Thursday 5 September 2019

Mind Fixing

Readers of this blog who mostly visit to see photos might want to skip this entry.
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My recent retirement has given me the opportunity to review some issues in my life. The trip around Morocco, Spain, Portugal and the UK was an opportunity to revisit places and people who had been special in my past. In this blog entry I want to review my career in psychiatry.

In 1975, when I was 26, I was working as a medical registrar in Palmerston North, NZ. 'Medical Registrar' means that one is in a training program, aiming at becoming a physician, or medical (not surgical) specialist. There are many different medical specialties, such as cardiology, rheumatology, endocrinology, etc.  I hadn't decided which of them to pursue, but was interested in endocrinology.

My mother, in particular, was very proud of this. She and my father had been the house doctors during the war for Professor Bruce Perry, the professor of Medicine at Bristol University. In her pantheon, Prof Perry was pretty much equal to God. The family has a strong tradition of medicine; I am in the fifth generation of doctors. With the exception of Uncle Jim, who was an anaesthetist, all the others have been GPs. The first of the medical line was born in 1816.

This was the context when I made the decision to leave the medical training program and shift to training in psychiatry.

'Oh, no!' said Mum, 'Where did I go wrong?'

My decision is discussed in an article The Phoenix Club: A Programme for Adults Who Were Traumatized in Childhood. Basically I had attended an encounter group in Wellington, and had been very impressed. I perceived the two career options of medicine or psychiatry as being a choice between a well established field (Medicine) in which the major building blocks of knowledge had been sorted (Double helix of DNA, principles of immunology, atherosclerosis, etc) and the relatively new area of psychiatry and neuroscience which might hopefully be at the beginning of a (say) 200 year expanding curve. I thought it would be more interesting to be in a novel field, than one in which I would be cooking with other peoples' recipes.

So how did it work out?

Firstly, it has given me an interesting working life, which permitted me more life-work balance than many doctors enjoy. I have no regrets on that score.

But I think my assumption that 1975 was at the beginning of a boom in neuroscience was wrong. 

A book I have found illuminating about some of these issues is: Mind Fixers: Psychiatry's Troubled Search for the Biology of Mental Illness. by Anne Harrington, a Professor of the History of Science at Harvard.

Good review/prĂ©cis herePsychiatry’s Incurable Hubris, by Gary Greenberg. 
Interview with Anne Harrington 'The Structure of Psychiatric Revolutions' by Awais Aftab.



Psychiatry's problem is that it lacks a secure philosophical foundation.

There have been many attempts to find a secure foundation for psychiatry over the last couple of centuries.

In the nineteenth century, the medical superintendents of big psychiatric hospitals tended to put their faith in post-mortem examinations of their patients brains. Not a lot came of it. 

Silas Weir Mitchell, a neurologist, said in 1894.

'What is the matter? You have immense opportunities, and, seriously, we ask you experts, what have you taught us of these 91,000 insane whom you see or treat? . . . Where are your annual reports of scientific study, of the psychology and pathology of your patients? . . . We commonly get as your contribution to science, odd little statements, reports of a case or two, a few useless pages of isolated post-mortem records, and these sandwiched among incomprehensible statistics and farm balance sheets.'

Emil Kraepelin (1856 –1926) tried to correct this. He agreed that post-mortems without clinical information were worthless, and emphasized detailed longitudinal histories. He classified different conditions and separated Dementia Praecox (now known as Schizophrenia) from Manic-Depression (now known as Bipolar Disorder). 

Adolf Meyer carried on Kraepelin’s perspective, and trained many psychiatrists in the US from his department at Johns Hopkins University from 1908.

There was a distinct split between the superintendents of the big lunatic asylums, who were called alienists, (later psychiatrists), and on the other hand neurologists, who mostly worked outside hospital and saw a different clientele.

The neurologists often saw patients for whom they could find no logical anatomical lesion, in particular hysterical paralyses. They became the professionals who tended to explore psychological approaches to mental disorder.

One of those neurologists was Sigmund Freud.


The tension between the organic psychiatrists and the psychological psychiatrists has persisted to this day. The former tended towards biological explanations and treatments like drugs and ECT. The latter tended towards psychotherapies. 

It was a major division during my training in the late 1970s. 

It is possible to see the swings between the biomedical model and the psychosocial model as following the pattern of a dialectic; Thesis, Antithesis, and Synthesis (which becomes the next Thesis).

There was a sort of armistice created by a physician/psychiatrist George Engel in 1977. He promoted his Bio-Psycho-Social model for both medicine and psychiatry. At best it has been a useful synthesis, at worst it has been a slogan for trying to keep the peace between pill doctors and talk doctors.

Derek Bolton and Grant Gillett (2019). An eBook, free to download.

Whereas for most of the postwar years most American psychiatric centres and Medical Schools had been dominated by Freudians, in the mid 1970s there was a revolt led from Washington University in St. Louis. It was expressed in a manifesto.

1) Psychiatry is a branch of medicine. 
2) Psychiatry should utilize modern scientific methodologies and base its practice on scientific knowledge. 
3) Psychiatry treats people who are sick and who require treatment for mental illness. 
4) There is a boundary between the normal and the sick. 
5) There are discrete mental illnesses. Mental illnesses are not myths. There is not one, but many mental illnesses. It is the task of scientific psychiatry, as of other medical specialties, to investigate the causes, diagnosis, and treatment of these mental illnesses. 
6) The focus of psychiatric physicians should be particularly on the biological aspects of mental illness. 
7) There should be an explicit and intentional concern with diagnosis and classification. 
8) Diagnostic criteria should be codified, and a legitimate and valued area of research should be to validate such criteria by various techniques. Further, departments of psychiatry in medical schools should teach these criteria and not depreciate them, as has been the case for many years. 
9) In research efforts directed at improving the reliability and validity of diagnosis and classification, statistical techniques should be utilized.
Gerald Klerman 1978

One of the leaders of the St Louis group, Robert Spitzer, played an important role in defusing the antagonism towards psychiatrists expressed by gays, after the Stonewall riots in 1969. He got the APA to depathologize homosexuality. He also led the development in 1980 of the third edition of the APA's Diagnostic and Statistical Manual (DSM-III) which radically changed the catalog of mental disorders. It represented a major shift away from the Freudian approach back towards the Biomedical approach.

Forty years on, how has the biomedical approach paid off?

Not too well. 

To give one example, in February 2018 there was a review of the efficacy and acceptability of 21 antidepressants done by a group at Oxford University.  



This shows the relative efficacy of the different antidepressants, with the best one being amitriptyline. Amitriptyline was released in 1961.

If there was general progress in this field, and one plotted efficacy against time, one would get a graph rising from low on the left to higher on the right as efficacy improved.

The Picture of Progress

But if one plots the drugs in this study by the dates of their release, this is what you get.

The Actual Picture

This does not show progress, in efficacy, over the last nearly 60 years.

One problem has been that most drug research uses mice, on the assumption that mice have similar biology to humans. This is increasingly in doubt. See this recent article. The mouse as a model for neuropsychiatric drug development. It includes the comment: 'We are in the midst of a crisis in neuropsychiatric drug development. Only 9% of neuropsychiatric drugs entering clinical trials succeed and go on to market, one of the lowest rates across all therapeutic areas'.


Critics of psychiatry commonly make the charge that the field has been corrupted by the pharmaceutical industry, known as Big Pharma. They allegedly make huge profits and persuade psychiatrists to become pill-pedlars pushing drugs rather than listening and caring about patients.

The inconvenient truth is that many of the most important drugs are actually pretty cheap, and don't make anyone much money. Furthermore, psychiatric drugs are a tiny part of the pharmaceutical industry, and far from making the companies lots of money, a majority of drug companies are abandoning psychiatry, or at least reducing their investment in it.

'The ‘annus horribilis’ suffered by European neuroscience in 2010 as the result of GSK, AstraZeneca, Pfizer, Merck and Sanofi all announcing significant reductions in their research efforts into traditional drug discovery for the treatment of neuropsychiatric disorders has been well documented'. (Nutt and Goodwin, 2011)



According to the CEO of NI Research, Harry Tracy, investments in psychopharmacological drugs have declined by 70% in the last 10 years.


Psychiatric drugs are pretty small beer


Within neuroscience, psychiatric disorders are a small part.


In another respect, confidence in the DSM approach to classification has also dropped. In 2013 the fifth edition DSM-5 was released. Dr Tom Insel, Director of the National Institute of Mental Health (NIMH) dissociated it from DSM. ‘It has 100% Reliability and 0% Validity’. ‘Biology never read that book!’

Looking back at Klerman's manifesto above, a cynic would reply to some of the items with 'You wish!' For example:

5) 'There are discrete mental illnesses.' 

It would be much easier if it were true. Many scientific methods are predicated on the idea of applying a discrete intervention to a discrete phenomenon and predicting and then confirming the consequence. Think of sending a discrete billiard ball at another discrete ball and predicting from speed and angle whether the ball would go into a pocket. 

But in psychiatry, although specific drug molecules are discrete, patients' collections of biological, psychological and social properties are not. And psychotherapy is not discrete. There is no sharp line between psychotherapy and a social conversation. So science in these areas is more like blowing a puff of smoke at another puff of smoke and trying to predict the outcome. Add in a bit of free will, and any attempt to claim 'scientific proof' requires a lot of unscientific faith.
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Thinking about it all in hind-sight, it seems to me that a series of serendipitous findings over the years have sparked excitement, with enthusiasts hoping that the discovery could be generalised widely. 

As if finding one nugget of gold could lead to a successful gold-rush.




To follow that analogy, a series of events led to hopes being raised, with wide generalisations failing to prove true.

1) The discovery by Richard von Krafft-Ebing (1840-1902) that General Paresis of the Insane (GPI) was caused by syphilis. He injected pus from syphilitics into the blood of GPI patients! They didn't develop syphilis, proving they had already had it before. Later (1913) spirochaetes were discovered in the brains of GPI patients. It led to hope that other mental disorders would prove to have an infectious origin.

2) Freud looked for unconscious trauma (as in the histories of hysterics).

3) Orthomolecular psychiatrists looked for the missing vitamin (like B3 in pellagra).

4) John Cade was a POW in Changi in WWII. He saw madness in prisoners, and thought it might have been caused by a toxin. After the war, he injected the urine of patients into guinea pigs. All died. He wanted to try urates, but most are insoluble. Lithium urate is soluble so he tried that. The guinea pigs seemed ‘chilled out’, so he tried lithium carbonate on himself, then manics, depressives and schizophrenics. Manics were helped most.

5) Chlorpromazine, the first anti-psychotic drug was discovered by accident when Rhone-Poulenc was trying to create an antihistamine.

6) Imipramine, a tricyclic anti-depressant, was discovered by accident when Geigy was trying to develop a cheaper anti-psychotic similar to chlorpromazine.

7) Mono-amine oxidase inhibitors, a class of anti-depressants, were discovered when iproniazid was used to treat patients with TB, and they became more cheerful.


8) Pharmacologists extrapolated back from drug effects to neurotransmitters (as worked with dopamine for Parkinson’s). But what was true for Parkinson's was not true for mood disorders.

9) Geneticists found the gene for Huntington’s. Now Genome-wide association studies show 108 loci for schizophrenia, and 44 for major depression. It isn't as simple as finding one mad gene.

Time and again hopes have been raised, only to be disappointed. 

‘To every complex question there is an answer that is simple, elegant, and wrong’. HL Mencken

My feeling now is that the weakness of psychiatry is unlikely to be resolved by a breakthrough in drug or psychotherapy research. Rather what is needed is a more solid epistemological base or philosophical foundation for the enterprise.

A tentative exploration of one such option can be found in the writings of Professor Paul McHugh in 'The Perspectives of Psychiatry'  This interview explains his ideas. Explanatory Methods in Psychiatry: The Importance of Perspectives.

He specifies four key perspectives:
  • Disease Perspective
  • Dimensional Perspective
  • Behavioral Perspective
  • Life Story Perspective
If I were teaching registrars today, I should suggest McHugh's book as part of the course.

Another interview 'The Rise and Fall of Pragmatism in Psychiatry' with Prof Nassir Ghaemi is interesting.

Aftab: If Robert Spitzer had never created DSM-III, do you think the field of psychiatry would be in a better or a worse place today? In other words, do you see DSM’s legacy as largely beneficial or harmful?

Ghaemi: I have no doubt psychiatry would have been better off without DSM-III and, more importantly, its successors DSM-IV and DSM-5. I know the usual mantra: DSM-III provided a common language in a time of Freudian babble; it allowed for reliability. This small advantage is far outweighed by what happened with DSM-IV and DSM-5: the dictionary of a common language became a fundamentalist Bible that we all have to believe and buy (to the benefit of the American Psychiatric Association treasury and the royalties of DSM leaders). Psychiatry has been frozen in 1980, and hence the absence of progress since then is no surprise. Thus, DSM’s legacy has been largely harmful. Forty years and two generations later, I do not understand how our profession can defend standing still.

Dr Thomas Insel wrote 'Healing: Our Path from Mental Illness to Mental Health'.  This book review gives a succinct account of the issues facing psychiatry. 'Thomas Insel Makes A Case for Abolishing Psychiatry' Robert Whitaker -April 30, 2022.

Tuesday 3 September 2019

Grass trees recovering after a bush-fire

We had a mini-break near Noosa, about three hours north of our home.

Near the AirBnB where we stayed, there had been a bushfire, probably deliberately lit as part of fire risk management. A mass of grass trees had resprouted after the fire, and I took these photos. I thought they provided a beautiful image of resilience and recovery.