Supplements for mood and depression
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.
83
Zinc
79
Inositol (high-dose, psychiatric)
79
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)
62
Chasteberry/Vitex standardised (BNO 1095)
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
46
Lithium orotate (low-dose)
Educational reference, not medical advice. Discuss any supplement change with a qualified clinician before acting on this list.