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Does St John's wort help with depression?

Trials find St John's wort works better than placebo and about as well as standard antidepressants for mild to moderate depression, with fewer side effects.

Published October 2026

Short answer

For mild to moderate depression, St John's wort works better than placebo and about as well as standard antidepressants, with fewer side effects. The catch: it interacts with many medicines, so ask a doctor or pharmacist first. Evidence grade B (Moderate). Meta-analyses of more than 30 randomised trials (about 7,000 people) agree the herb beats placebo; downgraded one level from A for substantial heterogeneity (I² up to 89%).

Key takeaways

  • Across 35 trials with 6,993 people, those taking St John's wort were more likely to improve than those taking placebo [1].
  • In 27 trials with 3,808 patients, St John's wort matched SSRIs for depression response and remission, and fewer people stopped taking it [2].
  • Side effects were similar to placebo in trials and fewer than with antidepressants, but most trials lasted only 4 to 12 weeks [1].
  • St John's wort speeds up the breakdown of many medicines, including hormonal contraceptives and warfarin, so they may work less well [3][4].
  • Severe depression has not been studied, and there are no reliable human data for pregnancy or breastfeeding [1][5].

The short version

St John's wort is one of the few herbal supplements with a large body of trial evidence behind it. In the biggest review — 35 randomised trials with 6,993 people — standardised extracts eased mild to moderate depression better than placebo, and worked about as well as prescription antidepressants in head-to-head trials, with fewer side effects [1][2]. The catch is interactions: St John's wort changes how the body clears many medicines, so some of them do not work as well [6].

What the studies show

Pooled across 35 trials, about 1.5 times as many people responded to St John's wort as to placebo (relative risk 1.53, 95% confidence interval 1.19 to 1.97), and depression scores fell by about half a standard deviation more (0.49, 95% CI 0.23 to 0.74) [1]. The reviewers rated this evidence moderate quality, with results varying widely between trials [1].

Against prescription antidepressants the two were neck and neck: response rates were almost identical (risk ratio 1.01, 95% CI 0.90 to 1.14) and symptom scores differed by 0.03 points on a standard scale [1]. A 2017 meta-analysis of 27 trials and 3,808 patients found the same for mild to moderate depression, and fewer people stopped St John's wort for side effects (odds ratio 0.59, 95% CI 0.48 to 0.70) [2]. A 2023 meta-analysis of 14 trials in 2,270 adults concluded St John's wort worked about as well as SSRIs with fewer side effects [7]. A 2026 network meta-analysis of 163 supplement trials found the extract ZE117 lowered depression scores against placebo (a standardised mean difference of 1.02 lower, 95% CI 1.90 to 0.15 lower), though it rated the certainty low to very low [8]. A 2025 review of milder depression found two St John's wort trials against fluoxetine with no meaningful difference in response (risk ratio 0.96) [9].

The nuances

Trials mostly took in adults with mild to moderate depression and lasted 4 to 12 weeks [1]. The reviewers found no trial focused only on severe depression [1]. An earlier US trial in 200 people with more severe symptoms (Hamilton score 20 or more) found no difference from placebo on its main measure, although more people taking the herb reached remission — 14% versus 5% [10].

Products differ. Most trials used standardised extracts (about 0.3% hypericin and 1-4% hyperforin) at 900 mg a day, and the review notes preparations vary in active content, making comparisons hard [1].

Interactions are the main safety issue. St John's wort speeds up the liver enzyme CYP3A4 and the drug transporter P-glycoprotein, which lowers blood levels of many medicines taken with it [6]. In four studies of combined oral contraceptives, hormone exposure fell and bleeding between periods became more common, with one study finding signs of ovulation despite the pill [3]. It is listed among herbs that can interact with warfarin [4]. Combining it with an SSRI can increase serotonin-related side effects, and reports describe serious reactions when the two were taken together [6][1].

For pregnancy and breastfeeding there are no reliable human trials; a review of the ten animal studies often used for guidance found them too poorly reported to trust [5]. In bipolar disorder, St John's wort appears in a systematic review among reported triggers of manic episodes, mostly in case reports [11].

What this means for you

If your low mood is mild to moderate and you take no other medicines, the trial evidence is encouraging: over 4 to 12 weeks the herb did about as well as standard antidepressants, with fewer side effects [1][2]. It is licensed as a medicine for depression in several European countries [2].

Because of the interactions, speak to a doctor or pharmacist before starting it, especially if you take an antidepressant, a hormonal contraceptive, a blood thinner or medicine for a serious condition [6][3][4]. In the trials, people took St John's wort instead of other antidepressants, not alongside them, and the combination has not been well studied [1].

See St John's wort for the full evidence and safety list.

Go deeper

  • St John's Wort — St John's wort extracts ease mild to moderate depression: in pooled trials they worked better than placebo and about as well as standard antidepressants, with…

References

  1. A systematic review of St. John's wort for major depressive disorder.. Syst Rev, 2016.
  2. Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis.. J Affect Disord, 2017.
  3. Co-administration of St. John's wort and hormonal contraceptives: a systematic review.. Contraception, 2016.
  4. Warfarin and food, herbal or dietary supplement interactions: A systematic review.. Br J Clin Pharmacol, 2021.
  5. The safety of St John's wort (Hypericum perforatum) in pregnancy and lactation: A systematic review of rodent studies.. Phytother Res, 2018.
  6. An update on clinical drug interactions with the herbal antidepressant St. John's wort.. Curr Drug Metab, 2008.
  7. The efficacy and safety of St. John's wort extract in depression therapy compared to SSRIs in adults: A meta-analysis of randomized clinical trials.. Adv Clin Exp Med, 2023.
  8. Nutraceuticals and phytoceuticals for the treatment of major depressive disorder: a systematic review and network meta-analysis.. Mol Psychiatry, 2026.
  9. Efficacy of Pharmacological Interventions in Milder Depression: A Systematic Review and Meta-Analysis.. Neuropsychopharmacol Rep, 2025.
  10. Effectiveness of St John's wort in major depression: a randomized controlled trial.. JAMA, 2001.
  11. Triggers for acute mood episodes in bipolar disorder: A systematic review.. J Psychiatr Res, 2023.