Depression is one of the most common mental health disorders. According to the World Health Organization (WHO), more than 280 million people worldwide suffer from this condition. It is a leading cause of mental disability and significantly reduces patients’ quality of life. The disease is not limited to low mood alone; it is often accompanied by loss of interest and motivation, sleep and appetite disturbances, decreased energy, difficulty concentrating, and low self-esteem. In more severe cases, it may lead to suicidal thoughts and attempts.
The treatment of depression is based mainly on pharmacotherapy and psychotherapy; however, natural substances are increasingly being used due to their lower incidence of side effects.
One of the best-studied herbal materials with antidepressant activity is St. John’s wort (Hypericum perforatum L.). Alcoholic extracts of this plant contain primarily hypericin, pseudohypericin, hyperforin, xanthones, flavonoids, and procyanidins. These compounds modulate serotonergic, dopaminergic, and noradrenergic neurotransmission, contributing to antidepressant effects.
The following clinical study compared the efficacy of St. John’s wort extract with placebo in patients suffering from mild or moderate major depressive episodes according to the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) of the American Psychiatric Association. The study was conducted by Siegfried Kasper and co-authors in 16 clinical centers in Germany. It was a randomized, double-masked trial lasting six weeks.
Participants received film-coated tablets containing a dry extract of St. John’s wort herb. The study included 332 individuals aged 18–65 years (both men and women), who were randomly assigned to three groups. The first group (123 participants) received WS® 5570 at a dose of 600 mg once daily. The second group (127 participants) received WS® 5570 at a total daily dose of 1200 mg, divided into two doses of 600 mg each. The third group (82 participants) received a placebo.
Treatment efficacy was evaluated based on changes in the 17-item Hamilton Depression Rating Scale (HAM-D-17) scores. Additional assessments included the CGI-S, CGI-I, and BDI scales. Follow-up visits took place at baseline, day 14, and day 42.
Results showed that clinical improvement was observed in 61% of patients taking 600 mg of the extract and 71% of those taking 1200 mg, compared with 45% in the placebo group. Complete remission of symptoms occurred in 31%, 40%, and 15% of participants, respectively. The HAM-D score improved by approximately 5–6 points more than in the placebo group. The main adverse effects reported were gastrointestinal disturbances, all mild and transient, with frequencies comparable to those with placebo.
Based on the results, it can be concluded that both treatment regimens were more effective than placebo, and that St. John’s wort extract is safe and well tolerated. In cases where conventional antidepressants are poorly tolerated or cause troublesome side effects, St. John’s wort extract may represent a safe therapeutic alternative. However, further long-term studies are necessary to confirm its efficacy and safety profile fully.
Based on: Kasper S, Anghelescu IG, Szegedi A, Dienel A, Kieser M. Superior efficacy of St John’s wort extract WS 5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial [ISRCTN77277298]. BMC Med. 2006 Jun 23;4:14. doi: 10.1186/1741-7015-4-14. PMID: 16796730; PMCID: PMC1538611.
