St. John's Wort for Depression

Verdict: Works for mild-to-moderate depression only

St. John's Wort has solid evidence for mild-to-moderate depression, where it outperforms placebo and rivals standard antidepressants with fewer side effects, but it does not work for severe (major) depression and carries serious drug-interaction risks.

B 🟡 B Preliminary Evidence Published with Warning

🔬Why this grade7-layer evidence engine

The Preliminary Evidence (B) grade reflects consistent benefit confined to a narrow population. A 2008 Cochrane review of 29 trials in 5,489 patients (PMID 18843608) found St. John's Wort superior to placebo (response RR 1.28) and roughly equal to standard antidepressants, with fewer dropouts. A 2016 systematic review of 6,993 patients (PMID 27589952; RR 1.53, SMD 0.49) and a 2017 meta-analysis of 3,808 patients (PMID 28064110) reached the same conclusion for mild-to-moderate depression.

It is not graded higher because the evidence is highly heterogeneous (I-squared 79-89%) and shows a clear trial-origin effect: German-speaking-country trials report markedly better results. Crucially, the NIH-funded U.S. trial in 340 patients with moderately severe depression (PMID 11939866) found no benefit over placebo (P=0.59), and an earlier 2005 Cochrane review (PMID 15846605) called the data inconsistent. The benefit does not extend to severe depression.

Regulators and clinics are split on use, not on the mild-to-moderate signal. The WHO monograph and Mayo Clinic acknowledge efficacy for mild-to-moderate depression, but the UK NHS does not recommend it because active-ingredient content varies by brand, and the FDA warns that St. John's Wort is a potent CYP450 inducer with major interactions affecting contraceptives, anticoagulants, immunosuppressants, antiretrovirals, and SSRIs (serotonin syndrome).

⚖️

Scoring transparency

All scores computed by a 7-layer evidence engine — fully auditable

Raw score 0.66

← counter-evidence / ineffectiveeffective / strong evidence →

Final grade

B · Published with Warning

Confidence

76%

Broadly consistent

Evidence level

Cochrane high-quality SR/MA

How strongly each layer supports this effect

lower = less supportive

L1 ExamineGlobal benchmark

0.50

L5 Clinical bodiesAuthoritative stance

0.53

L11 AI re-checkIndependent read

0.65

L2 PubMedPrimary literature

0.75

L3 MechanismPlausibility

0.75

Against Mixed Supports

▸View the full decision path (audit trail)

compute_raw_score — 加權公式: L2×0.30 + L3×0.25 + L5×0.25 + L11×0.10 + L1×0.10 = 0.661
tier_from_score — 依分數區間映射至 tier letter
apply_hec_rules — 高品質 SR/MA 顯示 positive (1 篇 > 0 negative)
tier_strict_requirement_check — Tier 條件達標，未降階
detect_disputes — 偵測到 0 個 hard + 0 個 soft dispute
decide_status — 依 tier + dispute 結果決定 status

📄PubMed studies (5)L2 · primary research & systematic reviews

St John's wort for major depression

PMID: 18843608 2008 Cochrane SR n = 5,489

Finding: Across 29 trials in 5489 patients, hypericum extracts were superior to placebo (combined response RR 1.28 in larger trials, 1.87 in smaller trials) and roughly equivalent to standard antidepressants (RR near 1.0), with fewer adverse-effect dropouts than older antidepressants (OR 0.24) or SSRIs (OR 0.53); the review explicitly flags that effect sizes vary by country of origin, with German-speaking trials reporting more favourable results.

🟢 High quality Effect size: [object Object]

View on PubMed

A systematic review of St. John's wort for major depressive disorder

PMID: 27589952 2016 系統性回顧 n = 6,993

Finding: In 35 studies (6993 patients), SJW yielded more treatment responders than placebo (RR 1.53, 95% CI 1.19-1.97, I-squared 79%) and greater symptom improvement (SMD 0.49, 95% CI 0.23-0.74, I-squared 89%); versus antidepressants there was no significant efficacy difference (RR 1.01, 95% CI 0.90-1.14) with fewer adverse events (OR 0.67); evidence rated moderate quality, limited by high heterogeneity and a lack of data in severe depression.

🟢 High quality Government Effect size: [object Object]

View on PubMed

Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis

PMID: 28064110 2017 統合分析 n = 3,808

Finding: Pooling 27 trials (3808 patients), SJW was statistically comparable to SSRIs for response (RR 0.98, 95% CI 0.92-1.04), remission (RR 1.01, 95% CI 0.89-1.13) and symptom severity (SMD -0.07, 95% CI -0.13 to 0.02), with significantly fewer dropouts than SSRIs (OR 0.59, 95% CI 0.48-0.70); the authors conclude SJW has comparable efficacy and safety to SSRIs for mild-to-moderate depression only.

Effect size: [object Object]

View on PubMed

Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial

PMID: 11939866 2002 RCT (double-blind) n = 340

Finding: In this NIH-funded US multicenter trial of 340 outpatients with moderately severe major depression, Hypericum did not differ significantly from placebo on HAM-D change (P=0.59) or full response (23.9% vs 31.9%, P=0.21), and sertraline beat placebo only on a secondary CGI measure — the trial failed to support efficacy of H. perforatum in moderately severe major depression.

🟢 High quality Government Effect size: [object Object]

View on PubMed

St John's wort for depression

PMID: 15846605 2005 Cochrane SR

Finding: This earlier Cochrane review version concluded that available evidence on hypericum extracts is inconsistent and confusing: larger placebo-controlled trials restricted to patients meeting strict major-depression criteria showed only minor effects over placebo, whereas trials in milder/heterogeneous depression and trials versus standard antidepressants showed comparable efficacy — anticipating the heterogeneity later quantified in the 2008 update.

View on PubMed

🏛️Regulatory & authoritative positionsL4/L5 · FDA / EMA / NIH ODS / Cochrane / Mayo …

L4a US FDA

Cautious

St. John's Wort appears to be an inducer of an important metabolic pathway, cytochrome P450. As many prescription drugs used to treat conditions such as heart disease, depression, seizures, certain cancers or to prevent conditions such as transplant rejection or pregnancy (oral contraceptives) are metabolized via this pathway, health care providers should alert patients about these potential dr… source↗

L4b EU EFSA

Cautious

L4c UK NHS

Against

St John's wort is a herbal treatment that some people take for depression. ... There's some evidence that it may help less severe depression, but it's not recommended by doctors. This is because the amount of active ingredients varies among individual brands and batches, so you can never be sure what sort of effect it'll have on you. Taking St John's wort with other medicines, such as anticonvu… source↗

L4d TW TFDA / 衛福部

Cautious

根據台灣衛生福利部的規定，聖約翰草不能當作一般食品原料使用，因此在台灣無法購買到合法含有聖約翰草的食品。 source↗

L4e WHO

Supportive

Herba Hyperici. WHO Monographs on Selected Medicinal Plants, Volume 2 (Geneva: World Health Organization, 2002), pp. 149-171. The crude drug herba hyperici consists of the dried flowering aerial parts of Hypericum perforatum L. Uses supported by clinical data include the symptomatic treatment of mild to moderate depressive disorders. Verbatim section text of the WHO monograph could not be extra… source↗

L5a NIH Office of Dietary Supplements

Cautious

L5b Mayo Clinic

Supportive

Many studies have found St. John's wort to be helpful in treating mild to moderate depression. In fact, some research has shown the supplement to work as well as many prescription antidepressants. However, it's unclear whether the supplement helps treat severe depression. St. John's wort interacts with many medicines, so it might not be a suitable choice, especially if you take any prescription… source↗

L5c Cleveland Clinic

Cautious

L5d Harvard Health

Neutral

L5e Specialty Society (condition-mapped)

Cautious

✓PMID 100% verifiedevery citation checked via NCBI Entrez

🔬5 PubMed studiesindependently re-checked by multiple sub-agents

engine_version: v1.0 claim_id: CLM-COND-depression-INT-st-johns-wort-001 繁體中文版 →