Why Evidence-Based Medicine Can, and Must, Be Applied to Psychiatry

In the second century ad, a brilliant physician had a powerful idea: 4 humours, in varied combinations, produced all illness. From that date until the late 19th century, Galen's theory ruled medicine. Its corollary was that the treatment of disease involved getting the humours back in order; releasing them through bloodletting was the most common procedure and was often augmented with other means of freeing bodily fluids (eg, purgatives and laxatives). For 17 centuries, physicians subscribed to this wondrous biological theory of disease. We bled our patients until they lost their entire blood supply, we forced them to throw up and to defecate and urinate, we alternated extremely hot showers with extremely frigid ones—all in the name of normalizing those humours.¹ Yet it all proved to be wrong.

This is not a Whiggish interpretation of history: it is not simply a matter of "they were wrong and we are right." Galen, Avicenna, Benjamin Rush—these were far more intelligent and creative men than we are. In fact, not only am I not Whiggish, I believe we are repeating these past errors, which have sunk deep into the flesh of the medical profession. As Sir George Pickering, Regius Professor of Medicine at Oxford, said in 1949,

Modern medicine still preserves much of the attitude of mind of the school men of the Middle Ages. It tends to be omniscient rather than admit ignorance, to encourage speculation not solidly backed by evidence, and to be indifferent to the proof or disproof of hypothesis. It is to this legacy of the Middle Ages that may be attributed the phenomenon... [of] "the mysterious viability of the false."²

We see this influence even today in articles such as Levine and Fink's accompanying critique of evidence-based medicine (EBM).

There are and have always been 2 basic philosophies of medicine. One is Galenic: There is only one correct theory. For our purposes, the content of the theory does not matter (it can be about humours, serotonin and dopamine(Drug information on dopamine) neurotransmitters,³ electroconvulsive therapy (ECT),⁴ or even psychoanalysis); what matters is that hardly any scientific theory (especially in medicine) is absolutely right.⁵ The error is not so much in the content but in the method of this way of thinking. It focuses on theory, not reality; on beliefs, not facts; and on concepts, not clinical observations.

There is a second approach that is much more humble and simple—the idea that clinical observation should precede any theory; that theories should be sacrificed to observations and not vice versa; that clinical realities are more basic than any other theory; and that treatments should also be based on observations, not ideas.

This approach was first promulgated clearly by Hippocrates and his school in the 4th century bc, but 500 years later Galen demolished Hippocratic medicine (while claiming its mantle), and it lay dormant until revived (more than 1000 years after Galen) during the Enlightenment.^6-9

Why all this historical background in a discussion of EBM? Because it is important to know what the options are and what the stakes are. We are Hippocratic or we are Galenic—either we value clinical observation or we value theories. The whole debate may come down to this distinction.

Perhaps readers, including critics of EBM, will claim they value clinical observation. If so, how can we validate this value? How do we know when our observations are correct and when they are false?

Confounding bias
The problem lies in confounding bias.¹⁰ As clinicians, we cannot believe our eyes. Confounding bias means that in the course of our clinical experience, there are many other factors of which we are not aware that can impact what we observe. Thus, it can appear that something is the case when it is not or that some treatment is improving matters when it is not. Furthermore, these confounding factors are present most of the time.

Perhaps most clinicians would admit that confounding factors exist, but it is important to examine both the clinical and scientific implications.

Clinically, the reality of confounding bias teaches us the deep need for a Hippocratic humility versus a Galenic arrogance (Galen once said: "My treatment only fails in incurable cases")—a recognition that we might be wrong (indeed, we often are, even in our most definitive clinical experiences). The end of Galenic treatments came about in the 19th century because of the development of EBM, through the "numerical method" of Pierre Louis who showed by counting about 40 patients rather than relying on single cases or clinical experience that bleeding accelerated death in pneumonia rather than curing it.¹

Many have thought Freud right for a century, but patients with manic-depressive illness who were given daily psychoanalysis instead of ECT or lithium(Drug information on lithium) (Eskalith, Lithobid) probably suffered and even died needlessly. The source of the greatest medical advances was EBM, not the exquisite case study, the brilliance of any specific person (be he Freud, Emil Kraepelin, or even our most prominent professors today), or decades of clinical experience. A. Bradford Hill, the founder of modern clinical epidemiology, made the point that the common distinction between clinical experience and clinical research is a false one.² After all, clinical experience is based on the recollection of usually a few cases; clinical research is simply the claim that such recollection is biased and that the remedy is to collect more than just a few cases, comparing them in ways that reduce bias. The latter point entails EBM (see below).

Truths of theory are transient. Galen is out-of-date and so is the much-vaunted catecholamine theory of depression; today's most sophisticated neurobiology will be passé by the end of the decade. Clinical observation and research, in contrast, is steadier. That same melancholia that Hippocrates described can be discerned in today's major depression; the mania that Aretaeus of Cappadocia explained in the first century ad is visible in current mania. Obviously, social and cultural factors come in- to play, and such presentations vary somewhat in different epochs, as social constructionists will point out.¹¹ Yet Karl Marx made this point long before Michel Foucault, and the limits of a purely social/economic interpretation of human existence should be obvious: the presence of social factors does not reduce an entity to nothing but a social construction.¹² Clinical research is the solid ground of medicine; biological theory is a necessary but changing superstructure. If these relationships are reversed, then mere speculation takes over and the more solid ground of science (interpreted nonpositivistically) is lost.

Scientifically, confounding bias leads to the conclusion that any observation, even the most repeated and detailed, can be (and often is) wrong; thus, valid clinical judgments can be made only after removing confounding factors.^10,13 Randomization, developed by the biologist Ronald Fisher in the 1920s and thereafter honed by Hill,¹⁴ is the most effective way to remove confounding bias. Hormone replacement therapy was the cure for many female illnesses. Decades of experience with millions of patients, huge observational studies with thousands of subjects, and the almost unanimous consensus of experts all came to naught when randomized studies proved the futility of the belief in that treatment (not to mention its carcinogenic harm).¹⁵