Double-blind, placebo-controlled cross-over study of intravenous S-adenosyl-L-methionine in patients with fibromyalgia.

RCTn = 34

Double-blind, placebo-controlled cross-over study testing the efficacy of intravenously administered S-adenosyl-L-methionine (SAMe) in 34 patients with fibromyalgia. No significant difference was found in tender point change between treatment groups, with only a tendency towards significance in subjective pain perception and overall well-being.

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1994·Alcohol and alcoholism (Oxford, Oxfordshire)·C Loguercio, G Nardi, F Argenzio, et al

Effect of S-adenosyl-L-methionine administration on red blood cell cysteine and glutathione levels in alcoholic patients with and without liver disease.

RCTn = 40

RCT measuring glutathione and cysteine concentrations in erythrocytes of chronic alcohol misusers with and without liver cirrhosis. Parenteral treatment with S-adenosylmethionine corrected erythrocyte thiol alterations, affecting the metabolism of SH compounds in alcoholic patients.

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1992·Psychiatry research·C Berlanga, H A Ortega-Soto, M Ontiveros, et al

Efficacy of S-adenosyl-L-methionine in speeding the onset of action of imipramine.

RCTn = 40Mood

Double-blind clinical trial evaluating the efficacy of S-adenosyl-L-methionine (SAMe) in speeding the onset of action of imipramine in 40 outpatients with moderate to severe depression. Patients receiving the SAMe-IMI combination showed earlier decreases in depressive symptoms compared to those receiving the placebo-IMI combination.

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1992·Acta psychiatrica Scandinavica·M Fava, J F Rosenbaum, R Birnbaum, et al

The thyrotropin response to thyrotropin-releasing hormone as a predictor of response to treatment in depressed outpatients.

RCTn = 32Mood -

Double-blind placebo-controlled trial of s-adenosyl-l-methionine (SAMe) in 32 depressed outpatients. The study found no significant difference between SAMe and placebo in terms of treatment response, as measured by changes in Hamilton Rating Scale for Depression scores.

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1989·The British journal of psychiatry : the journal of mental science·M W Carney, T K Chary, T Bottiglieri, et al

The switch mechanism and the bipolar/unipolar dichotomy.

RCTn = 29Mood

Open trials and a placebo-controlled trial of intravenous and oral S-adenosyl methionine (SAM) in 29 patients showed that nine of 11 bipolar patients switched into elevated mood states, while six endogenous unipolar patients improved. No non-endogenous or placebo patients responded for more than 14 days. Biochemical data suggested further exploration of the dopaminergic system.

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1988·Scandinavian journal of clinical and laboratory investigation·S Gentile, M Persico, C Orlando, et al

Effect of different doses of S-adenosyl-L-methionine (SAMe) on nicotinic acid-induced hyperbilirubinaemia in Gilbert's syndrome.

RCTn = 10

RCT evaluating the effects of two dosages of S-adenosyl-L-methionine (SAMe) on nicotinic acid-induced hyperbilirubinaemia in 10 male inpatients with Gilbert's syndrome. The study found that 800 mg/day SAMe significantly reduced unconjugated bilirubin levels and plasma nicotinic acid half-life compared to placebo, while 200 mg/day did not have a significant effect.

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1984·Hepatology (Baltimore, Md.)·M Frezza, G Pozzato, L Chiesa, et al

Reversal of intrahepatic cholestasis of pregnancy in women after high dose S-adenosyl-L-methionine administration.

RCTn = 18Womens Health

Randomized, single-blind clinical trial investigating the effect of S-adenosyl-L-methionine (SAMe) on intrahepatic cholestasis of pregnancy (ICP) in 18 women. The study found that 800 mg per day of SAMe significantly reduced serum transaminases, conjugated bilirubin, total bile acids, and pruritus, indicating a trend toward remission of ICP.

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2014·Journal of pain & palliative care pharmacotherapy·Ba X Hoang, Hung Q Tran, Ut V Vu, et al

Palliative treatment for advanced biliary adenocarcinomas with combination dimethyl sulfoxide-sodium bicarbonate infusion and S-adenosyl-L-methionine.

Studyn = 9

Pilot open-label study investigating the efficacy and safety of a combination of dimethyl sulfoxide-sodium bicarbonate infusion and S-adenosyl-L-methionine oral supplementation in nine patients with advanced nonresectable biliary tract carcinomas. The treatment improved pain control, blood biochemical parameters, and quality of life, with a 6-month progression-free survival for all patients.

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2004·Journal of clinical psychopharmacology·Jonathan E Alpert, George Papakostas, David Mischoulon, et al

S-adenosyl-L-methionine (SAMe) as an adjunct for resistant major depressive disorder: an open trial following partial or nonresponse to selective serotonin reuptake inhibitors or venlafaxine.

Studyn = 30Mood

Open trial evaluating the safety, tolerability, and efficacy of S-adenosyl-L-methionine as an adjunct for major depressive disorder in 30 antidepressant-treated adult outpatients. The trial showed a 50% response rate and a 43% remission rate, with gastrointestinal symptoms and headaches as common side effects.

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2000·Movement disorders : official journal of the Movement Disorder Society·A Di Rocco, J D Rogers, R Brown, et al

S-Adenosyl-Methionine improves depression in patients with Parkinson's disease in an open-label clinical trial.

Studyn = 13Mood

Pilot study of S-adenosyl-methionine (SAM) in 13 depressed patients with Parkinson's disease. SAM was administered for 10 weeks, resulting in at least a 50% improvement in depression scores for 10 out of 11 patients who completed the study. The study suggests SAM may be a safe and effective alternative to traditional antidepressants.

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1995·Psychiatry research·M Fava, A Giannelli, V Rapisarda, et al

Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-L-methionine.

Observationaln = 195Mood

Open, multicenter study of 195 patients receiving 400 mg of SAMe parenterally for 15 days. Depressive symptoms remitted after both 7 and 15 days of treatment, with no serious adverse events reported. Suggests SAMe may be a safe and fast-acting antidepressant.

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1989·Drugs·H A Friedel, K L Goa, P Benfield

S-adenosyl-L-methionine. A review of its pharmacological properties and therapeutic potential in liver dysfunction and affective disorders in relation to its physiological role in cell metabolism.

ReviewMood

Review of S-Adenosyl-L-methionine (SAMe) highlighting its pharmacological properties and therapeutic potential in liver dysfunction and affective disorders. SAMe has been shown to restore normal hepatic function in chronic liver diseases and has antidepressant properties, with good tolerability compared to tricyclic antidepressants.

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