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Lithium: a slow burner
  1. Andrew J Lees
  1. Reta Lila Weston Institute, Institute of Neurology, University College London, London WC1N 1PJ, UK
  1. Correspondence to Professor Andrew J Lees, Reta Lila Weston Institute, Institute of Neurology, University College London, London WC1N 1PJ, UK; andrew.lees{at}

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It took Mogens Schou and his collaborators two decades to get lithium accepted for the prevention of mania. Along the way he was vilified and his scientific objectivity questioned. These regrettable delays led to many unnecessary suicides. More profitable rebranded anticonvulsants with less efficacy now threaten lithium’s primacy as the gold standard treatment for bipolar 1 disorder

In 1949, Cade reported that lithium could quieten patients with acute manic excitement without causing drowsiness. The rationale for his pilot trial stemmed from a series of experiments he had carried out single-handedly in a disused kitchen in a psychiatric hospital where he demonstrated that lithium salts reduced seizures and deaths in guinea pigs injected with toxic doses of urea. He had also noted that the animals became docile and immobile. Before proceeding to test lithium salts on patients, he then took lithium carbonate himself in increasing doses to evaluate its safety.1

Stimulated by Cade’s paper, Noack and Trautner then gave lithium salts to 100 psychiatric patients and confirmed its selective efficacy for the treatment of mania. They also demonstrated that the clinical measurement of serum lithium levels was feasible and might be a useful addition to careful clinical evaluation in detecting toxicity.2 Cade’s findings published in the Medical Journal of Australia had appeared at a time when reports of toxic reactions caused by excessive intake of a lithium-based salt substitute by cardiac patients were in the headlines in the USA. One or two other Australian psychiatrists also then confirmed lithium’s potential as a better treatment for mania than the current practice of repeated electroshock therapy and high-dose barbiturates but also drew attention to its risks. The dose required to see benefit was close to the toxic range and a fatality that occurred in one of Cade’s own patients led him to temporarily ban lithium’s use following his appointment as the new Medical Superintendent at the Royal Park Mental Hospital in Melbourne.

The treatment of manic psychoses by the administration of lithium salts

Authors: Schou M, Juel-Nielsen N, Stromgren E, and Voldby H

Year published: 1954

Number of times cited: 617

Lithium therapy was teetering on the brink …

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