St John's wort → Depression
A rise in St John's wort does not identify a change in Depression.
The Hypericum Depression Trial (Davidson 2002) found that LI-160 St John's wort did not beat placebo on eight-week Hamilton change among 340 US outpatients with major depression and a baseline score of at least 20 (-8.68 versus -9.20, P=0.59). Sertraline, the active comparator, also missed that primary.
Randomized trial · Contested · N=340
Supported by an experiment or a tightly identified design. Read the caveats.
Mechanism
Authors treat a hypericin-standardized extract as an antidepressant. The main US trial does not find a Hamilton move versus placebo. Davidson, Gadde, Fairbank and the Hypericum Depression Trial Study Group (2002) assigned 340 adults at 12 US clinics to H. perforatum LI-160 (900 to 1,500 mg), sertraline (50 to 100 mg), or placebo for eight weeks. HAM-D change: placebo -9.20, Hypericum -8.68 (P=0.59), sertraline -10.53 (P=0.18 versus placebo). Full response: 31.9, 23.9, and 24.8 percent. Sertraline beat placebo on a secondary CGI improvement item. Moreno, Teng, Almeida and Tavares (2006) assigned 72 Brazilian outpatients with mild-to-moderate depression to Hypericum 900 mg, fluoxetine 20 mg, or placebo for eight weeks. Intention-to-treat scores did not differ. In observed cases, remission was 12 percent on Hypericum, 34.6 percent on fluoxetine, and 45 percent on placebo (P=0.016).
Caveats
Researchers assigned people to an extract or a control, so this is a trial stamp. The main result missed. Extra papers do not settle the claim. HDTSG is a failed assay: sertraline also missed the Hamilton primary. That is why confidence stays contested. It is still the cleanest Hypericum-versus-placebo contrast in major depression in the files on this page. Moreno's observed-case remission puts Hypericum below placebo. That does not turn this page into a harm claim. It is a small third arm. This is a journal entry, not medical advice and not a reason to start or skip an extract.
Effect
qualitative. HDTSG 2002: HAM-D change -8.68 Hypericum vs -9.20 placebo, P=0.59, N=340. Full response 23.9% vs 31.9%. Sertraline also missed primary. Moreno 2006 ITT NS, N=72; OC remission lowest on Hypericum.
Nodes
Named confounders
Cite this page
What Causes What. “St John's wort → Depression.” https://whatcauseswhat.org/edges/e-sjw-depression (atlas updated 2026-09-02).
Papers
- Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial.
JR Davidson, KM Gadde, JA Fairbank, KRR Krishnan, RM Califf, C Binanay, CB Parker, N Pugh · 2002 · JAMA
- Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression: a randomized double-blind trial in a Brazilian sample.
RA Moreno, CT Teng, KM Almeida, H Tavares Junior · 2006 · Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)