You can get away with a lot in the medicines business, but there is one basic requirement - a drug should do you some good. This has to be proved in at least two controlled studies. These large-scale clinical trials often cost millions of dollars and must consist of at least two arms: one of people who are given the test drug and a second group who act as a means of comparison.
This second group is given a placebo, a sugar pill with no powers other than those evoked through the power of suggestion. The placebo effect shows what the mind and body are capable of achieving in the absence of real drugs but with the expectation of benefit. Potential participants in a trial are filtered through various entry criteria such as age, severity of disease and so on, and then selected at random. It can be conducted in a single hospital or in a network of clinical centres around the world. It can last weeks, months or years. The most important thing is that neither doctor nor patient knows who is taking the drug and who is not.
The placebo, despite containing no active ingredient, often proves a surprisingly strong contender. Its performance in clinical trial after clinical trial shows patients inherently possess vast amounts of untapped healing power. They want to be well so much, their bodies respond to the mere expectation that they will be.
These hopes are easily exploited by pharmaceutical companies when they want to extend the reach of a drug, increasing the number of conditions the single drug is used to treat. In this sense medicines are packaged science. The package, or label, plus what the doctor tells them, is all most people get to know of the drug and what its expected effects will be.
Where some antidepressant drugs are concerned, the label can say almost whatever you want it to say. It could be for painful periods, for depression, to stop smoking, to become more engaged in the world, for panic attacks, irritable bowels, incontinence, shyness - for virtually anything that has some kind of anxiety at its root.
The active ingredient can be the same, but its effect will depend on what it is being tested for. If it has been shown in a trial to treat irritable bowels or help smoking cessation, and it has been approved by the regulators for that indication, then that is what it will say on the label. And the drugs work according to what the label says, what the doctor says, and what we believe. Our minds and bodies respond, in other words, to what we are told the drug will do. GlaxoSmithKline's Zyban for giving up smoking, for example, is a long-acting form of Wellbutrin for depression by another name. And the antidepressant, Zispin, is also marketed for sleeping disorders, one of the top symptoms in diagnosing depression. Many lifestyle drugs are prescribed under a number of different names. Different studies are done to get different licensing data to get them known as different drugs so they can operate in different therapeutic markets.
What makes a smoker more likely to kick their habit on Zyban than on the identical drug posing as an antidepressant is the fact that this is what the doctor says, and what the data from clinical studies corroborates.
Such drugs are a triumph of branding - a triumph of making maximum use and maximum profit from a single compound. Packages of symptoms that might otherwise be interpreted as fairly normal in the kind of fast, attention-deficit world we live in, become new diseases and new opportunities for medication.
Few new drugs are being produced, yet the amount spent on drugs steadily soars. And it is not only drug companies who benefit from the widespread belief that we could all be a lot healthier than we are. Most natural forms of healing are thought to work largely because they evoke a placebo response through the trust patients have in the treatment, the practitioner, or both.
Pharmaceutical companies stand accused of actively trying to get people to internalise morbid messages that suggest they are ill. "The way to sell drugs is to sell psychiatric sickness. If you are Paxil and you are the only manufacturer who has the drug for social anxiety disorder, it's in your interest to broaden the category as far as possible and make the borders as fuzzy as possible," said US bioethicist Carl Elliott. Paxil's product director, Barry Brand, told the journal Advertising Age that the company GlaxoSmithKline had been largely successful in this respect. "Every marketer's dream is to find an unidentified or unknown market and develop it. That's what we were able to do with social anxiety disorder."
As more research dollars are poured into the workings of our mind, a rapidly growing range of conditions is being developed that, ostensibly at least, can be treated pharmacologically.
Diagnosing mental illness is difficult: what appears to one psychiatrist to be depression might be diagnosed by another as schizophrenia, manic depression, or just ordinary grief. Meanwhile, the number of officially recognised disorders soars. In the American Psychiatric Association's manual of 1980, 106 disorders were listed; the figure had risen to 300 in the 1994 edition. The new categories include attention-deficit disorder (ADD), antisocial personality disorder (impulsivity or failure to plan ahead), dissociative fugue (an overwhelming urge to travel away from home or one's customary place of work) and many other things most of us will have experienced at some time or other.
Companies have been very clever at peppering the medical literature with ghost-written editorials and review papers that promote off-label use of their drugs. In the words of Dr Jay Pomerantz, of Harvard University: "If what we are seeing is a pattern of widespread antidepressant prescribing for subsyndromal, amorphous patient complaints, it suggests antidepressants have become the modern-day sugar pill, or placebo... [if this is the case] taxpayers are paying the pharmaceutical industry a mighty high price for fool's gold."
The placebo effect is directly related to trust. Good doctors, who have the complete confidence of their patients, exert a placebo effect in how they listen and their general ability to convince patients they are being taken seriously. If patients believe a medicine will work, so the placebo effect of that drug is enhanced. The US writer Norman Cousins, who famously recovered from an incurable disease himself and wrote the book Anatomy Of An Illness As Perceived By The Patient, cites an experiment into the role of doctors.
"Patients with bleeding ulcers were divided into two groups," he says. Members of the first group were informed by the doctor that a new drug had just been developed that would undoubtedly produce relief. The second group was told by nurses that a new experimental drug would be administered, but that very little was known about its effects. Of the people in the first group, 70% received sufficient relief from their ulcers. Only 25% of the patients in the second group experienced similar benefit. Both groups had been given the identical "drug" - a placebo.
Cousins also cites the late Dr Henry K Beecher, an anaesthesiologist at Harvard, who analysed the results of 15 studies involving 1,082 patients. He discovered that across the broad spectrum of these tests, more than a third (35%) of the patients consistently experienced "satisfactory relief" when placebos were used instead of regular medication. The medical problems included severe post-operative wound pain, seasickness, headaches, coughs and anxiety. Other biological processes known to be affected by placebos include rheumatoid and degenerative arthritis, blood-cell count, respiratory rates, vasomotor function, peptic ulcers, hypertension, hay fever and spontaneous remission of warts.
Ted Kaptchuk, who heads a placebo working group at Harvard Medical School, is leading a trial involving a drug that treats an intractable, common stomach disorder. Half the patients are treated with the drug by a doctor who is positive about the medicine and who listens attentively to their account of how the symptoms manifest. The others are treated by a doctor who gives a fairly matter-of-fact presentation of the medicine before leaving the room. The idea is to demonstrate the worth not of drugs but of doctors.
How the placebo works is the subject of endless discussion. American medical writer Berton Rouché, in an article in the New Yorker magazine back in 1960, said the placebo derives its power from the "infinite capacity of the human mind for self-deception". Others believe the placebo is powerful not because it tricks the mind of the patient but because, as Cousins says, it translates the will to live into a physical reality. "The fact that a placebo will have no physiological effect if the patient knows it is a placebo only confirms something about the capacity of the human body to transform hope into tangible and essential biochemical change."
Consider the dilemma facing the pharmaceutical industry. In clinical trials for depression, people taking Prozac improved on average by 8.3 percentage points on a standard scale that quantifies the severity of the disease. Those on the placebo arm, however, also did well, improving by 7.34 points. People on Paxil/Seroxat improved by 9.88 points, and on the placebo arm by 6.67 points. The scores for Zoloft were 9.96 (placebo, 7.93); Effexor, 11.54 (placebo, 8.38); Celexa, 9.69 (placebo, 7.71).
The relatively poor show of the antidepressants is replicated in study after study. A couple of years ago, for example, a $6m study found the herbal remedy St John's wort was less effective than a placebo, apparently as a vindication of conventional medicine. While the herb had managed to help only 24% of cases of moderate to severe depression, the placebo scored 32%. It later emerged that Zoloft was also part of the trial and had helped 25%.
It is ironic that the areas of medicine where the placebo effect has been shown to be most powerful - pain and depression - are precisely the areas at the centre of the recent regulatory storms. And the irony shows succinctly how self-defeating healthcare systems can be if trust is allowed to slip away. The placebo effect works on trust. But the revelations about the new wave of antidepressants, SSRIs - that it was more difficult to come off them than anticipated, and that they made some people feel suicidal - together with the withdrawal of the painkiller Vioxx, did nothing to improve that trust.
The central issue remains whether drugs are always the best solution. Pharmaceutical companies are always pushing for a more direct relationship with the public, where they paint a picture of the consumer as king. They may have the regulators on their back, the science against them, patents expiring, everyone screaming for lower prices, but the zeitgeist is with them: it is not hard to convince people that it is more of a crime to suffer in silence from a condition than to take something that can cure it instantly.
If patients really were king, they would resist the medicalisation of society and query the terms of reference, for instance, of studies that suggest 80% of people can expect to suffer depression at some time in their lives, or that 43% of women suffer an unhealthy response when having sex. Instead, as with the effect of pharma marketing on doctors, there is a sort of drip effect. Even if people genuinely try to ignore such commercially inspired drivel, some of it gets through. Journalist Ray Moynihan located the original study detailed in the Journal of the American Medical Association which showed that 43% of women suffered from female sexual dysfunction (FSD); he found the authors had close links to Pfizer, which was testing Viagra in women at the time. He also found 1,500 women, aged between 18 and 59, had been asked if they had experienced any of seven problems for two months or more over the previous year. One was a lack of desire for sex and another anxiety about sexual performance. No questions were asked about the length of their relationships - a major factor in many people's sex lives - nor about what else the women did, how many children they were looking after, and so on.
The results of that study were widely quoted in the press. In this way, medicine enters the most intimate areas of our lives, despite evidence that our bodies respond in ways we want them to without the help of drugs. Pfizer, for example, did every-thing it could to show Viagra could work in women. It carried out several large-scale trials in women with apparent FSD only to find the women on Viagra responded but those on placebo responded more.
The drugs don't work
· The global spend on pharmaceuticals has risen 25-fold over the past three decades, from $20bn in 1972 to more than $500bn in 2004. '[In 2002] the combined profits for the 10 drug companies in the Fortune 500 ($35.9bn) were more than the profits for the other 490 businesses put together ($33.7bn),' Dr Marcia Angell writes in her book The Truth About The Drug Companies. The breakdown of pharma finances for 2003 is: 14% on research and development, 17% on profits, 31% on marketing and admin, the rest on manufacturing and distribution.
· The pharmaceutical industry is reckoned to spend more than $5.5bn to promote drugs to doctors in the US each year - more than all US medical schools spend on educating medical students.
· Dr David Graham of the FDA told a US Senate hearing in October 2004 that his agency's approval of Vioxx led to the 'single greatest drug safety catastrophe in the history of this country or the world'. Vioxx is a painkiller introduced with much fanfare because it avoided the side-effects of aspirin and ibuprofen, which occasionally result in intestinal bleeding. Merck spent more than $150m a year on its Vioxx ads in the US, more than was spent advertising Pepsi-Cola or Budweiser. By the time Vioxx was withdrawn in September 2004 - because it had been shown to double the chances of heart attack or stroke - it was earning $2.5bn. Graham said 28,000 Americans suffered ill effects from it while the FDA argued about what action to take. Since then Vioxx has been cleared for use in the US, subject to caveats and warnings.
· The Pharmaceutical Journal guestimated that half of all medicines prescribed in the UK are not taken. The UK industry's association puts the figure at 80%.
· For decades, stomach ulcers were attributed to gastric acidity, stress, smoking, alcohol and genetic disposition, and treated with antacids. Yet the bacterium that causes ulcers had been identified in 1982 and can be treated with antibiotics. Similarly, Paul W Ewald argues in his book Plague Time, thousands of women probably suffered and died 'because cervical cancer was treated as bad luck rather than a preventable sexually transmitted disease'.
· 'Metabolic syndrome' covers a cluster of common metabolic disorders, such as abnormal lipid levels, obesity and high blood pressure. It is now said to be approaching epidemic levels, with 115 million sufferers. Such a syndrome was not even recognised before 1988.
· This is an edited extract from Big Pharma, by Jacky Law, to be published on February 9 by Constable & Robinson at £12.99.
