MEDSCAPE: Psychiatric Ads May Mislead Re: 'Chemical Imbalance'

[mindfreedom-news at intenex.net]

BELOW is a forwarded news article
published by MEDSCAPE about how
psychiatric drug corporations may
be misleading the public with
advertisements about a "chemical
imbalance" that has not been found.

~~~~~~~~~

MEDSCAPE MEDICAL NEWS

Advertisements for SSRIs May Be Misleading

by Laurie Barclay, MD

Nov. 8, 2005 -- Advertisements in the
U.S. for selective serotonin reuptake
inhibitors (SSRIs) are not based on
science, according to an essay
published in the December issue of
the Public Library of Science (PLoS)
Medicine. Since the 1960s,
investigators have proposed the
"serotonin hypothesis," which
implicates low brain levels of
serotonin in depression. However,
extensive research to date has failed
to confirm this theory.

In 1965, Joseph Schildkraut suggested
that depression was linked to low
levels of norepinephrine, but
investigators subsequently proposed
that serotonin was the responsible
neurotransmitter. Numerous studies to
identify reproducible changes in
neurotransmitter levels in the
cerebrospinal fluid of clinically
depressed patients, or to induce or
correct depression by manipulating
brain serotonin levels, were
inconclusive and fraught with
methodological limitations.
Contemporary research has failed to
prove any serotonergic lesion in any
mental disorder, according to the
PLoS Medicine essay.

Consumer advertisements for SSRIs in
the U.S. "typically claim that
depression, or other psychiatric
condition, is probably caused by a
chemical imbalance of the
neurotransmitter serotonin, and that
SSRIs correct this imbalance," lead
author Jeffrey R. Lacasse, MSW, a PhD
candidate at Florida State University
College of Social Work in
Tallahassee, told Medscape. "They
routinely use visual portrayals of a
nerve synapse demonstrating the
action of SSRIs, showing a 'chemical
imbalance' which is then 'corrected'
by the medication."

Gordon McCarter, PhD, an assistant
professor of biological sciences at
the College of Pharmacy of Touro
University in Vallejo, California,
agreed that the evidence for an
"imbalance" in neurotransmitters
causing depression is
"circumstantial" and "more and more
tenuous." He noted the dearth of
studies showing any measurable
difference in serotonin or
norepinephrine between depressed
patients and controls, with the
limited positive findings based on
suicide victims. Dr. McCarter was not
involved in the PLoS Medicine essay.

"This doesn't mean there isn't a
difference, [but] it may be too
localized and too small to measure
with current techniques," Dr.
McCarter told Medscape. "Serotonin
clearly plays a role in some [cases
of] depression and blocking its
reuptake clearly helps many depressed
patients, but this may be a
symptomatic approach. Current
thinking is that genetics, perhaps
regarding serotonin-handling
molecules in some cases, combined
with life history affects the
likelihood that stressful life events
will trigger a depressive episode.
Stating that depression is caused by
a chemical imbalance is extremely
simplistic."

The evidence that is usually used to
support the claim of a serotonin
imbalance, according to Mr. Lacasse,
is the efficacy of SSRIs. Because
SSRIs have an effect on depression,
and SSRIs affect serotonin, the
conclusion touted in the ads is that
depression is due to serotonin
imbalance. However, this line of
reasoning may be inherently flawed;
aspirin may relieve headache, but we
do not therefore conclude that
headaches are caused by low levels of
aspirin in the brain.

Another difficulty with using the
efficacy of SSRIs in depression to
bolster the serotonin hypothesis is
that the efficacy itself is
problematic. A meta-analysis cited in
the PLoS Medicine essay reviewed all
clinical trials of antidepressants
submitted to the U.S. Food and Drug
Administration (FDA). This
meta-analysis showed that placebo
duplicated about 80% of the
antidepressant response, and that
more than half of pharmaceutical
company-sponsored trials failed to
show a statistically significant
difference between antidepressant and
placebo. Moreover, antidepressants
that do not affect serotonin are as
effective as SSRIs in reducing
symptoms of depression, and even
placebo and nonpharmacologic
treatments have been shown to have
robust effects.

"The etiology of depression and
anxiety is still a mystery, and this
is reflected in the scientific
literature," senior author Jonathan
Leo, PhD, a professor of neuroanatomy
at Lake Erie College of Osteopathic
Medicine in Bradenton, Florida, told
Medscape. "The Diagnostic and
Statistical Manual of Mental
Disorders does not list serotonin as
a cause of any mental disorder; it is
simply one neurotransmitter that
continues to be investigated. And the
prescribing information for the SSRIs
does not claim that their mechanism
of action is to correct a chemical
imbalance, although this is exactly
what the advertisements claim."

The PLoS Medicine essay cites a
recent review article on depression
published by John Mann in the New
England Journal of Medicine, which
lists a dozen chemicals potentially
involved in depression, and several
pharmacologic interventions that do
not affect serotonin; and a Cochrane
review showing no major difference in
efficacy between SSRIs and tricyclic
antidepressants. Bupropion and
reboxetine, which do not
significantly affect serotonin, were
shown to be as effective as SSRIs in
the treatment of depression. In
recent randomized controlled trials,
St. John's wort and placebo were each
more effective for depression than
SSRIs, and exercise was as effective
as the SSRI sertraline.

"The pharmaceutical industry has
managed to convey a misleading
picture," Joanna Moncrieff, MD, a
senior lecturer in psychiatry at
University College London, U.K., told
Medscape. "I speak to quite a few
journalists, and they are shocked to
hear that the link between serotonin
and depression is very tenuous and
the research conflicting and not
convincing. The psychiatric
profession and academic researchers
are probably also partly to blame for
glossing over the weakness of the
research."

The FDA is charged with the duty of
regulating direct-to-consumer
advertising (DTCA), and with ensuring
that it is grounded in scientific
evidence. However, the PLoS Medicine
essay points out the "remarkable, and
possibly unparalleled" disconnect
between the scientific literature and
the SSRI ads.

"All prescription drug advertising is
to be fair and balanced, with an
accurate portrayal of the benefits
versus the risks," FDA spokesperson
Crystal Rice, from the Trade Media
and Exhibits Center for Drug
Evaluation and Research, told
Medscape. "There would be no
difference with regard to these drugs
-- as with any drug, these same rules
apply. Concerning what information
must be disclosed and in what manner,
and how that would apply specifically
to this situation, this is done on a
case-by-case basis and dependent on
the specific product and specific
promotional piece."

The FDA requires that drug
advertising present the most serious
risks and the most common risks,
according to Ms. Rice. The Division
of Drug Marketing, Advertising, and
Communications works closely with the
medical review divisions and others in
the FDA in determining which specific
risks should be presented. The FDA
has requested a labeling change for
antidepressants, now requiring that
drug companies include the warning
about increased risk of suicidality
in their advertising promotion. Until
Feb. 28, 2006, the FDA has an open
docket seeking the public's input on DTCA
http://www.fda.gov/OHRMS/DOCKETS/98fr/05-18040.htm.

"I don't really think [DTCA
statements about serotonin in
depression] are untrue, especially if
they are presented with qualifiers
such as 'research suggests' and
'scientists believe,' but they might
be bordering a little on unbalanced,
so I think the FDA could be doing a
little better in this regard," Dr.
McCarter said. "By implying that
depression is 'only' a chemical
imbalance, [the ads] are leaving out
very important aspects of the
depression story. A 'balanced'
statement on the etiology and
treatment of depression directed at
consumers should note that certain
forms of counseling or psychotherapy,
in particular cognitive-behavioral
therapy, is equally effective in the
treatment of major depression as
antidepressant medication, and that
together they are even better."

The PLoS Medicine essay notes that
SSRIs are now among the best-selling
drugs in medical practice, thanks in
large measure to successful
advertising campaigns. The marketing
emphasis in SSRI ads on a theoretical
serotonin imbalance appears to be
specific to the U.S., causing
"striking differences" from
advertising in the EU. Unlike the
U.S., the EU does not allow DTCA.

"Two very different pictures emerge
of the same exact medication,
depending on government regulation
and marketing practices," Dr. Leo
said. "It's two very different
political climates. We suspect that
one important factor is the amount of
influence that pharmaceutical
companies hold in a particular
society."

The British equivalent of the FDA,
known as the Medicines and Healthcare
products Regulatory Agency (MHRA), and
U.K. medical literature published in
the British Medical Journal and
elsewhere have preceded the FDA in
their open criticism of U.S.
marketing practices for SSRIs.

"I personally feel that all drug
advertising should be banned both to
professionals and patients," said Dr.
Moncrieff, who is also a founding
member and cochair of the Critical
Psychiatry Network. "Information
about drugs should come from
independent sources that people can
access if required, and not be
constantly shoved into people's
faces. We currently have a
manufactured epidemic of
psychological disorders, and the drug
industry is at least partly to blame."

However, Dr. Leo and Mr. Lacasse are
not convinced that a ban on DTCA
would eliminate misinformation about
the serotonin theory.

"We suspect that this theory is
repeated to patients by physicians,
and that the problem is not limited
to DTCA," they explain. "Depression
and anxiety are complicated issues
that cannot be explained in a
30-second commercial.... When the
serotonin theory is portrayed with
clever visual portrayals that do not
accurately represent the neuroscience
research, consumers are led to believe
that medication is necessary for the
treatment for depression."

Ostensibly absent from commercials is
information concerning alternatives to
medication, including evidence from
randomized controlled trials that
psychotherapy and exercise are
effective in the treatment of
depression; and significant adverse
effects from SSRIs, including very
high rates of sexual dysfunction.
Other issues typically omitted from
DTCA are difficulty in withdrawing
from SSRIs in some patients; the
self-limited nature of depression for
many people, in whom it lasts for only
several months; and the robust placebo
effect documented in the overwhelming
majority of clinical trials.

Dr. McCarter suggests that the FDA or
even the National Institutes of Health
might provide clear and concise
information on the issues surrounding
specific prescription drug classes,
and treatments for diseases in
general.

"Perhaps drug companies could be
required, whenever they wish to
advertise a prescription drug, to pay
into a fund that provides public
service announcements regarding that
particular therapeutic area," he
said. "Maybe there should be required
a general 'balance statement,'
produced by the FDA to accompany any
advertising -- short and sweet, not
like the notorious 'brief summaries'
that were fired out in staccato or
squished into microscopic text on the
next page."

Another important concern embedded in
DTCA is the issue of informed consent,
which Mr. Lacasse and Dr. Leo believe
is essential to an ethical and
productive physician-patient
relationship.

"If a patient comes into the office
believing the serotonin theory and
the doctor doesn't take the time to
correct them, we wonder where that
leaves the issue of informed consent,
and especially the issue of potential
risks and benefits," they point out.
"We suspect that many consumers
believe the serotonin theory to be
more scientifically based than it is,
and that they might have chosen an
alternative approach to their
distress if they were fully informed.
These ads work to confound informed
consent, essentially."

One example is a television ad for
sertraline (Zoloft), which portrays a
serotonin imbalance and claims,
"Prescription Zoloft works to correct
this imbalance." DTCA for fluoxetine
(Prozac), Paxil, escitalopram
(Lexapro), and other SSRIs has voiced
comparable messages.

"In terms of real-life effects of
this advertising, we are concerned
that this oversimplified theory has
become the intellectual justification
for 10-minute office visits which
result in the prescription of
antidepressants for a variety of
ill-defined conditions," Mr. Lacasse
concluded. "In general, people need
to be more skeptical regarding claims
of chemical imbalance as explanation
for psychological distress."

On the other hand, Dr McCarter
believes that heightening consumer
awareness of depression may produce
some positive effects.

"While the 'chemical imbalance'
message is overly simplistic and may
mislead the audience away from an
understanding of the cognitive and
behavioral aspects of depression, if
it gets someone who is suffering from
this disease to think about seeing a
doctor or even just to consider for
the first time that there is a
biological aspect to it, then some
overall benefit has been achieved,"
he said. "I just wish there were
other equally prominent information
sources that were not produced under
a profit motive."

Drs. Lacasse and Leo report no
competing interests and no commercial
funding for this work.

PLoS Med. 2005;2(12):e392

Reviewed by Gary D. Vogin, MD

- end of forwarded MEDSCAPE article -

~~~~~~~~~~

ACTION: Please help inform the public
by forwarding this news article to
appropriate places on and off the Internet.

WOULD YOU LIKE MORE INFORMATION about
psychiatric drug industry false advertising
about a "chemical imbalance"?

See the MindFreedom alert about the
PLoS essay referred to by MEDSCAPE here:

http://www.intenex.net/pipermail/mindfreedom-news/2005-November/ 
000014.html

or use this smaller url:

http://tinyurl.com/cbzzu

~~

THE FULL TEXT OF PLoS ESSAY:

http://medicine.plosjournals.org/perlserv/?request=get- 
document&doi=10.1371/journal.pmed.0020392

or use this smaller url:

http://tinyurl.com/8vywy

~~~~~~~~~

PRINT PDF (205 K) VERSION OF PLoS ESSAY:

http://medicine.plosjournals.org/archive/1549-1676/2/12/pdf/ 
10.1371_journal.pmed.0020392-p-L.pdf

or use this smaller url:

http://tinyurl.com/bcwf3

~~~~~~~~~

See MindFreedom's debate with Pfizer, Inc.,
manufacturer of Zoloft:

http://www.mindfreedom.org/mindfreedom/pfizerlies.shtml

Also see the historic debate with the
American Psychiatric Association resulting
from MindFreedom's 2003 hunger strike:

http://www.mindfreedom.org/mindfreedom/hungerstrike.shtml

~~~~~~~~~~

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