International Journal of Molecular Sciences · 2 authors, 1 centre
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This narrative review summarizes the epidemiology, pathophysiology, and treatment of depression, with a focus on phytopharmacotherapy. It finds that medicinal plants such as St. John's wort and saffron crocus show comparable efficacy to standard antidepressants for mild-to-moderate depression, with fewer side effects. The review highlights the anti-inflammatory mechanisms of these plants as a key component of their antidepressant action.
**Background:** Depression is a major mood disorder affecting 3.8% of the world's population, with a prevalence of 5.0% in adults and 5.7% in adults over 60 years. It is a leading cause of disability globally. The pathophysiology is multifactorial, involving monoamine deficiency, HPA axis overactivity, inflammation, oxidative stress, gut microbiota dysbiosis, genetic factors, and epigenetic changes. Classical pharmacotherapy includes SSRIs, SNRIs, TCAs, and others, but these are associated with significant adverse drug reactions. Given the high and increasing use of antidepressants, there is interest in safer alternatives, including herbal medicines. This narrative review aims to summarize the epidemiology, pathophysiology, symptomatology, and treatment of depression, with a particular focus on phytopharmacotherapy and the anti-inflammatory effects of medicinal plants.
**Methods:** This is a narrative review employing a non-systematic literature search of PubMed and Google Scholar databases. Search terms included 'depression', 'epidemiology', 'pathophysiology', 'symptomatology', 'management', 'treatment', 'medicinal plants', 'phytopharmacotherapy', and 'phytopharmacodynamics'. One author (LD) selected relevant articles based on titles and abstracts, supervised by a second author (KG). Both review articles and original full-text articles were considered, with preference for results from the last ten years, but older papers deemed important were also included.
**Key Results:** The review discusses the epidemiology of depression globally, noting that approximately 280 million people worldwide suffer from depression. In Europe, the overall prevalence of current depressive disorder is 6.38%, ranging from 2.58% in the Czech Republic to 10.33% in Iceland. In the USA, 6.5% of adults had depressive disorder in 2019. The pathophysiology section covers the monoamine hypothesis, HPA axis dysfunction, inflammatory processes (involving cytokines such as IL-1, IL-6, TNF-α, and CRP), oxidative stress, the microbiota-gut-brain axis, genetic factors (heritability rate of about 37%), and epigenetic mechanisms. The treatment section notes that SSRIs are first-line drugs, and a meta-analysis by Cipriani et al. found agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine to be more effective than other antidepressants. Adverse drug reactions are common; for SSRIs, gastrointestinal problems occur in 17% of subjects, tiredness in 45%, and headache in 34%. The phytopharmacotherapy section details the mechanisms and clinical evidence for several plants: St. John's wort (SJW), saffron crocus, lemon balm, lavender, ginkgo, Korean ginseng, roseroot, magnolia bark, borage, brahmi, and mimosa tree. For SJW, a meta-analysis of 27 trials (3126 patients) found no difference from SSRIs in clinical response or remission, but a significantly lower rate of adverse events. For saffron, a meta-analysis of 5 trials (177 patients) showed reduction in depression symptoms in adults with MDD. The review emphasizes that the antidepressant effects of these plants are due to synergistic and polyvalent actions, including inhibition of monoamine reuptake, MAO inhibition, and importantly, anti-inflammatory effects. For example, SJW inhibits COX-2, IL-6, and iNOS; saffron decreases NF-κB, TNF-α, and IL-6; and brahmi inhibits COX-2 and reduces TNF-α and IL-6.
**Clinical Implications:** Phytopharmacotherapy offers a valuable alternative for mild-to-moderate depression, with a lower risk of side effects compared to classical antidepressants. The greatest clinical experience is with St. John's wort and saffron preparations. However, clinicians must be aware of potential side effects and interactions, particularly with SJW, which can induce cytochrome enzymes and cause serotonin syndrome when combined with SSRIs. The anti-inflammatory properties of these plants align with the psycho-neuro-immuno-endocrinological model of depression, suggesting that future research should focus on immunoregulatory effects. The review calls for more high-quality, large-scale clinical trials to confirm efficacy and safety, as current studies have limitations such as small sample sizes and short follow-up periods.