By Dr. Irving Kirsch
antidepressant medication is widely regarded as effective, a
recent meta-analysis of published clinical trials indicates
that 75 percent of the response
to antidepressants is duplicated by placebo.
analyses the data submitted to the U.S. Food and Drug
Administration (FDA) for approval of recent antidepressant
We analyzed the
efficacy data submitted to the FDA for the six most widely
prescribed antidepressants approved between 1987 and 1999:
- Serzone and
reported from all well controlled efficacy trials of the use
of these medications for the treatment of depression. FDA
medical and statistical reviewers had access to the raw data
and evaluated the trials independently. The findings of the
primary medical and statistical reviewers were verified by at
least one other reviewer, and the analysis was also assessed
by an independent advisory panel.
More important, the FDA data constitute the basis on
which these medications were approved. Approval of these
medications implies that these particular data are strong
enough and reliable enough to warrant approval. To the extent
that these data are flawed, the medications should not have
In order to
generalize the findings of the clinical trial to a larger
patient population, FDA
reviewers sought a completion rate of 70% or better for these
typically 6-week trials. Only 4 of 45 trials, however, reached
trials, the effect of the active drug is assumed to be the
difference between the drug response and the placebo response.
showed that the FDA clinical trials data indicate that 18% of
the drug response is due to the pharmacological effects of the
medication. Overall, the drug/placebo difference was less than
2 points on the HAM-D, a highly reliable physician-rated scale
that has been reported to be more sensitive than patient-rated
scales to drug/placebo differences.
differences were small, most of them favored the active drug,
and overall, the difference was statistically significant.
There were only 4 trials in which mean improvement scores in
the placebo condition were equal to or higher than those in
the drug condition, and in no case was placebo significantly
more effective than active drug. This may indicate a small but
significant drug effect. However, it is also possible that
this difference between drug and placebo is an enhanced
placebo effect due to the breaking of blind.
These data raise
questions about the criteria used by the FDA in approving
antidepressant medications. The FDA required positive findings
from at least two controlled clinical trials, but the total
number of trials can vary. Positive findings consist of
statistically significant drug/placebo differences. The
clinical significance of these differences is not
To summarize, the
data submitted to the FDA reveal a small but significant
difference between antidepressant drug and inert placebo. This
difference may be a true pharmacological effect, or it may be
an artifact associated with the breaking of blind by clinical
trial patients and the psychiatrists who are rating the
severity of their conditions.
In any case, the
difference is relatively small (about 2 points on the HAM-D),
and its clinical significance is dubious. Research is
therefore needed to assess the additivity of antidepressant
drug and placebo effects. If there is a powerful
antidepressant effect, then it is being masked by a
nonadditive placebo effect, in which case current clinical
trial methodology may be inappropriate for evaluating these
medications, and alternate methodology need to be developed.
the drug effect is as small as it appears when drug/placebo
differences are estimated, then there may be little
justification for the clinical use of these medications.
then, would be to find an alternative, as the clinical
response to both drug and placebo is substantial. Placebo
treatment has the advantage of eliciting fewer side effects.
However, the deception that is inherent in clinical
administration of placebos inhibits their use. Thus, the
development of nondeceptive methods of eliciting the placebo
effect would be of great importance.
Prevention & Treatment, Volume 5, Article 23, July 15,
First Posted in Red Flags
Weekly July 17, 2002
profoundly important study reviews the very foundation that
the pharmaceutical companies used to justify to the FDA that
their drugs work. There is only a small difference between
these drugs and placebo, the review makes clear.
Does this mean
the drugs don't work? Absolutely not. These drugs do prevent
suicides for many. However, the drug may not be working at the
supposed pharmacological or drug level. In many cases, the
effect is due to the power of the person's mind in believing
that the drug will work. Physicians and patients are quick to
discount the placebo effect as due to random chance.
be further from the truth.
effect is indeed quite real and profoundly effective. It
really should be renamed as it has such a poor association. It
might be more accurate to refer to it as the psychological
manifestation effect, which is really the power of one's mind
to manifest into reality what one's consistent and persistent
subconscious is completely neutral with respect to whatever
you believe in. If you continually focus your attention on the
belief that very powerful pills will work in your brain to
make you feel better, they will indeed frequently do just
view that as a beneficial effect, but your mind could just as
easily manifest the opposite effect if you believed that the
pills would not work.
numerous studies documenting the effect that the color or
shape of the pill has on the response. This is obviously
unrelated to the biochemical effect, but still, it makes a
major difference in the outcome of the response. This is
further proof of the psychological manifestation
So what does
this mean for you?
You don't have
to rely on expensive and possibly toxic pills to relieve your
depression or anxiety. You can use simple targeted techniques
acupressure, of which EFT is a preferred technique. If you
are challenged implementing the technique yourself, you can
consult with one of the many well-trained clinicians
across the country. I also have a 9-hour
video set that was recently updated and has an entire new
45-minute section on how you can actually use psychological
acupressure to implement positive goals in your
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