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Tuesday, 26.05.2020

INHN: Celebration of Max Fink’s 96th birthday
Donald F. Klein for Max Fink’s 96th birthday

 

            I must set the context for this note to the long-forgotten days of the 1950s. 

            In 1958 I was a research scientist at Creedmoor State Hospital in New York. It was a leisurely life with ample time for reading, as well as driving into Manhattan for my training in analysis at the New York Psychoanalytic Institute.

            During this time, I participated in two published clinical trials. One showed that the touted phenothiazine, Mepazine,was placebo equivalent as an add on;the drug was withdrawn. The other,a placebo-controlled trial, showed that the anticoagulant dicoumarol extended the life of demented patients but did not improve cognition.  These were not heartening experiences.

            Meanwhile, I had heard that the 200-bed, psychoanalytic Hillside Hospital in New York had a research opening and told my training analyst, Dr. Kronold, of the possibility to do enhanced human experimentation.  He discouragingly averred: "That was my sadism." Nonetheless, I applied and was cordially interviewed by the new hospital Director, Louis Robbins, an open-minded training psychoanalyst who had supervised the Outpatient Department of the Menninger Clinic in Houston for many years.  When I told him of my bright idea to investigate extra-sensory perception in rats, he did not flinch but sent me to Max Fink, Director of the Department of Experimental Psychiatry at Hillside, who briskly reviewed my training and work. Max was taken aback by my need for psychoanalytic training time off since his principles did not allow time off. Therefore,I was hired on a ¾-time basis. In 1962 I quit psychoanalytic training to become full time.

            Joining Max’s research staff caused my professional life to abruptly change.

            Max was clearly the boss. Remarkably quick, decisive, erudite and substantially more skeptical than me,he was involved in ECT analysis using an EEG analyzer that occupied most of a room. I was hired to find out if the new drugs of the ‘50s actually did new things.

            Max believed that psychiatric diagnosis had been shown to be nonsense (I agreed) and, surprisingly, that antipsychotics and antidepressants were not actually different. In those ancient times, New York City supported costly psychiatric inpatient facilities for indigent citizens. To cap costs there was a 90-day treatment limit.  Amazingly, Hillside had negotiated an indefinite length of stay that averaged 10 months. We did not realize that this was a completely unique setting for psychopharmacological research. The standard treatment by the residents was psychotherapy three times a week. Drugs were disdained but used (also the pattern at the psychoanalytic Menninger Clinic and Yale Psychiatric Institute in Connecticut) and were closely supervised by senior analysts whose training was quite obscure.  

            Max strikingly believed that clinical routines should be subservient to research needs and was quite successful in negotiating changes. For instance, Max and Lou Robbins agreed that all psychopharmacological orders were to be written by me.  I would write any resident's orders, but they had to talk to me first. I never disagreed but pressed for their exact reasons. Further,I would interview the patient, the supervisor and the ward staff, taking verbatim notes. This continued every week.  It exposed me to the far-from-systematic range of pharmacologic practice and patient response. Patients were regularly admitted to Hillside while on several drugs. They were maintained on the basis of not rocking the boat. 

            Max took the stand that the need for hospitalization clearly indicated the drug’s uselessness, so they should be withdrawn. This became a clinical mandate: every patient was weaned from all psychopharmacological agents during their first month. This went remarkably smoothly. Any emergency call for medication was promptly answered by me. The majority did not need any emergency medication.                                              

             Two papers emphasizing changes induced by imipramine (IMI) and chlorpromazine (CPZ) were published in 1962.These also established useful dosages for our clinical trial.

            Max proved to be an exact, demanding editor. My first paper was submitted to him expecting usual perfunctory approval.  It was returned with a mass of specific criticisms. Rewritten and resubmitted it was promptly returned with a new critical mass.  As I recall this exasperating cycle repeated about 17 times interspersed with much argument. However, it was an invaluable learning experience. Such close critical review is not a feature of standard psychiatric research education.

            Max's skepticism about diagnosis and drug effect was put to experimental test by our major study. All patients regardless of diagnosis who required medication were referred to the research department. Most entered our clinical trial.

            After much discussion, eventually including Lou Robbins, it was decided to do a fixed-dose, 6-week, randomized, double-blind clinical trial of placebo, IMI (increased to 300 mg/d by 4 weeks), CPZ modified by anticholinergic procyclidine (increased to 1200 mg/d CPZ by week4 + 15 mg procyclidine). All medications were delivered in a highly flavored liquid vehicle. This prevented knowledge of weekly dosage changes. This trial was initiated before the era of informed consent. There was much methodological suspicion that patients’ knowledge that they might receive a placebo would radically alter their behavior. Therefore,the hospital Director, Lou Robbins,  agreed that patients would not be informed of the nature of this clinical trial so that  change evaluations should be as unbiased as possible. 

            We found that the distinction between schizophrenics who were retarded or activated (which probably included some misdiagnosed  psychotic depressives) and depression was sound, since IMI was of substantially less benefit than CPZ in those schizophrenics. CPZ did not benefit normoactive schizophrenics.

            Max’s beliefs were partially supported since IMI and CPZ had equivalent marked benefit for depressives. This was not due to CPZ benefits for agitation that quickly occurred. But like IMI, there was a marked mood shift at about three weeks. So-called antipsychotic treatment disappeared from depression treatment when knowledge of tardive dyskinesia (TD) developed. Besides it did not fit any of the “basic” theories of causation of depression. With the current development of antipsychotics, with less potential for TD, they are being used, so far, as adjuncts to anti-depressives. The lack of fit with theory continues to be ignored. This trial reaffirmed the benefit of IMI for apparently spontaneous panics. It was independently replicated 15 years later.

            Max departed to be head of the promising brand-new Missouri  Institute of Psychiatry in 1963.

 

January 17, 2019