Dr. Ron’s Research Review – June 13, 2012

This week’s research review focuses on Lithium with an emphasis on its history.

Before its introduction into modern psychiatry, lithium was widely consumed, usually in water from lithium springs. The lithium content was negligible - at least 150,000 gallons per day of Buffalo Lithia Water would have to be consumed to obtain a therapeutic dose.

Medicinal interest in lithium began in the mid-1800s when A. Lipowitz and Alexander Ure described the ability of lithium solutions to dissolve uric acid crystals in vitro. In 1871, William A. Hammond, M.D., former U.S. Surgeon General, described the use of lithium bromide as a treatment for mania.

John Cade is credited with discovering the calming anti-manic effect of lithium in the late 1940's.  Conducting experiments in his kitchen, he found that guinea pigs ingesting urine concentrates from manic patients showed toxic effects, whereas that from normal individuals did not. Urea ingested alone produced toxicity, but to a lesser degree. He hypothesized that uric acid is a possible contributor to this phenomenon. In order to test his hypothesis he increased the solubility of uric acid by adding lithium carbonate to urine. After administering lithium carbonate along with the urea and creatinine, Cade observed a significant reduction in toxicity. Cade speculated that mania might be caused by lithium deficiency. (Abhishekh and Faizan 2012)

The main student and proponent of lithium use was the Danish psychiatrist Mogens Schou (1918-2005). Schou started to examine the clinical properties of lithium as a young psychiatrist during the early 1950's. Lithium remained his “life-long obsession.” He published well over 500 articles on lithium.  (Schou, Juel-Nielsen et al. 1954)

Dr. Ron


Abstracts

John Cade (1912-1980)

            (Abhishekh and Faizan 2012) Download

It was in his kitchen in Bundoora, Victoria, Australia that John Cade conducted the experiments that would convey his name to posterity. During the course of his experiments he found that guinea pigs ingesting urine concentrates obtained from manic patients showed toxic effects, whereas guinea pigs ingesting urine concentrates from normal individuals did not. He also found that urea ingested alone produced toxicity, but to a lesser degree. He hypothesized that uric acid is a possible contributor to this phenomenon. In order to test his hypothesis he increased the solubility of uric acid by adding lithium carbonate to urine. After administering lithium carbonate along with the urea and creatinine, Cade observed a significant reduction in toxicity (Cade, 1949).

Old but still gold: Lithium in stabilizing the mood

            (Balon 2009) Download

Lithium--early development, toxicity, and renal function

         (Johnson 1998) Download

The report of the effectiveness of lithium in the treatment of mania by John Cade was followed by a number of studies confirming his observations and developing guidelines for safe and effective use. Premature rejection of lithium on safety grounds denied many patients the benefit of treatment and may have cost more lives than it saved. A similar safety alarm was triggered by reports of kidney damage in the late 1970s. Subsequent reports have questioned the significance of anatomical findings, and functional impairment and relationship to lithium treatment. Recent findings support the conclusion that progressive impairment of glomerular and tubular function in patients during lithium maintenance is the exception rather than the rule and is related more to lithium intoxication, maintenance plasma lithium levels, concurrent medications, somatic illness, and age than on time on lithium. Guidelines for lithium use and monitoring of renal function are outlined.

The treatment of manic psychoses by the administration of lithium salts

            (Schou, Juel-Nielsen et al. 1954) Download

References

Abhishekh, H. A. and S. Faizan (2012). "John Cade (1912-1980)." Aust N Z J Psychiatry 46(1): 68-9.

Balon, R. (2009). "Old but still gold: Lithium in stabilizing the mood." Indian J Psychiatry 51(2): 157-8.

Focosi, D., A. Azzara, et al. (2009). "Lithium and hematology: established and proposed uses." J Leukoc Biol 85(1): 20-8.

Johnson, G. (1998). "Lithium--early development, toxicity, and renal function." Neuropsychopharmacology 19(3): 200-5.

Schou, M., N. Juel-Nielsen, et al. (1954). "The treatment of manic psychoses by the administration of lithium salts." J Neurol Neurosurg Psychiatry 17(4): 250-60.