Bad Medicine

“Flacking for Big Pharma” (The American Scholar)

“The Epidemic of Mental Illness: Why?” (The New York Review of Books)

No one wins a Pulitzer for easy, happy-ending success stories. It’s all about uncovering government corruption and exposing corporate malfeasance. Maybe that’s the reason for the recent focus on the dark side of the medical industry. Even disregarding the insurance situation, the health care industry in this country is a mare’s nest of drug advertising, illegal kickbacks and “speaking fees” from Big Pharma that boost doctors’ incomes into the seven-figure range. Let’s be clear: I’m no conspiracy theorist, and I don’t think all big companies are evil. I don’t necessarily agree with every wild-eyed assertion made in some of the following articles. But I do think that, together, they reveal a side of the medical profession that often goes unnoticed. Drug companies make headlines when they’re caught lying about the side effects of blockbuster drugs like Vioxx or Paxil, but more subtle skewing of American medicine happens all the time. It’s just less obvious — and unfortunately, less Pulitzer-worthy.

Harriet Washington’s “Flacking for Big Pharma,” in the Summer 2011 edition of The American Scholar, is a predictably left-wing assault on the sneaky marketing techniques of Eli Lilly, Phizer, et. al. Beyond the usual objections to the lucrative research deals and tropical conference getaways that major drug companies bestow on medical professionals, however, Washington enumerates some shady and genuinely surprising tactics used to further the industry’s goals.

Medical journals like the New England Journal of Medicine and the British Medical Journal are seen as sacrosanct — neutral distributors of rigorous scientific research. But the average person doesn’t spend much time flipping through these publications. I didn’t realize, for example, that full-color, multi-page drug advertisements are not exclusive to Time and Glamour. As borderline-creepy as direct-to-consumer advertising is (after all, why go to the doctor if pharmaceutical makers can tell you what you need?), the industry’s effort to influence “thought leaders” — doctors, researchers, hospital administrators — is even sketchier. “Medical journals are utterly dependent upon pharmaceutical advertising,” Washington writes, “which can provide between 97 and 99 percent of their advertising revenue.” When fashion magazines blur the line between editorial and advertising — it’s no coincidence when a Nice ‘N’ Easy ad runs next to a story on hair dye, which also happens to recommend Clairol products — it’s annoying, but when medical journals reject articles that portray advertisers in a negative light, the scientific process is undermined.

Washington demonstrates the ways in which drug makers manipulate the results of the field’s supposed gold standard, the double-blind trial. Data is cherry-picked to make medicines look more effective than they truly are, a subject also addressed in The New York Review of Books when Marcia Angell points out that placebos are often as effective as psychiatric drugs (more on this later). Trial participants are often sorted into various subgroups to make the case that, though a drug may underperform overall, it is beneficial for a segment of the population. To illustrate the dangers of such data mining, Washington describes the efforts of Dr. Peter Sleight, who took a study on aspirin and “sorted the patients’ responses by astronomical subgroup.” He found that “taking aspirin was associated with a good outcome for all birth signs except for Libra and Gemini, who were more likely to die when given aspirin.” Washington compares this to industry-sponsored studies that purport to find benefits only for women or African-Americans. Though the parallel is not exact — is it so far-fetched to think that a drug which works well in the female body could produce less impressive results in males? — it is nevertheless instructive.

A lot of the ground covered by “Flacking for Big Pharma” has been traversed before. Publication bias, the notion that positive studies are more likely to be published than negative ones, is an inherent problem in science and was neither invented nor first abused by drug makers. Payments to doctors from drug companies are obviously an issue, despite protestations from the medical profession, but Washington breaks little new ground in her survey. The ghostwriting of medical journal articles is likewise an important but not revolutionary dilemma. Most interesting is an incident from 2003, when Elsevier, which publishes the prestigious journal The Lancet, “sullied its reputation by publishing an entire sham medical journal devoted solely to promoting Merck products.” This was not a typical advertorial, in which the disclaimer “this is an advertisement” is at least printed in small type at the top of the page, but rather a fake purporting to be the real thing: an independent journal that just happened to “lavish unalloyed praise on Merck drugs, such as its troubled painkiller Vioxx.”

Washington makes little pretense of neutrality; she is clearly out to skewer Big Pharma, and she does a serviceable job of it. The criticism, however, must be taken with a grain of salt, as any picture painted solely in shades of black and white is unlikely to hold up in the grays and half-shades of the real world. Yes, drug companies are sneaky, but they have also helped millions of people live longer and healthier lives. Not every executive is a money-hungry, ethics-eschewing Dr. Frankenstein. Washington recommends several “impeccably researched guides to sniffing out manipulation,” including Overdosed America and The Truth About the Drug Companies: How They Deceive Us and What to Do About It. Neither title promises an evenhanded survey of the drug industry.

As it happens, the author of The Truth About Drug Companies, Marcia Angell, a former editor-in-chief of the New England Journal of Medicine and currently a Harvard professor, recently wrote a meditation on psychiatric drugs for The New York Review of Books (June 23, 2011). In “The Epidemic of Mental Illness: Why?” Angell discusses, and largely agrees with, three new books on the topic. The titles do more than hint at the authors’ positions; words like “crisis” and “unhinged” pop up, and one book professes to “explod[e] the antidepressant myth.” Mental illness is indeed on the rise in the United States; Angell notes that it is “the leading cause of disability in children, well ahead of physical disabilities like cerebral palsy of Down syndrome.”

As with other “epidemics” — autism, food allergies, etc. — the changing rates of mental illness may have more to do with changing definitions and diagnoses than with actual increases in prevalence. The definition of “mood disorder,” for example, is so broad that almost anyone having a down day could be a potential sufferer. Angell asks if mental disorders are really becoming more common, or if we are “learning to recognize and diagnose mental disorders that were always there.” Or, “on the other hand, are we simply expanding the criteria for mental illness so that nearly everyone has one?”

The question of what constitutes mental illness is in some ways a philosophical inquiry as much as a medical one, and Angell does not spend long probing the topic. Instead, she acknowledges that, whatever their causes, mental disorders are treated primarily by psychoactive drugs. It is these drugs, and their efficacy, that Angell and the three books she discusses find so disturbing. “None of the three authors subscribes to the popular theory that mental illness is caused by chemical imbalance in the brain,” she writes. “Popular theory” understates the power of this assumption; for patients as well as doctors, the illustrations showing smiley-faced globules of serotonin and dopamine floating in the space between axon and dendrite have become gospel. When Angell argues that this model is based upon erroneous thinking and a backwards use of the scientific process, she can be convincing. Psychoactive drugs worked before scientists could say how they worked, and in the absence of an explanation, the chemical changes doctors observed in their patients’ brains became the method by which mental illness worked its madness. “Because certain antidepressants increase levels or the neurotransmitter serotonin in the brain, it was postulated that depression is caused by too little serotonin.” It is not an outlandish assumption; certainly there is logic behind connecting one change (an increase in serotonin) caused by the drug to another (an alteration of mood), especially when both changes seem to originate in the brain. But correlation, as science so often reminds us, is not causation. Antidepressants can also cause dizziness and dry-mouth, but no one is suggesting that depression is alleviated via changes in the inner ear or the salivary glands. Angell likens it to arguing “that fevers are caused by too little aspirin.” True, fevers are not caused by a lack of aspirin; however, it is also true that studying how aspirin reduces fever may provide important insights into the workings, if not the cause, of the malady.

If psychoactive drugs can ease depression or temper schizophrenic episodes, the question of how those drugs work their magic amounts to so many angels dancing on the head of a pin. After all, one need not know how aspirin works to enjoy its benefits. The greater problem, as Angell sees it, is that medical science cannot say definitively that psychoactive drugs work. Like Harriet Washington, she maintains that drug companies design and publish only the studies which support their products. However, she also discusses a further, less intentionally malicious form of bias. One of the books she reviews, Irving Kirsch’s The Emperor’s New Drugs, compares antidepressants to placebos. Using data from the FDA, Kirsch determined that “overall, placebos were 82 percent as effective as the drugs.” The average difference between placebo and drug was only 1.8 points on a depression rating scale, “a difference that, while statistically significant, was clinically meaningless.”

What, then, of the positive trials, the ones so heavily publicized by the drug companies? What about the studies in which the drugs worked 18 percent better than the placebo? Angell notes that “what all these ‘effective’ drugs had in common was that they produced side effects.” Kirsch’s research suggests that patients who experience side effects assume that they are receiving the active medication, not the placebo. Convinced that their pills are the real thing, these patients are also convinced that their symptoms are improving. Tellingly, trials that used “active” placebos — that is, placebos whose side effects mimic those of antidepressants — showed no difference between the drug and the fake.

Though Kirsch is not the first to argue against the efficacy of psychoactive drugs, the implication is profound: If these drugs work no better than sugar pills, the entire foundation of modern psychiatric treatment begins to crumble. Consumers start to look a lot more like the dupes of Big Pharma that Harriet Washington assumes them to be. In evaluating Kirsch’s argument, it is impossible not to view his skepticism of drugs through the lens of personal experience. I find myself resorting to the very sort of anecdotal evidence that scientists are loath to employ. Everyone knows a neighbor or a cousin whose life has been changed by Prozac or Zoloft or Zyprexa. Over the past ten years, I have tried nearly every SSRI on the market, from Paxil to Celexa to Effexor. While none has really achieved its goal, I do believe they alter my mood in ways a placebo would not. I experience no side effects, so there are no physical signs when I stop taking the medication. In fact, the impact is so subtle that I am not very good about taking the pills. It is only when I realize how irritable I’ve been, or when a friend points out how snappish I am being, that I realize I’ve forgotten my Effexor for two weeks. Though it’s debatable whether the drugs work well enough to justify my taking them, I’m fairly confident that they do take the edge off my mood.

It is also hard to believe that, if psychoactive drugs were as useless as Kirsch maintains, thousands of intelligent psychiatrists and physicians would continue to prescribe them. Surely these doctors must see improvement in their patients; otherwise, even those most in the sway of Big Pharma would begin to have doubts. And if the drugs are working, does it matter (disregarding cost) if they are no better than placebos? The authors of the books Angell reviews would say yes; in fact, one author goes so far as to conflate the rising rates of mental illness with the increasingly widespread use of drugs. Robert Whitaker, author of Anatomy of an Epidemic, believes “that psychoactive drugs disturb neurotransmitter function, even if that was not the cause of the illness in the first place.” I am not knowledgeable enough to refute this supposition, but it seems unlikely to me that Prozac and its imitators are wreaking some sort of mental havoc on society. Perhaps some people attempting to come off antidepressants experience the devastating withdrawl symptoms that Whitaker describes, but if serotonin levels truly “fall precipitously” when Celexa is withdrawn, leading to a depressed state which is “often confused with relapses of the original disorder,” I have failed to experience it. In fact, the difference between being on and off Celexa was, for me, negligible.

I just can’t muster the level of outrage that Washington and Angell seem to share. That’s partly because I resent the implication that we — doctors, patients, the public in general — are stupid enough to be taken in by the Big Pharma marketing department. I am not the sort of person with whom the “advertising is brainwashing” position flies. At the same time, a lot the tactics Washington details in The American Scholar disgust me, and Angell’s evaluation of three standouts of the anti-drug movement makes for thought-provoking reading.

A final note: Anyone looking to experience real outrage should check out Vanity Fair’s “Deadly Medicine” (January 2011), which exposes practices of Big Pharma far shadier than any medical journal ghostwriting. Drug trials are increasingly conducted overseas, in Eastern European or Asian countries where the population is poorer, more vulnerable and less savvy about the dangers of unproven medications. Desperate for treatment or cash (and sometimes both), the patients are enrolled in studies about which they are unable to give “informed consent.” Kickbacks to doctors and sleazy magazine ads are one thing, but this is where Big Pharma’s disregard for ethics really has the capacity to astound.

For further stomach-turning reading, unrelated to Big Pharma but very related to medical ethics, check out the excerpt from Scott Carney’s The Red Market on the Wired Magazine website. The demand for the blood used in transfusions in India gives new meaning to the term “blood money.” Unwilling donors are imprisoned and repeatedly drained of blood by black-market dealers who sell the blood to hospitals willing to look the other way. The scarcity of blood is such that a patient scheduled for an operation must bring his own blood — or that of a paid donor. Carney describes the scene of a “blood factory”:

They sprung the lock and revealed a medical ward fit for a horror movie. IV drips hung from makeshift poles and patients moaned as if they were recovering from a delirium. Five emaciated men lying on small woven cots could barely lift their heads to acknowledge the visitors. The sticky air inside was far from sterile. The sun beating down on the tin roof above their heads magnified the heat like a tandoor oven. One man stared at the ceiling with glassy eyes as his blood snaked through a tube and slowly drained into a plastic blood bag on the floor. He was too weak to protest.

It’s a situation more suited to post-apocalyptic fiction than a corner of the 21st-century world. As an American only an ambulance ride away from a clean, professional hospital, I find it nearly beyond comprehension.