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 focussed 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 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.

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The study, “Demographic and health characteristics associated with fish and n-3 fatty acid supplement intake during pregnancy: results from pregnancy cohorts in the ECHO program” was led by investigators at the Harvard Pilgrim Health Care Institute and published February 27 in Public Health Nutrition. The study is timely, arriving as the World Health Organization and U.S. National Academies both plan to issue reports on the risks and benefits of fish consumption in pregnancy later this year.

“Omega-3 fatty acids are essential nutrients for supporting positive health outcomes. Getting enough of these nutrients during pregnancy is vital for preventing preterm birth and promoting optimal child health and neurodevelopment,” said the study’s lead author Emily Oken, Harvard Medical School professor and chair of the Department of Population Medicine at the Harvard Pilgrim Health Care Institute.

Prior research looking at the demographic characteristics associated with fish and supplement intake during pregnancy has been limited, involving fewer participants and older data that may not represent current intake. The study team addressed this research gap using information on fish consumption reported by 10,800 pregnant women, and supplement intake information from 12,646 pregnant women from cohorts across the U.S. participating in the Environmental influences on Child Health Outcomes (ECHO) program.

Study results showed that nearly 25% of participants reported not eating fish or eating it less than once per month, and only 16% took supplements. Contrary to expectations, supplement use was less common among those who consumed less fish, putting that group at even higher risk for insufficient omega-3 fatty acid intake.  Similar to supplement use, older participants with a higher income and education consumed more fish. However, unlike supplements, fish consumption was higher in those with racial/ethnic identities other than non-Hispanic White and in those who used tobacco and nicotine products. The highest likelihood of supplement intake was among those who were older, had a higher education and income, and were non-Hispanic White or Asian. Additionally, supplement use was less common among those at higher risk for adverse pregnancy outcomes as a function of using tobacco or nicotine products or having a higher BMI.

“Current evidence shows that the benefits of maternal consumption of low-mercury fish, or in its place, omega-3 supplements, outweigh any potential  risks,” says Dr. Oken. “Our study provides updated information to inform much needed public health advice and resources to support clinical conversations to encourage consumption of low-mercury fish during pregnancy and intake of omega-3 supplements among those who do not consume fish.”

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