Large Review Establishes Evidence for Natural Antidepressants

Depression is too prevalent and become more prevalent every day. Several natural supplements have ben extensively studied. This massive review evaluates some of that evidence.

This massive review included 209 studies. The most studied natural supplements were omega-3’s, St. John’s wort, saffron and probiotics. The most impressive were St. John’s wort and saffron.

St. John’s wort is the king of depression herbs. The review notes a 2017 meta-analysis (J Affect Disord. 2017;210:211–221) of 27 studies that found that St. John’s wort was as effective as, and safer than, antidepressant drugs. In the current review, St. John’s wort was better than placebo. More impressively, when compared to a drug, St. John’s wort equaled the drug 11 times, beat it 4 times and lost only once.

Saffron may be the herb with the fastest growing, most exciting body of research for depression. The review notes a 2019 meta-analysis (Planta Med. 2019;85:24–31) of 9 studies that concluded that saffron is better than placebo and as effective as antidepressant drugs. In the current review, saffron was better than placebo and as good as the drugs.

The review also found that probiotics and vitamin D outperform placebo.

Though they had fewer studies, the review found promising results for folic acid, lavender, zinc, tryptophan, rhodiola, lemon balm, bitter orange and chamomile tea.

Most of the studies that reported on safety found no safety issues with the natural supplements.

This important review adds to the growing body of evidence for the efficacy and safety of natural antidepressants.

Front Pharmacol. July 2025;16:doi.org/10.3389/fphar.2025.1609605.