St John's wort for major depression.
The Cochrane evidence for St. John's wort is for mild-to-moderate major depression over a few weeks — does my depression fit that, and does St. John's wort interact with anything else I'm taking?
Well-supported by good-quality research. how we score evidence
Caveat on this rating: All three review authors disclosed financial relationships with Schwabe, a hypericum manufacturer: one had received a research grant and conference speaking fees, and all three had accepted travel reimbursement. The review itself flags that country of origin and trial size both predicted the result, which the authors say "complicates the interpretation" — plain language for probable bias in the underlying literature. The review is from 2008 and has not been updated.
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 29 randomised double-blind trials in 5,489 patients with major depression, hypericum extracts beat placebo on response rate — but the size of the advantage depended on the trial: in the nine larger trials the response rate ratio was 1.28 (95% CI 1.10-1.49) versus 1.87 (95% CI 1.22-2.87) in the nine smaller ones, a classic sign that small trials inflate the effect. Against standard antidepressants it was equivalent (RR 1.00, 95% CI 0.90-1.11 versus SSRIs, 12 trials) and fewer people dropped out for side effects (OR 0.53 versus SSRIs). Trials from German-speaking countries reported systematically more favourable results.
Worth asking
The Cochrane evidence for St. John's wort is for mild-to-moderate major depression over a few weeks — does my depression fit that, and does St. John's wort interact with anything else I'm taking?
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
St John's wort for major depression. — Linde K, Berner MM, Kriston L. (2008)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1002/14651858.CD000448.pub3
DOI: 10.1002/14651858.CD000448.pub3
How this was scored
- Study design
- Meta-analysis of randomised trials
- Funding
- Funding not disclosed
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 5,489
- Preregistered
- Yes
- 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. 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 76 out of 100 on our published rubric. One caveat travels with that badge: All three review authors disclosed financial relationships with Schwabe, a hypericum manufacturer: one had received a research grant and conference speaking fees, and all three had accepted travel reimbursement. The review itself flags that country of origin and trial size both predicted the result, which the authors say "complicates the interpretation" — plain language for probable bias in the underlying literature. The review is from 2008 and has not been updated. 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?
St John's wort for major depression. — Linde K, Berner MM, Kriston L. (2008). Published in: Top-tier peer-reviewed journal. DOI: 10.1002/14651858.CD000448.pub3. 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 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 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.