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Legacy AI grade · Sources dated 2026-07-25. Not expert reviewed. Coverage is limited to the listed sources. About the new summary workflow

Creatine for Depression

Verdict: Published with Warning

Across 4 PubMed studies, the evidence for Creatine in Depression grades Tier C — weak evidence. Effective, but with safety or population caveats.

C 🟠 C Weak Evidence Published with Warning

🔬Why this grade7-layer evidence engine

Creatine shows a modest signal for depression in some trials, but evidence is limited. PMID 41189312 is a depression-focused meta-analysis; PMID 41558805 is a systematic review only.

The anchor RCT (PMID 22864465) in women with MDD showed benefit, while PMID 29177955 in bipolar disorder was null. Evidence is population-specific and not broadly generalizable.

Tier C appropriately reflects weak, mixed evidence. Do not extrapolate anxiety or athletic performance creatine data to depression treatment.

⚖️

Scoring transparency

All scores computed by a 7-layer evidence engine — fully auditable
Raw score 0.47
D
C
B
A
S
← counter-evidence / ineffectiveeffective / strong evidence →
Final grade
C · Published with Warning
Confidence
79%
Broadly consistent
Evidence level
E2
Multiple high-quality MAs (≥2 independent, consistent)

How strongly each layer supports this effect

lower = less supportive
L2 PubMedPrimary literature
0.45
L3 MechanismPlausibility
0.45
L1 ExamineGlobal benchmark
0.50
L5 Clinical bodiesAuthoritative stance
0.50
L11 AI re-checkIndependent read
0.50
Against Mixed Supports
▸View the full decision path (audit trail)
  1. compute_raw_score — 加權公式: L2×0.30 + L3×0.25 + L5×0.25 + L11×0.10 + L1×0.10 = 0.472
  2. tier_from_score — 依分數區間映射至 tier letter
  3. apply_hec_rules — 高階證據未達主導 (1 positive vs 1 negative)，由 raw_score 決定
  4. tier_strict_requirement_check — Tier 條件達標，未降階
  5. detect_disputes — 偵測到 0 個 hard + 1 個 soft dispute
  6. decide_status — 依 tier + dispute 結果決定 status

📄PubMed studies (4)L2 · primary research & systematic reviews

Creatine supplementation for treating symptoms of depression: a systematic review and meta-analysis
PMID: 41189312 2025 統合分析 n = 1,093
Finding: Across 11 RCTs (n=1093) creatine produced a statistically significant but clinically trivial reduction in depressive symptoms (SMD -0.34, 95% CI -0.68 to -0.00; ~2.2 HAM-D points, below the 3.0-point minimal important difference), with GRADE-rated very-low certainty and trim-and-fill indicating bias favouring creatine.
Effect size: SMD -0.34 (95% CI -0.68 to -0.00); remission OR 3.60 (95% CI 1.76-7.56, 3 trials); no significant effect on treatment response
View on PubMed
The Effect of Creatine Monohydrate on Mental Disorders: A Systematic Review of Randomized Controlled Trials
PMID: 41558805 2026 系統性回顧 n = 238
Finding: A narrative synthesis of 5 RCTs (6 articles; 126 creatine vs 112 placebo) found creatine added to escitalopram superior to SSRI+placebo (Cohen's d=1.13 at 8 weeks) and beneficial as CBT augmentation, but no significant benefit in adolescent females or bipolar depression, concluding creatine is a promising adjunct that still needs large trials.
Effect size: Cohen's d=1.13 at 8 weeks for creatine+escitalopram vs SSRI+placebo (single-trial estimate, not pooled); null in adolescent and bipolar subgroups
View on PubMed
A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder
PMID: 22864465 2012 RCT (double-blind) n = 52
Finding: Women receiving 5 g/day creatine plus escitalopram had significantly greater HAM-D improvement than placebo as early as week 2 and through week 8, with no difference in adverse events, suggesting creatine accelerates and enhances SSRI response in women with MDD.
🟠 Limited quality Government Effect size: Significantly greater HAM-D improvement from week 2 (between-group p<0.05); creatine n=25 vs placebo n=27
View on PubMed
A randomized, double-blind, placebo-controlled, proof-of-concept trial of creatine monohydrate as adjunctive treatment for bipolar depression
PMID: 29177955 2018 RCT (double-blind) n = 35
Finding: The primary endpoint was null (MADRS change creatine vs placebo p=0.560, Cohen's d=0.231), though a secondary remission analysis favoured creatine (52.9% vs 11.1%, p=0.012, OR=9.0); 2 of 17 creatine patients developed hypomania/mania.
🟠 Limited quality Academic Effect size: MADRS change p=0.560, Cohen's d=0.231 (primary, null); remission 52.9% vs 11.1%, p=0.012, OR 9.0 (secondary)
View on PubMed

🏛️Regulatory & authoritative positionsL4/L5 · FDA / EMA / NIH ODS / Cochrane / Mayo …

L4a US FDA
Supportive
FDA has no questions source↗
L4b EU EFSA
Supportive
cause and effect relationship has been established source↗
L4c UK NHS
Not addressed
Supplements containing creatine are widely used by athletes to improve performance source↗
L5a NIH Office of Dietary Supplements
Supportive
May increase strength, power source↗
L5c Cleveland Clinic
Neutral
Researchers are also looking into whether creatine supplements may help people with cognitive (mental) conditions, including dementia. If you have bipolar disorder, creatine may also increase your risk of mania. source↗
L5e Specialty Society (condition-mapped)
Cautious
The current study suggests that creatine augmentation of SSRI treatment may be a promising therapeutic approach that exhibits more rapid and efficacious responses in women with major depressive disorder. source↗
✓PMID 100% verifiedevery citation checked via NCBI Entrez
🔬4 PubMed studiesindependently re-checked by multiple sub-agents
engine_version: v1.0 claim_id: CLM-COND-depression-INT-creatine-001 繁體中文版 →