A comprehensive new review published in Frontiers in Pharmacology offers critical insight into over-the-counter (OTC) treatments for depression, clarifying which supplements and herbal remedies truly help and which fall short.
This extensive study analyzed 209 randomized controlled trials (RCTs) involving adults aged 18 to 60, exploring dietary supplements, herbal products, and non-prescription medications commonly used without medical guidance to manage depressive symptoms.
Researchers from Liverpool John Moores University and University College London aimed to cut through confusion surrounding these alternative therapies, which many turn to due to limited access to conventional antidepressants or concerns about side effects.
Study Approach
The team sifted through nearly 24,000 records from five major medical databases up to December 2022, focusing only on oral OTC products tested for at least one week.
They evaluated products against placebos, untreated controls, prescription drugs, or other OTC treatments, categorizing results by product type, population studied, and whether the product was used alone or alongside other treatments. Safety data were also collected where available.
Key Findings on Popular OTC Treatments
Omega-3 Fatty Acids (39 trials): Despite widespread use and substantial research, results were mixed, with over half showing no significant benefit. However, omega-3s may be helpful when combined with antidepressants.
St. John’s Wort (38 trials): This herbal remedy demonstrated efficacy comparable to some prescription drugs and outperformed placebos, though it carries potential drug interaction risks.
Saffron (18 trials): Known as an expensive spice, saffron consistently showed positive effects, especially in postpartum and metabolic-related depression, with few side effects reported.
Probiotics (16 trials): Evidence on mental health benefits is mixed but leans positive; however, studies are small and varied in probiotic strains used.
Vitamin D (14 trials): Mostly beneficial in individuals with deficiency or as an adjunct treatment, though findings were not universally consistent.
The review also noted promising, but less studied, supplements such as folic acid, tryptophan, and zinc, which showed encouraging results particularly as add-ons to other treatments. Some herbal remedies like lavender, lemon balm, chamomile, and Rhodiola had positive but inconclusive evidence.
Safety Profile
Most trials (about 70%) reported on adverse events, with 85% indicating no safety concerns. Side effects, when reported, were typically mild. Only one omega-3 study noted an increase in serious adverse events, but without clear causal links.
Conclusion
While many people seek “natural” options for depression relief, robust evidence supporting their use remains limited. Nevertheless, folic acid, saffron, and St. John’s Wort have shown enough promise to merit further research. According to Dr. Rachael Frost, senior author from Liverpool John Moores University, some supplements may benefit mild depression, but definitive clinical recommendations are still premature.
