St. John's Wort Equivalent to World's Best-selling Antidepressant
St. John's wort (Hypericum perforatum L., Clusiaceae) is
one of the world's best-researched phytomedicines. One criticism
from the medical community, however, has been that most of the
clinical research on St. John's wort (SJW) has matched it against
the tricyclic antidepressants, rather than newer, more commonly
used agents. It should be noted that during the time at which
most SJW research was conducted, doctors favored the tricyclic
antidepressants. Now, physicians claim that in order for research
results to be truly meaningful, SJW must be compared with selective
serotonin reuptake inhibitor (SSRI) antidepressants.
The latest clinical trial investigating the antidepressant effects
of SJW does just that, by comparing it to fluoxetine (Prozac®)
- the world's best selling antidepressant (Schrader, 2000). This
German study was funded not by a pharmaceutical company, or by
a company that manufacturers SJW extract, but by the German medical
insurance system. The results were impressive. The study concluded,
the two treatments are essentially equipotent in their
antidepressant effects." Furthermore, the researchers asserted
that there was "
no evidence to suggest an advantage
in treating these patients with fluoxetine."
The randomized, double-blind, six-week study involved 240 outpatients
from seven different internal medicine practices. One hundred
and fourteen participants took fluoxetine at a dose of 20 mg twice
daily; 128 took hypericum extract at a dose of 250 mg twice daily.
The hypericum extract used in the study (Ze 117, Zeller AG, Switzerland)
was a 50 percent ethanolic extract with an herb to extract ratio
of 4-7:1. All patients were evaluated by psychiatrists using the
Hamilton Depression Scale (HAM-D), a standard test used to evaluate
symptoms of depression.
After six weeks of treatment, improvement in the two groups was
nearly identical. Beginning with mean HAM-D scores of 19.5 and
19.65 for the fluoxetine and hypericum groups, respectively, at
endpoint the two groups had scores of 12.2 and 11.54, respectively.
The results were also virtually identical for sub-scores of the
depression index. For example, the depression sub-score (4.0 vs.
3.7) and anxiety sub-score (2.7 vs. 2.5.) for SJW and Prozac,
respectively, were deemed equivalent, as measured by the latest
scientific research model, using what pharmaceutical science considers
the best treatment for depression.
Perhaps more importantly, however, safety as measured by this
study was far superior for SJW, which caused consistently fewer
and less serious side effects. Of all the side effects reported
in the study, 72 percent were reported by the fluoxetine group,
and only 28 percent by the SJW group. In addition, side effects
were much more serious in the fluoxetine group, and included "retching,
dizziness, tiredness, anxiety-associated symptoms, and erectile
dysfunction." The only significant side effect seen with
SJW was gastrointestinal upset, but according to the researchers,
this was "mild and did not compromise the efficacy or patient
On the other hand, the seriousness of side effects with fluoxetine
"may have reduced the magnitude of its beneficial effects.
Unlike severely depressed patients, those mildly affected are
less tolerant of side effects of antidepressants." In fact,
the authors pointed out that "patients with mild illnesses
are often reluctant to accept treatments that cause side-effects
that are as upsetting as the symptoms of their underlying disease."
This may be reflected in the dramatic difference in "responder
rate" in the study, which was 60 percent in the SJW group
and only 40 percent among those taking fluoxetine. "Responders"
were defined as those who had a reduction of 50 percent or more
in depression score.
The authors summarize the results of this study in a way that
clearly outlines the superiority of SJW as the medication of choice
for mild to moderate depression. They noted, "A clear advantage
of hypericum over fluoxetine with regard to safety seems incontrovertible,
whether one considers the overall incidence of side-effects, the
number of patients reporting events, or the type of event. The
one type of event reported on hypericum, GI disturbance, is still
less frequently reported for this treatment than for the synthetic
antidepressant. When treating patients with mild to moderate depression,
hypericum (in the form of St. John's wort Ze 117 extract tablet)
should be considered as one of the first treatment options based
upon both efficacy and safety, particularly in cases where treatment
is a choice between fluoxetine and hypericum."
The SJW extract used as the test substance is standardized, but
this detail was omitted from the research publication. Ze 117
is standardized to 0.5 mg hypericin per 250 mg tablet, according
to the manufacturer's CEO (Hasler, 2000). - Rob McCaleb, HRF
[Hasler A. July 12, 2000. Personal communication.
Schrader E. Equivalence of a St. John's wort extract (Ze 117)
and fluoxetine: a randomized, controlled study in mild-moderate
depression. International Clinical Psychopharmacology 2000;