The Hastings Center Report, March 2000
v30 i2 p19
Good Science or Good Business? DAVID HEALY.
Author's Abstract: COPYRIGHT 2000 Hastings Center
In the 1950s, estimates of the incidence of depression were fifty
people per million; today the estimate is 100,000 per million. What
was once defined as "anxiety" and treated with tranquilizers in the
wake of the crisis of benzodiazipine dependence and the development
of selective serotonin reuptake inhibitors became "depression." And
as SSRIs have been shown to be effective for treating other nervous
conditions, such as panic disorder, estimates of their frequency
have increased markedly as well. Disease increasingly means whatever
we have a reimbursable treatment for.
Full Text: COPYRIGHT 2000 Hastings Center
When Listening to Prozac emerged in 1993, it was one of the few
books dealing with psychiatry to become an international best-seller
since Freud's and Jung's works and the only book on
psychopharmacology ever to do so. The book dealt with the effects of
an "antidepressant" on conditions that often looked more like states
of alienation than classic depressions. For many, this was their
first awareness that antidepressants were drugs distinguishable from
minor tranquillizers. For others, Peter Kramer's book and the notion
of cosmetic psychopharmacology that it introduced raised interesting
ethical and philosophical dilemmas. But the argument here is that
the attraction of the book has depended on a series of engineered
transformations in the way we think about mental well-being. The
"alienation" Prozac and similar therapies "treat" has very commonly
been defined in terms of the interests of the medico-pharmaceutical
complex, and the arguments on offer about the merits of Prozac look
more like descriptions of the interests of their proponents than
dependable accounts of reality.
The interface between mental health and alienation traces to the
emergence of psychodynamic therapy at the turn of the century, but
this new industry remained at one remove from psychiatry until the
1950s. While the therapists took charge of such problems as
alienation, psychiatrists dealt with those suffering from full-blown
psychoses. In the interim, there was considerable recourse to
do-it-yourself pharmaco "therapy" that employed alcohol, opiates,
bromides, and barbiturates to manage community nervousness (that is,
nervous conditions that do not lead to hospitalization), but this
use, unconstrained by a therapy establishment, gave rise to little
talk of alienation among philosophers. Indeed one can wonder whether
many philosophy departments would be able to function without
alcohol to facilitate social intercourse.
When imipramine, the first antidepressant, was introduced,
clinicians and pharmaceutical company executives could see little
rationale for it. The frequency of affective disorders appeared
vanishingly low and these conditions responded to antipsychotics or
ECT. Clinicians used the antidepressants sparingly,[1] and the very
word "antidepressant" only begins to appear in dictionaries in the
mid-1980s. Unlike the antipsychotics, the antidepressants had no
clear niche. However, they did seem capable of making some
difference to a large number of people, even if those people might
have to be persuaded that they needed this difference in their
lives. As early as 1958, Roland Kuhn, the discoverer of imipramine,
had noted that some sexual perversions responded to imipramine and
that many patients, when they recovered, felt better than well.[2]
Such transformations opened up significant philosophical and ethical
issues--claims now strongly suggestive of Kramer's agenda. But
whereas Kramer's book became a runaway best-seller, Kuhn's
speculations had minimal impact. The philosophers who were excited
by the new psychotropic compounds in the 1950s and are now
interested in neuroscience and Prozac were not interested in
imipramine.
Market Development
The developmental trajectory for the antidepressants was largely
determined by a critical external event--the thalidomide disaster.
The public reaction to the birth defects caused by thalidomide,
which had been taken by pregnant women to combat "morning sickness,"
led to the 1962 Food and Drug Act amendments, which channeled drug
development toward clear diseases. Drug availability was restricted
to prescription-only medicines, placing it in the hands of
individuals who supposedly would make drugs available for problems
stemming only from diseases rather than for those stemming from
other sources. These developments radically changed psychiatry,
first by putting a premium on "categorical" rather than
"dimensional" models of disease, so that psychiatrists were more
likely to treat diseases as conditions that patients either have or
lack rather than have to some degree, and second because
prescription-only status brought nervousness within the psychiatric
ambit.
Initially, the straitjacket of the 1962 amendments had the
outcomes intended. But if drugs are made available only for
diseases, it was perhaps predictable that there would be a mass
creation of disease. There has been, and these developments shape
our perceptions of how alienation is being managed. In the 1950s, it
was thought that only fifty people per million were depressed.
Nowadays no one blinks on being told that depression affects over
100,000 per million and that it leads to more disability and
economic disadvantage than any other disorder.[3] But this change
plainly requires a major change in our view of what constitutes
disease. If 10 to 15 percent of the population is depressed, the
label "disease" does not make sense if understood in terms of the
biological disruption that bacterial infections produce. What is
meant can be grasped only if the "disease state" is framed in terms
of temperamental factors and only if what is aimed at is a state of
comparative well-being rather than cure.
Oddly enough, the widespread acceptance of our views of
depression conceals the process by which they were changed. When
first faced with the question of what community nervousness is, the
psychiatric profession and the pharmaceutical industry understood it
in terms of anxiety, and they resorted to Valium and other
anxiolytics to treat it. This led to the first debates about the
ethics of treating "problems of living" in this way.[4] In the West,
however, the 1980s crisis surrounding benzodiazepine dependence led
to the eclipse of both the minor tranquilizers and the whole notion
of anxiolysis. This ushered in the antidepressant era. In contrast,
in Japan, where dependence is less of a problem, the anxiolytics
remain the most widely used drugs for nervousness and the
antidepressant market remains small--in fact, Prozac is unavailable.
Depression as it is now understood by clinicians and at street
level is therefore an extremely recent phenomenon, largely confined
to the West. Its emergence coincides with the development of the
selective serotonin reuptake inhibitors (SSRIs), which in the
mid-1980s appeared capable of development as either anxiolytics or
antidepressants.[5] Since their initial launch as antidepressants,
various SSRIs have been approved for the treatment of panic
disorder, social phobia, post-traumatic stress disorder,
obsessive-compulsive disorder, and other anxiety-based conditions.
In a number of these disorders, the SSRIs are more effective than
they are in depression. Indeed, it has not been possible to show
that Prozac is effective in classic depressive disorders. Worse,
there is some evidence that far from reducing rates of suicide and
disability associated with depression, antidepressants may actually
increase them. Prozac and related drugs are prescribed to over four
million children and teenagers per annum in the United States, yet a
preponderance of evidence suggests that such prescriptions are not
warranted.[6]
The designation of Prozac as an antidepressant means that some
efficacy in some milder depressions can be shown for this compound
and it is accordingly not illegal to market it as a treatment for
depression, but the fact that Prozac "works" for some people does
not mean that they have classic depression. That it was marketed
this way stems from business rather than scientific calculations.[7]
Changes in the way we think about problems of living are not
restricted to depression. The research demonstrating that SSRIs
could be useful for treating other nervous conditions has been
associated with marked increases in estimates of their frequency as
well.[8] Obsessive-compulsive disorder has increased a thousand-fold
in apparent frequency. Panic disorder, a term coined in the
mid-1960s and first appearing in diagnostic classification systems
in 1980, has become one of the most widely recognized psychiatric
terms at street level. Social phobia, all but invisible until the
1990s, now appears to affect the population in such epidemic
proportions that the launch of Paxil as an anti-shyness agent was a
media event.
These changes have very likely been brought about by the
pharmaceutical industry itself, through its highly developed
capacities for gathering and disseminating evidence germane to its
business interests. The methods that might have this effect include
convening consensus conferences and publishing the proceedings,
sponsoring symposia at professional meetings, and funding special
supplements to professional journals. The industry may also
establish and support patient groups to lobby for treatments. The
claim here--though defended elsewhere--is that these and other
techniques for marketing information are sufficiently well developed
that significant changes in the mentality of both clinicians and the
public can be produced within a few years.[9] In effect, the
industry has educated prescribers and the public to recognize many
other kinds of cases as depression.
These changes are facilitated by a broader social shift. When
dynamic therapies occupied the citadels of orthodoxy in psychiatry,
their terminology leaked out into popular language. A variety of
terms were used in ways that technically were wholly inaccurate but
that nevertheless became part of the way in which we thought of
ourselves and conceptualized alienation. Recently, the psychobabble
prevalent during much of the century has begun to give ground to a
newly minted biobabble. A rootless patois of biological terms--"low
brain amines," for example--has settled into the popular
consciousness, with consequences for our self-conception that can
only be guessed at.[10]
Possibly, Prozac's success has also depended partly on a lack of
information. Prozac has been shown to "work" using clinician-based
disease-specific rating scales, but when patient-based, nonspecific
quality of life instruments have been used, it has not been shown to
work for depression--although this information has not seen the
light of day.[11] Current methods to estimate the side effects of
drugs in clinical trials actually underestimate them, according to
some tallies, by a sixfold factor.[12] Finally, the SSRIs have been
sold on the back of a claim that the rate of suicide is 600 per
every 100,000 patient years. But this is the rate for people with
severe depression, for which Prozac does not work. The rate for
primary care depression is on the order of 30 out of every 100,000
people. Yet in these populations, suicide rates of 189 for every
100,000 on Prozac have been reported.[13] Thus there are good
grounds to believe that Prozac can trigger suicidality. The
pharmaceutical companies are not investigating, however; one wonders
whether they are receiving legal advice echoing that given to the
tobacco companies, that any investigation of these issues may
increase product liability. From this vantage point, Prozac might
seem better cast as a symbol of the alienation that large
corporations can visit on people rather than as a symbol of the
"treatment" of alienation that a psychotropic agent can bring about.
Lifestyles and the Disease Model
The public perception of Prozac, as shaped by Listening to
Prozac, was that the drug had been rationally engineered, in the
sense that it had been developed so as to achieve highly
reproducible clinical outcomes. If it is important that a drug be
rationally engineered, it seems clear that Kuhn's discovery of
cosmesis, in contrast to Kramer's, could not have gone anywhere.
However, Kramer's mythic account of the development of Prozac was
mistaken. It was perhaps prophetic, since neuroimaging technologies,
pharmacogenetic techniques, and other novel strategies will make the
development of psychotropic drugs increasingly rational in this
industrial sense, but none of this applied to Prozac. While Prozac
works for some people, it has not been possible to offer any
guarantees as to the quality of clinical outcomes when using it.
Lacking such guarantees does not matter as much in treating genuine
disease, since when patients are in danger, even doing something
risky is by consensus preferable to doing nothing. But poor outcomes
are much less tolerable in the management of less severe conditions.
Thus a disease model offers pharmaceutical companies and clinicians
a valuable escape from quality standards.
A disease model offers other advantages to pharmaceutical
companies. It acts powerfully to legitimate drug-taking, allowing
Prozac, for example, to escape the flak that Valium drew in the
1970s. And it can function as a means of resolving problems about
equitable access to health resources, since it is widely accepted
that there are greater difficulties with inequities in health care
than with inequities in the access to computers or digital
televisions.
Prozac is of course only one of a growing number of agents that
modulate lifestyles rather than cure diseases. Viagra is another
good example of this trend. Viagra's designation as a lifestyle
agent depends in good part on the reliability with which the
intended responses can be elicited. What is interesting about Viagra
is that we have had other drugs for two decades now that have
comparable effects on sexual function. The SSRIs may have weak and
unpredictable effects on depression, but they can reliably delay
orgasm, and other antidepressants can advance it.[14] Thus we have
had the capacity to "engineer" sexual performance for some time; the
pharmaceutical companies have simply not marketed pills for such
uses, presumably because they were uncertain about the acceptability
of a "lifestyle market" for their wares.[15] Seen against this
background, the promotion of Viagra marks an important turning point
in the way drugs are developed.
In general, clinical therapeutics is increasingly comprised of a
series of domains removed to varying degrees from the management of
bacterial infections. The provision of oral contraceptives on a
prescription-only basis is notionally underpinned by a disease
model. Hormone replacement therapy is likewise presented as
treatment for a disease. "Treatments" for baldness, age-induced skin
changes, obesity, and a range of other lifestyle agents wait in the
wings. All of these raise the question of what qualifies as a
disease. In recent history, a disease has been thought of as an
entity established by an underlying biological lesion. Previously,
illnesses were anything that made the individual feel less well, a
definition which potentially included halitosis. Latterly, the
emergence of agents that can modify natural variations in hair loss
or ejaculatory latency push us closer to making explicit one of the
currently implicit but increasingly important definitions of
disease, which is that it is, in practice, something that
third-party payers will reimburse on.
Before 1962, tonics flourished along with treatments for
halitosis and other problems of living. Cyproheptadine, an
imipramine-like agent, which reliably improves appetite and sleep
and less reliably cures depressions, was on sale as a tonic. The
1962 amendments required redesignation of agents like this as
antidepressants rather than tonics, but in many ways they might have
had greater public acceptability if classified as tonics, a usage
hallowed by centuries of practice rather than as antidepressants,
since as drugs they quickly became associated with risks of
addiction. Would we be talking about alienation if it were
over-the-counter tonics rather than prescription-only
antidepressants that were involved--or if we were, would the public
take our debate seriously? Could it be that much of the current
debate is predicated on a combination of pseudoscientific mystique
and regulatory artifact? Consider in this connection one of the
dilemmas raised by Kramer: because of its prescription-only status,
Prozac raises special moral problems for the physician, who is now
called on to decide whether it would be a good thing to reduce the
general level of melancholy in the community, with the consequent
loss of spirituality or creativity that might go with that.
These dilemmas would be transformed if the power to make these
decisions were returned to the consumer. We may be unwittingly
alienated choosing to purchase automobiles, but we would certainly
feel alienated if it were the prerogative of the automobile salesmen
to decide which brand of vehicle we should get.
References
[1.] D. Healy, "The Three Faces of the
Antidepressants," Journal of Nervous and Mental Disease 187 (1999):
174-80.
[2.] R. Kuhn, "The Treatment of Depressive States with G22355
(Imipramine Hydrochloride)," American Journal of Psychiatry 115
(1958): 459-64.
[3.] C. Murray and A. Lopez, The Global Burden of Disease
(Cambridge, Mass.: Harvard University Press, 1996).
[4.] M. C. Smith, A Social History of the Minor Tranquillizers
(Binghamton, N.Y.: Haworth Press, 1991).
[5.] D. Healy and D. Nutt,
"Prescriptions, Licences and Evidence," Psychiatric Bulletin 22
(1998): 680-84; D. Healy, "The Marketing
of 5HT," British Journal of Psychiatry 158 (1991): 737-42.
[6.] See ref. 5, Healy, "The Marketing
of 5HT."
[7.] R. L. Fisher and S. Fisher, "Antidepressants for Children:
Is Scientific Support Necessary? (With commentary by L. Eisenberg
and E. Pellegrino)." Journal of Nervous & Mental Disease 184
(1996): 98-108.
[8.] D. Healy, The Antidepressant Era
(Cambridge, Mass.: Harvard University Press, 1997).
[9.] For a full defense, see ref. 8, Healy, The Antidepressant Era.
[10.] See E. S. Valenstein, Blaming the Brain (New York: Free
Press, 1998).
[11.] See ref. 1, Healy, "The Three
Faces of the Antidepressants."
[12.] S. Stecklow and L. Johannes, "Questions Arise on New Drug
Testing: Drug Makers Relied on Clinical Researchers Who Now Await
Trial," Wall Street Journal 15 August 1997.
[13.] D. Healy et al., "Suicide in the
Course of the Treatment of Depression," Journal of
Psychopharmacology 13 (1999): 94-99.
[14.] See ref. 8, Healy, The
Antidepressant Era.
[15.] See ref. 8, Healy, The
Antidepressant Era.
David Healy, "Good Science or Good
Business?," Hastings Center Report 30, no. 2 (2000): 19-22.
David Healy is a reader in psychiatry,
consultant psychiatrist, and director of the North Wales Department
of Psychological Medicine. He has published The Antidepressant Era
(Harvard University Press, 1997). Forthcoming books include
histories of Prozac and of the antipsychotics.
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