St. John’s wort as Effective as Popular Prescription Anti-Depressant

New Trial Demonstrates Herb’s Benefit and Safety Compared to Paroxetine

(Austin, TX). A new clinical study shows that a proprietary standardized extract of St. John’s wort (SJW) was as effective as a common prescription antidepressant drug in reducing symptoms of depression. The study was published Friday, February 11 in the British Medical Journal.1

According to the randomized, double-blind, reference-controlled trial, patients who took 900mg per day of a SJW extract known as WS® 5570 (W. Schwabe, Karlsruhe, Germany) had as much benefit as the pharmaceutical drug paroxetine (Paxil®, GlaxoSmithKline). Paroxetine is a prescription antidepressant drug in the class known as SSRI’s (selective serotonin reuptake inhibitors). In some clinical outcomes, including the primary efficacy endpoint (a decrease of the depression scale score), WS 5570 was superior to the pharmaceutical antidepressant.

A reference-controlled trial is different than a placebo-controlled trial where some of the patients take a placebo (a dose with no active ingredient) as a control to test the effect of the herb or drug being studied. In a reference-controlled trial, the substance being tested is compared directly to a known active material, in this case, the FDA-approved prescription antidepressant drug, paroxetine.

The trial took place in various centers in Germany on patients from the ages of 18 to 70 during the years 2000 to 2003. The full treatment period was for 6 weeks. The patients had been diagnosed to have moderate to severe levels of major depression.

In the study, 251 patients were randomized to receive either 900 mg/day of WS 5570 or 20 mg/day of paroxetine. If a patient did not experience a measurable response after 2 weeks, the dose was doubled. Patients in the SJW group experienced significantly better improvement as measured by the Hamilton Depression Rating Scale (HAMD), an internationally accepted severity scale for depression.

The trial results showed that the SJW actually produced a better HAMD improvement than the pharmaceutical drug; patients in the SJW group experienced a three-point greater decrease in the average HAMD total score compared to the original scores (baseline) than did those taking paroxetine. The improvement in the SJW patients was considered clinically significant: there was a responder rate (50% improvement on HAMD) of 70% for the SJW patients versus 60% for those on paroxetine and a remission rate (HAMD equal or less than 10) of 50% for SJW versus 35% for paroxetine. Further, in the secondary efficacy measures (other standard depression scales including the clinical global impression), SJW was rated superior.

Regarding the safety aspects of the trial, the SJW produced significantly fewer adverse side effects than the drug. The paroxetine patients reported 269 adverse effects compared to only 172 for those on SJW. The most frequently reported adverse effect for both treatments was stomach upset, a fairly common side effect in many clinical trials of this type.

“This trial can help resolve some of the confusion surrounding the potential benefits of St. John’s wort,” said Mark Blumenthal, founder and executive director of the nonprofit American Botanical Council. “Most of the clinical trials show that several types of St. John’s wort extracts produce clinically measurable and significant benefits.”

The results of this trial are consistent with a previously published larger trial in France. In that double-blind, randomized, placebo-controlled trial conducted on 375 subjects, 900 mg per day of the same SJW extract (WS 5570) showed more benefit for depressed patients than did the placebo.2

St. John’s wort (Hypericum perforatum) is a traditionally used herbal remedy for “melancholy” and related depressive states. Numerous clinical trials have demonstrated the overall effectiveness and safety of various SJW preparations. In 1996 the British Medical Journal published a meta-analysis of 23 previously published clinical trials on the hypericin-standardized SJW extract (hypericin is one of the compounds in SJW) concluding that the SJW was safe and effective in treating mild to moderate forms of major depression.3 A highly publicized trial in 2002 funded by the National Center for Complementary and Alternative Medicine of the National Institutes of Health concluded that a hypericin-standardized SJW preparation and the popular prescription antidepressant drug sertraline (Zoloft®, Pfizer) were ineffective in treating patients with chronic moderate to severe depression.4 A follow-up meta-analysis confirms that SJW preparations are more effective than placebo in mild to moderate depression.5

A dietary supplement product of identical strength to WS® 5570 is available in health food stores in the United States under the trade name Perika® (Nature’s Way Products, Springville, UT). Marketed for helping to create a positive mood, this product (known as WS® 5572) contains the same patented, standardized extract as WS 5570. Both WS 5570 and WS 5572 are standardized to SJW’s hyperforin (another of the compounds in SJW) content at levels of 3-5 percent. Most other clinical trials on SJW have utilized an SJW extract standardized to 0.3 percent levels of total hypericins (LI 1370 aka Jarsin 300, Lichtwer Pharma, Berlin, Germany).

SJW has recently received public attention because of its ability to interact with a variety of pharmaceutical drugs, lowering their levels and effectiveness. Blumenthal noted, “The American Botanical Council recommends that consumers who are taking conventional drugs and who also might be considering using St. John’s wort should first consult with a qualified healthcare practitioner to determine if the herb might interact with their drugs.”

About the American Botanical Council

Established in 1988, the American Botanical Council (ABC) is the leading nonprofit, member-based international organization working to educate consumers, healthcare professionals, researchers, educators, industry, and the media on the safe and effective use of medicinal plants. ABC is located on a 2.5 acre site in Austin, Texas where it publishes HerbalGram, a peer-reviewed journal. ABC is also the publisher of The ABC Clinical Guide to Herbs, a continuing education and reference book, which contains extensive monographs on the safety and efficacy of 29 popular herbs, including St. John's wort. More information is available at


1 Szegedi A, Kohnen R, Dienel A, Kieser M. Acute Treatment of Moderate to Severe Depression with Hypericum Extract WS® 5570 (St. John’s Wort): Randomized, Controlled, Double-Blind, Non-Inferiority Trial versus Peroxetine. British Medical Journal 2005, BMJ Online First.

2 Lecrubier Y, Clerc G, Didi R, Kieser M. Efficacy of St. John's Wort Extract WS® 5570 in Major Depression: A Double-Blind, Placebo-Controlled Trial. American Journal of Psychiatry 2002;159(8):1361-1366.

3 Linde K, Ramirez G, Mulrow C, Pauls A, Weidenhammer W, Melchart D. St. John's wort for depression—an overview and meta-analysis of randomized clinical trials. BMJ 1996; 313(7052):253–8.

4 Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St. John’s wort) in major depressive disorder. JAMA 2002;287:1807-14.

5 Linde K, Mulrow CD. St John’s wort for depression. Cochrane Database Syst Rev 2004;(4):CD000448.


Cheryl Dipper Ruiz
Phone: 512-926-4900;
Fax: 512-926-2345
E-mail: [email protected]
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