Over-the-counter (OTC) products like St John’s wort and omega-3s have long been touted for helping with depression, but after 64 different products were tested in clinical trials, researchers found varying levels of evidence.
The good news is none had safety concerns, they said in their findings, published in Frontiers in Pharmacology. But on the down side, only a few actually seem to be effective.
Some well-known options – like St John’s wort, saffron and probiotics – showed encouraging results, sometimes comparable to antidepressants. Others, like folic acid, lavender and lemon balm, show emerging promise.
Although few safety concerns were reported, researchers stress the need for better safety reporting and more studies, especially on commonly used but understudied herbal remedies.
While most people have heard of St John’s wort and omega-3s there are a whole lot more over-the-counter herbal products and supplements targeting depression, they said.
Thousands of people seeking help try over-the-counter products, which are widely available and accessible from supermarkets, pharmacies, health food shops, and online.
But how to know what is evidence-based? Which products are effective? Are they safe?
How it was done
The research team led by University College London reviewed 23 933 study records and 1 367 papers. Overall, they found 209 clinical trials that assessed 64 OTC products for depression where the product was taken for more than one week.
The team focused on the most rigorous way of evaluating the effectiveness and safety: clinical trials.
Studies in adults aged 18-60 years with depression symptoms or a diagnosis were included, and they also checked for an age bias by reviewing trials in older people separately – and found there is.
This project is part of a larger series of studies, also looking into products for anxiety and insomnia.
It can be challenging to classify OTC products, as different countries have different regulations, and some products are commonly used in some places but not in others.
The team said two volunteers from the public helped them to narrow their choices, helping them to exclude some very obscure products, such as eels’ head powder.
More than 200 were looked at. These were not always straightforward – some tested multiple doses or products, some were in addition to antidepressants, and in some trials, people had a range of physical conditions in addition to depression.
Findings were grouped into products with substantive evidence (more than 10 trials), emerging evidence (between two and nine trials), and single trials only.
The products with substantive evidence are those that are well known – omega-3s (39 trials), St John’s Wort (38), probiotics (18) and vitamin D (14) – as well as saffron (18), which is important in the Middle East and parts of Asia.
Compared with placebo, fewer omega-3 trials found effects for depression than those that found no effects. However, St John’s Wort and saffron more often showed effects compared with placebo, and similar results to prescription antidepressants. Probiotics and vitamin D were more likely to reduce depressive symptoms than placebo.
Out of the 18 products with emerging evidence, folic acid, lavender, zinc, tryptophan, rhodiola, and lemon balm were the most promising. Bitter orange, Persian lavender, and chamomile tea also showed positive effects in two trials each.
Some products that are gaining in popularity, such as melatonin, magnesium, and curcumin, showed mixed effects upon depression across multiple clinical trials.
Mixed results were also found for cinnamon, echium, vitamin C, and a combination of vitamin D plus calcium. Prebiotics, which support the good bacteria in our gut, and a supplement called SAMe did not seem to be better than placebo, while 41 products had only a single trial available.
This is helpful as a starting point, but does not give conclusive evidence.
Very few safety concerns arose from any of these products, whether they were taken alone or in combination with antidepressants.
The researchers said a higher standard of safety reporting in trials is essential – only 145 (69%) of the examined studies fully reported any side effects from the products.
Suggestions
Although 89 trials tested products in combination with antidepressants, few looked at whether taking OTC products while having talking therapies has an additional effect.
Only one study looked at whether taking an OTC product (folic acid) saved the health service money: it was not more effective than placebo and did not lead to savings, but knowing more about this would be useful in future.
Some evidence is also available for often overlooked OTC products. The outcome was relatively conclusive evidence for some products.
“When we looked at surveys of what people commonly take, chamomile, lavender, lemon balm, and echium emerged as commonly consumed products with an emerging evidence base, which we recommend be studied further. Other commonly used herbal medicines for depressive symptoms are ginseng, gingko, lime flowers, orange blossom, and peppermint, but no studies have evaluated these products.
“Thus, our study has pioneered an exploration into what research is needed to further assess such widely used health care products,” the study authors wrote.
Study details
Understanding the research landscape of over-the-counter herbal products, dietary supplements, and medications evaluated for depressive symptoms in adults: a scoping review
Rachael Frost, Aiman Zamri, Silvy Mathew et al.
Published in Frontiers in Pharmacology on 15 July 2025
Summary
Background
Over-the-counter (OTC) products such as herbal medical products (HMPs) or dietary supplements are a valued part of preventative and supportive self-care for depressive symptoms, but there is a wide array of products available, with differing levels of clinical evidence. It is unclear what the optimal directions for future research in this field are.
Aim
We aimed to explore the size and nature of the evidence base available for OTC products for depression in adults aged 18–60.
Methods
We carried out a scoping review following Joanna Briggs Institute guidance. We searched MEDLINE, Embase, PsycINFO, AMED, and CENTRAL from inception to December 2022, and 10% of the results were screened by two authors and the remainder by one author. We included randomised controlled trials of products commonly available OTC in multiple countries in participants with symptoms or a diagnosis of depression. Results were narratively summarised by the product and volume of evidence available.
Results
Out of 23,933 records found, we screened 1,367 full texts and included 209 trials. The largest volume of evidence was for omega-3s, St John’s Wort, saffron, probiotics, and vitamin D. Among a range of herbal medical products with promising evidence, those most commonly used and thus warranting further research were lavender, lemon balm, chamomile, and Echium. For 41 products, we found only single trials. Few products presented safety issues, whether used alone or adjunctively with antidepressants.
Conclusion
Products with limited but promising evidence included folic acid, lavender, zinc, tryptophan, Rhodiola, and lemon balm, and future research should focus on these products. There is a need for further evaluation of herbal medical products as adjuncts to antidepressants and for exploring their potential benefits when used adjunctively with psychological therapies to support a more integrative approach. Safety reporting in these trials needs to be further improved.
See more from MedicalBrief archives:
Caution vital for combined herb-drug use
Studies show little or no benefit from omega-3 supplements and slight risk
Depression risk fed by ultra-processed foods – Australian study