St. John's Wort

Also known as: Hypericum perforatum, SJW, Ze 117

Grade A — Strong Evidenceherbantidepressant

Recommended Dosage

300–900 mg

With meals, 3x/day. Full antidepressant effect at 4-6 weeks.

Cochrane-validated antidepressant comparable to SSRIs for mild-moderate depression. CRITICAL: interacts with many drugs via CYP induction.

😊Mood
Last reviewed: 2026-03-09

Evidence Rating: Grade A — Strong Evidence

Multiple high-quality RCTs, systematic reviews, or meta-analyses with consistent findings.

Interaction Warnings

Oral contraceptivesHigh Risk

Reduces efficacy — CONTRACEPTIVE FAILURE possible via CYP3A4 induction

WarfarinHigh Risk

Reduces efficacy — INCREASED CLOTTING RISK

HIV antiretroviralsHigh Risk

CONTRAINDICATED — subtherapeutic drug levels

Cyclosporine/tacrolimusHigh Risk

Organ rejection risk — CONTRAINDICATED

SSRIs/SNRIsHigh Risk

Serotonin syndrome risk

⚠️ Important Notes

  • ⚠️ MAJOR CYP3A4/CYP2C9/P-gp INDUCER — affects many drugs
  • Must inform ALL prescribing physicians
  • Avoid in bipolar disorder
  • Only for MILD-MODERATE depression

Clinical Evidence (3 studies)

Cochrane review: SJW for depression

Linde K et al. (2008) — Cochrane Database Syst Rev

More effective than placebo for depression, similar to SSRIs, fewer side effects

View on PubMed

SJW not effective for SEVERE depression

Shelton RC et al. (2001) — JAMA

Important negative study: not for severe depression

View on PubMed

SJW Ze 117 vs fluoxetine: non-inferiority

Kasper S et al. (2006) — Int Clin Psychopharmacol

Non-inferiority to fluoxetine confirmed

View on PubMed

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