Study Analyzes 64 Natural Remedies for Depression, and Only a Few Really Work

A review of over-the-counter (OTC) supplements and herbal products aimed at treating depression found that while some natural remedies show real promise, the evidence for many is weak or non-existent.

Researchers analyzed 23,933 study records and 209 clinical trials, covering 64 different OTC products ranging from well-known options like St John’s Wort and omega-3 fatty acids to more obscure remedies like bitter orange and rhodiola. The findings, published in Frontiers on July 14, 2025, suggest that only a handful of these products have strong scientific backing.

The Most Recognized: St John’s Wort, Saffron, Probiotics, and Vitamin D

Among the products with the most substantial evidence:

• St John’s Wort (38 trials) and saffron (18 trials) often showed positive effects, performing similarly to prescription antidepressants

• Probiotics (18 trials) and vitamin D (14 trials) also showed consistent benefits compared to placebo.

• Omega-3 fatty acids (39 trials) had mixed results, with fewer studies showing a significant effect compared to placebo.

  
  

Emerging Contenders

A group of 18 products showed “emerging evidence,” meaning they’ve been tested in multiple trials but need more research. The results so far are promising though. Notable names include:

• Folic acid, lavender, zinc, tryptophan, rhodiola, and lemon balm, which demonstrated encouraging results in several studies.

• Chamomile tea, Persian lavender, and bitter orange, which each showed positive effects in trials.

On the other hand, popular supplements such as melatonin, magnesium, and curcumin produced mixed results, and SAMe and prebiotics did not outperform placebo.

What About Safety?

The review found very few safety concerns overall, even when products were taken alongside antidepressants. However, the authors noted a lack of consistent safety reporting—only 69% of studies fully documented side effects. They recommend that anyone considering OTC supplements for depression consult a healthcare professional to avoid potential drug interactions.

What’s Next for Natural Remedies for Depression?

The authors stress the need for more high-quality trials, especially for herbal remedies widely used by the public but barely studied, such as ginseng, ginkgo, peppermint, and orange blossom. They also call for more research into whether combining OTC products with therapies like counseling or medication could offer added benefits.

With depression affecting an estimated 11% of adults in the UK alone (and another 21 million U.S. adults), the findings could help guide both consumers and clinicians toward evidence-based natural options. But the researchers caution against assuming all “natural” remedies are effective without proper data.