Lithium: A Brilliant Discovery

Colette Dowling, M.S.W.


Lithium is drug whose fascinating history not many people know about. The modern era of pharmacotherapy began in 1949, when Australian psychiatrist John Cade serendipitously discovered a cure for mania. "What happened was one of those wild bounces that makes this kind of research both fascinating and a humbling game," wrote the noted research psychiatrist Nathan Kline, tracing the early history of mood-ltering drugs in "From Sad to Glad".

Cade didn't begin with grand expectations. He suspected that manic behavior might be the result of some toxic substance from the nervous system, and he wondered if excesses of it might turn up in the urine. To compare the urine of manic depressives with that of ordinary depressives, schizophrenics and normal controls, he relied on a method he knew was primitive. He injected guinea pigs with urine samples from the four types of subjects. Some animals barely reacted at all;others were seized with violent convulsions. One fact immediately became apparent: the urine from the manic depressives produced these seizures with doses three to four times SMALLER than urine from the other groups.

Cade thought there must have been some catalyst in the urine of the manic depressives--possibly uric acid. He ran the tests again with an extra injection of uric acid, which he diluted in a solution using lithium salts, since they combine readily with the acid. When it turned out that the solution was indeed less toxic, he tried injecting lithium alone--and hit bingo. Lithium produced remarkably calming efffects on the laboratory animals.

Cade tried his new idea on ten manic patients. One of his patients was "a wizened little man of 51 who had been in a state of chronic manic excitement for five years." Restless, dirty, and interfering, he had been thought a nuisance on the back wards and "bid fair to remain there," said Cade, "for the rest of his life." The treatment began on March 29,1948. Five days later it was obvious that the man was more settled, tidier, less disinhibited. "From then on, there was steady improvement, so that in three weeks he was enjoying the unaccustomed and quite unexpected amenities of a convalescent ward." In two months Cade's "wizened little man", who had been hospitalized for years, was able to return home to a normal life.

It took the careful work of others, in particular Mogens Schou of Denmark, to establish that lithium is reliable in the long-term maintenance of bipolar (manic depressive) mood disorder. By the 1960s, lithium was successfully used in some forty countries--but not in the United States. Here it remained restricted to experimental use until 1971. "When we complained, we were informed that other countries lacked our high standards of safety," wrote Nathan kline, a pioneer in the use of drug therapy for mental illness in the United Sates.

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Colette Dowling is best known for uncovering women's psychological conflicts with independence in her best-selling The Cinderella Complex: Women's Hidden Fear of Independence. She has also written on the unique mental health issues of midlife women in her book, Red Hot Mamas: Coming Into Our Own at Fifty.

Colette is a graduate of The Smith College School for Social Work, where she received an M.S.W. She has done advanced training at The Institute for Contemporary Psychotherapy, in New York city. Ms. Dowling has a private therapy practice in New York and specializes in the treatment of women and couples.

For more information on mood disorders, or to seek a consultation with Colette Dowling, see her profile at Psychology Today.

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Copyright Colette Dowling, 2006-2010
Contact: dowlingcolette@earthlink.net