Depression is an epidemic, and the best weapons against it are
prescription drugs called selective serotonin re-uptake inhibitors
(SSRIs). We all have a substance called serotonin in our brains and
low levels of it are the cause of depression. SSRIs work by bringing
them back to normal. The pills have unpleasant side-effects for some
people, but this is outweighed by the relief they offer from
wretchedness. This has been the prevailing view in medicine for
nearly two decades, during which time the prescribing of
antidepressants in the United States has tripled - more than 100
million prescriptions were written last year.
But change is afoot. The depression model centred on low
serotonin has been seriously undermined by hard facts dug out of
medical research by public health activists - chiefly in Britain
(possibly because it is the natural home of glum stoicism). Those
facts are set out in a new book: Medicines out of Control?
Antidepressants and the Conspiracy of Goodwill. It is a
carefully substantiated and elegantly written indictment of the drug
companies that make SSRIs, explaining why their claims for the
benefits of the drugs are unfounded, and who has hidden this
information from us and how. It is a classic expose and an essential
corrective to the 1990s bestsellers on antidepressants -
Listening to Prozac, Prozac Nation, and The Noonday
Demon - all of which examined the pros and cons of the new
generation of antidepressant drugs and concluded strongly in their
favour.
The book's chief author is Charles Medawar, director of Social
Audit - a British spin-off of Ralph Nader's Public Citizen network -
and a blistering critic of modern medicine from deep within the fold
of Britain's scientific and medical elite (his book's subtitle is
borrowed from the writings of his father, Peter Medawar, who won the
Nobel prize for medicine in 1960). The drug companies want their
drugs to work well, just as much as doctors and patients do, but all
three groups, along with government regulators, conspire to promote
a "grand delusion" that hugely overestimates the effectiveness of
pills.
The book explains the background to some of the intriguing scraps
of bad news about antidepressants that have emerged in recent
months. In May, the New York Attorney-General, Eliot Spitzer, filed
fraud charges against Glaxo SmithKline - the world's second-largest
drug maker - for hiding negative findings of clinical trials of the
SSRI called Paxil (Seroxat in the UK). In March, the food and drug
administration in the US warned, for the first time, that both adult
and juvenile patients on SSRIs can become suicidal in the early
weeks of therapy, and it asked drug companies to display prominently
details of possible side-effects on labels for these medicines. That
announcement came weeks after the revelation in a book by a Rutgers
anthropologist, Helen Fisher, of how SSRIs can disrupt the sex
drive. In late April, a Lancet editorial about the role of
antidepressants in child suicide condemned "the medical and
pharmaceutical establishment" for hiding vital evidence of the
risks. "The idea of a drug's use being based on the selective
reporting of favourable research should be unimaginable," it
proclaimed.
Since last autumn, newspapers on both sides of the Atlantic have
carried reports of drug companies refusing to release research
evidence that SSRIs have virtually no benefits for children. But
they failed to explain why one of these drugs was cleared by the FDA
for use by juvenile patients last year. That drug, Prozac, was also
the lone exemption from the list of SSRIs that Britain's department
of health warned doctors against prescribing to adolescents last
December.
So why was Prozac spared? The answer in Britain, Medawar and his
co-author Anita Hardon tell us, is that government-appointed
investigators into the effects of SSRIs on children found that
"about one child in 10 might be helped by Prozac: the benefits for
them were presumed to outweigh the lack of benefits or risks to the
other nine". In other words, the British authorities, like their
American counterparts, gave doctors a green light for medicating
nine out of 10 child patients with a drug with no measurable
benefits for them at all.
The FDA, still looking at drug company studies of the risks and
effectiveness of antidepressants for children, has so far decided
not to follow the British authorities in advising against
prescribing SSRIs for them. Never mind that an analysis of those
studies and several others by British university researchers,
published in the Lancet on April 23, said that four widely
used SSRIs did seem to increase the risks of children thinking of,
or attempting, suicide.
An intriguing footnote about halfway through Medicines out of
Control? tells of a private session during a World Health
Organisation conference on adverse drug reactions in Sweden in 2001,
at which there was earnest discussion of John le Carre's novel
The Constant Gardener, which is about drug company
intimidation of government regulators. And what these authors have
to say supports much of le Carre's argument - and even his dire
pronouncement, in an essay in the Spectator, that the drug
companies, "whether they know it or not, are engaged in the
systematic corruption of the medical profession, country by
country". If we have learned little of this from the media, he
wrote, it is because the subject is "too complicated, often
deliberately, for the layman".
Just how complicated is clear from even a brief summary of
Medawar's and Hardon's upending of the depression model. For a
start, the "selective" in SSRI turns out to be unwarranted.
"Prozac," Elizabeth Wurtzel wrote in Prozac Nation, "is very
pure in its chemical objectives ... and tends to have fewer
side-effects." The truth, Medawar and Hardon say, is that SSRIs are
"highly unspecific and unpredictable in action". It turns out that
the term "selective serotonin re-uptake inhibitor" came not from any
hard-won insight into the cause of depression from medical research,
but was coined as a marketing device. SmithKline Beecham (as it then
was) - the company behind the antidepressant paroxetine (sold as
Paxil or Seroxat) - had to find some way of catching up with the
market leader, Prozac, made by Eli Lilly. SKB knew that "paroxetine
made more serotonin available than competing drugs". Though there
was no "clinical evidence" that more serotonin was better, SKB
"decided to emphasise the unparalleled importance" of this brain
chemical for curing depression. Noting the market's spectacular
response to this spotlighting, other companies began to call their
products "SSRIs" too.
There is, in fact, no proof that depression is a "deficiency
disease" caused by a lack of brain serotonin. In trials, Medawar and
Hardon say, SSRIs do no more good than other antidepressants on the
market, like lofepramine, which cause no change at all in serotonin
levels. A second reason for scepticism is that while SSRIs increase
the level of this chemical almost immediately, antidepressant
effects take at least two weeks to begin. "If serotonin were a
simple key," the authors argue, "why would antidepressants not work
in about one case in three and often prove hardly more effective
than a placebo?"
It was not until the late 1990s, roughly 10 years after SSRIs
began to be widely prescribed, that results from several controlled
studies of them were examined together. These comparisons suggested
that placebo effects did in fact "account ... for about three
quarters of the benefits misleadingly attributed to drugs".
The fact that SSRIs do not really work as advertised is bad
enough, but that is not the worst of what the book has to say about
them. It lays out the evidence from many quarters - including drug
companies' own research - of their addictiveness and side-effects.
Unwanted reactions have a lot to do with the - highly unselective -
action of the pills, and follow from serotonin being "widely
distributed in the body". Addiction is the worst of the more common,
unwanted effects, and Medicines out of Control? describes the
lengths to which drug companies have gone to obscure or conceal the
facts about this. The consequences of stopping treatment with SSRIs
can include insomnia, depressed libido, shock-like sensations in
patients' heads, and suicide.
In an internal company memo that Medawar and Hardon quote,
GlaxoSmithKline instructed its PR department to tell the media that
"discontinuation problems are completely different to addiction or
dependence". This even confused doctors, who were not asked to watch
for symptoms of dependence. Government regulators in both the US and
UK - portrayed here as craven and corrupt - were persuaded to inform
the public that SSRIs were not habit-forming. It was left to
European regulators to resist drug company pressure and insist on
the packaging mentioning "withdrawal reactions".
There are a few bright spots in this melancholy picture. One was
the blocking by the European parliament in 2002 of a proposal that
would have seen Europe following America by allowing
direct-to-consumer advertising of prescription drugs. Medawar and
Hardon show how the SSRI makers expanded the US market for their
products through a combination of lavishly funded advertising
campaigns and teams of "sponsored experts" who redefined depression
from the 106 officially recognised categories in 1952 to 357
variants in 1994. "Shyness" and "embarrassment" were reconceived by
the drug company marketing departments as "social anxiety disorder"
or SAD, which "out of the blue ... became America's third most
common mental illness". In America, direct advertising "produced the
'patient pull' that resulted in millions of prescriptions for
SAD".
Although well written, Medicines out of Control? demands
close attention. The reward for slogging through its complexities is
the feeling, at the end, of having been given both a microscopic and
telescopic understanding of its subject.
*Medicines out of Control? By Charles Medawar and Anita
Hardon. Transaction.
Cheryll Barron is a former computer correspondent for
The Economist.