Edward Shorter: The Rise and Fall of the Age of Psychopharmacology 


Peter Martin’s comment


        Edward Shorter takes the reader on a voyage through the very recent history of humankind wherein we have attempted to improve upon disordered psychic functioning using pharmaceutical agents manufactured for tremendous profits by industry.  He relates how scholars of the human condition, who foolishly had hopes and expectations for better, were greatly disappointed by the corporate world that took over from independent clinical scientists who had begun the Age of Psychopharmacology.  Their focus each year became producing a new model, and thereby, reaping still higher revenues.  Unfortunately, instead of improving pharmaceuticals, industrial production seems to have worsened in quality.  Moreover, as a result we are continuing to acquire psychiatric disorders that require pharmacologic treatment at a rate that was previously unimagined but certainly have enhanced profits.  

        Edward Shorter demonstrates in this treatise how it is possible to learn a discipline by examining its history and how history offers a perspective that is insufficiently taught to our young when they begin their own journey in their chosen discipline thereby opening their eyes about what lies ahead.  One important point I should raise at the very start is that I was taught by my high school history teacher Mr. Shackleton that “history is my pack of lies against your pack of lies!”  I found Edward Shorter’s pack of lies compelling and highly educational with the caveat that some may certainly not agree with his views.

        As a psychiatrist from a generation or so after the Founding Fathers of Psychopharmacology I learned much reading this book that I was never taught.  As a resident I was trained to use the tricyclic antidepressants and monoamine oxidase inhibitors, lithium and the first-generation antipsychotics (not to mention the anticholinergics and the benzodiazepines) and started my practice accordingly.  I also learned to tailor treatment to diagnosis as well as to symptomatic and “biologic” endpoints.  I was seduced by selective serotonin reuptake inhibitors and their relative lack of overdose deaths and second-generation neuroleptics that hardly ever required anticholinergics.  Using receptor binding characteristics of new psychopharmacologic agents struck me as profoundly scientific. 

        I personally knew many of those leaders of psychopharmacology and hangers-on who pushed for these advances and was enthralled by the legends of safety and efficacy they told —until my patients were not getting much better without more than one medicine.  This really bothered me because as a clinical pharmacologist I was very much against polypharmacy!  Also, my patients kept complaining of putting on weight (somehow, they didn’t seem to complain about putting on weight as much earlier in my career as they do now) and wanting to try the latest medication about which they learned on television.

        I began to recognize how futile it was to enhance brain functioning by changing the concentrations of individual monoamines (“biochemical imbalance”) and was pleased with the arrival of more “broad spectrum” agents that seemingly modeled the TCAs “without their side effects.” Perhaps as a result of my own basic science research on the role of intermediary metabolism, I became enchanted with the milieu interieur of neurons rather than extracellular concentrations of the monoamines.  I recognized the value of changing neuronal excitability rather than enhancing the activity of one or more monoamine systems.  I began to believe that the real answers resided not in inhibition of bioamine reuptake, but within the cell itself where metabolism and homeostatic mechanisms were regulated in connection with cell channel functioning. 

        I started using anticonvulsants to treat not only bipolar disorders but also depression in impulsive individuals, progressing to irritability and impaired concentration related to personality styles and subclinical brain injury, addiction and most-recently PTSD.  Additionally, my use of lithium has continued to escalate, and I have avoided stimulants.  Of note, the majority of these disorders are still treated with SSRIs by many of my colleagues.  (To be truthful, I must confess that I also treated everything with SSRIs earlier in my career.)  And now the world has come to ketamine, a drug of abuse which is now considered a panacea in modern psychopharmacology!  Of course, the mechanism of action of ketamine harkens to viewing psychiatric illnesses as “channelopathies” rather than insufficiencies of monoamines which supports what I said above.  Addictive potential is concerning as it is for recently rediscovered opioid agonists and psychedelics which have become areas of research interest for various forms of psychopathology.  I could go on, but I will not at the risk of boring the reader. 

        In conclusion, I heartily recommend this book to junior psychiatrists for its historical perspective which hopefully will fill in some of the blind spots in current psychiatric education.  Older psychiatrists will relive their professional lives in an entertaining manner.  For me, this was a journey well worth taking.


May 19, 2022