St John's Wort and Depression.

(February 2002)

The concern about the effectiveness of the St John's Wort in depression centers on the design and methodology of the studies. A report in British Medical Journal, December 11, 1999 from Germany summarizes a well-conducted study on 259 patients, most of whom had moderate depression. One group of 106 patients received St John's Wort 350 milligrams three times a day; the second group of 106 patients were given an older standard drug (imipramine); and 47 controls were given no active drug. Five different measures were used to analyze improvement over an eight-week period.

During that study period, the control group improved significantly; but, in each measurement, St John's Wort showed an additional 25 to 40 percent benefit and was at least as good and probably better than the imipramine.

St John's Wort looked better in two respects; the actual scores in the different tests and a higher percentage of patients who showed a definite response to treatment (up to 20 percent more patients showed a significant response).

An anxiety scale was included in the five measurements of St John's Wort's effectiveness. It appeared to offer significant benefit for anxiety at six weeks, but not at eight weeks.

There were no serious adverse effects among those given St John's Wort.

The authors concluded:

"At an average dose of 350 milligrams three times daily, Hypericum (St John's Wort) extract was more effective than placebo and at least as effective as 100 milligrams of imipramine daily in the treatment of moderate depression. Treatment with hypericum extract is safe and improves quality of life. Since hypericum products may vary considerably in composition, the results cannot be generalized to other extracts. Hypericum extract may be considered as an alternative first choice treatment in most cases of mild to moderate depression without psychotic symptoms."

Commentary: This is a good study, but there are still some issues. The very significant improvement by the controls mandates caution in interpreting the additional modest benefit for those given St John's Wort. Additionally, it was not ideal to test St John's Wort against an older anti-depressant instead of using more effective newer drugs - and, even then, the dose of imipramine was kept deliberately low. On the other hand, the dose of St John's Wort was 1050 milligrams - equivalent to 6 grams of crude herb - higher than the usually recommended dosage.

Another study, based on forty psychiatric, internal medicine, and general medicine practices, from Germany published in the September 2, 2000 issue of the British Medical Journal comes to the similar conclusion. In this study, proper doses of both St John's Wort and imipramine were used. St John's Wort also reduced anxiety. However, in this more recent study, treatment lasted only six weeks so there was no determination whether the benefit lasted beyond that time. Furthermore, there was no control group receiving an inactive placebo, so it is impossible to say how much better St John's Wort was than an inactive placebo.

for treatment of mild to moderately severe (but not severe) depression. St John's Wort does look reasonably good for that degree of depression, but there are two caveats. First, the herb has only been shown to be effective for short-term treatment; there is no evidence that supports its use beyond eight weeks. Second, qualified health care personnel, not the person suffering from depression, family, or friends, will have to determine whether the depression is deeper than mild to moderately severe. Additionally, for definitive judgment on St John's Wort, we will still need to await the results of the large study now being conducted in the United States. That should be available soon. It is also likely there will be some surprises in regard to safety - either relating to St John's Wort itself or to interactions with other drugs. In this regard, two brief reports in the respected British journal The Lancet, February 12, 2000 documented that St John's Wort interfered with the actions of a powerful drug used to treat HIV/AIDS and a drug used to prevent rejection after organ transplantation. More such unpleasant surprises are virtually guaranteed. It may also interfere with some other prescription drugs.

Preparations sold in the United States vary in the amount of active ingredient; in part because of an inadequate oversight by the Food and Drug Administration.

There are those who advocate using St John's Wort for anxiety, but, there are inadequate data supporting that claim. The finding in one of the studies of apparent improvement at six weeks, but no significant benefit at eight weeks, mandates caution.

for treatment of anxiety.

Philipp, M, Kohner, R, Hiller, K.D. Hypericum extract versus imipramine or placebo in patients with moderate depression. British Medical Journal. Vol 319. (December 11) Pgs 1534-1539. 1999.

Woelk, H., et al. Comparison of St John's Wort and imipramine for treating depression. British Medical Journal. Vol 321. (September 2) Pgs 536-540. 2000.