Barry Blackwell: Pioneers and Controversies in Psychopharmacology
Chapter 21:What to believe going forward?
The Baby and the Bathwater
Preamble
Chapter 20 comprises three recent contributions to the INHN network, the original Baby and the Bath Water essay, the response from Edward (Ned) Shorter, a distinguished psychiatric historian, and my reply.
This series raises an important question; how to find an epistemological standard for discriminating the baby from the bathwater in today’s murky environment?
Shorter states that “experienced clinicians often have a gut feeling for what works.” This is a valuable reminder that is true of the earliest effective discoveries in psychopharmacology (Chapters 3, 5, 6 and 7). After decades of observing futile asylum attempts to alleviate the major psychotic disorders clinicians, nurses, relatives and patients themselves were appropriately pessimistic but primed to acknowledge real change. The benefits of the first drugs like lithium, chlorpromazine and imipramine were so dramatic they did not need to impose an epistemological standard to confirm what was clearly in plain sight.
But in todays contaminated and toxic environment who are the “experienced clinicians” we can trust? Conflict of interest is a buzz word, highly rewarded, seldom defined and never prosecuted. It is important to recall that in the pre-FDA days, before thalidomide, most of placeboes, panaceas and snake oils were enthusiastically endorsed by self-nominated experts with their accompanying biases.
A final puzzle that remains to be solved is how can we establish a valid epistemological standard for drug trials? Placebo controlled trials may be rendered obsolete when so many chemophilic subjects with a pre-exiting ailment may have responded to numerous highly promoted drugs with seductive “mechanisms of action” making placebos and hypothetical new drugs impossible to distinguish. Even by an expert bribed to do so.
Barry Blackwell: The Baby and The Bath Water
Recent writing assignments have brought to mind the idiomatic expression; “Don’t throw out the baby with the bath water.” The phrase originates from a German book by Thomas Murner, Appeal to Fools, written in 1512, more than half a millennium ago. It is illustrated by a woodcut of a woman tossing out a baby along with waste bathwater. The use of the idiom acquired philosophical connotations in the writings of Martin Luther, Goethe and Thomas Mann, among others, presumably to denigrate those who they believed advocated foolish ideas.
Its modern usage is allied to another philosophical term, Epistemology – OED: The theory of knowledge, especially with regard to methods, validity and scope. From episteme, Greek for knowledge.
Applied to the contemporary domain of science in general and psychiatry in particular, the idiom expresses what is appropriately retained as essential and truthful or rejected as false and inessential. In medicine it can be used to segregate placebos, panaceas and snake oil from safe and effective remedies. Psychiatry probably has the most difficulty in determining what to keep and what to discard due to a paucity of valid and reliable outcome measures. Recent examples come to mind: Freud’s seductive use of deductive reasoning, embraced by John Cade (Blackwell, 2017), but artfully debunked by Michael Shepherd in his short book, Sherlock Holmes and the case of Dr. Freud, (Shepherd 1985). Also, the veracity of double-blind placebo-controlled trials, initially regarded as the gold standard in biological psychiatry, now manipulated and debased by the pharmaceutical industry under the FDA’s blind eye (Blackwell 2017b). Psychoanalysis and me-too drugs become candidates to be flushed with all the other forms of therapy considered lacking in value.
A willingness to throw out remedies is facilitated by false promises, such as the Nobel award for pre-frontal lobotomy and the intractable worldwide delusion that insulin coma cured schizophrenia. Such examples encourage skeptics and scientologists to metaphorically pull the plug on all biological treatments. At mid-century Peter Breggin, biological nihilists and conspiracy theorists colluded to succeed in persuading Congress to cut off all funding for brain stimulation research, effectively ending the career of Jose Delgado (Blackwell 2013).
Such incidents have encouraged other attempts to throw out all biological treatments including ECT, lithium and even the modest effective use of a spectrum of specific drug treatments most discovered by serendipity between 1952 and 1975, but effective enough to meet contemporary epistemological standards. Primary and most forceful have been the nine books written in the 12 years between 2004 and 2016 (Blackwell 2016) which present a compelling story of over diagnosis and drug usage described by two authors as “an epidemic” (Whitaker 2010; Schwartz 2016). Incriminated have been ill considered legislation, a corrupt pharmaceutical industry, complicit psychiatrists, many of them academic superstars and, finally, a lax FDA, economically in thrall to the industry it regulates (Blackwell 2017).
Some of this information is inaccurate or hyperbolic, but much is true and compelling so the overall effect is to blur the epistemological boundary between truth and falsehood, muddying the bath water and concealing a biological baby that is beloved and retained by some or reviled and cast out by others.
Applying a metaphor that has survived more than 500 years becomes a game of blind man’s bluff. Now that commerce and money trump epistemology where is the baby and who are the fools?
References:
Blackwell B. A distinguished but controversial career: Jose Manuel Rodriguez Delgado. INHN. Biographies. 5.30.2013.
Blackwell B. Corporate corruption in the pharmaceutical industry- revised. INHN. Controversies 16.3.2017.
Blackwell B. Book Review: Finding Sanity: John Cade, lithium and the taming of bipolar disorder. De Moore G, Westmore A. Melbourne, Allen & Unwin, 2016. INHN. Biographies; 2.2.2017.
Murner T. Narrenbeschwoerung, 1512.
Schwartz A. A.D.H.D. Nation. New York: Scribner; 2016.
Shepherd M. Sherlock Holmes and the case of Dr. Freud. London: Tavistock; 1985.
Whitaker R. The Anatomy of an Epidemic: magic bullets, psychiatric drugs and the astonishing rise of mental illness in America. New York: Crown Publishing; 2010.
Edward Shorter's Comment
Barry Blackwell's thoughtful and learned comment immediately invites the response: (1) What is baby and what is bathwater? And (2) How do we tell them apart?
On (1):
Most of the field probably agrees on the following judgments: psychoanalysis (throw); neurotransmitters (keep); insulin coma therapy (throw); mood stabilizers (keep). These are not really scientific judgments but cultural opinions based on optics. We cling to neurotransmitters (despite 50 years of failure in drug discovery), because neurotransmitters have made a good marketing trope for the pharmaceutical industry. We throw out psychoanalysis because we find biological treatments more effective, even though the many illnesses caused by stress and misery do not respond to biology; we discard insulin coma therapy because it looks awful (and that nasogastric tube at the end, please!); and we like mood stabilizers because we buy into a theory that a special kind of illness causes mood "instability" and that this illness requires special treatments. All of these judgments are questionable, at least. So, throw vs keep, let's proceed with caution here.
On (2):
How do we tell baby from bathwater? How do we decide what to throw and what to keep?
Barry Blackwell rightfully casts doubt upon the usefulness of randomly controlled trials: In theory, they should be a gold standard of evidence; in practice, the influence of the pharmaceutical industry has hopelessly corrupted the integrity of many trial reports -- and therewith the integrity of much of the literature -- and it would be rash indeed to base one's judgment of whether SSRIs represent important drugs for depression on the basis of the trial literature. Here, as Barry Blackwell and others have shown, the literature has been heavily influenced by senior clinicians who have really cashed out in alliance with Pharma (and are now disparagingly referred to as KOLs)
So, how do we sort out baby and bathwater? Here clinical science comes to our aid. Experienced clinicians often have a gut feeling for what works and what doesn't, despite what "the literature" says. Take, for example, the issue: Do the SSRI-style antidepressants evoke suicidality in a subset of depressive patients? The epidemiological literature has been unable to confirm a connection. Yet many clinicians have seen in their practices patients becoming suicidal or homicidal after initiating a course of SSRI treatment. Here there is no question: the temporal relationship is powerful and immediate; It happens to their own patients under their own eyes!
If we aggregate these impressions, what we have is clinical science. It is a science not bolstered by epidemiology, because the relationships are submerged in the great mass of numbers. It is a science not bolstered by genetics, because, when you get right down to it, what diseases are reliably caused by genetics? Family tree, for sure, and in our schizophrenic and melancholic patients there are illnesses all over the family tree. But genetics? So far, little has panned out. "Schizophrenia" does not breed true. Yet we know, in our heart of hearts, that these pathological affinities exist in family trees, and it is not a stretch to call this certainty clinical science. The field needs to give this more thought.
One final comment: Barry Blackwell trashes insulin coma therapy as bathwater, a dangerous antique that, thank God, we are rid of. I think a second opinion is possible on ICT. It definitely helped many patients, and not all these patients would have been relieved by neuroleptics. There was something there, something about the effect of insulin on the brain that you have to see to know that it exists, but after you see it, you know it.
Barry Blackwell's Reply to Edward Shorter
Ned Shorter’s comment gives added scope to the issue raised in my essay. One could go further to note that throughout our everyday life we are constantly retaining or discarding all manner of ideas, situations or acquisitions, often on slender or intuitive grounds. However, we tend to cling to what we need, value or pleases us.
But in scientific matters we rely on epistemology to rid us of those domestic reflexive responses in evaluating our own or colleague’s opinions or conclusions. (OED: epistemology; “The theory of knowledge, especially with regard to the methods, validity or scope”).
As a trainee at the Maudsley in the early 1960s under Aubrey Lewis and Michael Shepherd, a core concept of the curriculum was a rigorous and skeptical analysis of all therapeutic claims, a reaction to centuries of speculative dogma and deductive reasoning bolstered and backed up by charismatic clinicians and their reputation among peers (Blackwell and Goldberg 2015).
It was Aubrey Lewis’s goal for the Institute he founded to transform European psychiatry into a scientific discipline on an equal footing with the rest of medicine while America was still mired in psychoanalytic mania (Goldberg, Blackwell and Taylor 2015). This scrupulous ideology sanctified controlled double-blind trial designs which promptly rid the world of insulin coma, but snared me in trouble over Schou’s discovery of lithium prophylaxis, the outcome of astute conclusions based on careful scrutiny of individual patients including his own brother who suffered from treatment resistant recurrent unipolar depression. Unfortunately, the design he chose to support his hypothesis was seriously flawed, encouraging us to make a critical rejection of the conclusions. With hindsight, we were wrong for the right reasons, but in the language of the metaphor “we threw the baby out with the bathwater.” Something we were justly castigated for.
So, this essay, with that title, was triggered by confronting a similar dilemma while writing two book reviews that together constitute a detailed biography of John Cade and his rediscovery of lithium for acute manic excitement in 1949 (Schioldann 2009; de Moore and Westmore 2016). This was the first substance, a metallic ion, to be effective for a specific psychiatric disorder; work which, years later, became the primary stimulus to Schou in his discovery of lithium prophylaxis for recurrent bipolar disorder.
I will not recapitulate the conclusions arrived at in my two reviews but read them for yourself and note they are heavily influenced by the fact that Cade and his discovery have attained a reputation of mythic proportions in Australia and around the world that is impervious to epistemological dispute in the absence of striking new contemporary or collateral evidence which is lacking. Both baby and bathwater remain intact, but the latter is somewhat muddied, blurring an observer’s conclusions.
Finally, I shall make a gentle riposte to Ned’s defense of insulin coma. Undoubtedly the treatment did something for some patients that encouraged a personal conviction of value among some clinicians (Cade was among them). Many more would maintain that, like chlorpromazine, it produced sufficient transitory benefit to justify discharge from an institution, but relapse and readmission were frequent outcomes.
The epistemology of insulin shock therapy leaves much to be desired. To begin with, patients were selected of good prognosis, recent onset and likelihood of remission. In fact, the remission rate did double but it did not reduce the relapse rate. The side effects were severe obesity, prolonged or irreversible coma, brain damage and death (1-5%).
The first and conclusive double-blind study was performed at the Maudsley in 1957 and published in the Lancet where it attracted international attention, provoking an immediate decline in the treatment (Ackner, Harris and Oldham 1957). Opinions were also influenced worldwide before and after the Maudsley study (Bourne 1953; Bourne 1958). Bourne’s succinct opinion was that “It made them (physicians) feel like real doctors instead of just institutional attendants.”
The world took note (Russia was slow), but the overall impact was clear, the baby was gone from the bathwater and nothing of significance remained.
References:
Ackner B, Harris A, Oldham AJ. Insulin treatment of schizophrenia, a controlled study. Lancet 1957; 272 (6969) 607-611.
Blackwell B, Goldberg DP, Sir Aubrey Lewis (minibio) on INHN.org in Biographies; 1.29.2015
Bourne H. The insulin myth. Lancet, 1953; ii 265, 964-968.
Bourne H. Insulin coma in decline. Amer.J. Psychiat. 1958, 114; 1015-1017.
de Moore G, Westmore A. Finding Sanity: John Cade and the taming of bipolar disorder. Australia: Allen & Unwin; 2016.
Goldberg DP, Blackwell B, Taylor DC. Sir Aubrey Lewis on INHN. Biographies. 02.09.2015.
Schioldann J. History of the Introduction of Lithium into Medicine and Psychiatry. Melbourne: Academic Press; 2009.
May 3, 2018