Barry Blackwell and David Paul Goldberg: Sir Aubrey Lewis and psychopharmacology

Edward Shorter’s Comment

            Barry Blackwell’s trenchant essay on Aubrey Lewis and Psychopharmacology is all the worthier of a second look now, given the continuing lack of progress in discovering new drugs.  Could Lewis’s wisdom possibly have helped us with this and if so, how?

            The key thought here is Lewis’s desire to develop critical thinking in trainees.  Blackwell writes that Lewis sought to inculcate in trainees the “internalization of a high standard of critical capacity.”  It would be fair to say that this is not a major objective of many programs today, where the pedagogic goal seems to be “the internalization of the conventional wisdom.”

            And it is precisely the conventional wisdom of Psychiatry that has led to the doldrums in drug development.  First, we lack suitable drug targets.  You can’t develop drugs for diseases that don’t exist and many of the major disorders in the DSM simply do not exist in nature.  There is no such thing as “Major Depression” and the term embraces a highly heterogeneous clinical population.  Drugs suitable for melancholia might be entirely unsuitable for neurasthenic depression.  There is no such thing as “Schizophrenia.” To be sure, we have not done a super job of unpacking the term into its component illnesses.  Yet, catatonia, at least, has now been withdrawn from the “schizophrenia” package and psychosis may be next.  So, bravo Sir Aubrey!  Encouraging critical thinking among the residents (registrars) will further the downfall of DSM and open the way to describing homogeneous clinical entities for which new agents might successfully be developed.  (It was unhelpful that Lewis himself believed there was only one depression, but never mind:  His critical registrars swiftly despatched this concept.)

            Secondly, critical thinking among trainees means skepticism about the current pharmacopoeia, where scads of “me-too’s” have taken the place of innovation.  Residents will note that current prescribing patterns are often like throwing pieces of spaghetti at the wall to see what sticks.  This is not drug science.  So, critically-thinking trainees (whose minds have not been deadened by decades of agitprop from Pharma) might possibly speculate about what else in the medicine chest could be effective — and they might succeed in persuading reluctant staffers to give it a go.  So much is out there, now forgotten, yet with an effective past record: amphetamines, MAOIs, meprobamate (Miltown), even some of the barbiturates such as sodium amytal.  Let’s think critically here:  Mr. X doesn’t require an “anxiolytic”; he requires sedation; Mrs. Y in the geriatric unit is down in the dumps.  Let’s try dexedrine rather than  risperidone.  These older agents were once successfully used for such indications.  It is entirely unclear that the current crop of SSRIs and “second-generation antipsychotics” (SGAs) are superior to them, but have twice the side effects.

            In many training programs in North America,  it’s all "MDD, MDD, MDD” — and "SSRIs for everything but let’s not forget about the all-important SGAs.”  In the current medicine chest, that’s it.   

            This is not critical thinking.  

            (I know that some readers will respond, “How about clozapine, clearly the most effective of the antipsychotics.  It’s an SGA!.”  Listen.  Clozapine was patented in 1966.)

            One last comment: Blackwell correctly acknowledges Lewis’s skepticism about “anxiety.”  But Emil Kraepelin beat him to the punch and Lewis, who read German fluently, would have been aware of this.  In Kraepelin’s vastly innovative nosology that he originated in the 1890s, there was no role for anxiety as an independent diagnostic entity.  Now we have 10 “anxieties.”  This is surely progress, isn’t it?

June 13, 2019