What's the evidence behind natural remedies for depression?

Hundreds of medicinal plants have been used in folk medicine to fight depression, according to research published by the International Journal of Innovative Science and Research Technology (IJISRT).^[]

Universal understanding of these plants may be compromised because they go by local names in different parts of the world, but certain ones have been recognized for their antidepressant effects, according to IJISRT.

Medicinal plants also inspire the development of novel agents for depression. These agents could prove useful in patients who are drug-refractory or struggle with adverse effects, as reported in an article published by Planta Medica.^[]

Why plants?

Synthetic antidepressants and anxiolytics can have adverse effects including sexual dysfunction, headaches, and dependency. But authors of a review published in Molecules found that herbal medicines used for the same indications as synthetic antidepressants led to a 45% decrease in adverse effects.^[]

Regulation of herbal supplements

Many of these herbal treatments are found in dietary supplements and over-the-counter medicines in the US and the rest of the Western world, according to the Molecules research.

Dietary supplements and ingredients are governed by different FDA regulations than those applied to “conventional” foods and traditional drugs. Manufacturers of dietary supplements and ingredients, for instance, are not allowed to market adulterated or misbranded products.

Although the manufacturers must evaluate their products’ safety and labeling, the FDA can move against any misbranded or adulterated product that makes its way to market.^[]

On the other hand, the FDA currently limits non-prescription drug products, such as those that can be labeled with sufficient information for consumers to appropriately self-select and use.

Limitations in labeling, however, can impair the communication of information necessary for consumers to choose what they need without the supervision of a physician, according to an FDA press release.^[]

Evidence-based examples

The following are four evidence-based examples of medicinal plants used for depression.

Lavender. For perspective, the European Medicines Agency has approved therapeutic indications for lavender based on traditional uses for mental stress, exhaustion, and sleep disturbance. Lavender can be served in tea or as a tincture or essential oil, according to the Molecules research.

Limited clinical research has pointed to improved outcomes in patients with mixed anxiety and depression who are taking lavender oil compared with those taking placebo, as reported in Molecules.

Patients who are hypersensitive to herbal supplements should avoid lavender. There are some cases in the literature of dermatitis secondary to lavender oil, as well as accounts of gynecomastia in three prepubertal boys.

Patients with open wounds should avoid lavender baths. The sedative effects of lavender could also result in sedation, which is dangerous in individuals operating heavy machinery, according to Molecules.

Lemon balm. The leaves of this perennial plant, which is also known as common palm, are used as herbal medicine. The European Medicines Agency has approved lemon balm for mental stress and as a sleep aid based on traditional uses.

Active ingredients include monoterpene aldehydes, sesquiterpene derivatives, monoterpene glycosides, and flavonoids. In rat brains, aqueous lemon balm had GABA transaminase activity; it had anxiolytic and sedative hypnotic effects in mice brains.

Although relying on heterogeneous studies, a 2021 meta-analysis of randomized clinical trials involving lemon balm showed that it improved acute anxiety and depression symptoms, as reported in the Molecules research.

Saffron. One of the world’s most expensive spices, saffron is also used in traditional medicine. Active ingredients include antioxidants. Regarding psychotropic mechanisms, the ingredients crocin, crocetin, and N-acetylcysteine are cited in the literature as helping alleviate symptoms of depression, according to the Molecules study.

A 2013 meta-analysis demonstrated that saffron can improve depressive disorder, with a 2014 systematic review suggesting the efficacy of saffron was comparable to synthetic antidepressants. These findings are backed up by additional randomized control trials.

As for adverse effects, saffron field workers have shown increased rates of miscarriage, and this is also the case in animal studies, as a result, this remedy should be avoided during pregnancy.

St. John’s wort. This perennial flower is endemic to Eurasia, and the flower is used as an herbal medicine. Active ingredients include phloroglucinol derivatives, flavonoids, procyanidins, tannins, and xanthones, according to Molecules.

Dry extracts block the reuptake of serotonin, noradrenaline, and dopamine, along with downregulating β-adrenergic receptors, which is also an action of synthetic antidepressants. Based on clinical evidence, the European Medicines Agency has approved St. John’s wort for the acute treatment of mild depression.

A 2017 meta-analysis demonstrated that the clinical benefits of St. John’s wort are comparable to those of SSRIs. It also reported a lower dropout rate in those taking this herbal medicine, according to the Molecules article.

St. John’s is notorious for its drug interactions, as it induces CYP3A4, CYP2D9, CYP2C19, and the P-glycoprotein. This supplement is incompatible with some drugs, as interactions could lead to increased toxicity or ineffectiveness.

Other potential adverse effects include gastrointestinal disturbance, restlessness, and fatigue. Overdose is also possible, which leads to seizures and confusion.