Most people have heard of St John’s Wort and omega-3s. But did you know there are a lot more over-the-counter herbal products and supplements out there targeting depression?In our review of clinical trials of these products, we found 64 different over-the-counter (OTC) products that have been evaluated for depression – but with differing levels of evidence for each.
Why look at this topic?
Depression is increasingly common, to the extent that it is sometimes described as an epidemic. In the UK, 11.3% of people report mild depressive symptoms, 4.2% moderate depressive symptoms, and 3.3% severe depressive symptoms. Many of us know someone who struggles with minor or moderate levels of depression, or we may struggle from depressive symptoms ourselves. Often, we will try many things to help, such as antidepressants, talking therapies, meditation, or exercise. One common treatment people try is OTC products which are widely available and accessible from supermarkets, pharmacies, health food shops, and online.
Once you start looking into which OTC product might be helpful, the list becomes endless. This is particularly the case if you read online blogs or look at social media promotion of various products. How do we know what is evidence-based? What products are effective? Are they safe?
Given my background, I was naturally interested in understanding which products might be helpful and where research should focus next.
What did we do?
As a team we reviewed 23,933 study records and 1,367 papers. Overall, we found 209 clinical trials that assessed 64 OTC products for depression where the product was taken for more than one week. We 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. We also checked if there was 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 – different countries have different regulations, and some products are commonly used in some places but not in others. Two volunteers from the public helped us to narrow our choices, which helped us exclude some very obscure products, such as eels’ head powder!
So what did we find?
We anticipated a lot of studies, but over 200 was more than we expected! We had to recruit an intern to help us to sort through the findings. Studies 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. We grouped our findings 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 to 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 to 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. 41 products had only a single trial available. This is helpful as a starting point, but does not give us conclusive evidence.
It’s good news that very few safety concerns arose from any of these products, whether they were taken alone or in combination with antidepressants. However, a healthcare professional should always be consulted on whether a product might interact with something else you are taking. 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.
What do we recommend for the future?
Whilst 89 trials tested products in combination with antidepressants, few looked at whether taking OTC products whilst having talking therapies has an additional effect. There was also only one study that 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.
So, what we have is relatively conclusive evidence for some products. When we looked at surveys of what people commonly take,chamomile, lavender, lemon balm, and echiumemerged 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.