Many people have heard of St John’s Wort or omega-3 supplements for depression, but there are many other over-the-counter (OTC) products that claim to help.
A new review has looked at what the evidence actually says. Researchers analyzed results from 209 clinical trials that studied 64 different OTC products used to treat depression.
These trials included adults with mild to severe symptoms and focused on treatments taken for more than one week.
Why does this matter? Depression is common and growing in many countries. In the UK, over 11% of people experience mild depressive symptoms, and around 7.5% have moderate to severe symptoms.
Many people turn to various treatments—like medication, therapy, or exercise—and OTC products are often part of the mix. These products are easy to buy at supermarkets, health stores, and online. But with so many choices, it’s hard to know which ones actually work.
The review team sorted through nearly 24,000 study records and over 1,300 papers. They found that some products were backed by more evidence than others. They grouped the findings into three categories: products with strong evidence (10+ trials), those with emerging evidence (2–9 trials), and those studied in only one trial.
The most studied products with strong evidence include omega-3 fatty acids (39 trials), St John’s Wort (38), saffron (18), probiotics (18), and vitamin D (14). Interestingly, saffron was just as effective as some prescription medications in several trials.
St John’s Wort also performed well, often matching the results of standard antidepressants. Probiotics and vitamin D showed moderate improvements in symptoms. However, the results for omega-3s were mixed—some studies found benefits, while others didn’t.
Other products with emerging evidence included folic acid, lavender, zinc, tryptophan, rhodiola, and lemon balm. These showed promise but need more research. Bitter orange, Persian lavender, and chamomile also had positive results in two studies each.
Meanwhile, melatonin, magnesium, and curcumin—popular supplements today—showed mixed effects. Prebiotics and a supplement called SAMe didn’t show better results than a placebo.
There were 41 products that had only one study each. While these results are a helpful starting point, they aren’t enough to make firm conclusions.
The good news is that most of these supplements appeared safe. Few side effects were reported, and most were safe to take alone or alongside antidepressants. However, it’s always best to speak with a doctor before trying something new, especially to avoid any drug interactions.
The review also found that only about 70% of the studies fully reported safety data, so more careful tracking of side effects is needed in future research.
What else is missing from current studies? Not many trials looked at whether taking OTC products alongside therapy improved results. Only one trial even looked at whether these supplements saved money for the healthcare system—and that one didn’t.
Some popular products like ginseng, gingko, lime flowers, orange blossom, and peppermint are commonly used but have not been studied in clinical trials at all.
In summary, this review shows that some OTC products have decent evidence to support their use for depression—especially St John’s Wort, saffron, probiotics, and vitamin D. Others like chamomile, lavender, and lemon balm also show early promise.
More research is needed to confirm which products work best, which are safe, and how they fit into overall treatment plans. For now, this review offers a helpful guide for anyone looking to understand which supplements might actually help with depression.
If you care about mental health, please read studies about how dairy foods may influence depression risk, and 6 foods you can eat to improve mental health.
For more mental health information, please see recent studies about top foods to tame your stress, and Omega-3 fats may help reduce depression.
The study is published in Frontiers in Pharmacology.
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