Pharmageddon (6 page)

If the SSRIs had been a bridge to a more effective group of compounds this again might have seemed acceptable, but since 2000 almost the only novelty has come from three isomers of earlier SSRIs. Many drugs come in mirror image, or left and right hand (isomer) forms. Typically only one of the hands is active. Until the 1990s it was inconvenient to attempt to separate these isomers. But then in the mid-1990s Sepracor isolated esfluoxetine and dexfluoxetine (Zalutria) from Prozac (fluoxetine). Lundbeck isolated escitalopram (Lexapro) from Celexa (citalopram), and Wyeth isolated desvenlafaxine (Pristiq) from Efexor (venlafaxine). The astonishing thing is that companies have been permitted to take patents out on these compounds, which are as alike to the parent compounds as two drops of water.
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The paucity of genuinely new drugs coming on the market in recent years is not some odd quirk of psychotropic drug development. The best-selling drug for minimizing acid secretion in the gut in the 1980s and 1990s was the proton pump inhibitor Prilosec (omeprazole). Before the patent on omeprazole expired in 2002, its parent company, Astra Zeneca, simply introduced Nexium (es-omeprazole), an isomer of Prilosec, and clinicians shifted from a cheap drop of water to an identical but vastly more expensive drop of water. If a drug does not come in isomeric forms, companies have instead in recent years patented the metabolites of a parent compound and released these as a novel drug with the approval of the US patent office and almost no resistance from medicine.

When the breakthrough drugs of the 1950s emerged, there were great hopes that not only would they offer remedies for illnesses that we did not have treatments for, but they would also shed light on the nature of the illnesses being treated. In 1896, the advent of diphtheria antitoxin had demonstrated that not all throat infections were diphtheria, thus opening up the idea that bacteriology would be able to carve a mass of respiratory, gut, and other problems into a series of discrete illnesses each of which could be tackled individually. In the 1950s, there were great hopes that the new treatments for disorders like arthritis, depression, hypertension, or schizophrenia might similarly clarify whether these were single diseases or the end result of common pathways into which several different diseases fed.

The new drugs, to use a celebrated phrase, would help us carve nature at its joints, just as distinctions among bacteria had enabled us to carve infectious diseases at their joints. But we have now arrived at almost the precisely opposite point. Rather than drugs being used to carve nature at its joints, nature instead is being used to differentiate drugs whose differences are essentially trivial.

With the new possibilities for profit opened up by a lax to nonexistent application of patent laws, the medical arena has ceased to be a domain in which scientists using new molecular tools push back boundaries. Indeed since the passage of the Bayh-Dole Act in 1980, which encouraged scientists, including medical academics, to consider patenting the products of their research, clinicians and scientists have seemed keener on making patent applications themselves and setting up start-up companies than in advancing medical knowledge or healthcare. Pharmaceutical companies meanwhile have no interest in what molecules might reveal about how humans work. Molecules are only interesting insofar as they can be used to capture market niches. Medicine may look the same as it has always done to onlookers; the marketers know it's not.

BRANDS AND PATENTS

The emergence of product patents transformed the importance of branding. By the 1980s, when H-2 blockers for ulcers, statins for cholesterol, SSRIs for depression, and other drugs were in the pipeline, branding had become so important to companies that the job was outsourced to specialist Manhattan-based companies like InterBrand and MediBrand. No longer would drugs be called Diuril or Tryptizol. We were about to get Prozac, Viagra, Zestril, and Nexium, names that bore no relation to the underlying chemical or disease but were aimed at differentiating between the new Nikes and Reeboks of the medical world and hinted at the restoration to youthful vigor that nineteenth-century brands had shamelessly promoted.

Branding now extends far beyond generating and market-testing fancy names for drugs. Brands nest within brands. The new marketers brand drug classes and diseases with far-reaching implications for medicine and society.

For instance when the makers of the new antidepressants of the 1990s needed to distinguish their drugs from older drug treatments, the term SSRI (selective serotonin reuptake inhibitor) emerged. This is not a medical or scientific term. Serotonin is a neurotransmitter in the brain, but both new and old antidepressants acted on it and the new drugs were in fact no more selective than some older drugs. The term SSRI came from the marketing department of SmithKline Beecham as part of their effort to distinguish their Paxil from Lilly's Prozac and Pfizer's Zoloft, but all three companies used the term to create the appearance of a new class of drugs and provide a common platform from which to launch marketing efforts designed to marginalize older—and demonstrably more effective—treatments.
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To this day, the brand names of drugs do not feature in medical textbooks, but these same books all include sections on statins, SSRIs, and ACE (angiotensin-converting enzyme) inhibitors as though these are medical terms, when in fact they are brand-like names that replace medical terminology. Statins such as Lipitor are just one subset of lipid-lowering drugs that include equally effective older drugs such as nicotinic acid. Zestril and its sister compounds hit the market in the 1980s as “ACE inhibitors,” rather than simply as antihypertensives, and became bestsellers as the SSRIs did—replacing cheaper and more effective antihypertensives.

One of the most striking instances of the branding of a new drug class has been creation of the idea of a “mood stabilizer.” This once rarely used term was summoned up by Abbott Laboratories in the 1990s and pressed into use in the marketing of their newly patented Depakote. Depakote as we have seen was approved by the FDA in 1995. But it was only approved for the treatment of the manic pole of what was once called manic-depressive illness. Such approval was not surprising—giving any sedative to manic patients will produce a change that can be portrayed as a benefit. More surprising was the company's application for approval. There are comparatively few manic patients, and a lot of sedatives were already in use to manage their illness. If there was to be any serious money in Abbott's move, it had to lie in the much larger market of people whose moods could be portrayed as fluctuating unhelpfully, who were in need of “mood stabilization.” But Abbott's license did not include warrants to claim Depakote was prophylactic—they couldn't claim it would stop moods swinging—or indeed even that it was a treatment for manic-depressive illness.

However, from the start ads for Depakote carried a claim that it was a mood stabilizer. Had Abbott said prophylactic, indicating that this drug had been shown to prevent mood swings, they would have broken the law. The beauty of the term mood stabilizer is that it had no precise meaning. But what else would a mood stabilizer be if not prophylactic? And this verbal construction would lead prescription writers to use it for that purpose, even though no controlled trials have ever demonstrated Depakote to be prophylactic. Far from being a well-grounded scientific idea, the term mood stabilizer was an almost perfect advertising term— as successful a brand as the term tranquilizer had been in the 1950s and SSRI in the 1990s.

All of a sudden everyone seemed to know what a mood stabilizer was. There was an exponential increase in the number of articles in medical journals with this term in the title—from none in 1990 to over a hundred per year by 2000. Within a few years, all psychopharmacology books had sections on mood stabilizers. It was as if in the middle of a TV drama series like
Buffy the Vampire Slayer
the main character is given a sister she never knew she had. When it comes to entertainment we can accommodate developments like this without blinking, but it is not the kind of thing we expect to be happening in science or medicine without solid evidence.

The emergence of mood stabilizers coincided with increasing estimates of the prevalence of what, in another successful piece of rebranding, was now almost always called bipolar disorder. Up to the launch of Depakote in 1995, almost everyone had heard of manic-depressive illness but soon this term all but disappeared, replaced by bipolar disorder. By 2005 over five hundred articles per year in the medical literature referred to bipolar disorder in their titles, with almost none mentioning manic-depressive illness.

This rebranding reengineered the disorder from the ground up. Manic-depressive illness had been a rare and serious condition affecting ten people per million, who invariably had to be admitted to hospital. Bipolar disorder, in contrast, supposedly affects up to 50,000 people per million, and efforts are now underway to persuade primary care clinicians that a wide range of the minor nervous problems they see are indicative of underlying bipolar disorder rather than anxiety or depression, and that these patients should be treated with newer and more costly mood stabilizers, such as Zyprexa or Seroquel, rather than older and cheaper antidepressants or tranquilizers.
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Bipolar disorder became intensely fashionable with extraordinary rapidity, promoted by assiduous disease awareness campaigns through direct-to-consumer advertising on television in the United States, and patient educational material in Europe, encouraging patients to complete self-assessments and ask their doctor whether bipolar disorder might be the cause of their problems. It became fashionable to the point where clothes and accessories could be bought online celebrating the wearer's bipolarity.
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Within a decade, one of the most serious of mental illnesses had gone from being a devastating disease to being a lifestyle option.

Everybody, it seems, stood to gain—physicians, companies, and patients. Bipolar disorder could be portrayed as a genetic disorder—not a parent's fault. While no one likes to have a biological disease, this one was portrayed in pharmaceutical company sponsored booklets
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and ads as a disease linked to creativity that supposedly had affected major artistic figures of the nineteenth and twentieth centuries from Vincent Van Gogh and Robert Schumann to Robert Lowell and Sylvia Plath. Public authorities meanwhile could support screening programs such as Teenscreen, introduced in many American schools beginning in 2005, to detect the condition and trigger treatment as early as possible in order to avoid any number of social and individual ills such as suicide, divorce, career failure, crime, and substance misuse that might stem from a failure to detect and treat.
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For the specialists new journals appeared—
Bipolar Disorder, The Journal of Bipolar Disorders, Clinical Approaches in Bipolar Disorders
, and others. made possible by unrestricted educational grants from pharmaceutical companies. From 1995 onward a slew of societies and global conferences appeared as well—The International Society for Bipolar Disorders, The International Review of Bipolar Disorders, The International Society for Affective Disorders, The Organization for Bipolar

Affective Disorders, The European Bipolar Forum, The Australasian Society for Bipolar Disorders, and many others.

In just the same way impotence vanished and was replaced by erectile dysfunction, frigidity by female sexual desire disorder, boisterousness in children by ADHD. The skill lies in understanding the market and positioning a drug accordingly. In 1980, for instance, the newly created panic disorder was viewed as a severe form of anxiety; the marketing goal for Upjohn was to get Xanax on the market for panic disorder in the expectation that creating the perception that Xanax was good for severe anxiety would lead to leakage into prescriptions for other forms of anxiety also.
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As we shall see in later chapters, marketing like this can conjure diseases like osteopenia, restless leg syndrome, and fibromyalgia out of thin air. This is now called disease mongering. But even more alarming, an “opportunity cost” of marketing like this is that medical diseases with a pedigree going back two millennia, such as catatonia, can vanish if no company stands to make money out of helping medical or nursing staff to recognize its presence and as a result patients may die, when the means to treat them may be lying inches away.
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Once the addition of a branded drug to a doctor's arsenal was a minor addition to medical culture, but now the insertion of a Viagra or a Vioxx into the medical marketplace will often replace existing medical culture in an area of treatment, as the examples of mood stabilizers and bipolar disorders illustrate. Disorders that were once defined by patients' needs for medical services and doctors' perceptions of their pathology are now increasingly defined by the goals of marketers. Furthermore this now happens on a global basis. Whereas once the brand names of drugs differed from country to country and huge differences existed between Japanese and American medicine, say, and between French and German medicine, from the mid-1990s drugs like Zyprexa, Lipitor, and Viagra have been launched globally with essentially the same marketing in every country. Partly as a result of these onslaughts, differences in medical cultures are flattening down to a common pharmaceutical denominator. Where almost no one had bipolar disorder, osteoporosis, or female sexual dysfunction two decades ago, these new conditions are now global epidemics.

Claims like these are cheap. If it were so simple to capture the institution of medicine just by coming up with fancy names for drugs, drug classes, and diseases, the proprietary medicines industry of the nineteenth century would never have died out. But driven by a real desire to care for the most vulnerable in society and a commitment to science, medicine eliminated these imitations of medical remedies for a century, with the exception of some holdovers from the former era such as Listerine and Clearasil. Good medicines clearly pushed out bad ones, in large part because they were based on good science. And good science continues—we now have astonishing developments in genetics and in medical imaging, so the argument presented here needs to pull back the curtains on the tricks of the pharmaceutical trade and show not only how modern marketing has closed in on the holy grail of fooling all of the people all of the time, but also why there has been so little resistance among doctors.