Aging Begins at 30

Lithium Continues To Work Well For Mania

Dr. John Cade watched psychiatrically ill prisoners in a Japanese POW camp in World War II. He decided they had a poison affecting their brain that he might be able to find in their blood or urine. In 1949 in Melbourne, released from captivity, he searched for the poison by injecting patients' urine into the abdomen of guinea pigs. They died. Then he tried fractions of the urine but had a hard time dissolving uric acid so he tried more soluble lithium urate. "After a period of about two hours the animals, although fully conscious, became unresponsive to stimuli." He could turn them on their back and instead of frantic efforts to right themselves they gazed placidly back at him. It also protected the guinea pigs from a convulsive death from urate poisoning.

Dr. Cade then gave lithium to ten manic patients, six schizophrenics, and three patients with major depressions. It didn’t affect the depressives and mildly calmed the schizophrenics, but it changed the manic patients dramatically. Patients who had been chronically maniacally excited, garrulous, violent, euphoric, restless, dirty, unkempt, destructive, and hard to take care of, became calmed and eventually normal. On drug withdrawal they were manic again. He published this result in the Medical Journal of Australia in September 1949.

In America there was a different attitude to lithium because two articles in JAMA in March 1949 demonstrated salt substitute (lithium) toxicity in 11 patients with two possible lithium deaths. But these patients all had low sodiums because of heart failure, and lithium had been continued despite drowsiness, weakness, and generalized tremors. This toxicity was confirmed in rats, but it was prevented by treating with sodium. The FDA banned the use of lithium until 1970. Dr. Cade may never have seen this article.

Lithium was discovered in 1817. The name is the Greek for stone as it was considered (wrongly) never to be in plants or animals. Lithium may be responsible for the reputed benefit of certain spring waters to patients with mental disease.

Lithium continues to work well in mania treatment. The response rate is 80% with a delay of one to two weeks. In practice most clinicians combine lithium with an antipsychotic such as Haldol or a benzodiazepine (such as Ativan) to begin treatment of acute mania. Mania is a component of manic depressive or bipolar disease. Without lithium mania recurs in over half. Lithium reduces this recurrence to less than a quarter in a three-year follow up. Alternatives are to use anticonvulsants such as carbamazepine (Tegretol) or valproate (Depakene), but lithium remains the standard against which all new mood stabilizing drugs are measured. It is safe to use if drug plasma levels are measured five days after any change in dosage. As noted above, sodium levels should be kept steady. The main problem is that when patients feel better they stop their medicine and mania or hypomania with grandiosity, flight of ideas, rapid sometimes incoherent speech, and sleep disturbance returns. Lithium can also be used to enhance the treatment value of standard antidepressant medicines. Hand tremor is troublesome in some patients, but it can usually be controlled with metropolol.

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