Amy Denney, The Epoch Times, Jul 18, 2025
For years, Stacey Stevens felt trapped in what she described as wanting to "unzip from her skin"-a darkness so consuming she didn't want to exist. The solution that finally lifted her depression wasn't found in a psychiatrist's office or on a prescription pad, but in the form of probiotics.
"I didn't want to be here. I didn't want to go anywhere. I didn't want to talk to anybody," she described her former self to The Epoch Times. "The hopelessness surrounded me. It was dark, and I really didn't like myself because I was in such a bad place."
Stevens's story isn't unique. Many are turning to readily available solutions for their depression, and for good reason.
After analyzing more than 25,000 studies, researchers have identified five over-the-counter products that perform as well as prescription antidepressants in clinical trials-a finding that may change how people think about naturally treating one of the most common mental health conditions affecting 21 million American adults.
A systematic review published in Frontiers in Pharmacology analyzed and categorized clinical evidence for 64 products, finding five to be highly effective and many others showing promise. From an original pool of more than 25,000 studies and papers, researchers narrowed their focus to 209 clinical trials in which adults aged 18 to 60 took a product for more than one week for depression.
The intent of the review was to help consumers separate fact from fiction about herbal remedies for depression, particularly in a social media landscape where content can exaggerate a single study regardless of merit, according to Rachael Frost, lead author of the study and senior lecturer at Liverpool John Moores University.
"I really wanted to map the landscape for the products that are out there in terms of where the evidence is and what we have a bit more confidence in, and where we need to focus future research efforts," she told The Epoch Times.
Products with substantive evidence were omega-3s, St. John's wort, probiotics, saffron, and vitamin D. St. John's wort and saffron outperformed placebos, with results similar to prescription antidepressants. Probiotics and vitamin D were also more likely to reduce depressive symptoms than placebos.
The most commonly studied herbal product, St. John's wort, was taken by people with a depression diagnosis and used as a monotherapy for those with no other diagnoses.
It was compared with a placebo in 26 trials, to a drug in 10 trials, and a lower dose in one trial. St. John's wort offered similar or better results compared with antidepressants.
Of note, however, St. John's wort can lessen the effect of oral contraceptives, cancer therapies, statins, and some drugs that suppress the immune system. Additionally, if taken with antidepressant medications, it can cause a dangerous buildup of serotonin in the body.
Subjects in 14 trials had a depression diagnosis, while four focused on those with depressive symptoms. Saffron products were mostly compared with a placebo and used as a monotherapy.
A range of extracts were evaluated, and subjects in the trials had a range of comorbid conditions, including cardiovascular disease, postpartum, menopause, and Type 2 diabetes. Eight trials found positive results compared with placebo, and saffron fared better than prescription medications in six trials.
Of 16 trials on probiotics, 13 involved strains of multiple microbes. All trials compared probiotics with a placebo. Eight trials involved subjects with a diagnosis of depression, while eight were for those with symptoms of depression. In five studies, subjects had a range of comorbidities, and six studies involved probiotics used as an adjunct to antidepressant therapy.
In eight of 14 trials on vitamin D, it was used alongside prescribed medication and cognitive behavioral therapy and compared with a placebo in nine trials, with six favoring the vitamin D. Of note, other types of comparisons showed mixed results.
Dosing varied from daily to weekly and from 1,000 IU to 100,000 IU. In nine trials, participants had a depression diagnosis, while six trials were done with those experiencing symptoms of depression.
Of 39 trials on omega-3s, 37 compared them with a placebo. In 26 trials, subjects had a depression diagnosis, while 12 trials used subjects with symptoms of depression, and one trial was unclear.
In 11 studies, subjects had a range of comorbidities, including six trials with subjects who were pregnant or postpartum. In 16 studies, omega-3s were used alongside antidepressant treatments.
Some over-the-counter products work by modulating neurotransmitters or the hypothalamic-pituitary-adrenal axis responsible for hormone production.
Other products improve symptoms because they are anti-inflammatory, antioxidant, or neuroprotective. Most have a beneficial effect on the gut, affirming the role gut health plays in brain function.
Probiotics work on gut health by introducing beneficial microbes into the gut, which can help establish a healthier gut microbiome and potentially eliminate problematic microbes.
The study also noted 18 additional products-the most promising being folic acid, lavender, zinc, tryptophan, rhodiola, and lemon balm-with emerging evidence of efficacy for depression symptoms. Bitter orange, Persian lavender, and chamomile tea showed positive effects with two trials each.
On the other hand, popular products for depression, such as melatonin, magnesium, and curcumin, had mixed results among multiple clinical trials for use with depression. Finally, 41 products had only a single trial available.
"I think that's heartening to see more opening up in this field. There were more products in this emerging category than I thought there might be," Frost said.
The authors suggested that future research focus more on products with fewer trials and less on those that are already established to be beneficial.
Ashley Murphy, an herbalist and the owner of ABECA Naturals, said she wasn't surprised by the study's findings.
"St. John's wort, I would say, is my fave," she told The Epoch Times. "But because it has some contraindications, I have a love-hate relationship with it. It's incredibly strong and well-studied, which the study talked about."
Only about 10 percent of Murphy's clients take St. John's wort by itself. She often recommends a combination of products rather than a single herb or supplement because clients are often contending with more than one health issue, she noted. It isn't unusual for someone with depression to experience fatigue and be low in vitamin D, magnesium, or micronutrients-or to struggle with another diagnosis.
"We've got to stop trying to just treat the brain when it comes to depression," Murphy said. "We need to make sure people are being systemically supported. I was thrilled to see probiotics as a top way to treat depression. Of course, this is really good news ... because many things can affect our mental health, like the way we digest our food."
The review noted that the products showed no safety issues, with only mild adverse effects, whether the products were used alone or in combination with antidepressants. Still, it's best to discuss new over-the-counter treatments with a health care provider.
"Be a bit cautious and at least tell them what you're taking," Frost said. "Give it a bit of a chance to work, monitor how you're doing, but if you don't see results, do make sure you reach out. If you are experiencing severe depression symptoms, always reach out to a health care provider first."
Anyone interested in trying any product should buy it from a reputable supplier, she said.
"Different dosages and different preparations were tested, and sometimes it's not easy to draw conclusions as to which one is best," Frost added, noting that over-the-counter products may have more adverse events than reported since they are often used outside clinical supervision.
A particular challenge when it comes to tea-a common preparation for herbal remedies-is that it's much harder to quantify. In fact, Frost said there was a lack of studies on teas used for depression-likely due to the difficulties in preparing a placebo for comparison-but that doesn't mean teas or fresh herbs aren't useful.
Another missing link in the research, Frost said, was a lack of trials assessing whether products used in conjunction with therapy-a first-line treatment for depression-have a more robust effect.
Stevens and Murphy both emphasized that mental health issues require a more holistic approach than product usage.
"Health is so multi-faceted, especially if you're dealing with the complexity of anxiety and depression," Stevens said. "If we say nutrition is going to fix all of this, we'd be lying to ourselves. It does help, but we're multi-dimensional-spiritual, emotional, mental, and physical."
For Stevens, who went from daily depression struggles to experiencing symptoms only a few days per month, the journey reinforced that healing often comes from multiple sources working together.
"God has given me the wisdom to know what works best for me, and probiotics is what has worked for me," Stevens said. "I'm just thankful, and my faith has allowed me to embrace some suffering as part of the human experience."
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