Monday, Apr. 20, 1970

Help for the Manic-Depressive

To the chemist and now to the psychiatrist, lithium is a fascinating substance, the lightest of all the solid elements. Its compounds have had a discouraging history in medicine. Last week, however, lithium carbonate was approved by the U.S. Food and Drug Administration for the treatment of mental patients in the overexcited mania phase of manic-depressive psychosis.

No less remarkable than the properties of the metal itself is the way its compound has won approval, primarily due to the work of Australian Psychiatrist John Frederick Joseph Cade. After 3 1/2 years as a prisoner of war, Cade began to work in a mental hospital at Bundoora, near Melbourne, concentrating on possible biochemical differences be tween the manic and depressive phases of the same patient. Nothing was farther from his mind than lithium, which had been discredited as a hypnotic and again in 1949 as a substitute for table salt. "One can hardly imagine," says Cade, "a less propitious year," especially as the work was being done "by an unknown psychiatrist, in a small hospital, with no research training, primitive techniques and negligible equipment."

No Patent. Cade was led indirectly to lithium by inconclusive experiments with other substances. What he learned from his crude equipment and his guinea pigs was that lithium carbonate had a profound effect on the manic patient.

He took it himself and suffered no harm. He gave it to a male patient, 51, who was "restless, dirty, destructive, who had been in a back ward for five years and bade fair to remain there the rest of his life." In three weeks the patient was better, and he soon went home and back to work. Lithium carbonate, Cade found, appeared to be of little or no value in the treatment of other psychotic states, notably schizophrenia, or in the depressive phase into which most manic patients usually subside.

Danish investigators extended Cade's findings: lithium-treated patients, after remission of their mania, did not become depressed as soon again or as often as those receiving other drugs. But lithium carbonate posed a problem for the drug industry. A common chemical, it could not be patented, so there could be little profit in its manufacture. Any schoolboy could buy it from a chemical supply house for his basement laboratory; the FDA insisted that only research psychiatrists could use it clinically, under rigid rules.

A doctor is still supposed to prescribe it for only one condition, the manic phase of manic-depressive psychosis. Some authorities are concerned that physicians may prescribe the drug too freely, for it may be dangerous. Double the usual prescribed dose can make a person miserably ill, and more might cause coma and death. Yet by this criterion lithium carbonate is no more dangerous than digitalis or insulin. Despite their poor profit prospects, three U.S. drug manufacturers are now marketing the compound as a public service. No one knows how many U.S. mental patients qualify for it: the figure most often quoted is around 100,000.

Researcher Cade could not resist the temptation, as he puts it, of plunging his hand again into the same lucky dip. He tried the salts of other metals closely related to lithium, and drew blanks. Then he turned to strontium, which competes with calcium in many vital biochemical processes and is some how involved in the body's handling of another trace element, magnesium. Again Cade picked the carbonate form as the least likely to upset the stomach. He recently told colleagues that he has tried it on himself and noted "a distinct tranquilizing effect," though he considers himself "a pharmacologically tough animal." He also has preliminary evidence that it relieves schizophrenia symptoms in some patients, although not in others.

No longer an unknown psychiatrist, Dr. Cade is in the U.S. this week to speak in Baltimore at a Taylor Manor Hospital symposium on discoveries in biological psychiatry. There he will suggest that other psychiatrists investigate strontium carbonate, to establish whether in this, as in lithium carbonate, he has found a common chemical to be a useful drug.

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