S-Adenosylmethionine (SAMe) for Neuropsychiatric Disorders: A Clinician-Oriented Review of Research.
Given that SAMe was linked to mania in the early studies, is there anything in my history — or my family's — that would make it a bad idea for me specifically?
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: Two of the authors have direct commercial ties to SAMe: the disclosure statement records that Dr Bottiglieri chaired the advisory board of and holds stock options in Methylation Sciences Inc. and is a scientific advisor to Gnosis S.p.A., and Dr Gerbarg receives royalties from books covering SAMe. The review received no funding, and it reports the mania risk plainly, but it is not written by parties independent of the product. It also pools trials of widely varying quality, dose, and route without a meta-analysis, so "promising but limited" is a judgement rather than an effect size.
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.
A work group of the American Psychiatric Association Council on Research screened 174 records and reviewed 132 studies (115 clinical trials, 17 preclinical) of SAMe across psychiatric and medical conditions, concluding that the evidence for major depressive disorder is "promising but limited" for both monotherapy and augmentation. The review documents that mania and hypomania seen in early SAMe studies is the reason subsequent trials confined themselves to unipolar depression — the clearest statement in the literature of why bipolar disorder is a contraindication.
Worth asking
Given that SAMe was linked to mania in the early studies, is there anything in my history — or my family's — that would make it a bad idea for me specifically?
Source
S-Adenosylmethionine (SAMe) for Neuropsychiatric Disorders: A Clinician-Oriented Review of Research. — Sharma A, Gerbarg P, Bottiglieri T, Massoumi L, Carpenter LL, et al. (2017)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.4088/JCP.16r11113
DOI: 10.4088/JCP.16r11113
How this was scored
- Study design
- Systematic review of observational studies
- Funding
- No external funding
- Published in
- Reputable peer-reviewed journal
- Sample size
- not recorded
- Preregistered
- No
- Conflicts disclosed
- Yes
- Independent of proponent
- No
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published August 19, 2026.
Questions
How strong is the evidence behind this?
Resolv rates this source "moderate evidence". Reasonable evidence with real limitations. It scores 63 out of 100 on our published rubric. One caveat travels with that badge: Two of the authors have direct commercial ties to SAMe: the disclosure statement records that Dr Bottiglieri chaired the advisory board of and holds stock options in Methylation Sciences Inc. and is a scientific advisor to Gnosis S.p.A., and Dr Gerbarg receives royalties from books covering SAMe. The review received no funding, and it reports the mania risk plainly, but it is not written by parties independent of the product. It also pools trials of widely varying quality, dose, and route without a meta-analysis, so "promising but limited" is a judgement rather than an effect size. 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-Adenosylmethionine (SAMe) for Neuropsychiatric Disorders: A Clinician-Oriented Review of Research. — Sharma A, Gerbarg P, Bottiglieri T, Massoumi L, Carpenter LL, et al. (2017). Published in: Reputable peer-reviewed journal. DOI: 10.4088/JCP.16r11113. 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 observational studies. Funding: No external funding. The researchers were not 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.