S-adenosyl methionine (SAMe) for depression in adults.
The only place SAMe showed a benefit was added on top of an antidepressant, in one 73-person study — given that, is it worth adding to what I'm taking, and what would you watch for?
Top of the evidence hierarchy, independently funded. how we score evidence
SAMe is sold in the US as a dietary supplement under DSHEA. The FDA has not approved it for depression, osteoarthritis, liver disease, or any other condition, and no premarket review of its safety or effectiveness applies.
Eight trials involving 934 adults with major depression produced no strong evidence that SAMe beats placebo as a standalone treatment (SMD -0.54, 95% CI -1.54 to 0.46, P=0.29; 142 participants, 2 studies; very low quality evidence) and no evidence it differs from imipramine (SMD -0.04, 95% CI -0.34 to 0.27; 619 participants) or from escitalopram (mean difference 0.12 points, 95% CI -2.75 to 2.99; 129 participants). The one positive signal was SAMe added on top of an SSRI, where a single 73-person study showed a 3.9-point advantage (95% CI 0.87 to 6.93) — low quality evidence from one trial. Two cases of mania or hypomania were recorded among 441 SAMe recipients.
Worth asking
The only place SAMe showed a benefit was added on top of an antidepressant, in one 73-person study — given that, is it worth adding to what I'm taking, and what would you watch for?
Source
S-adenosyl methionine (SAMe) for depression in adults. — Galizia I, Oldani L, Macritchie K, Amari E, Dougall D, Jones TN, Lam RW, Massei GJ, Yatham LN, Young AH. (2016)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1002/14651858.CD011286.pub2
DOI: 10.1002/14651858.CD011286.pub2
How this was scored
- Study design
- Systematic review of randomised trials
- Funding
- Independently funded
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 934
- Preregistered
- Yes
- Conflicts disclosed
- Yes
- Independent of proponent
- Yes
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published August 19, 2026.
Where we put this study in context
Questions
How strong is the evidence behind this?
Resolv rates this source "gold standard". Top of the evidence hierarchy, independently funded. It scores 95 out of 100 on our published rubric. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
S-adenosyl methionine (SAMe) for depression in adults. — Galizia I, Oldani L, Macritchie K, Amari E, Dougall D, Jones TN, Lam RW, Massei GJ, Yatham LN, Young AH. (2016). Published in: Top-tier peer-reviewed journal. DOI: 10.1002/14651858.CD011286.pub2. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Systematic review of randomised trials. Funding: Independently funded. The researchers were independent of whoever benefits from the result. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is same, s-adenosyl methionine, s-adenosyl-l-methionine, sam-e, ademetionine FDA approved for this use?
No. Its current status is: Not FDA-evaluated for this use. SAMe is sold in the US as a dietary supplement under DSHEA. The FDA has not approved it for depression, osteoarthritis, liver disease, or any other condition, and no premarket review of its safety or effectiveness applies.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.