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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
Mixed evidence
4 of 9 studies with measurable effects showed benefit.
Top outcomes
Verdict
Mostly mechanism / observational
Top outcomes
Shared outcomes (1)
Outcomes where both St. John's Wort and Trazodone have evidence — compare verdict strength side-by-side.
300mg 3x daily (900mg total)
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
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
As effective as standard antidepressants for mild-moderate depression
Efficacy of Pharmacological Interventions in Milder Depression: A Systematic Review and Meta-Analysis
Neuropsychopharmacology reports (2025) · Meta analysis · n=1049
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).
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
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.
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
Based on multiple meta-analyses (n>5000) showing efficacy comparable to SSRIs for mild-moderate depression. Effect plateau around 900-1200mg. Not effective for severe depression. Requires standardized extract (0.3% hypericin).
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 improve deep 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.