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Head-to-head evidence comparison — which supplement is right for you?
SAMe vs Trazodone: SAMe has the stronger overall evidence (6.5 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.
SAMe wins 3 of 3 categories. Both are solid choices — the best pick depends on your specific goals.
Verdict
Too few graded studies
0 of 1 studies with measurable effects showed benefit.
Top outcomes
Verdict
Too few graded studies
Top outcomes
Shared outcomes (2)
Outcomes where both SAMe and Trazodone have evidence — compare verdict strength side-by-side.
400-1,200 mg for mood, 600-1,200 mg for joints. The cited trials used 1,200 mg for knee osteoarthritis and 200 mg a day with probiotics. Label products for mood go up to 1,600 mg, above the highest dose in the cited trials.
On empty stomach, Morning and/or midday
Enteric-coated tablets (SAMe tosylate or butanedisulfonate)
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 5 more not shown
Risk of serotonin syndrome.
Do not combine without prescriber supervision.
2-6 weeks
4-8 weeks
4-8 weeks
1-7 nights
Days to weeks
2 weeks
Morning after the first dose
S-Adenosylmethionine for osteoarthritis of the knee or hip
The Cochrane database of systematic reviews (2009) · Meta analysis · n=656
Four placebo-controlled trials with 656 patients were included, of poor methodological quality.
Efficacy of Pharmacological Interventions in Milder Depression: A Systematic Review and Meta-Analysis
Neuropsychopharmacology reports (2025) · Meta analysis · n=1049
Eight RCTs comprising 1049 participants met inclusion criteria.
S-Adenosylmethionine (SAMe) for Liver Health: A Systematic Review
Nutrients (2024) · Systematic review
Systematic review of 15 studies of SAMe in liver disease, all rated 4 or 5 out of 5 for quality.
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
SAMe has a higher evidence score (6.5/10 vs 3.8/10) and wins in 3 of 3 categories.
Caution: Risk of serotonin syndrome. Do not combine without prescriber supervision. Always consult a healthcare provider before combining these supplements.
The right pick depends on your goals. Answer a few quick questions for a personalised recommendation — or dig into the full evidence on each.