Many people have heard of St John’s Wort or omega-3 supplements for depression, but there are dozens more over-the-counter (OTC) products being promoted for mood and mental health.
A new review looked at clinical trials of these products to see which have real evidence behind them.
Depression is common worldwide. In the UK, over 11% of people report mild symptoms, 4% moderate symptoms, and more than 3% severe symptoms.
People often try a range of treatments, including antidepressants, therapy, exercise, meditation, and OTC supplements, which are easy to buy in shops or online. But with so many products available, how do we know which ones actually work?
To answer this, researchers reviewed nearly 24,000 study records and more than 1,300 papers, narrowing them down to 209 clinical trials that tested 64 different OTC products for depression over at least one week.
These trials involved adults aged 18–60 with symptoms or a diagnosis of depression. Some studies tested products on their own, others alongside antidepressants, and a few involved people with other health conditions.
The review grouped products into three categories based on evidence:
– Substantive evidence (more than 10 trials)
– Emerging evidence (two to nine trials)
– Single-trial evidence (only one study).
Products with the strongest evidence included omega-3 fatty acids (39 trials), St John’s Wort (38), probiotics (18), vitamin D (14), and saffron (18). Results varied: omega-3s showed benefits in some trials but no effect in others.
St John’s Wort and saffron often worked as well as prescription antidepressants. Probiotics and vitamin D tended to reduce depressive symptoms compared to placebo.
Among the 18 products with emerging evidence, the most promising were folic acid, lavender, zinc, tryptophan, rhodiola, and lemon balm. Other products like bitter orange, Persian lavender, and chamomile tea showed benefits in two trials each.
Popular supplements such as melatonin, magnesium, and curcumin had mixed results, as did cinnamon, echium, vitamin C, and vitamin D combined with calcium. Prebiotics and SAMe did not perform better than placebo.
Forty-one products had only been tested in a single trial, meaning there’s not enough data to draw firm conclusions. Interestingly, some widely used herbal remedies—like ginseng, ginkgo, lime flowers, orange blossom, and peppermint—have never been tested in clinical trials for depression.
The good news is that few safety concerns were reported. Most products appeared safe when used alone or with antidepressants, but interactions are possible, so it’s important to check with a healthcare provider before starting any supplement. However, safety reporting in trials could be better—only about two-thirds of studies fully documented side effects.
The review also found gaps in the research. Few studies examined whether combining OTC products with therapy could boost results, and only one study looked at potential cost savings to healthcare systems (folic acid did not show savings or added benefit).
The authors recommend more research into herbal products that are already popular but have little scientific backing, such as chamomile, lavender, lemon balm, and echium. They also highlight the need to study other common remedies that haven’t been tested at all.
This work provides a clearer picture of which OTC products have real evidence for helping with depression, which are promising but need more study, and which may not be worth the money—yet.
If you care about mental health, please read studies about Cannabis use disorder linked to increased risk of these mental diseases and findings of Some mental health drugs can cause rapid weight gain.
If you care about mental health, please read studies about One sleepless night can reverse depression for days and findings of Scientists find better treatment for older adults with depression.
The study is published in Frontiers in Pharmacology.
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