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BACKGROUND AND OBJECTIVES: St. John's wort (SJW) extracts are currently being used to treat depression of various degrees of severity. While many studies have shown it to be superior to placebo, data regarding the effectiveness of using SJW as a stand-alone treatment compared with standard antidepressants has yet to be proven conclusively. This study aims to understand the advantages and disadvantages of SJW as a treatment modality for depression.

METHODS: The authors searched PubMed, JAMA network, Springer Link, Elsevier, Google Scholar, and Scientific Progress databases, from 2011 through August 2021, using the following keywords: St John's wort, Hypericum perforatum, depression, antidepressant, complementary alternative medicine, economic evaluation depression St. wort, St John's wort and depression, antidepressant interactions. This yielded a total of 27 papers following a thorough removal of irrelevant content and dissemination in languages other than English.

RESULTS: In patients with mild and moderate depression, SJW proved superior to placebo. Certain studies comparing the efficacy of SJW versus selective serotonin reuptake inhibitors (SSRIs), especially fluoxetine, reported SJW to be more efficacious, while the majority reported no significant difference. Tricyclic antidepressants were also found to have similar efficacy as SJW. Moreover, treatment with SJW was also found to reduce postmenopausal depression. Regarding the safety profile, although SJW is better tolerated with fewer adverse effects when compared to standardized antidepressants, its predisposition to causing fatal serotonin syndrome, when used in conjunction with other serotonergic agents and drug interactions noted with CYP 450 drugs, raises a question in the safety profile.

CONCLUSION: It is essential to acknowledge that SJW has been used as a treatment measure in Germany. Despite being only listed as a dietary supplement by the FDA and not a drug, SJW has shown to be comparable, if not more efficacious, than most standard treatment options for depression. SJW does prove to be an exciting piece of pharmacotherapy in the realm of mental health and post-menopausal treatment. More prospective studies will help us better understand its efficacy in mild and moderate depression and its ability to serve as a long-term agent. Considering its mechanism of action, its role in relieving patients suffering from an anxiety disorder is also worth considering.

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