St. John’s Wort for Depression: A Systematic Review

Source: Gaster B, Holroyd J. Arch Intern Med 2000;160:152-156.

In order to address whether st. john’s wort is useful, Gaster and Holroyd systematically reviewed the literature. Gaster and Holroyd chose strict criteria for studies to be included in the analysis. Studies had to be 1) randomized, controlled, and double blinded; 2) limited to patients with depression; 3) had to test St. John’s wort alone and not in combination with other antidepressants; and 4) had to present original data. Articles meeting these criteria were then reviewed to make sure they were methodologically sound. Of the initial 388 citations, only eight studies met both the inclusion criteria and were felt to be methodologically sound. In six of the eight trials, the dose was 300 mg three times daily of 0.3% hypericum extract.

Of the four studies testing hypericum extract against placebo, all found significant improvement in Hamilton depression scale (HAMD) scores. Four studies tested hypericum extract in comparison to tricyclic antidepressants. These studies were marred by the use of low doses of TCAs which may have reduced the response rate for patients on TCAs. Even so, in these studies, TCAs were slightly more effective than hypericum or similar in efficacy.

Hypericum was generally well tolerated. The most frequently reported side effects were nausea, rash, fatigue, restlessness, and photosensitivity. Among these, the most common side effects were nausea (0.6%) and rash (0.5%). Only 1.2% of patients in the eight studies had to discontinue hypericum because of side effects. In five of the eight studies, laboratory monitoring was performed and there were no changes in cell counts, liver function tests, or creatinine.

Comment by Martin Lipsky, MD

Depression is one of the most commonly encountered problems in primary care. One barrier to treatment is the resistance of many patients to prescription medications. For many individuals, an increasingly popular alternative is St. John’s wort that is available as an over-the-counter preparation. Many of our patients are either taking St. John’s wort or want to know more about it.

Unfortunately, there are only a paucity of good studies that examine the effectiveness of St. John’s wort. This paper, which reviewed the available literature, suggests that St. John’s wort is effective for mild to moderate depression. particularly impressive is the side effect profile. However, despite the few side effects noted, recent articles indicate that St. John’s wort may have drug interactions with medications such as digoxin.1,2

Proponents argue that St. John’s wort is a low-cost alternative for patients with mild depression. However, before it becomes a first-line agent, more information is needed to determine its role among the various agents available for treating depression. For example, no study has compared it to better tolerated antidepressants such as SSRIs. In addition, the lack of standardization among the different preparations remains an obstacle for recommending its use. Still, it may have a role for patients who view it as a more acceptable medication or who cannot afford or tolerate standard antidepressants.


1. Johne A, et al. Clin Pharmacol Ther 1999;66:338-345.

2. Barber MF. Intern Med Alert 2000;22:9-10.

Dr. Lipsky is Professor and Chair, Department of Family Medicine, Northwestern University Medical School, Chicago, IL.

Which of the following statements is false?

a. St. John’s wort is effective for mild to moderate depression.

b. St. John’s wort is more effective than tricyclic antidepressants.

c. St. John’s wort is better tolerated than many other antidepressants.

d. St. John’s wort is an inexpensive alternative for treatment of mild to moderate depression.