This is a story about an herb that is commonly used as a first-line
remedy for the blues, hypericum perforatum, generally known as St. John's
wort. "Popular Herbal Remedy Fails to Relieve Depression," headlines
trumpeted in April 2001, based on a report in the Journal of the American
Medical Association (JAMA).
But depression is a shadowy world in many ways. Somewhere before
the blues turn black and self-perpetuating, the joy drains out of life.
Is that a normal trough or a diagnostic category? It all depends on how
(and when) people suspect that something is wrong.
The shadows inherent in a malady like depression lengthen
dramatically when there are agents to be tested for treating it. On
precisely which nerve ending does psychic pain dance and how do you
target it? To get right down to it, how do you interpret a study which
showed that, indeed, St. John's wort failed to produce a therapeutic
response -- but which failed to drop the other shoe in public. Not only
did St. John's wort not work, neither did the placebo pill it was pitted
against, when placebos have a 30% to 50% response against depression on
their own.
In response to numerous questions raised by the JAMA study, and
concerns about the outcome of a major study of St. John's wort funded by
the National Institutes of Health and due to be released later this
summer, the Council for Responsible Nutrition recently convened a press
conference to air important issues in the evaluation of drugs against
depression. Among the points:
* Depression is a difficult disorder in which to test drugs. Fifty
percent or more of trials of antidepressants fail to show a
response.
* "No one single trial can ever be considered definitive," declared
neuropsychopharmacologist Jerry Cott, Ph.D., former chief of
psychopharmacology research at the National Institute of Mental Health.
"You have to weigh all of the clinical trials."
* There are at least 31 trials of hypericum in the peer-reviewed
literature showing it is beneficial for mild to moderate depression.
"When one shows no benefit, you just don't discard 31 trials and change
clinical practice," explained Tieraona Low Dog, M.D., assistant clinical
professor of family medicine at the University of New Mexico.
* Patient selection is crucial. Patients selected for the JAMA
study were chronic refractory depressives, observed Norman E. Rosenthal,
M.D., clinical professor of psychiatry at Georgetown University. "On
average they had depression for two years with many agents having been
tried before. In my experience with depression at that level and with
that history, any simple intervention is unlikely to work."
* A study must be designed with enough sensitivity to demonstrate
effects. One important way of achieving this is to include a comparison
antidepressant of known effect. However, no such comparison drug was used
in the JAMA study.
* There is no one magic drug for all people. Depression is a
complex disorder having many pathways through brain and body. Synthetic
antidepressants do not work on all patients, nor are they acceptable to
all.
* Many patients and physicians wish to have available a therapeutic
agent that is not stigmatizing, has minimal side effects and that allows
patients to make decisions for themselves about how to cheer themselves
up.
What kills so many studies in depression is the high level of
placebo response. One way to minimize the placebo effect is by increasing
the severity of the illness. "Unfortunately," said Dr. Cott, "there's a
very fine line between reducing the placebo response and reducing the
response in the therapeutic category. There may have been a legitimate
desire to improve the power of the study but it may not have had the
desired effect."
Tags:
alternative medicine,
american medical association,
depression,
diagnostic category,
herbal remedy,
institute of mental health,
jama study,
journal of the american medical association,
malady,
national institute of mental health,
national institutes of health,
nutrition,
placebo pill,
psychic pain,
remedies,
st john s wort,
trough
