Pharmageddon. David Healy

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СКАЧАТЬ revolutionary ferment in France, Philippe Pinel, the general physician now commonly seen as the father of modern psychiatry, working at the Salpêtrière asylum, became the first to commit medicine to an evidence-based approach. At the time typical treatments for mental illness included bloodletting, brutality, forced immersion in cold baths, being hosed down with water jets or subjected to a variety of purgatives, emetics, diuretics, and other drugs. Although there were elegant rationales for some of these treatments, and in some cases the treatments stemmed back to antiquity and had been advocated by history's most distinguished medical names, Pinel was skeptical. Patients often seemed to get better when the doctor waited to intervene, he had observed. Learning the typical course of a disorder, he reasoned, would make it possible to predict when patients might turn a corner for the better on their own. This appreciation underpinned his dictum that the greater art in medicine lay in knowing when to refrain from treatment.⁵

      Between April 1802 and December 1805, 1,002 patients were admitted to the Salpêtrière, and Pinel was able to follow these individuals during their stay to see who recovered and who didn't, whether patients in particular diagnostic groups fared better than others—and hence whether diagnoses in use at the time were worthwhile or not. This was a first example of what later came to be called a statistical approach to illness. Why do it? Pinel laid out his reasons.

      In medicine it is difficult to come to any agreement if a precise meaning is not given to the word experiment, since everyone vaunts their own results, and only more or less cites the facts in favor of their point of view. However, to be genuine and conclusive, and serve as a solid basis for any method of treatment, an experiment must be carried out on a large number of patients following the same rules and a set order. It must also be based on a consistent series of observations recorded very carefully and repeated over a certain number of years in a regular manner. Finally it must equally report both events, which are favorable and those which are not, quoting their respective numbers, and it must attach as much importance to one set of data as to the other. In a nutshell it must be based on the theory of probabilities, which is already so effectively applied to several questions in civil life and on which from now on methods of treating illnesses must also rely if one wishes to establish these on sound grounds. This was the goal I set myself in 1802 in relation to mental alienation when the treatment of deranged patients was entrusted to my care and transferred to the Salpêtrière.⁶

      There had never been anything like this in medicine before. Overall, 47 percent of the patients recovered, Pinel found, but of those who had been admitted for the first time, who had never been treated elsewhere, who had a disorder of acute onset, and who were treated only using Pinel's methods, up to 85 percent responded. When left to recover naturally, many more of the first-timers did so than did those among the patients who had been treated previously by other methods. Not only that, within a short time of admission Pinel could tell who was likely to recover and who was not based on their clinical features. In other words there seemed to be different disorders, and people suffering from some types would recover if left alone while inmates with some other types would not regardless of what treatments they were given. Finally, following the patients after discharge brought a whole new group of periodic disorders into view for the first time, laying the basis for the later discovery of manic-depressive illness and other recurrent mental disorders.

      Aware of the pioneering nature of his research, Pinel presented his data, on February 9, 1807, to the mathematical and physical sciences faculty at the National Institute of France rather than to the country's Academy of Medicine. This was hard science and the first time in medicine that results were presented as ratios across a number of patients studied, rather than as accounts of individual cases.

      In reporting these findings, Pinel showed that he was well aware that his personal bias could have colored the results. But, as he noted, while an individual patient in London could not properly be compared to one in Paris or Munich, the results of complete groups of patients could be, and the registers of Salpêtrière patients were publicly available. So he confidently challenged others to contest his findings based on their outcomes.

      The scientists were impressed. The physicians weren't. It took thirty years before another French physician picked up the baton and further unsettled the medical establishment with numbers. In 1836, Pierre Louis outlined a new numerical method that controlled for variations by using large numbers of patients: “in any epidemic, let us suppose five hundred of the sick, taken indiscriminately, to be subjected to one kind of treatment, and five hundred others, taken in the same manner, to be treated in a different mode; if the mortality is greater among the first than among the second, must we not conclude that the treatment was less appropriate, or less efficacious in the first class than in the second?”⁷

      The treatment Louis assessed was bleeding—which in fact works well in disorders such as heart failure. But when he compared bleeding to doing nothing in a sufficiently large number of patients during the course of an epidemic, he sparked a crisis in therapeutics. Doctors expected bleeding to work better than doing nothing, but “the results of my experiments on the effects of bleeding in inflammatory conditions are so little in accord with common opinion [those who were bled were more likely to die, he found] that it is only with hesitation that I have decided to publish them. The first time I analyzed the relevant facts, I believed I was mistaken, and I repeated my work but the result of this new analysis remains the same.”⁸

      These results led to howls of outrage from physicians who claimed that it was not possible to practice medicine by numbers, that the duty of physicians was always to the patient in front of them rather than to the population at large, and that every doctor had to be guided by what he found at the bedside.

      Ironically, it was Louis and Pinel who were calling on physicians to be guided by what was actually happening to their patients, not by what the medical authorities traditionally had to say. As the marketers from GlaxoSmithKline and other companies might have told Louis and Pinel, though, for many physicians to be convinced there has to be a theory, a concept about the illness and its treatment, to guide the doctor. “The practice of medicine according to this [Louis's] view,” went one dismissal, “is entirely empirical, it is shorn of all rational induction, and takes a position among the lower grades of experimental observations and fragmentary facts.”⁹

      Louis's struggles in Paris had their counterpart in Vienna where, in 1847, Ignaz Semmelweis noted that mortality was much higher on an obstetric ward run by physicians and medical students than one run by student midwives. Suspecting that the physicians were coming to women in labor with particles of corpses from the dissection room still on their hands, he got them to wash more thoroughly with a disinfectant and was able to show that antiseptic practice made a difference. No one paid any heed. A few years later, in 1860, Joseph Lister introduced antiseptic practice to the Glasgow Royal Infirmary, and postoperative putrefaction rates subsequently declined. The later discovery that infection with bacteria led to putrefaction provided a concept to explain these observations, but until then Lister, like Semmelweis, had trouble getting his colleagues to take his findings seriously.

      One of the weaknesses in these early manifestations of evidence- based medicine, as the examples of Pinel, Louis, Semmelweis, and Lister make clear, was their inability to shed much light on what lay behind the figures—they showed associations but explained nothing about cause. There are commonly tensions between broad associations of this type, the specific evidence that comes from laboratory experiments, the evidence of our own eyes, and what currently dominant theories may dictate. To the relief of most doctors, the tensions between broad associations and more specific evidence were eased to a degree with the emergence in the second half of the nineteenth century of laboratory science, which more clearly linked cause and effect.

       THE CAUSES OF DISEASES

      In the 1870s, a set of laboratory sciences emerged to form the bedrock of the new scientific and diagnostic work that would transform much of medicine and underlie the practice of doctors like Richard Cabot and the rise of hospitals such СКАЧАТЬ