Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis.
All the head-to-head studies of St. John's wort against SSRIs lasted twelve weeks or less — if I need treatment for longer than that, what do we actually know?
Well-supported by good-quality research. how we score evidence
Caveat on this rating: The abstract reports p<0.001 alongside pooled risk ratios whose 95% confidence intervals comfortably include 1.0, which is internally inconsistent; read the confidence intervals, which show equivalence rather than superiority. This meta-analysis also inherits the industry funding and country-of-origin biases present in the underlying trial literature, and it did not assess drug interactions at all.
In the United States St. John's wort is sold as a dietary supplement under DSHEA, which means it reaches the shelf without FDA review of efficacy, safety, or potency and the FDA can act only after a problem emerges. It has never been FDA-approved to treat depression or anything else. The FDA issued a Public Health Advisory on 10 February 2000 warning that St. John's wort substantially lowered blood levels of the HIV drug indinavir through CYP3A4 induction and that the same mechanism would affect many other medicines. In Germany and several other European countries, by contrast, standardised hypericum extracts are licensed medicines that doctors prescribe for depression, which is why most of the trial evidence comes from German-speaking countries. Because US products are supplements rather than drugs, hypericin and hyperforin content varies widely between brands and batches — and hyperforin content is what drives the drug interactions, so two bottles labelled identically can behave very differently.
Pooling 27 trials that compared St. John's wort head-to-head with SSRIs in 3,808 patients, response rates were statistically indistinguishable (RR 0.983, 95% CI 0.924-1.042) as were remission rates (RR 1.013, 95% CI 0.892-1.134), and fewer people stopped St. John's wort than stopped the SSRI (OR 0.587, 95% CI 0.478-0.697). Every included trial ran only 4 to 12 weeks, and the authors state it is unclear whether St. John's wort helps people with severe depression or high suicide risk.
Worth asking
All the head-to-head studies of St. John's wort against SSRIs lasted twelve weeks or less — if I need treatment for longer than that, what do we actually know?
What to watch for
Evidence quality tells you whether to trust the finding — not whether the treatment is safe. These are the risks this research reports.
- Serotonin syndrome
- Psychosis & mania
- Interactions with other medicines
- Fertility & pregnancy risk
- Unverified product content
- Acne & skin effects
Source
Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis. — Ng QX, Venkatanarayanan N, Ho CY. (2017)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.1016/j.jad.2016.12.048
DOI: 10.1016/j.jad.2016.12.048
How this was scored
- Study design
- Meta-analysis of randomised trials
- Funding
- Funding not disclosed
- Published in
- Reputable peer-reviewed journal
- Sample size
- 3,808
- Preregistered
- No
- Conflicts disclosed
- No
- Independent of proponent
- Yes
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published August 19, 2026. Last verified September 10, 2026.
Where we put this study in context
Questions
How strong is the evidence behind this?
veisund rates this source "strong evidence". Well-supported by good-quality research. It scores 73 out of 100 on our published rubric. One caveat travels with that badge: The abstract reports p<0.001 alongside pooled risk ratios whose 95% confidence intervals comfortably include 1.0, which is internally inconsistent; read the confidence intervals, which show equivalence rather than superiority. This meta-analysis also inherits the industry funding and country-of-origin biases present in the underlying trial literature, and it did not assess drug interactions at all. 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?
Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis. — Ng QX, Venkatanarayanan N, Ho CY. (2017). Published in: Reputable peer-reviewed journal. DOI: 10.1016/j.jad.2016.12.048. 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: Meta-analysis of randomised trials. Funding: Funding not disclosed. 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 st-johns-wort, hypericum perforatum, sjw, hypericum, klamath weed, tipton's weed, li 160, ws 5570, stw3-vi, ze 117 FDA approved for this use?
No. Its current status is: Not FDA-evaluated for this use. In the United States St. John's wort is sold as a dietary supplement under DSHEA, which means it reaches the shelf without FDA review of efficacy, safety, or potency and the FDA can act only after a problem emerges. It has never been FDA-approved to treat depression or anything else. The FDA issued a Public Health Advisory on 10 February 2000 warning that St. John's wort substantially lowered blood levels of the HIV drug indinavir through CYP3A4 induction and that the same mechanism would affect many other medicines. In Germany and several other European countries, by contrast, standardised hypericum extracts are licensed medicines that doctors prescribe for depression, which is why most of the trial evidence comes from German-speaking countries. Because US products are supplements rather than drugs, hypericin and hyperforin content varies widely between brands and batches — and hyperforin content is what drives the drug interactions, so two bottles labelled identically can behave very differently.
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.