Mental illness, big pharma and agent-based simulation

The New York Review of Books has an absorbing two-part piece by Marcia Angell on mental illness, psychiatry, and big pharma (link, link). (The NYRB Facebook page provides a good way of following the NYRB.)  Angell provides an in-depth discussion of books by Irving Kirsch, Robert Whitaker, and Daniel Carlat. There has been an explosion in the numbers of patients diagnosed with a list of mental disorders, and there has been an explosion in the profits associated with the drugs prescribed in treatment of these disorders as well.

It seems that Americans are in the midst of a raging epidemic of mental illness, at least as judged by the increase in the numbers treated for it. The tally of those who are so disabled by mental disorders that they qualify for Supplemental Security Income (SSI) or Social Security Disability Insurance (SSDI) increased nearly two and a half times between 1987 and 2007—from one in 184 Americans to one in seventy-six. For children, the rise is even more startling—a thirty-five-fold increase in the same two decades. Mental illness is now the leading cause of disability in children, well ahead of physical disabilities like cerebral palsy or Down syndrome, for which the federal programs were created. (Angell, part 1)

What is going on here? Is the prevalence of mental illness really that high and still climbing? Particularly if these disorders are biologically determined and not a result of environmental influences, is it plausible to suppose that such an increase is real? Or are we learning to recognize and diagnose mental disorders that were always there? On the other hand, are we simply expanding the criteria for mental illness so that nearly everyone has one? And what about the drugs that are now the mainstay of treatment? Do they work? If they do, shouldn’t we expect the prevalence of mental illness to be declining, not rising? (Angell, part 1)

To oversimplify, the thrust of several of these books is that the psychoactive drugs created the mental illnesses through the profit incentives and strategies of big pharma, rather than the diseases creating the drugs (through research and development aimed at treating the diseases).

This is over-simple, of course, since no one would question that mental illnesses exist prior to drugs. But the explosion of treated disorders like depression, anxiety, sleep disorders, and attention deficit disorder in children -- the "epidemic" to which Angell refers -- seems to conform to the reverse order. Deliberate strategies of marketing, influence on physicians, and influence on guiding medical documents such as the DSM seem to have produced a much larger patient base in specific mental disorders, with large profits accruing to pharma as a consequence.  (Ian Hacking looks at the degree to which mental illnesses are socially constructed in The Social Construction of What?.)

Here is the main thrust of the interpretation offered by the books that Angell reviews:

First, [the authors] agree on the disturbing extent to which the companies that sell psychoactive drugs—through various forms of marketing, both legal and illegal, and what many people would describe as bribery—have come to determine what constitutes a mental illness and how the disorders should be diagnosed and treated. (Angell, part 1)

A couple of pieces of evidence are especially pertinent in support of this telling of the story. One is the observation that psychiatrists as a profession are the largest beneficiaries of funding by pharma, by a large margin.

As psychiatry became a drug-intensive specialty, the pharmaceutical industry was quick to see the advantages of forming an alliance with the psychiatric profession. Drug companies began to lavish attention and largesse on psychiatrists, both individually and collectively, directly and indirectly. They showered gifts and free samples on practicing psychiatrists, hired them as consultants and speakers, bought them meals, helped pay for them to attend conferences, and supplied them with “educational” materials. When Minnesota and Vermont implemented “sunshine laws” that require drug companies to report all payments to doctors, psychiatrists were found to receive more money than physicians in any other specialty. The pharmaceutical industry also subsidizes meetings of the APA and other psychiatric conferences. About a fifth of APA funding now comes from drug companies.

Drug companies are particularly eager to win over faculty psychiatrists at prestigious academic medical centers. Called “key opinion leaders” (KOLs) by the industry, these are the people who through their writing and teaching influence how mental illness will be diagnosed and treated. They also publish much of the clinical research on drugs and, most importantly, largely determine the content of the DSM. In a sense, they are the best sales force the industry could have, and are worth every cent spent on them. Of the 170 contributors to the current version of the DSM (the DSM-IV-TR), almost all of whom would be described as KOLs, ninety-five had financial ties to drug companies, including all of the contributors to the sections on mood disorders and schizophrenia.  (Angell, part 2)

A second piece of evidence is a recounting of the drafting of the Diagnostic and Statistical Manual of Mental Disorders (DSM) through five editions, especially the third edition. In each case there is a strong suggestion of swaying of medical and scientific opinion through financial incentives.

These efforts to enhance the status of psychiatry were undertaken deliberately. The APA was then working on the third edition of the DSM, which provides diagnostic criteria for all mental disorders. The president of the APA had appointed Robert Spitzer, a much-admired professor of psychiatry at Columbia University, to head the task force overseeing the project. The first two editions, published in 1952 and 1968, reflected the Freudian view of mental illness and were little known outside the profession. Spitzer set out to make the DSM-III something quite different. He promised that it would be “a defense of the medical model as applied to psychiatric problems,” and the president of the APA in 1977, Jack Weinberg, said it would “clarify to anyone who may be in doubt that we regard psychiatry as a specialty of medicine.”

When Spitzer’s DSM-III was published in 1980, it contained 265 diagnoses (up from 182 in the previous edition), and it came into nearly universal use, not only by psychiatrists, but by insurance companies, hospitals, courts, prisons, schools, researchers, government agencies, and the rest of the medical profession. Its main goal was to bring consistency (usually referred to as “reliability”) to psychiatric diagnosis, that is, to ensure that psychiatrists who saw the same patient would agree on the diagnosis. To do that, each diagnosis was defined by a list of symptoms, with numerical thresholds. For example, having at least five of nine particular symptoms got you a full-fledged diagnosis of a major depressive episode within the broad category of “mood disorders.” But there was another goal—to justify the use of psychoactive drugs. The president of the APA last year, Carol Bernstein, in effect acknowledged that. “It became necessary in the 1970s,” she wrote, “to facilitate diagnostic agreement among clinicians, scientists, and regulatory authorities given the need to match patients with newly emerging pharmacologic treatments.”  (Angell, part 2)

Another element of the strategy used by the drug companies to promote their products, according to these authors, is the selective way that clinical studies are used in order to establish the safety and effectiveness of a given psychoactive drug:

For obvious reasons, drug companies make very sure that their positive studies are published in medical journals and doctors know about them, while the negative ones often languish unseen within the FDA, which regards them as proprietary and therefore confidential. This practice greatly biases the medical literature, medical education, and treatment decisions. (Angell, part 1)

What this story made me think of was ... slime molds. Here's what I mean. Japanese researchers have discovered that certain examples of optimizing processes can be simulated with slime molds and food supplies distributed across space. Here is an example of this research in the context of rail networks: the researchers found that a colony of slime mold essentially reproduces the configuration of existing rail networks when food is distributed in a configuration mirroring major cities (Tero et al 2010; link, link). Here is the experiment based on the configuration of cities around Tokyo:

After about a day of growth, the slime mold has established a network of tunnels connecting the food supplies, and this network looks strikingly similar to the configuration of Japanese railroads in the region.

So here's the question for consideration here: what if we attempted to model the system of population, disease, and the pharmaceutical industry by representing pharma as the slime organism and the disease space as a set of disease populations with different profitability characteristics? Would we see a major concentration of pharma slime around a few high-frequency, high profit disease-drug pairs? Would we see substantial underinvestment in pharma slime on low frequency low profit "orphan" disease populations? And would we see hyper-concentrations around diseases whose incidence is responsive to marketing and diagnostic standards?

I'm just speculating here, but I'm guessing that a Petri dish designed with these characteristics would produce the outcome described in the books included in the Angell reviews: a hyper-concentration of the slime organism around the "plastic" diseases that display positive feedback from marketing to incidence.  Essentially the model would suggest that the pharma industry "grows" into the space of emerging diseases, making investments in research and marketing that allow for growth of revenues around the disease segments of the population.

I suppose that this thought experiment simply supports a dismal but familiar finding: that profit-maximizing firms will aggressively seek out new sources of profits; that they will be particularly interested in opportunities where the possibility exists of strategically increasing the demand market; and that they will find creative ways of inducing other actors to behave in ways that enhance their business interests. Unfortunately, in this case the business optimal outcome seems to have very negative consequences for public health. And it seems to cast some doubt on the ability of professional ethics and conflict of interest policies to keep the medical profession as a whole on the track of placing the patient's health as the highest priority.

(I think this thought experiment could be recast as an agent-based simulation, with similar results.)