Samuel Gershon: History of Lithium
Gordon Johnson’s comment


This selective and abbreviated review of lithium focuses on the 80-year period from1947 to 2018 during which lithium generated world-wide interest in its clinical utility and mode of action in the neurosciences and coincided with the author’s professional life in psychiatry and intimately with lithium, giving him a unique and personal experience in this field.

The major focus is a critical review of John Cade’s work with lithium leading to his publication in1949: Lithium salts in the treatment of psychotic excitement (Cade, 1949).

Two sources of information were Johan Schioldann’s 2009 “History of the Introduction of Lithium into Medicine and Psychiatry” and Barry Blackwell’s 2017 review of same and comments and questions raised by contributors to the INHN network. The bulk of the review aims to deconstruct the details and specifics of his studies to obtain a more satisfying explanation of the events recorded and interpreted and whether they meet scientific standards to establish Cade’s studies as original, authentic contributions.

Gershon, a recognised pioneer in lithium research, puts forward a strong argument that it does not. Details of events include the interpretation of the lethargy reported following injection of lithium in guinea pigs. It was speculated that the observed behavior could be a result of lithium toxicity. For Cade this was the “explicable” link leading to his clinical trial of lithium in patients presenting with psychotic excitement. Similarly, the statement that the starting dose of lithium in the clinical trials was a fortunate guess. Cade reported that the doses of lithium contemplated produced no discernible ill effects on the investigator himself. The original therapeutic dose decided fortuitously proved to be the optimum. Is it reasonable to assess scientific standards based on doubts and speculations rather than contrary evidence?

The studies were original although a study of lithium treatment in mania by Hammond in 1871 is cited. Review of lithium use following the publication of Cade’s paper in 1949 is outlined, some of which has been published on the INHN network, including the critical development of a plasma lithium assay by Trautner (which was ground-breaking) allowing safe use of lithium demonstrated in the trial carried out by Noack and Trautner in 1951.

Were Cade’s findings chance or serendipity or as an explicable outcome of his search for an indigenous toxin as he states? Instead he found a treatment, which suggests serendipity. Alternately, Cade recognised quickly the significance of the behavior in his guinea pigs following lithium, which is suggested, moving to a clinical trial in patients with psychotic excitement, which favours chance.

A historical review of lithium use in psychiatry is included with particular emphasis on the work of the Lange brothers in Denmark who used lithium in the treatment of depression.

While questions remain on Cade’s studies, the findings of the clinical trial launched lithium as a specific antimanic drug and the birth of modern psychopharmacology - certainly a scientific legacy.



Ayd FJ, Blackwell B. Discoveries in Biological Psychiatry. Philadelphia:JB Lippincott; 1970.

Blackwell B. Review: Johan Schioldann: History of the Introduction of Lithium into Medicine and Psychiatry: Birth of Modern Psychopharmacology 1949. Adelaide: Academic Press: 2009, The lithium Controversy: A historical autopsy. November 11, 2017.

Cade JFJ. Lithium salts in the treatment of psychotic excitement. Med J. Aust. 1949, 2:349-52.

Hammond WA. Treatise on Diseases of the Nervous System. New York: Appleton; 1871; Mania (358-366) and Treatment (380- 381).

Noack CH, Trautner EM. The lithium treatment of maniacal psychosis. Med J Aust. 1951; 38: 219-22.

Schioldann J. History of the Introduction of Lithium into Medicine and Psychiatry. Birth of Modern Psychopharmacology 1949. Adelaide: Adelaide Academic Press; 2009, pp. 29-31, 100, 140, 147, 230-231, 275, 289.


October 11, 2018