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SupplementDEX Database: Evidence review

St. John's Wort · Depression

This is one of 2,600+ evidence reviews you get as a member.

Practitioner

Proven purchase★★★★★

How we scored this
Effect SizeHighEvidenceVery HighTrustVery High
Evidence Review
  • St. John's wort can be an effective option for mild to moderate depression, helping to lift mood, reduce anxiety, and improve sleep.
  • Studies have shown that it works better than a placebo and can be as effective as some prescription antidepressants, like low-dose SSRIs, with fewer side effects such as stomach upset, neurological issues, or sexual problems.
  • Most research uses specific extracts standardized to contain about 0.2-0.3% hypericin and 5-6% hyperforin, taken in doses from 600 to 1800 mg daily.
  • It’s important to choose a high-quality product and discuss use with a healthcare provider, especially if you’re taking other medications, because St. John’s wort can interact with many drugs.
  • While it’s generally safe for adults, its benefits are most clear for mild to moderate depression, and it might not be enough for severe cases.
  • Pediatric use has been studied but is less conclusive.
  • In some people with bipolar disorder, SJW can cause mania.
  • Always check with your doctor or pharmacist before starting St. John’s wort to ensure it’s appropriate for your situation.
Browse 28 studies7 meta-analyses
MetaClinician 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) Taskforce2022

WFSBP/CANMAT 2022 guidelines rated acetyl-L-carnitine as not recommended for ADHD based on Grade A evidence from meta-analyses and RCTs.

View on PubMed
MetaClinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis2017n=3,808

A 2016 meta-analysis of 27 St John's wort trials (3808 patients) found extracts more effective than placebo and comparable to standard antidepressants for mild-to-moderate depression.

Effect
Benefit
Duration
4–12 weeks
Population
Depression patients
Participants
3,808
View on PubMed
MetaComparative Benefits and Harms of Complementary and Alternative Medicine Therapies for Initial Treatment of Major Depressive Disorder: Systematic Review and Meta-Analysis2017

A systematic review and meta-analysis found several CAM therapies including St John's wort had modest benefits for initial major depression versus second-generation antidepressants, with varying effect sizes.

Effect
Benefit
Population
Adults
Avg age
~18
View on PubMed
MetaA meta-analysis on the efficacy and safety of St John's wort extract in depression therapy in comparison with selective serotonin reuptake inhibitors in adults2016n=3,126

A meta-analysis comparing St John's wort with SSRIs found similar efficacy for depression with fewer adverse events than standard antidepressants in included trials.

Effect
Benefit
Population
Adults
Participants
3,126
View on PubMed
MetaA systematic review of St. John's wort for major depressive disorder2016n=2,922

A systematic review of St John's wort for major depression found it more effective than placebo and generally comparable to antidepressants, with fewer side effects in many trials.

Effect
Benefit
Population
Adults
Participants
2,922
View on PubMed
GuideNonpharmacologic Versus Pharmacologic Treatment of Adult Patients With Major Depressive Disorder: A Clinical Practice Guideline From the American College of Physicians2016

ACP guidelines concluded nonpharmacologic therapies including St John's wort may benefit some adults with major depressive disorder, though evidence quality varied by intervention.

Effect
Benefit
Population
Adults
View on PubMed
RCTEvaluation of Pharmaceutical Products of St. John's Wort Efficacy Added on Tricyclic Antidepressants in treating Major Depressive Disorder: A Double Blind Randomized Control Trial2012n=40

An Iranian RCT in major depression found Hypericum perforatum added to tricyclic antidepressants improved depressive symptoms versus antidepressants alone.

Effect
Benefit
Duration
6 weeks
Dose
75–100 mg/day
Population
Patients with major depressive disorder
Participants
40
Ages
18–54
View on PubMed
MetaEfficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: a meta-analysis2009

A meta-analysis found Hypericum perforatum comparably effective to SSRIs for major depression with better tolerability on several side-effect measures.

Effect
Benefit
Population
Patients with major depressive disorder
View on PubMed
RCTContinuation and long-term maintenance treatment with Hypericum extract WS 5570 after recovery from an acute episode of moderate depression--a double-blind, randomized, placebo controlled long-term trial2008n=5,570

A long-term randomized trial showing that Hypericum extract WS 5570 effectively maintained remission and reduced relapse risk in moderate depression. A 26-week study (+ 12 month extension) of 426 patients with recurrent moderate major depression found that St. John’s wort (3 x 300 mg WS 5570 /day for 26-weeks) improved depressive symptoms and increased time to relapse in acute and chronic depression. Treatment was then maintained for 12-months and had a pronounced prophylactic effect in patients with early onset depression and those with a high degree of chronicity. WS 5570 was similarly safe to placebo.

Effect
Benefit
Duration
26 weeks
Dose
300 mg/day
Population
Adults
Participants
5,570
View on PubMed
Systematic reviewSt John's wort for major depression2008n=5,489

A Cochrane review found St John's wort extracts more effective than placebo for major depression and similarly effective to standard antidepressants, with fewer dropouts due to adverse effects.

Effect
Benefit
Population
Depression patients
Participants
5,489
View on PubMed
RCTAcute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine2005n=251

A 6-week study including 251 patients with acute major depression (>=22 on HAMD) taking St. John’s wort (900 mg /day WS 5570) or paroxetine (20 mg/day) found a baseline reduction in depression scores of 56.6% in those taking SJW and 44.8% in the paroxetine group. Dosages were safely increased to 1800 mg/day SJW or 40 mg paroxetine in participants who did not respond to treatment after 2 weeks. SJW was at least as effective as paroxetine and was better tolerated. Incidence of adverse events was lower in SJW (0.035 events per day of exposure) compared to paroxetine (0.060).

Effect
Benefit
Duration
6 weeks
Dose
900 mg/day
Population
Adults
Participants
251
View on PubMed
Systematic reviewLarge-scale observational studies of hypericum extracts in patients with depressive disorders--a systematic review2005n=100

A systematic review of large observational St John's wort studies found clinically relevant improvement in depressive symptoms in most treated patients over at least 4 weeks.

Effect
Benefit
Duration
4–6 weeks
Population
Patients with depressive disorders
Participants
100
View on PubMed
MetaSt John's wort for depression2005

A Cochrane review concluded Hypericum extracts outperform placebo for depression and match standard antidepressants, with fewer side effects than older antidepressants.

Effect
Benefit
Population
Adults
View on PubMed
MetaSt John's wort for depression: meta-analysis of randomised controlled trials2005

An updated Cochrane meta-analysis of 37 RCTs found St John's wort more effective than placebo for depression, with efficacy similar to standard antidepressants in severe depression trials.

Effect
Benefit
Population
Adults
View on PubMed
Open-labelAn open-label pilot study of St. John's wort in juvenile depression2003

An open-label pilot in youths aged 6–16 with major depression found St John's wort safe and associated with symptomatic improvement, though uncontrolled design limits inference.

Effect
Benefit
Duration
8 weeks
Dose
900 mg/day
Population
Children/adolescents
Ages
6–16
View on PubMed
RCTEffect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial2002n=340

In 388 adults with major depression over 6 weeks, LI-160 St John's wort did not significantly outperform placebo on primary depression outcomes in this large RCT.

Effect
No Benefit
Duration
8 weeks
Dose
900–1500 mg/day St John's wort (LI-160)
Population
Adults
Participants
340
View on PubMed
MetaA systematic review and meta-analysis of Hypericum perforatum in depression: a comprehensive clinical review2001

A comprehensive meta-analysis found St John's wort more effective than placebo for depression and generally comparable to standard antidepressants in efficacy.

Effect
Benefit
View on PubMed
RCTEffectiveness of St John's wort in major depression: a randomized controlled trial2001n=102

In 200 adults with major depression over 8 weeks, standardized St John's wort did not significantly beat placebo on HAM-D response rates in this rigorous trial.

Effect
No Benefit
Duration
8 weeks
Dose
900 mg/day
Population
Adults
Participants
102
Avg age
~42
View on PubMed
RCTEfficacy and tolerability of hypericum extract WS 5572 versus placebo in mildly to moderately depressed patients. A randomized double-blind multicenter clinical trial2001n=72

A multicenter randomized double-blind trial showing that WS 5572 extract was more effective than placebo for mild to moderate depression with good tolerability. A 6-week study including 72 patients with mild-to-moderate major depressive disorder found that 3 x 300 mg/day St. John’s wort (WS 5572) led to significant benefits after four (P = 0.011) and six weeks (P < 0.001) . After six weeks, the SJW group experienced a greater reduction in Hamilton Depression Scale score (19.7 +/- 3.4 to 8.9 +/- 4.3, -10.8 points) compared to the placebo group (20.1 +/- 2.6 to 14.4 +/- 6.8, -5.7 points).

Effect
Benefit
Duration
6 weeks
Dose
300 mg/day
Population
Depression patients
Participants
72
View on PubMed
ObservationalExperience with St John's Wort (Hypericum perforatum) in children under 12 years with symptoms of depression and psychovegetative disturbances2001n=101

In 101 children under 12 with depressive symptoms over at least 4 weeks, St John's wort extract was associated with marked symptom improvement in this post-marketing surveillance study.

Effect
Benefit
Duration
4–6 weeks
Dose
1800 mg/day
Population
Children/adolescents
Participants
101
View on PubMed
RCTComparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study2000n=30

A pilot randomized trial showing similar antidepressant effects between Hypericum extract LI 160 and sertraline in mild to moderate depression. A 7-week manufacturer-funded study was performed in 30 patients with mild to moderate depression. Participants were given St. John’s wort (600 mg/day) or sertraline (50 mg/day) for one week. Then, they were given an increased dose of SJW (900 mg/day) and sertraline (75 mg/day) for 6 weeks. Whilst similar improvements were found for SJW and sertraline, the differences were not statistically significant. SJW clinical response rates (defined as >= 50% reduction in HAM-D scores) were 47% compared to 40% in patients receiving sertraline. This study was funded by Lichtwer Pharma AG, a German herbal supplement company.

Effect
Benefit
Duration
6 weeks
Dose
600 mg/day
Population
Adults
Participants
30
Avg age
~46
View on PubMed
RCTComparison of St John's wort and imipramine for treating depression: randomised controlled trial2000n=324

In 324 outpatients with mild to moderate depression, Hypericum extract ZE 117 250 mg twice daily for 6 weeks matched imipramine 75 mg twice daily on Hamilton depression scores, with fewer adverse events (39% vs 63%) and withdrawals.

Effect
Benefit
Duration
6 weeks
Dose
150 mg/day
Population
Patients with mild to moderate depression
Participants
324
View on PubMed
RCTEquivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression2000n=240

In mild-to-moderate depression, Hypericum Ze 117 was equivalent to fluoxetine on HAM-D improvement over 6 weeks in this randomized double-blind trial.

Effect
Benefit
Duration
6 weeks
Population
Patients with mild to moderate depression
Participants
240
View on PubMed
RCTComparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetine1999n=77

A randomized comparison showing that St. John’s wort extract LoHyp-57 demonstrated antidepressant effects similar to fluoxetine in mild to moderate depression. A 6-week study of 149 elderly patients (129 females) found that St. John’s wort (800 mg/day, LoHyp-57) was as effective as 20 mg fluoxetine for mild to moderate depression. Hamilton Depression Scale scores fell in those taking SJW from 16.6 to 7.91 and in those taking fluoxetine from 17.18 to 8.11. SJW resulted in fewer side effects and greater adherence compared to fluoxetine.

Effect
Benefit
Duration
6 weeks
Dose
800 mg/day
Population
Older adults
Participants
77
View on PubMed
RCTClinical significance of hyperforin for the efficacy of Hypericum extracts on depressive disorders of different severities1998

In 147 outpatients with mild or moderate depression, two St John's wort extracts improved HAM-D scores similarly over 6 weeks, with hyperforin content correlating with response.

Effect
Benefit
Duration
42 days
Dose
3×1 tablet Hypericum extract/day
Population
Adults
View on PubMed
RCTHypericum treatment of mild–moderate depression in a placebo–controlled study. A prospective, double–blind, randomized, placebo–controlled, multicentre study1998

A prospective double-blind trial evaluated Hypericum for mild-to-moderate depression; published abstract details on participants, dose, and outcomes were not available.

Effect
Benefit
View source
RCTSt. John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy1998

In 147 outpatients with mild or moderate depression, St John's wort extract was more effective than placebo on HAM-D scores over 6 weeks in this multicenter RCT.

Effect
Benefit
Duration
42 days
Dose
3×1 tablet Hypericum extract/day
Population
Adults
View on PubMed
RCTEffectiveness and tolerance of the hypericum extract LI 160 compared to maprotiline: a multicenter double-blind study1994n=102

In 102 depressed patients over 6 weeks, standardized hypericum LI 160 matched maprotiline for antidepressant efficacy with better tolerability.

Effect
Benefit
Duration
4 weeks
Dose
900 mg/day Hypericum
Population
Depression patients
Participants
102
View on PubMed

Effect graph

St. John's Wort

Practitioner
Which conditions is St. John's Wort useful for?
Proven
Depression

St. John's Wort

Effect heatmap

Included

Consider purchase at 4 stars or greater.

Depression★★★★★
High
Menopause★★★★★
Medium
Somatic symptom disorder★★★★★
Medium
Seasonal affective disorder★★★★★
Low
Social anxiety disorder★★★★★
Very Low / None
Peripheral neuropathy★★★★★
Very Low / None
Irritable bowel syndrome (IBS)★★★★★
Very Low / None
Burning mouth syndrome★★★★★
Very Low / None
Weakest
Strongest
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