SAMe for Depression
Verdict: Published with Warning
Across 4 PubMed studies, the evidence for SAMe in Depression grades Tier B — preliminary evidence. Effective, but with safety or population caveats.
B 🟡 B Preliminary Evidence Published with Warning
Why this grade7-layer evidence engine
⚖️
Scoring transparency
All scores computed by a 7-layer evidence engine — fully auditableRaw score 0.49
D
C
B
A
S
← counter-evidence / ineffectiveeffective / strong evidence →
Final grade
B · Published with Warning
Confidence
74%
Broadly consistent
Evidence level
E1
Cochrane high-quality SR/MA
▸View the full decision path (audit trail)
- compute_raw_score — 加權公式: L2×0.30 + L3×0.25 + L5×0.25 + L11×0.10 + L1×0.10 = 0.491
- tier_from_score — 依分數區間映射至 tier letter
- apply_hec_rules — 高階證據未達主導 (0 positive vs 1 negative)，由 raw_score 決定
- tier_strict_requirement_check — Tier 條件達標，未降階
- detect_disputes — 偵測到 0 個 hard + 0 個 soft dispute
- decide_status — 依 tier + dispute 結果決定 status
PubMed studies (4)L2 · primary research & systematic reviews
Efficacy and acceptability of S-adenosyl-L-methionine (SAMe) for depressed patients: A systematic review and meta-analysis
Finding: Across 23 trials, SAMe was significantly superior to placebo as monotherapy (SMD -0.58, 95% CI -0.93 to -0.23, I2 68%). SAMe did not differ significantly from antidepressants (SMD 0.06, 95% CI -0.06 to 0.18) nor from placebo when added to ongoing antidepressants (SMD -0.22, 95% CI -0.63 to 0.19). Subgroup analysis: intramuscular (SMD -0.92) and oral (SMD -0.66) routes effective, intravenous route not (SMD -0.16). No significant difference in dropout rates.
View on PubMed S-Adenosylmethionine (SAMe) as an adjuvant therapy for patients with depression: An updated systematic review and meta-analysis
Finding: Across 14 trials (1522 subjects), no significant difference in depression outcome was found between SAMe and the comparator across monotherapy vs placebo, SAMe vs imipramine/escitalopram, and adjunctive vs placebo comparisons. SAMe provided relief comparable to established antidepressants, but authors urge caution given limited trial number and highly variable dosing.
View on PubMed S-adenosyl methionine (SAMe) for depression in adults (Cochrane Systematic Review)
Finding: Across 8 RCTs (934 adults): no strong evidence of a difference between SAMe and placebo as monotherapy (very low quality evidence). SAMe equivalent to tricyclic antidepressants (imipramine) and to SSRI (escitalopram) with fewer adverse effects than imipramine (low quality). SAMe as add-on to SSRIs showed superiority over placebo (low quality). Authors concluded the absence of high-quality evidence precludes firm conclusions; large high-quality RCTs needed.
View on PubMed Adjunctive S-adenosylmethionine (SAMe) in treating non-remittent major depressive disorder: An 8-week double-blind, randomized, controlled trial
Finding: In 107 treatment non-remittent MDD outpatients, adjunctive SAMe 800 mg/day showed no significant between-group difference vs placebo (p=0.51). Response 54.3% SAMe vs 50.0% placebo; remission 43.5% vs 38.3%. No effect on any secondary outcome. Authors concluded 800 mg/day SAMe is not an effective adjunctive treatment in MDD.
View on PubMed Regulatory & authoritative positionsL4/L5 · FDA / EMA / NIH ODS / Cochrane / Mayo …
L4a US FDA
Cautious
A lab-made form of SAMe is sold as a dietary supplement in the U.S., but SAMe has been sold as a prescription drug in parts of Europe for decades. source↗
L4d TW TFDA / 衛福部
Neutral
從 1970 年代起，歐洲已廣泛使用 SAMe 來治療憂鬱症及其他生理狀況；1999 年美國則依《膳食補充劑健康與教育法》核准口服腸溶 SAMe 劑型，使消費者得於零售通路購買。 source↗
L5a NIH Office of Dietary Supplements
Cautious
L5b Mayo Clinic
Cautious
While research has shown that SAMe has a positive effect in treating depression, most studies weren't well designed and included a small number of people. However, SAMe appears to be safe and might be effective in treating depression and osteoarthritis. source↗
L5c Cleveland Clinic
Neutral
L5d Harvard Health
Cautious
L5e Specialty Society (condition-mapped)
Cautious