Pharmageddon. David Healy

to demonstrate by means of controlled trials that their remedies did in fact work.

      There can be few better symbols of Pharmageddon than prescription only drugs becoming among the most consumed drugs in pregnancy in the face of strengthening warnings that they cause birth defects. The answers to how this could happen lie in great part in how the pharmaceutical companies have managed to capitalize on the very protections put in place by Senator Kefauver in his 1962 bill and in the reforms that defeated him. Prescription-only status has made doctors the targets of a marketing exercise that is far more sophisticated than placing even billions of pages of advertisements in medical journals and bribing doctors to use drugs. As outlined in chapter 1, the patent status of drugs has given companies an incentive to chase blockbuster profits—doing so regardless of patient welfare. Controlled trials have given the companies a means to persuade doctors that snake oil works so well that withholding it in pregnancy would be unethical, and also a means to make problems consequent on treatment vanish. But all of these hinge on the fact that these drugs are available by prescription only.

       WHAT THE DOCTOR ORDERED

      When Alfred Worcester or Richard Cabot wrote a prescription for a remedy at the dawn of the twentieth century, they were following a centuries-old tradition of asking an apothecary to take certain ingredients and mix them according to a formula (Rx = Recipe). If there was more than one ingredient in the mix, each should have a particular purpose. If the remedy worked, patients were able to take the prescription back to the pharmacy on numerous occasions asking for refills for themselves without further endorsement from the doctor. Alternatively, having once obtained something by prescription that worked, they could revisit the pharmacist and ask for the same medicines again, for family members. A prescription from a doctor was only one means by which people could access the drugs they believed they needed.

      Because in Cabot’s day all medicines, including opiates, bromides, barbiturates, chloral hydrate (used for sedation), antiseptics, remedies for the gut, urinary system, and heart and respiratory system were available without recourse to a doctor, the threshold for visiting a doctor was far higher than it is today. Until the middle years of the twentieth century, there was no one being treated for latent diabetes, latent hypertension, or raised lipids. Aside from a few wealthy people engaged in psychoanalysis, no one had contact with the mental health system other than those relatively few who had psychoses and were committed to asylums.

      When the US Congress passed the 1906 Food and Drugs Act, it contained no prescription requirement, only a requirement that medicine manufacturers state the contents of the product on the label. The pharmaceutical industry lobbied hard against the act, but once it was in place many enterprising manufacturers found ways of working the new situation to their advantage, for instance, by labeling their product “as approved by the Chemical Bureau.”²

      There were no implications here for traditional medical practice. But another regulatory step taken soon thereafter had profound implications. The nineteenth century saw a growing concern about opiate and cocaine abuse, as well as alcoholism. These problems had been of little concern to medicine. Drug addiction, like alcoholism, was considered a social problem, except where the affected people became patients by virtue of cirrhosis or psychosis. After a variety of social approaches to treating the problems of addiction floundered, in 1914 the US Congress passed the Harrison Narcotics Act, which introduced prescription-only status for opiates and cocaine.³ The problem of addiction would be managed, or so it was thought, by making these drugs legally available only through a medical practitioner.

      After the contaminated sulfanilamide tragedy of 1937, the 1938 Food, Drugs and Cosmetics Act encouraged a move toward making new drugs available by prescription only. The calculation was that the sulfa drugs were better categorized with insulin and the steroid and thyroid hormones, which were typically if not exclusively administered by doctors. After World War II, in 1951, the prescription-only status for new medicines in the United States was copper-fastened in place with the Humphrey-Durham amendments to the 1938 act, despite vigorous, sustained, and widespread opposition to the move. Critics complained that a system put in place for addicts was inappropriate for free citizens. But by the early 1950s, one of the side effects of having medicines that really worked was becoming clear—drugs that could really benefit, could really harm also. In 1952, Leo Meyler’s Side Effects of Drugs appeared, a first-ever medical compendium of drug-induced injuries.⁴ This new potential for harm took dramatic shape in 1961 with limbless babies born to mothers who had taken thalidomide during pregnancy as a supposedly safer hypnotic than the older barbiturates.⁵

      When it came to his hearings in 1959, Senator Kefauver was exercised by the prescription-only status of the new drugs, a unique characteristic found in no other market. As he put it, “He who orders does not buy; and he who buys does not order.” As a consequence, when it came to drugs available by prescription only ordinary consumers could not protect themselves against the monopoly element inherent in trademarks or patents. Patients were critically dependent on their doctors to be uninfluenced by trademarks, patents, or marketing ploys. Doctors had a choice whether to give their patients the latest on-patent and branded drug or perhaps an older, more effective and less expensive drug, but patients had little choice other than to do as prescribed by their doctor.⁶

      Thalidomide had been available over the counter in many European countries but exactly the same problems arose in the United States where the premarketing samples were available by prescription only. Indeed the problems may have come to light as quickly as they did because doctors in Germany were not inhibited in recognizing the potential for harm of an over-the-counter drug, as they might have been in the case of a drug essential to their livelihoods. But in the United States in 1962, in the face of the thalidomide disaster, retaining the prescription-only status of drugs seemed to make sense: doctors retained some patina of skepticism about drug claims due to medicine’s long-standing opposition to quackery, and doctors appeared to be the people who would be able to quarry information from drug companies about possible adverse side effects of their products.

      Before 1962 prescription-only status was still something of a novelty—after 1962 it became the center of the distribution system for new drugs when companies were required not only to make their drugs available only through doctors but also to prove that their drugs worked for some medical condition in order to get FDA approval. This combination of controls must have looked pretty foolproof in 1962, but it has not turned out to be an effective way to constrain the pharmaceutical industry within a medical framework. Quite the reverse. When a pharmaceutical company gets a drug on the market for lowering cholesterol, for osteoporosis, or for erectile dysfunction, this now marks the point at which the company begins to sell the condition, the point at which they can gear up to reengineer the medical marketplace to suit their product, as Abbott did with bipolar disorder to make it Depakote-friendly. It seems extraordinary now that no one in 1962 seems to have realized that if pharmaceutical companies were restricted to marketing drugs for diseases, they might start to market diseases.

      Had pharmaceutical companies not been required to demonstrate a drug’s efficacy in treating a particular disorder, we might all have ended up with a lot fewer diseases recorded in our medical records. The first antidepressants would have been marketed as tonics or stimulants. To get St. John’s wort, an herb with SSRI properties, we just have to feel stressed and buy it over the counter where it is sold as a tonic, but to get Prozac now, we have to be officially diagnosed as depressed. In a similar fashion, the statins might have been marketed on the promise of restoring inner youthfulness, or getting our arteries in shape, rather than for a supposed cholesterol disorder, or the biphosphonates might have been aimed at restoring youthful bones rather than for osteoporosis. As insurance companies reimburse in response to diagnoses, fewer diagnoses would likely have reduced our need for doctors in addition to reducing the number of diseases.

      The third medical requirement of the 1962 amendments was that companies demonstrate their products worked in well-controlled clinical trials. This was smuggled into the final bill through the efforts of Louis Lasagna, a professor of pharmacology and a believer in controlled trials, who was attempting at the time to encourage some use of controlled trials, rather than trying to make them mandatory.⁷ Lasagna himself had undertaken the only controlled trial of thalidomide ever done, through which