Supplements for mood
Saffron, EPA, SAMe, and curcumin — the four monotherapies that beat antidepressants in the 2025 NMA.
The 2025 Cheng network meta-analysis (192 trials, 17,437 patients) ranks four nutraceuticals as monotherapy superior to standard antidepressants: saffron (SMD 0.69), curcumin (0.62), omega-3 EPA+DHA (0.60), and SAMe (0.52). As ADJUNCTS to antidepressants, zinc adds the largest effect (SMD 1.59). Caution: every serotonergic supplement on this list (5-HTP, tryptophan, SAMe, St John's Wort, saffron, rhodiola) carries serotonin-syndrome risk if combined with SSRI/SNRI/MAOI without psychiatrist input.
Evidence summary
The numbers on the cards are the same composite as the supplement pages: efficacy, safety, research, onset, cost, and drug-interaction ratings, from 20 to 100. The strongest records on this page are Zinc, Inositol (high-dose, psychiatric), and Inositol myo-form (PCOS/metabolic). A higher score is a stronger record in the database, not a personal recommendation.
Who should be careful
- Pregnancy, breastfeeding, children, and anyone taking a prescription drug should talk with a clinician before using this list.
- Do not stack products from this list that sedate, thin the blood, or lower blood sugar with medicines that do the same thing.
Comparisons and topic guides
81
Zinc
72
Inositol (high-dose, psychiatric)
72
Inositol myo-form (PCOS/metabolic)
78
Folate (5-MTHF)
72
Saffron (Crocus sativus)
72
Lactobacillus casei Shirota
72
Lactobacillus helveticus/B. longum R0052/R0175
70
Bifidobacterium longum
69
Saffron Affron (standardised extract)
65
Algal EPA (standalone)
65
Uridine monophosphate (UMP)
64
Vitex / Chasteberry (Vitex agnus-castus)
62
S-Adenosylmethionine (SAMe)
44
Mucuna pruriens
60
St. John's Wort
59
Black cohosh (Cimicifuga racemosa)
56
Activated B complex (methylated)
56
DLPA (DL-Phenylalanine)
55
Lion's mane mushroom
53
Tryptophan (L-tryptophan)
52
Hericium erinaceus mycelium (Amyloban 3399)
50
Cannabigerol (CBG)
48
Agmatine sulfate
46
5-HTP
Educational reference, not medical advice. Discuss any supplement change with a qualified clinician before acting on this list.