SAMe (S-adenosyl-L-methionine) and depression

What 6 graded rows on same (s-adenosyl-l-methionine) agree on for depression, and where they differ. Counted side by side, never averaged.

Consensus finder Rows from the SAMe (S-adenosyl-L-methionine) page, reviewed Oct 21, 2026 How it decides

What the rows agree on

Each block and row is one graded row from the SAMe (S-adenosyl-L-methionine) page, with its PubMed record.

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Depression6

Supplement

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SAMe (S-adenosyl-L-methionine) and depression

6 rows · 4,929 people

Split. 2 rows found an improvement, 3 found no difference and 1 had mixed results.

No difference or mixed

Improved

Each block is one evidence row, sized by how many people it enrolled, with its grade inside. Outlined: mixed results.

Grade C× 4
Grade D× 2

Rows: 6
Trials: 19; At least: a review without a trial count
People: 4,929; Pooled reviews may count some twice

Where they differ

From the rows

Trial sizeWho was studied

The best-graded row, grade C, is a meta-analysis of 2,183 people (2024) and found an improvement.

The 2 rows that found an improvement were larger: a median of 1,128 people, against a median of 189 people for the 3 rows that found no difference.

Only the 3 rows that found no difference name children or teens in their population.

1 row with mixed results is left out of this comparison.

The rows

2 improved · 3 no difference · 1 mixed

Grade CDepressive symptoms, alone or added to antidepressants · No difference
Meta-analysis, 14 studies · n 1,522 · 2024 · Adults with major depressive disorder in 14 trials
200–3,200 mg/day · 2–12 weeks
No significant difference in depression with SAMe versus placebo (alone or added to antidepressants) or versus imipramine or escitalopram.
Row on the SAMe (S-adenosyl-L-methionine) page · PubMed 38199136 (opens PubMed)
Grade CDepression versus escitalopram and placebo · No difference
RCT · n 189 · 2014 · Outpatients with major depressive disorder
1,600–3,200 mg/day · 12 weeks
All three arms improved by about 5–6 points on the Hamilton scale; neither SAMe nor escitalopram separated from placebo.
Row on the SAMe (S-adenosyl-L-methionine) page · PubMed 24500245 (opens PubMed)
Grade DDepression when added to trauma-focused therapy · No difference
RCT · n 28 · 2026 · Adults with depression and a history of childhood trauma
1,200 mg/day · 12 weeks of therapy, with 6-month follow-up
Depression improved in both groups with psychotherapy; SAMe added no clinical benefit and did not raise plasma SAMe levels.
Row on the SAMe (S-adenosyl-L-methionine) page · PubMed 42027147 (opens PubMed)
Grade CDepressive symptoms versus placebo · Improved
Meta-analysis · n 2,183 · 2024 · Adults with depression in 23 randomized trials
Varied across trials · Varied across trials
SAMe reduced depressive symptoms more than placebo (SMD −0.58, 95% CI −0.93 to −0.23) with high heterogeneity (I² 68%); as an add-on to antidepressants it did not clearly beat placebo.
Row on the SAMe (S-adenosyl-L-methionine) page · PubMed 38423354 (opens PubMed)
Grade DAdd-on to SSRIs in non-responders · Improved
RCT · n 73 · 2010 · Adults with major depressive disorder not responding to an SSRI
Target 800 mg twice daily · 6 weeks
Response (36% vs 18%) and remission (26% vs 12%) rates were higher with SAMe than placebo added to the SSRI.
Row on the SAMe (S-adenosyl-L-methionine) page · PubMed 20595412 (opens PubMed)
Grade CDepressive symptoms (Cochrane review) · Mixed
Systematic review · n 934 · 2016 · Adults with depression, inpatients and outpatients
Varied across trials · Varied across trials
No strong evidence of a difference from placebo as monotherapy (SMD −0.54, 95% CI −1.54 to 0.46; 2 trials; very low-quality evidence).
Row on the SAMe (S-adenosyl-L-methionine) page · PubMed 27727432 (opens PubMed)

Read onRead the full evidenceThe full evidence chapter on its page, with every outcome and its sources.