St. John's Wort
St. John's wort is studied for mild-to-moderate depression. It has major drug-interaction risks.
Overview
What is St. John's wort?
St. John's wort (Hypericum Perforatum) is a leafy herb that is commonly used to treat depression.
The active ingredients in St. John's wort, hypericin and hyperforin, have been shown in many studies to reduce symptoms of depression. However, due to its mechanism of action, St. John's wort can interact with a large number of drugs.
While St. John's wort is not FDA-approved, some of its actions are similar to those of FDA-approved drugs for treating depression.
Dosage
A typical dose of St. John's wort is 450 to 900 mg per day.
For depression, studies have used an initial dose of 450 mg/day (3 x 150 mg) increasing to 900 mg/day (3 x 300 mg) if the lower dose is ineffective after 2 weeks.
Effect graph
Effect heatmap
SupplementDEX Database
8 conditions for , , and rated at least stars. All purchase bands. No minimum star filter.
Database Snapshot
Most st. john's wort research is concentrated in a handful of conditions.
- Depression accounts for 28 of 40 studies (70%).
- Menopause accounts for 4 of 40 studies (10%).
- Seasonal affective disorder accounts for 2 of 40 studies (5%).
- Sparse coverage remains for Seasonal affective disorder, Somatic symptom disorder, Burning mouth syndrome.
Dietary Sources
Dietary sources
St. John's wort is typically consumed through supplements or herbal blends rather than as a regular dietary ingredient.
Safety
Dose windows
Short-term
It can reduce or eliminate the effects of oral contraceptives and increase the likelihood of unplanned pregnancy. In the short term it has been used at up to 900 mg per day for 12 weeks; in the long term up to 900 mg per day for 1 year or longer. Common side effects include agitation, anxiety, constipation, dizziness, diarrhea, dry mouth, fatigue, headache, insomnia, nausea, photosensitivity and stomach discomfort. Serious side effects include hypomania, suicidal and homicidal thoughts, and tachycardia. St. John's wort interacts with a large number of drugs; consult a healthcare provider before use.
Special populations
Pregnancy & breastfeeding
AvoidSt. John's wort is generally well tolerated but should not be consumed by pregnant or lactating women as it can increase the possibility of birth defects.
Frequently Asked Questions
References
Sources40 references
SupplementDEX uses only high-quality sources to determine supplement effectiveness.
SupplementDEX Database · Depression
28 references1.SupplementDEX Database: Depression — 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) Taskforce2022
WFSBP/CANMAT 2022 guidelines rated acetyl-L-carnitine as not recommended for ADHD based on Grade A evidence from meta-analyses and RCTs.
2.SupplementDEX Database: Depression — Comparative 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.
3.SupplementDEX Database: Depression — Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis2017
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.
4.SupplementDEX Database: Depression — A meta-analysis on the efficacy and safety of St John's wort extract in depression therapy in comparison with selective serotonin reuptake inhibitors in adults2016
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.
5.SupplementDEX Database: Depression — Nonpharmacologic 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.
6.SupplementDEX Database: Depression — A systematic review of St. John's wort for major depressive disorder2016
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.
7.SupplementDEX Database: Depression — Evaluation of Pharmaceutical Products of St. John's Wort Efficacy Added on Tricyclic Antidepressants in treating Major Depressive Disorder: A Double Blind Randomized Control Trial2012
An Iranian RCT in major depression found Hypericum perforatum added to tricyclic antidepressants improved depressive symptoms versus antidepressants alone.
8.SupplementDEX Database: Depression — Efficacy 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.
9.SupplementDEX Database: Depression — St John's wort for major depression2008
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.
10.SupplementDEX Database: Depression — Continuation 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 trial2008
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.
11.SupplementDEX Database: Depression — St 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.
12.SupplementDEX Database: Depression — Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine2005
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).
13.SupplementDEX Database: Depression — St 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.
14.SupplementDEX Database: Depression — Large-scale observational studies of hypericum extracts in patients with depressive disorders--a systematic review2005
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.
15.SupplementDEX Database: Depression — An 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.
16.SupplementDEX Database: Depression — Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial2002
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.
17.SupplementDEX Database: Depression — A 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.
18.SupplementDEX Database: Depression — Efficacy and tolerability of hypericum extract WS 5572 versus placebo in mildly to moderately depressed patients. A randomized double-blind multicenter clinical trial2001
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).
19.SupplementDEX Database: Depression — Effectiveness of St John's wort in major depression: a randomized controlled trial2001
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.
20.SupplementDEX Database: Depression — Experience with St John's Wort (Hypericum perforatum) in children under 12 years with symptoms of depression and psychovegetative disturbances2001
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.
21.SupplementDEX Database: Depression — Comparison of St John's wort and imipramine for treating depression: randomised controlled trial2000
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.
22.SupplementDEX Database: Depression — Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression2000
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.
23.SupplementDEX Database: Depression — Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study2000
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.
24.SupplementDEX Database: Depression — Comparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetine1999
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.
25.SupplementDEX Database: Depression — Hypericum treatment of mild–moderate depression in a placebo–controlled study. A prospective, double–blind, randomized, placebo–controlled, multicentre study. See external source1998
A prospective double-blind trial evaluated Hypericum for mild-to-moderate depression; published abstract details on participants, dose, and outcomes were not available.
View source199826.SupplementDEX Database: Depression — Clinical 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.
27.SupplementDEX Database: Depression — St. 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.
28.SupplementDEX Database: Depression — Effectiveness and tolerance of the hypericum extract LI 160 compared to maprotiline: a multicenter double-blind study1994
In 102 depressed patients over 6 weeks, standardized hypericum LI 160 matched maprotiline for antidepressant efficacy with better tolerability.
SupplementDEX Database · Menopause
4 references29.SupplementDEX Database: Menopause — Hypericum perforatum L. preparations for menopause: a meta-analysis of efficacy and safety2014
A meta-analysis found Hypericum perforatum preparations more effective than placebo for menopausal symptoms, with safety comparable to placebo in included trials.
30.SupplementDEX Database: Menopause — Effect of St John's wort on severity, frequency, and duration of hot flashes in premenopausal, perimenopausal and postmenopausal women: a randomized, double-blind, placebo-controlled study2010
In premenopausal and perimenopausal women, St John's wort reduced hot flash frequency and severity versus baseline in this controlled study.
31.SupplementDEX Database: Menopause — Effects of Hypericum perforatum (St. John's wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial2009
In a pilot RCT in symptomatic perimenopausal women, St John's wort improved hot flashes and quality of life versus placebo, though sample size was small.
32.SupplementDEX Database: Menopause — St. John's Wort extract: efficacy for menopausal symptoms of psychological origin1999
In 111 women with menopausal symptoms over 12 weeks, St John's wort 900 mg/day improved psychological and vasomotor menopausal symptoms versus baseline.
33.SupplementDEX Database: Somatic symptom disorder — Treatment of somatoform disorders with St. John's wort: a randomized, double-blind and placebo-controlled trial2004
In 184 outpatients with somatoform disorders over 6 weeks, St John's wort LI 160 reduced somatic symptom scores more than placebo.
34.SupplementDEX Database: Somatic symptom disorder — St John's wort extract (LI 160) in somatoform disorders: results of a placebo-controlled trial2002
In somatoform disorder patients, St John's wort extract LI 160 improved somatic complaints versus placebo in this multicenter double-blind trial.
35.SupplementDEX Database: Burning mouth syndrome — Hypericum perforatum extract in burning mouth syndrome: a randomized placebo-controlled study2008
In burning mouth syndrome, a double-blind RCT found Hypericum perforatum extract reduced pain and improved quality of life versus placebo over the treatment period.
36.SupplementDEX Database: Irritable bowel syndrome (IBS) — A randomized, double-blind, placebo-controlled trial of St John's wort for treating irritable bowel syndrome2010
In irritable bowel syndrome, a double-blind RCT found St John's wort did not significantly improve IBS symptoms versus placebo over the treatment period.
37.SupplementDEX Database: Peripheral neuropathy — St. John's wort has no effect on pain in polyneuropathy2001
In painful polyneuropathy, St John's wort did not significantly reduce pain versus placebo over the trial period in this randomized study.
38.SupplementDEX Database: Seasonal affective disorder — Hypericum in seasonal affective disorder (SAD)1999
In seasonal affective disorder, 168 patients taking Hypericum (Kira) for 8 weeks reported mean symptom scores falling from 21.3 to 13.0 versus baseline.
39.SupplementDEX Database: Seasonal affective disorder — Hypericum in the treatment of seasonal affective disorders1994
In seasonal affective disorder, Hypericum perforatum was comparable to light therapy for depressive symptom improvement in this controlled trial.
40.SupplementDEX Database: Social anxiety disorder — St. John's wort versus placebo in social phobia: results from a placebo-controlled pilot study2005
In a social phobia pilot RCT, St John's wort did not significantly improve social anxiety symptoms versus placebo over the study period.