Summary
St. John's Wort (Hypericum perforatum) has reached Preclinical as its most advanced recorded development stage across any indication, and the database holds no approval for Major Depressive Disorder. ClinicalTrials.gov lists 4 registered trials linking St. John's Wort (Hypericum perforatum) to Major Depressive Disorder: 4 have completed. The most advanced is Phase 3 (NCT04315597). It plans or enrolled 398 participants. Registration activity spans 1998 to 2009. The literature layer holds 1 publication for this pair: 1 clinical trial publication. The dated items are from 2012. These are primary trial reports rather than syntheses, so results have not yet been pooled or graded independently.
The RepurpOS disease-intelligence file for Major Depressive Disorder ranks 580 candidate therapeutics from Open Targets, ChEMBL, DGIdb and PubMed; only a minority carry direct clinical evidence, and this page covers one of those. Spontaneous remission context recorded for the condition: Relapse in 19-45% within 1 year of antidepressant discontinuation after remission; relapse risk ratio (off-medication vs on) falls from 3.69x at 2 months to 1.34x at 5 years.
Evidence table
| Evidence tier | C · Preliminary |
|---|---|
| Evidence score | 20.0 (trials 13.0, literature 2.0, tier 5, approved bonus 0.0) |
| Registered trials | 4 total: 0 recruiting, 0 active / not yet recruiting, 4 completed, 0 other |
| Linked publications | 1 (1 clinical trial publication) |
| Agent type | Supplement (Herbal) |
| Development stage (any indication) | Preclinical |
| Mechanism / class | Integrative interventions for improving outcomes in depression: a narrative review · Halma M, Plothe C, Marik PE · 2024 |
| Data sources | OSMF Chronic Disease Review |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT04315597 | Study to Learn About Relapse Prevention of Hypericumextract (a Drug Based on the Plant St. John Wort) in Outpatients Suffering From Moderate Depressive Episodes 2009 | completed | Phase 3 | 398 |
| NCT00451516 | St. John's Wort And Kava In The Treatment Of Major Depressive Disorder With Comorbid Anxiety 2007 | completed | Phase 2 | 50 |
| NCT00005013 | Treatment of Major Depression With St. John's Wort (Hypericum) 1998 | completed | Not applicable | — |
| NCT05477472 | Low Dose St John's Wort for Depression 2005 | completed | Not applicable | 55 |
Published literature
- Clinical trial publication St John's wort (Hypericum perforatum) versus sertraline and placebo in major depressive disorder: continuation data from a 26-week RCTSarris J, Fava M, Schweitzer I et al. · Pharmacopsychiatry · 2012 · PMID 22592504
Mechanism and notes
Recorded mechanism or class: Integrative interventions for improving outcomes in depression: a narrative review · Halma M, Plothe C, Marik PE · 2024.
OSMF's existing evidence tier for this pair is C (Preliminary), derived from the strength of the disease association recorded in OSMF Chronic Disease Review. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is St. John's Wort (Hypericum perforatum) approved for Major Depressive Disorder?
St. John's Wort (Hypericum perforatum) has reached Preclinical as its most advanced recorded development stage across any indication, and the database holds no approval for Major Depressive Disorder. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is St. John's Wort (Hypericum perforatum) in clinical trials for Major Depressive Disorder?
ClinicalTrials.gov lists 4 registered trials linking St. John's Wort (Hypericum perforatum) to Major Depressive Disorder: 4 have completed. The most advanced is Phase 3 (NCT04315597). It plans or enrolled 398 participants. Registration activity spans 1998 to 2009.
What does the evidence show for St. John's Wort (Hypericum perforatum) in Major Depressive Disorder?
St. John's Wort (Hypericum perforatum) has 4 completed trials and 1 linked publication for Major Depressive Disorder. Completed trials may or may not have posted results; follow the NCT links to check. OSMF's existing evidence tier for this pair is C (Preliminary), derived from the strength of the disease association recorded in OSMF Chronic Disease Review. The tier describes how well the drug-disease link is documented, not how well the drug works.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-07-05. Page built 2026-10-07.