History of the Introduction of Lithium
In the test tube, lithium combines with uric acid to produce a soluble
solution, seeming to raise the possibility of removing gouty nodules as well
as preventing uric acid accumulation. Lithium was tried in the 19th century in
the treatment of a large variety of disorders such as uraemia, renal calculi,
gout and rheumaticism. Enthusiasm extended into proprietary medicines and led
to the widespread use of bottled curative waters, many of which are still on
the market eg. Vichy, Perrier, promoted at one time for their high lithium
During the late 1940s, evidence accumulated suggesting cardiac and
hypertensive patients would benefit from a salt-free diet and lithium chloride
seemed an ideal alternative to table salt. Medical reports appeared in 1949
describing severe poisonings and three deaths connected with lithium chloride
and drug manufacturers voluntarily withdrew all lithium salts from the market.
Cade (1949) reasoned that mania was caused by a normal product of the body
circulating in excess. He found that concentrated fresh urine of manic
patients injected intraperitoneally into guinea pigs was often found to kill
more readily than urine from normal persons, schizophrenics or melancholics.
Urea was identified as the toxic substance and in trying to establish how much
uric acid increased the toxicity of urea, lithium urate, as the most soluble
urate, was injected with a urea solution into guinea pigs, seeming to produce
a protective effect. To determine whether lithium salts by themselves had any
discernible effects, lithium carbonate was injected and after a period of
about two hours the animals, although fully conscious, became extremely
lethargic and unresponsive to stimuli for a few hours before once again
becoming normally active. As Cade himself admits "It may seem a long way from
lethargy in guinea pigs to the control of manic excitement, but as these
investigations had commenced in an attempt to demonstrate some possibly
excreted toxin in the urine of manic patients, the association of ideas is
explicable", even if totally fallacious. It can be conjectured that the
docility of the guinea pigs was due to lithium toxicity. Not unusually in
medicine, lithium was introduced through a mistaken hypothesis.
Cade J (1949) Lithium salts in the treatment of psychotic excitement.
Med J Australia 36 349