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St. John's Wort · Depression
This is one of 2,600+ evidence reviews you get as a member.
Proven purchase★★★★★
WFSBP/CANMAT 2022 guidelines rated acetyl-L-carnitine as not recommended for ADHD based on Grade A evidence from meta-analyses and RCTs.
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.
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.
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.
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.
ACP guidelines concluded nonpharmacologic therapies including St John's wort may benefit some adults with major depressive disorder, though evidence quality varied by intervention.
An Iranian RCT in major depression found Hypericum perforatum added to tricyclic antidepressants improved depressive symptoms versus antidepressants alone.
A meta-analysis found Hypericum perforatum comparably effective to SSRIs for major depression with better tolerability on several side-effect measures.
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.
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.
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).
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.
A Cochrane review concluded Hypericum extracts outperform placebo for depression and match standard antidepressants, with fewer side effects than older antidepressants.
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.
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.
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.
A comprehensive meta-analysis found St John's wort more effective than placebo for depression and generally comparable to standard antidepressants in efficacy.
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.
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).
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.
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.
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.
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.
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.
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.
A prospective double-blind trial evaluated Hypericum for mild-to-moderate depression; published abstract details on participants, dose, and outcomes were not available.
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.
In 102 depressed patients over 6 weeks, standardized hypericum LI 160 matched maprotiline for antidepressant efficacy with better tolerability.
St. John's Wort
St. John's Wort
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 |