The findings are thought to be the first to demonstrate that the herbal can reduce depression symptoms in people with a severe form of the condition.
Hypericum extracts have already been shown to help in patients with minor depression but in patients with more severe depression, the efficacy has been disputed. The only randomized controlled trial to date in patients with severe depression was underpowered, according to the authors.
In the online issue of the British Medical Journal (10.1136/bmj.38356.655266.82), they report that half of those who took St John's Wort for six weeks found their symptoms in decline, while only a third of those taking the widely used anti-depressant Paroxetine went into remission.
The team from Charite Medical School in Berlin and Dr Willmar Schwabe Pharmaceuticals recruited 301 men and women aged 18-70 who had moderate to severe depression from German mental health centres.
They took either 900mg of the hypericum extract WS 5570 three times daily or 20mg a day of the anti-depressant drug Paroxetine, a well-known selective serotonin reuptake inhibitor (SSRI) drug, for six weeks.
Participants taking Paroxetine also suffered more side-effects, reporting 269 adverse effects over the treatment period compared to 172 adverse effects (most commonly stomach disorders in both groups) reported by those taking the herbal.
This is important because severe depression has a high risk of chronicity.
The World Health Organisation predicts that depression will become the second leading disease in 2020 after heart disease, based on its burden to healthcare. It is currently the fourth most significant, affecting more than 120 million people worldwide.
"The results thus indicate that in a group of patients in whom the appropriateness of hypericum extract was previously disputed, the antidepressant efficacy of the herbal drug is at least comparable with the effect of one of the leading synthetic antidepressants," write the authors.
They also welcome more research in this area.
"The convincing results for hypericum extract observed in this trial deserve independent confirmation by other research. We are assessing efficacy in long-term treatment for which the drug can be an interesting option because of its favourable ratio between efficacy and tolerability in the ongoing continuation phase," they add.
Dr Jochen Muehlhoff, marketing information manager at Dr Willmar Schwabe, told NutraIngredients.com that the study had generated a strong media response and would likely have a big impact on sales.
"It will definitely have a big impact on sales to physicians who follow clinical trials closely," he said.
He noted however that it is not clear how the results would impact the more volatile supplement market. The WS 5570 extract is sold as a supplement in the US but on the OTC market in Germany.
Leading anti-depressant drugs, such as the one tested in this trial, make annual sales above $1 billion.