Sj9.0

St. John's Wort Research

40 peer-reviewed studies · Evidence score: 9/10

Efficacy of Pharmacological Interventions in Milder Depression: A Systematic Review and Meta-Analysis

Urata M et al. • Neuropsychopharmacology reports (2025)

This review demonstrates that certain supplements, such as eicosapentaenoic acids and Rhodiola rosea, are therapeutic options for mild depression.

A meta-analysis found no significant difference in response rates between the two treatments (risk ratio [RR] = 0.96, 95% CI: 0.78-1.18) or dropout rates (RR = 1.08, 95% CI: 0.62-1.88).
Eicosapentaenoic acid and Rhodiola rosea demonstrated significant improvements in depressive symptoms compared to placebo.
Conversely, S-adenosylmethionine did not produce significant improvements relative to placebo.

Meta-Analysisn=1,049

DOI

Herbal medicine for treating psoriasis: A systematic review

Anheyer M et al. • Complementary therapies in medicine (2025)

Herbal therapies present a diverse array of options for psoriasis management, but further research is essential to elucidate their safety profile and true effectiveness.

Herbal therapies present a diverse array of options for psoriasis management, but further research is essential to elucidate their safety profile and true effectiveness.
Healthcare providers should engage in shared decision-making with patients, considering individual preferences and treatment goals while remaining vigilant in guiding towards evidence-based treatments.
Further research warranted to confirm findings

Systematic Reviewn=1,115

DOI

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

Zhao X et al. • Advances in clinical and experimental medicine : official organ Wroclaw Medical University (2023)

Our research supports the use of SJW as it reduced the number of depressive patients and their HAMD scores while having fewer risks and side effects than conventional medications.

For patients treated with either SSRIs or SJW, a pooled OR of 2.44 with a 95% confidence interval (95% CI) of 1.33-4.45 was obtained.
The data were heterogeneous, with a tau2 value of 0.54, χ2 value of 31.05, degrees of freedom (df) value of 7, I2 value of 77%, and an overall Z-value of 2.90 with p = 0.004.
Our research supports the use of SJW as it reduced the number of depressive patients and their HAMD scores while having fewer risks and side effects than conventional medications.

Meta-Analysisn=2,270

DOI

Review & meta-analysis: isopropanolic black cohosh extract iCR for menopausal symptoms - an update on the evidence

Castelo-Branco C et al. • Climacteric : the journal of the International Menopause Society (2021)

With its good safety profile in general and at estrogen-sensitive organs, iCR as a non-hormonal herbal therapy can also be used in patients with hormone-dependent diseases who suffer from iatrogenic climacteric symptoms.

Effect sizes were larger when higher dosages of iCR as monotherapy or in combination with St.
The clinical data did not reveal any evidence of hepatotoxicity.
Hormone levels remained unchanged and estrogen-sensitive tissues (e.g. breast, endometrium) were unaffected by iCR treatment.

Meta-Analysisn=43,759

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Bioactive Compounds Effective Against Type 2 Diabetes Mellitus: A Systematic Review

Egbuna C et al. • Current topics in medicinal chemistry (2021)

John's wort, green beans, cucumber, spinach, tea, Rosmarinus officinalis, Aloe vera, Moringa oleifera, tomatoes, potatoes, oregano, lemon balm, thyme, peppermint, Ocimum basilicum, red cabbage, pears, olive oil and walnut.

Systematic review examining Ginkgo Biloba efficacy
Further research warranted to confirm findings

Systematic Reviewn=6,464

DOI

Antidepressants for smoking cessation

Hughes JR et al. • The Cochrane database of systematic reviews (2014)

The antidepressants bupropion and nortriptyline aid long-term smoking cessation.

There was high quality evidence that, when used as the sole pharmacotherapy, bupropion significantly increased long-term cessation (44 trials, N = 13,728, risk ratio [RR] 1.62, 95% confidence interval [CI] 1.49 to 1.76).
There was moderate quality evidence, limited by a relatively small number of trials and participants, that nortriptyline also significantly increased long-term cessation when used as the sole pharmacotherapy (six trials, N = 975, RR 2.03, 95% CI 1.48 to 2.78).
There is insufficient evidence that adding bupropion (12 trials, N = 3487, RR 1.9, 95% CI 0.94 to 1.51) or nortriptyline (4 trials, N = 1644, RR 1.21, 95% CI 0.94 to 1.55) to nicotine replacement therapy (NRT) provides an additional long-term benefit.

Meta-Analysisn=13,728

DOI

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

Ng QX et al. • Journal of affective disorders (2017)

For patients with mild-to-moderate depression, St John's wort has comparable efficacy and safety when compared to SSRIs.

The pooled SMD from baseline HAM-D scores (pooled SMD -0.068, 95% CI -0.127 to 0.021, p<0.001) also support its significant clinical efficacy in ameliorating depressive symptoms.
For patients with mild-to-moderate depression, St John's wort has comparable efficacy and safety when compared to SSRIs.
Follow-up studies carried out over a longer duration should be planned to ascertain its benefits.

Meta-Analysisn=3,808

DOI

St John's wort for major depression: A systematic review and meta-analysis of randomised clinical trials

Apaydin EA et al. • Systematic Reviews (2016)

St. John's wort was significantly superior to placebo and comparable to standard antidepressants for treating major depression with fewer side effects.

St. John's wort was significantly more effective than placebo for major depression (SMD -0.49)
Efficacy was comparable to SSRIs with no significant difference in response rates
Adverse event rates were significantly lower than conventional antidepressants

Meta-Analysisn=5,489

DOI

Hypericum perforatum for depression: Updated systematic review and meta-analysis of clinical effectiveness and safety

Ng QX et al. • Journal of Affective Disorders (2017)

St. John's wort extract at 600-1200 mg/day showed comparable efficacy to SSRIs for mild-to-moderate depression.

St. John's wort showed comparable response rates to SSRIs (OR 1.01, 95% CI 0.82-1.25)
Dropout rates due to adverse effects were significantly lower with St. John's wort
Standardized extracts (WS 5570, STW 3-VI) at 600-1200 mg/day were most effective

Meta-Analysisn=3,808

DOI

Triggers for acute mood episodes in bipolar disorder: A systematic review

Rodrigues Cordeiro C et al. • Journal of psychiatric research (2023)

This is the first systematic review about triggers/precipitants of relapse in BD.

This is the first systematic review about triggers/precipitants of relapse in BD.
Despite the importance of identification and management of potential triggers for BD decompensation, there is a lack of large observational studies addressing this topic, with most of the included studies being case reports/case series.
Notwithstanding these limitations, antidepressant use is the trigger with the strongest evidence for manic relapse.

Systematic Reviewn=108

DOI

Systematic Review and Network Meta-Analysis of the Effects of Plant Extracts on Cognitive Function and Quality of Life in Stroke Patients

Li J et al. • Phytotherapy research : PTR (2025)

Future longer follow-up, larger samples, and more methodologically rigorous randomized controlled trials are recommended to clearly establish the effects of different dosages on cognitive function and quality of life in stroke patients.

John's Wort extract (SUCRA 71.2%) was the most effective in reducing NIHSS scores, Berberine (SUCRA 84.1%) was most effective in reducing mRS scores, and St.
John's Wort extract (SUCRA 99.1%) showed the highest efficacy in enhancing ADL scores.
Ginsenosides were the most effective in improving Barthel Index (SUCRA 74.7%), MMSE (SUCRA 93%), and MOCA (SUCRA 79.7%) scores.

Meta-Analysis

DOI

Warfarin and food, herbal or dietary supplement interactions: A systematic review

Tan CSS et al. • British journal of clinical pharmacology (2021)

While most food, herbs and supplements can be safely taken in moderation, healthcare professionals should be aware of the increased risk of bleeding when taking several food and herbs.

These reports described potentiation with 45 (57.7%) herbs, food or dietary supplements while 23 (29.5%) reported inhibition and 10 (12.8%) reported limited impact on warfarin pharmacokinetics and pharmacodynamics.
While most food, herbs and supplements can be safely taken in moderation, healthcare professionals should be aware of the increased risk of bleeding when taking several food and herbs.
These include Chinese wolfberry, chamomile tea, cannabis, cranberry, chitosan, green tea, Ginkgo biloba, ginger, spinach, St.

Systematic Reviewn=149

DOI

Herbal extracts in orofacial pain: a systematic review and direct and indirect meta-analysis

Barrera SD et al. • Scientific reports (2024)

This meta-analysis examined the effects of St. John's Wort.

The findings indicated a pain-attenuating effect of herbal extracts such as cannabis, turmeric, capsaicin, licorice, ginger, chamomile, clove, Hypericum perforatum, and Arnica montana.
These findings revindicate that herbal extracts may be valuable alternatives to traditional pain medications and promising source for the development of new active ingredients for pharmaceuticals.
Further research warranted to confirm findings

Meta-Analysisn=62

DOI

The role of diet and non-pharmacologic supplements in the treatment of chronic neuropathic pain: A systematic review

Frediani JK et al. • Pain practice : the official journal of World Institute of Pain (2024)

Based on the review, we cannot recommend any supplement use for the management of CIPN, although further research into N-acetyl-cysteine, l-carnosine, crocin, and magnesium is warranted.

Based on the review, we cannot recommend any supplement use for the management of CIPN, although further research into N-acetyl-cysteine, l-carnosine, crocin, and magnesium is warranted.
Acetyl-l-carnitine was found to be likely ineffective or harmful.
Alpha-lipoic acid was not found effective.

Systematic Reviewn=22

DOI

Effectiveness of Shugan Jieyu capsules for psychiatric symptoms of epilepsy: a systematic review and meta-analysis

Kim S et al. • BMC complementary medicine and therapies (2024)

Our results suggest that SJC may be effective in treating depression in patients with epilepsy.

Compared with AD, SJC showed significant differences in the improvement of depression (SMD: 3.82, 95% CI: 3.25, 4.39) and reduction in seizure frequency (MD: 0.39 times/month, 95% CI: 0.28, 0.50).
SJC showed more beneficial results than antiepileptic drugs (AED) in terms of antidepressant effects (SMD: 1.10, 95% CI: 0.69, 1.51) and QoL (MD: 11.75, 95% CI: 10.55, 12.95).
When patients were prescribed AED, the additional administration of SJC improved depression symptoms (SMD: 0.96, 95% CI: 0.28, 1.63).

Meta-Analysis

DOI

Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce

Sarris J et al. • The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry (2022)

Based on the current data and clinician input, a range of nutraceuticals and phytoceuticals were given either a supportive recommendation or a provisional recommendation across a range of various psychiatric disorders.

Based on the current data and clinician input, a range of nutraceuticals and phytoceuticals were given either a supportive recommendation or a provisional recommendation across a range of various psychiatric disorders.
However several had only a weak endorsement for potential use; for a few it was not possible to reach a clear recommendation direction, largely due to mixed study findings; while some other agents showed no obvious therapeutic benefit and were clearly not recommended for use.
It is the intention of these guidelines to inform psychiatric/medical, and health professional practice globally.

Meta-Analysis

DOI

Modulation of the hypothalamic-pituitary-adrenal (HPA) axis by plants and phytonutrients: a systematic review of human trials

Lopresti AL et al. • Nutritional neuroscience (2022)

For most phytonutrients, the effects of supplementation on HPA-axis activity in humans is unclear.

For most phytonutrients, the effects of supplementation on HPA-axis activity in humans is unclear.
Before more definitive conclusions about the effects of phytonutrients on the HPA-axis can be made, further research is required.
Further research warranted to confirm findings

Systematic Review

DOI

Interaction of herbal products with prescribed medications: A systematic review and meta-analysis

Awortwe C et al. • Pharmacological research (2019)

John's wort (SJW) significantly decreased the AUC (p < 0.0001) and clearance (p = 0.007) of midazolam.

John's wort (SJW) significantly decreased the AUC (p < 0.0001) and clearance (p = 0.007) of midazolam.
Echinacea purpurea (EP) significantly increased the clearance of midazolam (p = 0.01).
Green tea (GT) showed significant 85% decrease in plasma concentration of nadolol.

Meta-Analysisn=32

DOI

Herbal medicines in the treatment of psychiatric disorders: 10-year updated review

Sarris J • Phytotherapy research : PTR (2018)

Aside from this, future focus should involve the incorporation of more biomarker analysis, in particular pharmacogenomics, to determine genetic factors moderating response to herbal medicines.

Other encouraging herbal medicines with preliminary evidence include Curcuma longa (turmeric) in depression, Withania somnifera (ashwagandha) in affective disorders, and Ginkgo biloba (ginkgo) as an adjunctive treatment in Schizophrenia.
Although depression and anxiety are commonly researched, many other mental disorders still require further prospective investigation.
Although the previous review suggested increasing the adjunctive study of select herbal medicines with pharmaceuticals, this was still only found to sparingly occur in research designs.

Systematic Review

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Dietary supplement interactions with antiretrovirals: a systematic review

Jalloh MA et al. • International journal of STD & AIDS (2017)

This systematic review shows the importance of screening all human immunodeficiency virus patients for dietary supplement use to prevent treatment failure or adverse effects related to an interaction.

John's wort, vitamin C, zinc sulfate, and multivitamins were all found to significantly decrease the levels of selected antiretrovirals and should be avoided in patients taking these antiretrovirals.
Cat's claw and evening primrose oil were found to significantly increase the levels of antiretrovirals and patients should be monitored for adverse effects while taking these dietary supplements with antiretrovirals.
Calcium carbonate, ferrous fumarate, some forms of ginkgo, some forms of garlic, some forms of milk thistle, St.

Systematic Review

DOI

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