Lithium Pharmacology - History

History

Lithium was first used in the 19th century as a treatment for gout after scientists discovered, at least in the laboratory, lithium could dissolve uric acid crystals isolated from the kidneys. The levels of lithium needed to dissolve urate in the body, however, were toxic. Because of prevalent theories linking excess uric acid to a range of disorders, including depressive and manic disorders, Carl Lange in Denmark and William Alexander Hammond in New York used lithium to treat mania from the 1870s onwards, though use in the form of spring waters to treat mania were reported in ancient Roman and Greek times. By the turn of the 20th century, this use of lithium was largely abandoned, according to Susan Greenfield, due to the reluctance of the pharmaceutical industry to invest in a drug that could not be patented.

As accumulating knowledge indicated a role for excess sodium intake in hypertension and heart disease, lithium salts were prescribed to patients for use as a replacement for dietary table salt (sodium chloride). This practice was discontinued in 1949 when reports of side effects and deaths were published, leading to a ban of lithium sales.

The use of lithium salts to treat mania was rediscovered by the Australian psychiatrist John Cade in 1949. Cade was injecting rodents with urine extracts taken from schizophrenic patients, in an attempt to isolate a metabolic compound which might be causing mental symptoms. Since uric acid in gout was known to be psychoactive (adenosine receptors on neurons are stimulated by it; caffeine blocks them), Cade needed soluble urate for a control. He used lithium urate, already known to be the most soluble urate compound, and observed it caused the rodents to be tranquilized. Cade traced the effect to the lithium ion itself. Soon, Cade proposed lithium salts as tranquilizers, and soon succeeded in controlling mania in chronically hospitalized patients with them. This was one of the first successful applications of a drug to treat mental illness, and it opened the door for the development of medicines for other mental problems in the next decades.

The rest of the world was slow to adopt this treatment, largely because of deaths which resulted from even relatively minor overdosing, including those reported from use of lithium chloride as a substitute for table salt. Largely through the research and other efforts of Denmark's Mogens Schou and Paul Baastrup in Europe, and Samuel Gershon and Baron Shopsin in the U.S., this resistance was slowly overcome. The application of lithium in manic illness was approved by the United States Food and Drug Administration in 1970. In 1974, this application was extended to its use as a preventive agent for manic-depressive illness.

Lithium has become a part of Western popular culture. Characters in Pi, Premonition, Stardust Memories, American Psycho, "Garden State", and An Unmarried Woman all take lithium. Sirius XM Satellite Radio in North America has a 1990s alternative rock station called Lithium, and several songs refer to the use of lithium as a mood stabilizer. These include: "Lithium Lips" by Mac Lethal, "Equilibrium met Lithium" by South African artist Koos Kombuis, "Lithium" by Evanescence, "Lithium" by Nirvana, "Lithium and a Lover" by Sirenia, "Lithium Sunset", from the album Mercury Falling by Sting, and "Lithium" by Thin White Rope.