Saturday, 25.03.2017

Comment by Samuel Gershon

THE LITHIUM CONTROVERSY - SAMUEL GERSHON’S COMMENT

To my colleagues, Grof, Angst and Blackwell, I wish to add a few comments, not to get into any controversy, but to broaden the picture and bring onto the stage other characters that influenced the nature of play. Firstly, all four of us were contemporaneous with the events starting from Cade’s first lecture on his findings in 1949 and then his publication in 1951. I was, close up, on front stage with the earliest events.

When I finished medical school at the University of Sydney it was necessary to do a rotating internship before you could go to a specialty. During the rotation I had three months psychiatry. The rotation was in 1951 and I read and heard about the lithium report in Victoria. The chief of psychiatry was open minded and did not think too highly of the science in psychiatry. I was allowed during my rotation to treat a few patients with mania with lithium and it went well. So, I decided to get a psychiatric residency in Victoria to have the chance to work at the Royal Park mental hospital, where Cade was medical superintendent. So far everything went well.  But, soon after my arrival to the hospital I learned from the senior resident that there were three death by this time with lithium.  Cade had one, in follow up of his 1950 report, Roberts (1950) had one which he published and Ashburner (1950) also had one in a state hospital. Then one aspect of real controversy began.  As a result of these deaths and verbal discussion in Victoria of lots of side effects, Cade made a public decision that lithium was unsafe for standard clinical usage. So by the time I came as a first year resident in psychiatry to work at Royal Park, Cade had banned the use of lithium in his own hospital. This decision was in effect although Noack and Trautner, in 1951, had published their very important paper using lithium in 100 psychiatric patients. The salient points of this paper were: 1) there were no deaths;   2) in an open setting there was positive efficacy of lithium in manic patients; and 3) Trautner had introduced for the first time the use of routine plasma monitoring of lithium levels in all 100 patients. This was a real controversy. It was heightened by heated statements made by Ashburner (1950) that Trautner’s work was of no value or interest to the practicing physician and this was the attitude adopted by the profession in Australia, except for two immigrant psychiatrists, Glesinger (1954) and Margulies (1955), who got in contact with Trautner and subsequently each published a paper with positive therapeutic responses in mania. 

So, I had fallen on my face. Where to turn for advice? We had started our University courses which included courses with Professor R.D. Wright the Chairman of the Department of Physiology, who was widely regarded as a very nice and helpful guy. So, when I was at the University, for lectures, I went to his secretary and she checked whether the professor was free. He was free and invited me to his office. We spoke for a while for him to decide whether I was a young kook or not. Then, he decided that what I should do is go upstairs to see Dr. Trautner who was working in his Department. My meeting with Trautner was most eventful. We agreed that there was a way to look at the lithium question and several paths will need to be followed to try to answer it. And we travelled this path as close friends, as well as mentor and pupil. It was great. Dr. Trautner was very supportive and we started a number of projects together and went on to publish a number of papers (Gershon 1971; Gershon and |Trautner 1956; Trautner, Morris, Noack and Gershon 1955).

Professor Wright was an important figure in the lithium story, very important in enabling the continuation of clinical work with the substance. He was big in the labour party in the state and he   managed to maneuver a laboratory and a technician for us to do our work. The state department hated him and me but with his help we could fight on.  Nothing was easy when you had the whole psychiatric establishment against you.

This is part of the background. The story of lithium in psychiatry begins in the 19th century (Yeregani and Gershon 1986). So, there was plenty of real and troublesome controversy before the Maudsley Hospital in London got involved.

I will try now as fairly as possible give some of the events at the Maudsley where in those years, in the 1950s, the efficacy of insulin coma therapy (ICT) was studied that I think colored the situation. At the time, the efficacy of insulin coma was a big question, as ICT had the reputation of being the most specific and most effective therapy for schizophrenia. This belief was held worldwide. It was like a delusion, or as Bourne (1953) put it, as a “myth”.  The researchers at the Maudsley could not support the claim for the effectiveness of ICT (Ackner, Harris and Oldham 1957). So, the Maudsley had a case in which they were “myth” busters. Now Shepherd and Blackwell published their criticisms of some of the previous studies of lithium based primarily, in my opinion, on valid scientific grounds. Grof and Angst address these questions in their first presentation in this series. There is no real problem in having a scientific discussion if it is in regard to the published evidence. However, in the next phase of this first Battle of Britain, there entered ad hominem components which were offered to bolster their argument. This was the unpleasant part of this controversy. Aubrey Lewis added some statements which further aggravated this “Controversy”. Barry Blackwell has addressed this issue in his first response to Grof and Angst. Dr. Moncrieff (1997) in her contribution to the old debate fueled only further unpleasantness.
           Now there was a second Battle of Britain, called the “balance study” by Geddes, Rendell and Goodwin (2002) which did produce additional valuable evidence of lithium activity to fill out the picture. So, my hope is that we can call a truce on this old controversy and move onto to some more modern controversies, which lack in great measure the principle of debating an issue based on a scientific and evidentiary basis. Let us get into some of these.

 

References:

Ackner B. Harris A, Oldham AJ. Insulin treatment of schizophrenia: a controlled study. The Lancet 1957; 272: 607-11.

Ashburner JV. .A case of chronic mania treated with lithium citrate and terminating fatally. Med J Austr 1950; 37 (2): 386.

Bourne H. The insulin myth. The Lancet 1953; 265: 964-8.

Cade JFJ. Lithium salts in the treatment of manic excitement. Med J Austr 1949; 2: 349-52.

CadeJFJ. The treatment of the psychiatric excitement with lithium Med J Austr      1951; 2: 219-22.

Geddes JR, Rendell JR, Goodwin GM. Balance: A large simple trial of maintenance treatment of bipolar disorder. World Psychiatry 2002; 1(1): 48-51. 

Gershon S.  Methodology for drug evaluation in affective disorders: mania. In: Levine J, Schiele BC, Bouthilet L, eds. Principles and problems in establishing the efficacy of psychotropic drugs. Washington: American College of Neuropsychopharmacology; 1971, pp. 123-35.

Gershon S, Trautner EM. The treatment of shock-dependency by pharmacological agents. J Med Austr 1956; 43 (2): 783-7.

Glesinger B. Evaluation of lithium in treatment of psychotic excitement. Med J Austr 1954; 34 (1): 277-83.
Margulies M. Suggestions for the treatment of schizophrenic and manic-depressive patients. Med J Austr 1955; 35 (1):137-41.

Moncrieff J. Lithium evidence reconsidered. Br J Psychiatr 1997; 171:1139. .                                  

Noack CH, Trautner EM. The lithium treatment of maniacal psychosis. Med J Austr 1951; 38 (2); 219-22.
Roberts E L. A case of chronic mania treated with lithium citrate and terminating fatally. Med J Austr 1950; 37(2):261-2.

Trautner EM, Morris R, Noack CH, Gershon S. The excretion and retention of ingested lithium and its effect on the ionic balance of man. Med J Austr 1955; 35: 20; 282-91.

Yeragani VK, Gershon S. Hammond and lithium: historical update. Biol Psychiat 1986; 21:1101-2.

 

Samuel Gershon

February 12, 2015