A large scoping review of more than 23,000 records identified 64 over-the-counter (OTC) supplements, herbal products, and nonprescription medicines that have been evaluated in clinical trials for depressive symptoms. The strongest and most consistent evidence supported St John’s Wort, saffron, probiotics, vitamin D, and omega‑3 fatty acids. Several other products — including lavender, zinc, chamomile, lemon balm, folic acid and rhodiola — showed promising results but need further, higher-quality trials to confirm benefits.
Many commonly used products had mixed or limited results. Melatonin, magnesium, and curcumin produced inconsistent findings across trials, while prebiotics and SAMe did not show clear advantages over placebo in the studies reviewed. Overall, safety concerns were uncommon, but reporting of adverse events was often incomplete, underlining the need for better safety data in future research.
Key Facts:
- Strongest evidence: St John’s Wort, saffron, probiotics, vitamin D, and omega‑3s showed benefit over placebo in multiple clinical trials.
- Emerging options: Folic acid, lavender, zinc, tryptophan, rhodiola, lemon balm, chamomile, and other botanicals have promising but still-limited evidence.
- Safety: Few serious safety signals were reported, whether products were used alone or alongside antidepressants, but trial safety reporting needs improvement.
Source: Frontiers
Overview
Depression is widespread and often treated with a combination of prescription medication, psychotherapy, lifestyle changes, and self-care approaches. Over-the-counter supplements and herbal remedies are commonly used by people seeking extra support for mood, driven by accessibility and public interest. However, the wide range of available products and variable quality of evidence make it difficult to know which options are effective and safe.
Why this review was done
Given the popularity of OTC products for mood and the patchwork of clinical evidence, the authors sought to map the research landscape: which products have been tested, how many trials exist, and where future research should focus. The review aimed to clarify which supplements and herbal medicines show enough promise to warrant larger, better-designed clinical trials.
What the researchers did
The team screened 23,933 records and reviewed 1,367 full-text papers. They included randomized controlled trials in adults aged 18–60 years with depressive symptoms or a diagnosis of depression, where the product was taken for more than one week. In total, 209 clinical trials assessing 64 different OTC products met the inclusion criteria. The review categorized products based on the volume of evidence: substantive (more than 10 trials), emerging (2–9 trials), and single-trial evidence.
Key findings
Products with the largest evidence base included omega‑3 fatty acids (39 trials), St John’s Wort (38 trials), probiotics (18 trials), saffron (18 trials), and vitamin D (14 trials). St John’s Wort and saffron often performed better than placebo and, in some trials, produced effects comparable to prescription antidepressants. Probiotics and vitamin D were more likely than placebo to reduce depressive symptoms in the trials reviewed. Omega‑3 studies were more mixed, with some showing benefit and others not.
Among the 18 products classified as having emerging evidence, folic acid, lavender, zinc, tryptophan, rhodiola, and lemon balm stood out as the most promising. A small number of trials also suggested positive effects for bitter orange, Persian lavender, and chamomile. Several widely used supplements — including melatonin, magnesium, curcumin, cinnamon, echium, and vitamin C — produced inconsistent outcomes. Prebiotics and SAMe did not demonstrate clear superiority over placebo. For 41 products only a single trial was identified, offering preliminary but inconclusive evidence.
Safety and reporting
Most trials reported minimal safety concerns, whether products were taken alone or alongside antidepressants. Still, the authors emphasize that safety data were frequently underreported: only 145 of the 209 studies (69%) fully reported adverse events. Clinicians and patients should discuss potential interactions, and future trials must improve safety monitoring and reporting standards.
Recommendations and research gaps
Research priorities identified by the review include well-powered trials for products with emerging evidence (lavender, lemon balm, chamomile, folic acid, zinc, rhodiola), more studies examining OTC products as adjuncts to psychological therapies, and economic evaluations of OTC interventions. Most trials examined adjunctive use with antidepressants; far fewer assessed combined use with talking therapies. The review also highlighted several commonly used herbs — ginseng, ginkgo, lime flowers, orange blossom, and peppermint — that lack clinical trials and deserve study given their widespread use.
About this depression and psychopharmacology research news
Author: Deborah Pirchner
Source: Frontiers
Contact: Deborah Pirchner – Frontiers
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Understanding the research landscape of over-the-counter herbal products, dietary supplements and medications evaluated for depressive symptoms in adults: A scoping review” by Rachael Frost et al. Frontiers in Pharmacology
Abstract
Understanding the research landscape of over-the-counter herbal products, dietary supplements and medications evaluated for depressive symptoms in adults: A scoping review
Background: Over-the-counter (OTC) herbal medical products and dietary supplements are widely used for self-care of depressive symptoms, but the clinical evidence varies widely across products. Prioritizing future research requires a clear map of the existing trial landscape.
Aim: To explore the size and nature of randomized trial evidence for OTC products used to address depressive symptoms in adults aged 18–60.
Methods: A scoping review was conducted following Joanna Briggs Institute guidance. Databases searched included MEDLINE, Embase, PsycINFO, AMED, and CENTRAL through December 2022. Randomized controlled trials of commonly available OTC products were included and results were summarized narratively by product and evidence volume.
Results: From 23,933 records, 1,367 full texts were screened and 209 randomized trials were included. The largest bodies of evidence were for omega‑3s, St John’s Wort, saffron, probiotics, and vitamin D. Several herbal products with promising preliminary data — notably lavender, lemon balm, chamomile, and Echium — warrant further study. For 41 products only a single trial was available. Few trials reported major safety issues, whether products were used alone or with antidepressants.
Conclusion: Stronger evidence supports St John’s Wort, saffron, probiotics, vitamin D, and omega‑3s. Products with limited but promising data include folic acid, lavender, zinc, tryptophan, rhodiola, and lemon balm. Future research should focus on these candidates, examine adjunctive use with psychological therapies, and improve safety reporting in clinical trials.