Pharmageddon. David Healy

operating table; it is schizophrenia that gives rise to a disfiguring neurological condition, tardive dyskinesia, rather than treatment with anti- psychotics. For thirty years the outcomes for lung cancer have remained almost unchanged. Millions of people have died during this period, after having radical surgery, intense radiotherapy, or intense chemotherapy. If these treatments extended the life of some yet overall life expectancy remained the same, there must also be an equal number whose lives were shortened by treatment, but you will hunt high and low to find any whose deaths are attributed to the treatment rather than the disease.

      When it comes to the harms following ingestion of over-the-counter or illegal drugs, from the end of the nineteenth century the medical profession had no difficulty seeing their problems and expressing opinions through bodies such as the AMA. But once the drugs are made available by prescription only through the clinician, there is no independent voice of any standing to urge caution. Against this clinical background, the dynamics of branding produce something close to a pure toxin for medical care.

      The contrasting fates of reserpine and Prozac bring this out. In the early 1950s, reserpine, one of the first antihypertensives and first tranquilizers, was linked to suicide induction. Owing to the differing patent regimes at the time, twenty-six different companies produced reserpine and so no one manufacturer could have made it into a proprietary blockbuster. Therefore no company had an incentive to defend it to the death, and as a result while many doctors refused to concede a treatment they gave might have caused a problem, the views of others could be heard. A link between reserpine and agitation was established and reserpine fell into disfavor.

      But in 1990, when similar concerns erupted that Prozac could trigger suicides, the situation was quite different. There was and could be only one Prozac, and Lilly had all their eggs in the Prozac basket. They could not readily admit their brand might have a flaw. As Leigh Thompson, Lilly’s chief scientific officer put it in an internal e-mail that later came to light in a court case:

      I am concerned about reports I get re UK attitude toward Prozac safety. Leber (FDA) suggested a few minutes ago we use CSM database to compare Prozac aggression and suicidal ideation with other antidepressants in UK. Although he is a fan of Prozac and believes a lot of this is garbage, he is clearly a political creature and will have to respond to pressures. I hope Patrick realizes that Lilly can go down the tubes if we lose Prozac and just one event in the UK can cost us that.¹¹

      Several years later company documents for Lilly’s post-Prozac blockbuster Zyprexa made it clear that

      The company is betting the farm on Zyprexa. The ability of Eli Lilly to remain independent and emerge as the fastest growing pharma company of the decade depends solely on our ability to achieve world class commercialization of Zyprexa.¹²

      Prozac, Zyprexa, and other such blockbusters are products that come with a life plan that covers their use in all global markets.¹³ Even before the launch of potential blockbusters, ways of promoting their use in children and the elderly, without undertaking clinical trials to demonstrate efficacy or safety, is envisaged. The necessity of acknowledging a side effect that might restrict this use is not part of the plan. When a company is faced with defending a brand that is essential to its survival, commercial logic dictates that it will take any steps necessary to preempt the emergence of a hazard, including doctoring the evidence. This commercial logic led to a relentless marketing of Zyprexa that ultimately saw it being given to children as young as twelve months of age, its clinician prescribers seemingly unable to see the massive weight gain it produces, the diabetes it triggers, the raised lipids it leads to, and the premature deaths it causes.¹⁴

      As the story of H-2 blockers and the treatment of ulcers suggests, drug companies have little interest in innovative treatments that would eradicate a condition for which they have on-patent drugs that manage it after some fashion. When ulcers vanished, after the introduction of antibiotics, companies like Astra-Zeneca with a new generation of gastric acid antagonists, such as Prilosec, turned to GERD (gastro esophageal reflux disease) to replace it. This disease, which now seems so widespread and crippling, was infrequently encountered when I was training, and as such it is difficult to believe it doesn’t stem at least in part from our increasingly unbalanced and artificial diets and lifestyles. While there are unquestionably severe cases that need urgent medical treatment, it also seems the case that a large number of digestive discomforts that might be better handled by changing lifestyles have now been medicalized and are managed with medication.

      Quite extraordinarily GERD has even spread into infancy, incorporating colic, a disorder that lasts a few months and responds to care in the real sense. The first drug treatment for GERD in infants—Prepulsid (cisapride)—killed significant numbers of children where colic had never been known to kill children before.¹⁵ The shock of Prepulsid-induced deaths did not lead to a return to traditional medical care of colic— children instead are now getting Prilosec (omeprazole) and other successors of Zantac.

      At the eighteenth annual Pharmaceutical Conference in Paris in June 1990, Christopher Adam, then the head of marketing at Glaxo told the meeting “we are moving into the mega-product age.”¹⁶ Right he was. Zantac had just become the first blockbuster. The next year all blockbusters combined only comprised 6 percent of the market, but by 1997, when SSRIs like Prozac were the darlings of the media, this had grown to 18 percent, and by 2001 to 45 percent, under the impact of Lipitor and the statins.¹⁷ There is no blockbuster that is a life-saving drug. They are all lifestyle or risk management drugs.

      In 1990, market analysts perceived two threats to Glaxo’s position as the largest drug company in the world—the possible expiry of its patent on Zantac and the emergence of Prilosec, a new drug for ulcers. In fact the danger came from Barry Marshall’s research. Prilosec did displace Zantac but for the GERD rather than the ulcer market, forcing Glaxo into a series of mergers in order to sustain its position among the leading companies. In 1995, it merged with Burroughs Wellcome, at which time its chief executive, Richard Sykes, made it clear he still regarded the company as a serious research company that would have nothing to do with lifestyle drugs like Prozac. Five years later it merged with SmithKline Beecham, whose fortunes rode on Paxil, the company’s biggest earner since. By this time Sykes was gone. The market was changing the character of drug companies and in turn the shape of medicine.

       THE FACE IN THE MIRROR

      The idea that brands such as Lipitor, Paxil, and Fosamax might now have penetrated medical practice in a way that brands like Clark Stanley’s Snake Oil or Beecham’s Pills never did and that these modern brands might now play as big a part in medicine as Nike and Reebok do for running shoes and Lexus and BMW do for cars is not an idea that sits comfortably with the medical profession’s idea of itself.

      In the world of medicine most doctors come from, drugs are good, though they are unfortunately sold by slick if rather sleazy salespeople to whom doctors might try to be polite but whom they otherwise try to avoid—unless “these people” are picking up the drinks tab. But in the new world of medicine, the person doing the selling is not the sleazy- looking suit standing by the exhibit. That person is there to distract attention from the fact that one by one doctors are having marketed back to them exactly what they say are the things that count for them. The industry needs a person out there whom the doctor can identify as a source of corruption, someone they can resist, the way they might resist an obvious honeypot. In this new world, if a group like No Free Lunch didn’t exist, the pharmaceutical industry would have to invent it.

      In other industries, when companies manufacture a product they have to move it from factory to retail outlets where it competes with other products and they have to generate demand among consumers. The ideal arrangement is to have a dedicated showroom, such as automobile makers and Apple do, where purchases become almost inevitable as there are no competing brands in sight and, in the case of cars, nothing praising the virtues of walking, running, cycling, or any other means of transport. In the case of a branded drug, the task is to get on a hospital’s or managed care company’s list of approved drugs as well as into national guidelines and to have key articles placed in all the prominent journals. We shall see in chapters 4 and 5 how companies manage this and manage to eliminate competing influences, so that when the doctor gets to the point of purchase,