Authors' objectives

To address whether St John's Wort is useful for the treatment of depression.

Searching

MEDLINE, EMBASE, PsychINFO, and the Cochrane Library databases were searched for articles published between January 1980 and September 1998, using the following search terms: wort and hyperic*. In addition, manual searches of reference lists were conducted. Trade journals, manufacturers and retail sellers, and experts in the fields of depression and herbal medicine were contacted to try and identify any further studies. Only English language articles were selected.

Study selection

Assessment of study quality

Articles were analysed for methodological quality using a standard checklist that included the following: presented original data that had not been published previously; reported baseline demographics; described steps taken to ensure blinding; used a standardised outcome measure as defined by the Consensus Conference on the Methodology of Clinical trials of Antidepressants; performed an intention-to-treat analysis; and provided a full accounting of all study drop-outs and reasons for their discontinuation. The authors do not state how the papers were assessed for quality, or how many of the reviewers performed the quality assessment.

Data extraction

The authors do not state how the data were extracted for the review, or how many of the reviewers performed the data extraction. Data extracted included: year of publication, name of drug treatment, dosage of drug treatment or comparator, number of participants and outcomes.

Methods of synthesis

Results of the review

Eight studies were included in the review (n=985). Four studies were comparisons of hypericum with placebo (n=374) and four others compared hypericum with other anti-depressants, all tricyclic antidepressants (TCA) (imipramine, maprotiline and amitriptyline) (n=985).

Of the four trials that compared hypericum with placebo, three found a statistically significantly (p<0.001) higher responder rate in the hypericum group: 67% vs 28%, 81% vs 26%, and 56% vs 15%. In the fourth study the ratio of responders on the two treatments was 70% vs 47% (p=0.15). Of the four studies that compared hypericum extract with TCA, three reported responder rates but none found a statistically (or clinically) significant difference between the treatments. The authors state that the doses of the TCA drugs used were all at the lower end of, or below, the manufacturers recommended dosages.

In the four trials that compared hypericum extract with TCA drugs, patients taking low-dose TCA were 78% to 33% more likely to experience an adverse effect than those taking hypericum. The most frequently reported side-effects of hypericum are reported to be nausea, rash, fatigue, restlessness and photosensitivity. The side-effects of TCAs are not reported. In five of the eight studies intensive laboratory monitoring was performed. This revealed no changes in complete blood cell count, liver function test results, or serum creatinine in patients taking hypericum extract.

Cost information

The review lists the per tablet and per month costs of five preparations of hypericum extract available in the USA. There is no economic analysis of the use of St John's Wort.

Authors' conclusions

Although larger, more methodologically rigorous studies are needed, there is a modest amount of data that suggests that hypericum extract is safe, well tolerated, and probably more effective than placebo in the treatment of mild to moderate depression. More data are required, however, to assess its use in severe depression and its efficacy in comparison with other agents.

CRD commentary

The review addressed a pertinent question with well defined inclusion and exclusion criteria. The literature search was comprehensive in terms of the databases searched and reference lists checked with adequate attempts to identify unpublished material. A flaw in the search strategy was it restriction of articles to those in the English language. Given the authors assertion the 'It (St John's Wort) has long been a popular antidepressant in Germany' it is possible that significant articles may have been missed. The quality assessment of the included studies was adequate although the authors do not state if this was conducted by one or more reviewers, or whether any checking of this assessment was performed. The details of the individual studies are summarised briefly in tables which give the dosage of hypericum extract, name of reference drug where available, number of patients and number of responders with p value. The narrative synthesis of the data appears adequate, although, given that all the placebo comparisons utilise the same outcome measures it is surprising that a quantitative pooling was not performed for these data. The data as presented in this review support the authors conclusions. The review provides only limited information on the adverse effects of St John's Wort.

Implications of the review for practice and research

Practice: St John's Wort is more effective than placebo in the treatment of mild to moderate depression.

Research: More data are required to assess the use of St John's Wort in severe depression and to compare its efficacy with that of other antidepressants.

Bibliographic details

Gaster B, Holroyd J. St John's Wort for depression: a systematic review. Archives of Internal Medicine 2000; 160(2): 152-156. [PubMed: 10647752]

Original Paper URL

http://archinte.ama-assn.org

Other publications of related interest

This additional published commentary may also be of interest. Stevinson C. Further confirmation of the efficacy of St John's wort for depression. FACT 2000;5:194-5.

Indexing Status

Subject indexing assigned by NLM

MeSH

Antidepressive Agents /adverse effects /therapeutic use; Depression /drug therapy; Double-Blind Method; Humans; Hypericum /adverse effects /therapeutic use; Phytotherapy; Plants, Medicinal; Randomized Controlled Trials as Topic

AccessionNumber

12000008102

Database entry date

31/03/2001

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.