Letter from Jonathan Cole to Jay Amsterdam in 2004 and e-mail exchange related to it between Max Fink and Jay Amsterdam in 2018


E-mail from Jay Amsterdam to Tom Ban with copies to Max Fink, Barry Blackwell and Edward Shorter, October 29-30, 2018 


I recently came across another, potentially historical, gem that follows on to the recent INHN running commentary about insulin coma therapy. I thought that this letter from Jonathan Cole may be of some interest to you, as well as to Max Fink (who makes a cameo appearance in it).  In the letter, Dr. Cole refers to a chapter that my (then) post-doctoral fellow and I wrote for Owen Wolkowitz’s book on psychoneuroendocrinology (published by the American Psychiatric Press in 2002). I have located the galley proof of the chapter and have also attached it.

When I have a few free moments, I will try to search through old computer files from the time of the letter (i.e., 2004) to see if I can locate any response from me to Dr. Cole.

I hope you enjoy this little slice of neuropsychopharmacology history.




E-mail reply from Max Fink to Jay Amsterdam with copies to Tom Ban, Barry Blackwell and Edward Shorter, October 29-30, 2018   


Thank you for the reminiscence of Jonathan Cole’s broad view of psychopharmacology that, for him, included insulin coma therapy.  He had personal experience with the procedure and was puzzled by the potential mechanisms.  The theories included Manfred Sakel’s Nazi concept that insulin selectively killed off the “bad” neurons of psychosis, the effects on memory (similar to ECT) and my thoughts that the limited efficacy was based on the induced seizures, that ICT was a weak form of Metrazole or ECT seizures.  He urged me and others (Haim Belmaker) to develop clinical studies.  By that time, I had published my RCT of ICT and CPZ, concluding that ICT was a high risk, occasionally fatal, riskful treatment that was no longer justified.  

At a later date I was consulted on the insulin coma applied to the Nobelist John Nash as described in the biography and film A Beautiful Mind. The filmmakers showed the induced seizure in the film. Alas, the benefits of the treatment were transient.  Attempts to sustain the benefits with CPZ devastated Nash physically and mentally.  As Sylvia Nasar wrote in the biography, Nash was offered ECT.  His Princeton colleagues dreaded the damage to "this beautiful mind" and convinced his wife to refuse consent.  (After reading the history and seeing a Nash interview, ECT as we were then learning to do, with C-ECT as an part of the treatment course, would have benefitted him much, since he met the criteria for catatonia, a treatable syndrome.)

Jonathan Cole also was a supporter of the science of pharmaco-EEG, funding worldwide studies that identified many active entities (mianserin, 6-aza-mianserin). discarded as inactive (flutroline), reclassified more appropriately for marketing (doxepin).  When presented with a request for funding of a unproven methodology that required an IBM 1800 computer system (about $1,000,000)  he did not flinch but organized funding across the NIH Institutes.  He had also funded (by a $10,000 supplement) an electronic frequency analyzer at Hillside Hospital  in 1958 through the ECDEU system.  


E-mail response from Jay Amsterdam to Max Fink’s reply Amsterdam’s e-mail with copies to Tom Ban, Barry Blackwell and Edward Shorter, October 29 -30, 2018   


Thanks so much for your thoughtful email. I’m glad that you enjoyed reading Dr. Cole’s letter.

I did not know Dr. Cole very well; although I did have the privilege of meeting with him on several occasions (and exchanged several correspondences with him). I remember him as being an extremely affable and down-to-earth individual – always pushing his bowl of M&Ms (sitting on his desk) toward whomever was sitting across from him.

In this regard, I recall, with fond memories, the day that he arranged for me to present a grand rounds lecture at Mclean Hospital, as a pretense for me to examine one of his private patients, so that I could provide him with a consult on how best to treat the patient with combined TCA / MAOI therapy for her TRD. At that time in my career, I was quite impressed with his humble character and thought how different his personable style was from the researchers that I was used to dealing with at Penn.

After sitting and examining Dr. Cole’s nice patient for about 90 minutes in his office, the three of us walked over to the lecture room where Dr. Cole and his patient listened to my talk on psychopharmacologic treatment approaches for advanced stage TRD.

I will always recall Dr. Cole as a very nice man, who I admired greatly and who I always regarded as one of the “giants” of modern psychiatry research.


March 7, 2019