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Head-to-head evidence comparison — which supplement is right for you?
St. John's Wort vs Trazodone: St. John's Wort has the stronger overall evidence (7.8 vs 3.8/10); take care combining them — there's a flagged interaction. Take the 60-second quiz for a pick tailored to your goals.
St. John's Wort wins 2 of 3 categories. Both are solid choices — the best pick depends on your specific goals.
Verdict
Likely helps
6 of 8 studies with measurable effects showed benefit.
Top outcomes
Verdict
Too few graded studies
Top outcomes
Shared outcomes (2)
Outcomes where both St. John's Wort and Trazodone have evidence — compare verdict strength side-by-side.
300mg 3x daily (900mg total) (a typical label dose, not the dose used in the cited trial, which gave 600 mg once a day or 600 mg twice a day)
With meals, Divided into 2-3 doses
Standardized extract (0.3% hypericin)
Prescription only — a clinician sets the dose. The doses studied for sleep are low: the placebo-controlled trials that show anything used 50 mg at bedtime (30 min before bed in the primary-insomnia study; 10 PM in the Alzheimer's study), and the systematic-review literature treats <100 mg/day as the 'low-dose' insomnia range versus ≥100 mg/day as the antidepressant range. This is entirely OFF-LABEL. The approved indication is major depressive disorder, where outpatient dosing goes up to 400 mg/day in divided doses (up to 600 mg/day in monitored inpatients).
Before bed
Immediate-release oral tablet, prescribed and dose-titrated by a clinician
and 21 more not shown
and 5 more not shown
Risk of serotonin syndrome, plus unpredictable trazodone levels from enzyme induction.
Avoid the combination. This is one of the clearest supplement-drug conflicts in the corpus — raise it with your prescriber before starting either.
4-6 weeks
4-8 weeks
During use
First 1-2 weeks
1-7 nights
Days to weeks
2 weeks
Morning after the first dose
St John's wort for major depression
Cochrane Database of Systematic Reviews (2008) · Meta analysis · n=5489
In nine larger placebo-controlled trials the combined response rate ratio was 1.28 (95% CI 1.10 to 1.49), and in nine smaller trials 1.87 (95% CI 1.22 to 2.87). Placebo-controlled results showed marked heterogeneity.
Efficacy of Pharmacological Interventions in Milder Depression: A Systematic Review and Meta-Analysis
Neuropsychopharmacology reports (2025) · Meta analysis · n=1049
Eight RCTs, 1049 participants. St. John's Wort was analysed in two trials, both comparing it to fluoxetine.
Systematic Review and Network Meta-Analysis of the Effects of Plant Extracts on Cognitive Function and Quality of Life in Stroke Patients
Phytotherapy research : PTR (2025) · Meta analysis · n=6599
48 RCTs covering 6599 stroke patients and nine plant extracts.
Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline.
Journal of Clinical Sleep Medicine (2017) · Systematic review
The AASM commissioned a task force of four sleep-medicine experts, ran a systematic review of randomised controlled trials, and graded the evidence with GRADE
Trazodone for the treatment of insomnia: a meta-analysis of randomized placebo-controlled trials.
Sleep Medicine (2018) · Meta analysis
Seven randomised placebo-controlled trials involving only 429 patients in total — the entire dedicated meta-analytic base for trazodone in insomnia
Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis.
The Lancet (2022) · Meta analysis
170 trials (36 interventions, 47,950 participants) in the systematic review; 154 double-blind RCTs (30 interventions, 44,089 participants) in the network meta-analysis
Both points come from one randomised, double-blind trial of the WS 5570 extract in 332 outpatients with mild or moderate major depression (PMID 16796730). Over 6 weeks, HAM-D scores fell 11.6 points on 600 mg once daily, 10.8 points on 600 mg twice daily and 6.0 points on placebo. Both doses beat placebo with comparable efficacy, so the curve is flat above 600 mg, although remission was more common at 1,200 mg. Adverse events were low in all groups. The Cochrane review (PMID 18843608, 29 trials) supports efficacy over placebo but did not compare doses, and no cited trial reports 300 mg, 900 mg or 1,800 mg a day, so no optimum is named.
AI-estimated from published studies. Interpret as directional guidance.
St. John's Wort has a higher evidence score (7.8/10 vs 3.8/10) and wins in 2 of 3 categories.
For perceived sleep quality, St. John's Wort has a higher relevance score (48 vs 30).
Caution: Risk of serotonin syndrome, plus unpredictable trazodone levels from enzyme induction. Avoid the combination. This is one of the clearest supplement-drug conflicts in the corpus — raise it with your prescriber before starting either. Always consult a healthcare provider before combining these supplements.
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The right pick depends on your goals. Answer a few quick questions for a personalised recommendation — or dig into the full evidence on each.