Review of supplements for sleep and mood reveals gaps in knowledge

The prevalence of depression, insomnia and anxiety are increasing in the UK​, and sales of OTC products​ for sleep reached £63 million in 2022. 

Researchers from the University College London, UK, conducted a scoping review of the research behind these supplements to discover the strength of scientific backing, with a focus on the older population.

The review, published in BMC Complementary Medicine and Therapies,​ included 47 trials and 10 ongoing trial protocols with most studies targeting insomnia (n=25), followed by depression (n=20) and mixed conditions (n=2). Where reported, most products appeared to be safe for use, but studies rarely included people with multiple comorbidities or taking concomitant medication.

Melatonin for insomnia (n=19) and omega-3 fatty acids for depression (n=7) had more substantive evidence compared to the other products.

"It is particularly important to assess products in older people, who may be taking other medications or have comorbid conditions, as surveys suggest concurrent use of OTC medication, herbal medicines, prescription medication and dietary supplements are common," the researchers stated.

The review​

After pilot searches in Medline and Embase to identify suitable keywords and subject headings, the team carried out a comprehensive search of CENTRAL, MEDLINE, EMBASE, PsycInfo, CENTRAL and AMED (inception to Dec. 19, 2022).

Depression​

For depression, omega-3 fatty acid capsules had the strongest scientific backing (n=7). Six out of seven studies comparing omega-3 fatty acids to placebo found a significant improvement in depression symptoms.

L-acetyl-carnitine was tested in two small studies (n=80 and n=28), which found the ingredient to be effective compared to fluoxetine and a placebo.

Vitamin D3 showed mixed effects across two studies compared to placebo, which may be attributable to large dosage differences (50,000 IU weekly vs 1,200 IU per day).

Vitamin B12 and folic acid effectively reduced depressive symptoms compared to placebo, but a combination of B6, B12 and folic acid showed no additional effects alongside citalopram in people with comorbidities.

5’-Methyltetrahydrofolic acid (50 mg/day for 8 weeks) showed no difference to Trazodone in people with dementia.

Six trials (sample sizes 60 to 161) evaluated six herbal products, including ashwagandha (Withania somnifera​) and vacha (Acorus calamus​ L.), Saraswata Churna (a powdered mixture of 13 herbs), gingko (Gingko biloba​ L.)​ as an adjunct to venlafaxine in people with ischaemic stroke, lavender tea (Lavandula​)​, St. John’s Wort (Hypericum perforatum​ L.) alone and with valerian (Valeriana officinalis​ L.). All showed positive effects.

Melatonin was the most commonly evaluated dietary supplement for sleep (n = 17 studies in 18 publications, samples sizes 22 to 930). Effects were found in both general older populations and people with cardiovascular disease, Parkinson’s disease and on haemodialysis, with mixed effects in Alzheimer’s disease and similar effects to Zolpidem in people with colorectal cancer.

Thirteen out of 18 studies reported safety data and indicated melatonin was well tolerated in older people with no or only mild adverse events (AEs) and few severe adverse events (SAEs).

Three other dietary supplements were evaluated. Magnesium reduced insomnia compared to a placebo in 46 people. Tart cherry juice reduced insomnia severity, but had no effect on other sleep parameters. Pear pulp with added magnesium, melatonin and zinc reduced all insomnia-related parameters compared to pear pulp alone.

Gaps in knowledge

The review concluded that "surprisingly few OTC products were investigated for depression, anxiety or insomnia in older people", and those that are out there were mostly tested in those without comorbidities or with a single specific comorbidity.

"Given 65% of people aged 65–84 have multiple long term conditions, rising to 82% in the over 85s, most trials have been conducted in unrepresentative populations," the researchers wrote.

They found few products had multiple trials, apart from omega-3 fatty acids (n=7), which had more substantive evidence for depressive symptoms, and melatonin (n=17) which had more substantive evidence for insomnia.

Most products had a good safety profile where this was reported, but 13 studies did not report safety data. There was a clear gap in the evidence base in products for anxiety in older people, OTC medications such as antihistamines and homeopathic products.

"There is a substantial gap in evidence for OTC products for anxiety in older people," the researchers concluded. "This should be addressed in future trials. Research should also focus on products that are widely used, and these need to be tested in older populations that are similar to those who would use them in practice.”

Source: BMC Complementary Medicine and Therapies​
doi: 10.1186/s12906-024-04585-0​
“A scoping review of over-the-counter products for depression, anxiety and insomnia in older people”
Authors: Frost, R. et al.